Automation of ePROMs in radiation oncology and its impact on patient response and bias.

PURPOSE: This study evaluates the impact of integrating a novel, in-house developed electronic Patient-Reported Outcome Measures (ePROMs) tool with a commercial Oncology Information System (OIS) on patient response rates and potential biases in real-world data science applications. MATERIALS AND METHODS: We designed an ePROMs tool using the NodeJS web application framework, automatically sending e-mail questionnaires to patients based on their treatment schedules in the OIS. The tool is used across various treatment sites to collect PROMs data in a real-world setting. This research examined the effects of increasing automation levels on both recruitment and response rates, as well as potential biases across different patient cohorts. Automation was implemented in three escalating levels, from telephone reminders for missing reports to minimal intervention from study nurses. RESULTS: From August 2020 to December 2023, 1,944 patients participated in the PROMs study. Our findings indicate that automating the workflows substantially reduced the patient management workload. However, higher levels of automation led to lower response rates, particularly in collecting late-phase symptoms in breast and head-and-neck cancer cohorts. Additionally, email-based PROMs introduced an age bias when recruiting new patients for the ePROMs study. Nevertheless, age was not a significant predictor of early dropout or missing symptom reports among patients participating. Notably, increased automation was significantly correlated with lower response rates in breast (p = 0.026) and head-and-neck cancer patients (p < 0.001). CONCLUSION: Integrating ePROMs within the OIS can significantly reduce workload and personnel resources. However, this efficiency may compromise patient responses in certain groups. A balance must be achieved between workload, resource allocation, and the sensitivity needed to detect clinically significant effects. This may necessitate customized automation levels tailored to specific cancer groups, highlighting a fundamental trade-off between operational efficiency and data quality.

[Burnout : Symptoms, diagnostics and treatment approaches]. / Burnout : Symptomatik, Diagnostik und Behandlungsansätze.

Burnout syndrome is characterized by the triad of symptoms exhaustion, mental distance from work activities and a feeling of ineffectiveness. The syndrome is not an independent mental disorder but can be coded in the 10th Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) as a problem related to difficulties in coping with life (Z73) and in ICD-11 as a qualifying diagnosis (QD85). This article discusses the prevalence and comorbidities of burnout syndrome, taking the methodological difficulties in conceptualizing and operationalizing the construct into account. In addition, it provides an overview of available measurement instruments and their validation. Furthermore, it discusses work-related and individual factors in the development of burnout syndrome as well as analysis of the effectiveness of treatment options.

Combined analysis of five non-interventional studies of the effectiveness, tolerability, and safety of the extrafine fixed dose beclomethasone/formoterol combination in the treatment of asthma in Austria.

OBJECTIVE: The real-world effectiveness and tolerability of an extrafine fixed dose beclomethasone/formoterol (BDP/FF) treatment of patients with partially or non-controlled asthma was evaluated in five non-interventional studies (NISs) from Austria. METHODS: Asthma patients enrolled in these five NISs were treated with beclomethasone/formoterol (Foster® or Foster® Nexthaler®) as maintenance and reliever over 12 weeks. Asthma control, lung function and symptom scores were assessed at baseline, after 4-8 weeks and at the end of the investigations in week 12. In addition, tolerability and handling of the devices were evaluated by questionnaires. RESULTS: The combined analysis included 891 patients (53% female, aged 49.3 years) demonstrating significant improvements in asthma control, lung function parameters (PEF, FEV1 and FVC) and symptom scores (reduction of breathlessness, wheezing, chest tightness and cough). These changes were already detectable after 4-8 weeks. The treatment was effective irrespective of smoking status, exercise, or previous medication. Tolerability of the therapy with extrafine BDP/FF was rated as "very good" or "good" in 98% of the patients. 95% of the patients intended to continue the treatment, and nearly all (99%) rated the handling of the device as "very good" or "good". No serious adverse reactions were reported. CONCLUSIONS: This combined analysis of five non-interventional studies confirms the effectiveness and tolerability of the extrafine fixed-dose BDP/FF combination (Foster® and Foster® Nexthaler®) in a heterogenous patient population suffering from partially or non-controlled asthma. Therapy was associated with a high patient satisfaction and the absence of serious adverse reactions.

Pectoralis major injuries in the military: a surveillance approach to reduce an underestimated problem.

INTRODUCTION: Multiple studies report increasing cases of surgically treated pectoralis major (PM) muscle and tendon ruptures in military populations. Studies associate this with a growing popularity of weight-training and bench press exercises. Mild-to-moderate non-surgical PM traumas and overuse injuries have not been included in these studies despite evidence that these types of outpatient injuries account for the majority of the military's injury medical burden. METHODS: To assess rates of all PM injuries (ruptures, tears, strains, overuse), regardless of form of treatment, a PM injury surveillance definition was derived from International Classification of Disease (ICD) diagnostic codes used in routine US Army injury surveillance. A detailed clinical examination of 2016 Active Duty Army medical records was used to identify ICD codes commonly associated with PM injuries. Cost data were calculated and the definition applied to medical data from 2016 through 2018to assess trends. RESULTS: The estimated incidence of PM cases among soldiers was over 95% greater than if only considering severe surgical cases. Over 96% of army annual PM injury costs (direct medical and indirect from lost labour) were for outpatient services. PM injury incidence rates were not statistically different from 2016 to 2018. CONCLUSIONS: The PM injury surveillance definition provides a consistent means to monitor trends over time and evaluate the effectiveness of prevention efforts. PM injuries have a larger military impact than previously recognised and prioritised prevention strategies are needed to reduce them. Future interventions could focus on the bench press given its observed association with PM injuries.

A spectrum of findings on computed tomography in paediatric abdominal and pelvic tumours in a Ghanaian teaching hospital

Objectives: To review the Computed Tomography( CT )features of pediatric oncological patients with abdominal and pelvic tumours and correlate these findings with their histopathological diagnosis Design: This was a retrospective cross-sectional facility-based study. Setting: This study was conducted in the Pediatric Oncology Unit and Radiology Department of the Korle Bu Teaching Hospital Participants: Fifty-six pediatric oncology patients with contrast-enhanced abdominal and pelvic CT scans. Data Collection: The abdominal and pelvic CT scans findings, patient biodata, and histopathology reports of oncology patients over four years were reviewed Statistical analysis: Simple descriptive statistics using frequency distribution, percentages, means, and standard deviation were used to describe the various variables and presented tables. Results: The four commonest tumours were nephroblastoma, neuroblastoma, lymphoma, and hepatoblastoma. The mean age at diagnosis was 4.8 years, with a slightly higher male predominance. The majority of the tumours were extremely large at presentation. Overall, the CT ­ histopathology concordance was 79.2%. Conclusion: Abdominal and pelvic CT scans play an important role in the diagnostic workup of pediatric malignancies by ensuring early and accurate diagnosis of these tumour

[Historical study of medical geography in Russia].

This article provides an overview of the change of topics in the medical-geographical studies in Russia. It highlights the conventional nature of this science, its dependence on political, ideological and scientific demands as well as institutional difficulties. It concludes that the goal of further historical research is to focus on the restoration of synchronous meanings of medical geography, its links with other disciplines and the elucidation of Russia's participation in the transnational project of medico-geographical research.

Expanding the injury definition: evidence for the need to include musculoskeletal conditions.

OBJECTIVES: The objectives of the study are to quantify the proportion of cumulative microtraumatic overuse injuries in a physically active population, evaluate their impact in terms of lost work time, and link them to precipitating activities to inform prevention initiatives. STUDY DESIGN: The study design is retrospective cohort study. METHODS: For a population of U.S. Army Soldiers, diagnoses from medical records (International Classification of Diseases [ICD]-9 800-999 and selected ICD-9 710-739) were matched with self-reported injury information. Common diagnoses, limited duty days, and activities and mechanisms associated with the injuries were summarized. RESULTS: Most self-reported injuries (65%) were classified by providers with diagnoses that described cumulative microtraumatic tissue damage, and these injuries led to a higher incidence of limited duty (85%) than acute traumatic injury diagnoses. Reported mechanisms and activities often indicated repetitive physical training-related onset. CONCLUSIONS: Because many diagnoses for cumulative microtraumatic musculoskeletal tissue damage are categorized as diseases to the musculoskeletal system in the International Classification of Diseases, they are often not included in definitions of injury. However, reported injury activities and mechanisms in this population provide evidence that cumulative microtraumatic injuries often arise from identifiable and preventable events. This finding confirms that these diagnoses should be classified as injuries in epidemiologic evaluations and surveillance to accurately represent injury burden.

A head coil system with an integrated orbiting transmission point source mechanism for attenuation correction in PET/MRI.

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) provides a benefit for diagnostic imaging. Still, attenuation correction (AC) is a challenge in PET/MRI compared to stand-alone PET and PET-computed tomography (PET/CT). In the absence of photonic transmission sources, AC in PET/MRI is usually based on retrospective segmentation of MR images or complex additional MR-sequences. However, most methods available today are still challenged by either the incorporation of cortical bone or substantial anatomical variations of subjects. This leads to a bias in quantification of tracer concentration in PET. Therefore, we have developed a fully integrated transmission source system for PET/MRI of the head to enable direct measurement of attenuation coefficients using external positron emitters, which is the reference standard in AC. Based on a setup called the 'liquid drive' presented by Jones et al (1995) two decades ago, we built a head coil system consisting of an MR-compatible hydraulic system driving a point source on a helical path around a 24-channel MR-receiver coil to perform a transmission scan. Sinogram windowing of the moving source allows for post-injection measurements. The prototype was tested in the Siemens Biograph mMR using a homogeneous water phantom and a phantom with air cavities and a Teflon (PTFE) cylinder. The second phantom was measured both with and without emission activity. For both measurements air, water and Teflon were clearly distinguishable and homogeneous regions of the phantom were successfully reproduced in the AC map. For water the linear attenuation coefficient was measured as (0.096 ± 0.005) cm-1 in accordance with the true physical value. This combined MR head coil and transmission source system is, to our knowledge, the first working example to use an orbiting point source in PET/MRI and may be helpful in providing fully-quantitative PET data in neuro-PET/MRI.

[Hereditary Macular Dystrophies]. / Hereditäre Makuladystrophien.

Hereditary macular dystrophies are part of the group of inherited retinopathies caused by mutations of specific genes. Challenging features are their rarity, enormous clinical and genetic heterogeneity, unspecific visual disturbances, and often only mild initial fundus changes. The onset of macular dystrophies may occur at any age. They manifest in the macular region, whereas fundus changes can reach the mid periphery as well. In some cases, macular dystrophy can progress into generalised retinal dystrophy, depending on the severity of the causative mutations. Funduscopy alone is often insufficient for diagnosis. However, correct diagnosis is essential for the patient for counseling, low vision aids, support, and therapeutic options. Retinal imaging, with fundus autofluorescence, near-infrared autofluorescence and optical coherence tomography, is very important, as it can show typical changes not visible on funduscopy. In cases where morphological changes are absent, retinal dysfunction must be detected by electrophysiological testing. There has been technical progress in molecular genetic testing in recent years. With the development of modern sequencing, an analysis for all known genes of hereditary retinal dystrophies has been established. The genetic defect can now be identified in more cases than before. However, a correct initial clinical diagnosis is still required for successful genetic analysis. The importance of a genetically confirmed diagnosis is increasing, as this is needed for patients who could have the chance in the near future to participate in therapeutic trials.

Cerebrospinal fluid lipocalin 2 in patients with clinically isolated syndromes and early multiple sclerosis.

BACKGROUND: Lipocalin 2 (LCN2) may be involved in the immunopathogenesis of multiple sclerosis (MS) and might further impact on iron homoeostasis. Brain iron accumulates in MS; however, the association to iron-related proteins is still unsolved. OBJECTIVE: To investigate cerebrospinal fluid (CSF) and serum LCN2, transferrin (Trf) and ferritin in early MS in relation to disease evolution and longitudinal brain iron accumulation. METHODS: We analysed CSF and serum LCN2 by enzyme-linked immunosorbent assay (ELISA) and Trf and ferritin by nephelometry in 55 patients (45 clinically isolated syndrome (CIS), 10 MS, median clinical follow-up 4.8 years) and 63 controls. In patients, we assessed sub-cortical grey matter iron by 3T magnetic resonance imaging (MRI) R2* relaxometry (median imaging follow-up 2.2 years). RESULTS: Compared to controls serum (p < 0.01), CSF (p < 0.001) LCN2 and CSF Trf (p < 0.001) levels were reduced in the patients. CSF LCN2 correlated with CSF Trf (r = 0.5, p < 0.001). In clinically stable patients, CSF LCN2 levels correlated with basal ganglia iron accumulation (r = 0.5, p < 0.05). In CIS, higher CSF LCN2 levels were associated with conversion to clinically definite MS (p < 0.05). CONCLUSION: We demonstrate altered LCN2 regulation in early MS and provide first evidence for this to be possibly linked to both clinical MS activity and iron accumulation in the basal ganglia.

[Heart and combined heart-lung transplantation. Indications, chances and risks]. / Herz- und Herz-Lungen-Transplantation. Indikationen, Chancen, Risiken.

Orthotopic heart transplantation (HTX) is nowadays the worldwide accepted gold standard for the treatment of terminal heart failure. The main indications for HTX are non-ischemic dilatative (54%) and ischemic (37%) heart failure. In the acute phase after HTX the survival rate is approximately 90%. Good short and long-term results with survival rates ranging from 81% after 1 year to more than 50% after 11 years demonstrate that there is currently no real treatment alternative to HTX for treatment of end-stage heart failure. In the case of irreversible pulmonary hypertension in combination with end-stage heart failure or complex congenital heart syndromes, a combined heart and lung transplantation (HLTX) is necessary. Compared with HTX the short-term survival of HLTX is reduced, mostly for technical reasons. Improved long-term results after HTX and HLTX are a result of highly specialized transplantation units and effective immunosuppression. However, a major problem is the shortage of organ donors in Germany and the resulting long waiting times for patients with frequently occurring blood groups of up to 10 months for transplantation. The consequence of the latter is the ever increasing number of implanted cardiac assist devices in patients not only as a bridge to transplant but also as destination therapy.

[Hereditary macular dystrophies in differential diagnosis of AMD]. / Hereditäre Makuladystrophien in der Differenzialdiagnose der AMD.

The onset of hereditary macular dystrophies may occur at all ages and may be the origin of visual disturbances even after the age of 50 years. During the disease course, many macular dystrophies change their fundus appearance, finally leading to a geographic chorioretinal atrophy making it difficult to distinguish the disease form dry AMD. Furthermore, a macular dystrophy associated CNV may be misleading to the diagnosis of wet AMD. Additional fundus autofluorescence and optical coherence tomography imaging are very valuable for delineating macular dystrophies from AMD. In this paper we provide an overview of the important hereditary macular dystrophies which should be considered as differential diagnoses for AMD.

Retinal vessel diameter, obesity and metabolic risk factors in school children (JuvenTUM 3).

BACKGROUND: The prevalence of childhood obesity is high and its association with future cardiovascular disease in adulthood is well established. The cross-sectional data presented analyze the prevalence of obesity and the association between metabolic risk factors, physical inactivity and retinal vessel diameter in young school children. METHODS: The examination included 578 school children aged 11.1±0.6 years from secondary schools in the District of Munich, Germany. Anthropometric measurements and blood sampling were conducted using standard protocols for children. Physical activity was evaluated by use of a questionnaire. Retinal microvascular diameters and the arteriolar to venular ratio (AVR) were assessed with a non-mydriatic vessel analyser (SVA-T) using a computer-based program. RESULTS: In our population, 128 (22.2%) children were overweight (ow) or obese (ob). The mean retinal arteriolar and venular calibres were 208.0±15.6 µm and 236.2±16.2 µm, respectively, with a mean AVR of 0.88±0.01. Girls had significantly wider arteriolar and venular diameters compared to boys (p<0.001). ow and ob children had a lower AVR compared to normal weight (nw) children (mean(95% CI); nw: 0.89(0.88-0.89); ow: 0.87(0.86-0.88); ob: 0.85(0.83-0.87); p≤0.05). Wider venular diameters were independently associated with higher BMI and higher hsCRP. Blood pressure was associated with retinal vessel constriction. Higher physical inactivity and BMI were independently associated with a reduced AVR (p=0.032 and p<0.001, respectively). CONCLUSIONS: Cardiometabolic risk factors and physical inactivity are associated with retinal microvascular alterations in young children, comparable to associations in adults. Retinal vessel imaging seems to be a feasible assessment for the detection of microvascular impairments in children at risk of developing cardiovascular disease in adulthood.

[Combined retinal artery and vein occlusions associated with interferon beta therapy]. / Kombinierter retinaler arteriovenöser Verschluss unter Interferon-ß-Therapie.

Interferon (IFN) beta is commonly used in the treatment of multiple sclerosis. Thromboembolic complications may be associated with this therapy. We describe a case of branch arterial occlusions combined with central vein occlusion in a female patient who had undergone IFN beta therapy for 10 years. Thromboembolic and cardiovascular risk factors responsible for this event were excluded. The appearance of retinal vein and artery occlusions in our patient indicates an association with the long-term use of IFN beta.

Extra cellular matrix remodelling after heterotopic rat heart transplantation: gene expression profiling and involvement of ED-A+ fibronectin, alpha-smooth muscle actin and B+ tenascin-C in chronic cardiac allograft rejection.

Chronic cardiac rejection is represented by cardiac allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) known to cause severe complications. These processes are accompanied by remarkable changes in the cardiac extra cellular matrix (cECM). The aim of our study was to analyse the cECM remodelling in chronic rejection and to elucidate a potential role of ED-A domain containing fibronectin (ED-A(+) Fn), alpha smooth muscle actin (ASMA) and B domain containing tenascin-C (B(+) Tn-C). A model of chronic rejection after heterotopic rat heart transplantation was used. Allografts, recipient and control hearts were subjected to histological assessment of rejection grade, to real-time PCR based analysis of 84 genes of ECM and adhesion molecules and to immunofluorescence labelling procedures, including ED-A(+) Fn, ASMA and B(+) Tn-C antibodies. Histological analysis revealed different grades of chronic rejection. By gene expression analysis, a relevant up-regulation of the majority of ECM genes in association with chronic rejection could be shown. For 8 genes, there was a relevant up-regulation in allografts as well as in the corresponding recipient hearts. Association of ASMA positive cells with the grade of chronic rejection could be proven. In CAV and also in CIF there were extensive co-depositions of ED-A(+) Fn, ASMA and B(+) Tn-C. In conclusion, chronic cardiac allograft rejection is associated with a cECM remodelling. ASMA protein deposition in CAV, and CIF is a valuable marker to detect chronic rejection. Interactions of VSMCs and Fibro-/Myofibroblasts with ED-A(+) Fn and B(+) Tn-C might functionally contribute to the development of chronic cardiac rejection.

[Dry eye syndrome and neurotrophic keratitis in childhood. Causes and therapy]. / Keratoconjunctivitis sicca und neurotrophe Keratopathie im Kindesalter. Ursachen und Therapie.

PURPOSE: The purpose of this review is to enhance the physician's awareness of dry eye syndrome and neurotrophic keratitis in children, to describe the most frequently associated conditions and to discuss the diagnostic and therapeutic options available. METHODS: A literature review of the pathogenesis of dry eye syndrome and neurotrophic keratitis in children was carried out, clinical cases from our pediatric ophthalmology office are presented as well as therapeutic strategies. RESULTS: Diseases of the cornea and ocular surface such as dry eye syndrome, neurotrophic keratitis and corneal ulcers are infrequent in children compared to adults. However, they do occur and should be diagnosed and treated as soon as possible in order to prevent long-term complications and amblyopia. CONCLUSIONS: Inflammatory diseases of the ocular surface can be easily overlooked in children due to the often unknown spectrum of differential diagnoses and the frequently reduced cooperation during examination of young children. Correct and early diagnosis is essential for prevention of long-term complications, e.g. corneal ulceration and scarring.

[Evidence-based diagnostic approach to inherited retinal dystrophies 2009]. / Evidenzbasierte Diagnostik hereditärer Netzhautdystrophien 2009.

BACKGROUND: Hereditary retinal dystrophies comprise a heterogeneous group of inherited retinal disorders with variable clinical presentation and multiple associated genes. Clinical diagnosis and differential diagnosis are difficult. The purpose of the current paper is to provide guidelines for an effective diagnostic approach. METHODS: A literature search was carried out and our own data on clinical (n = 3200) and molecular genetic (n = 4050) diagnosis of patients with retinal dystrophies were evaluated. RESULTS: For an early diagnosis it is of importance to include inherited retinal dystrophies in the differential diagnosis of unexplained visual disturbances. The most important clinical test is the full-field electroretinogram (ERG), which allows detection or exclusion of generalised retinal dystrophies. If the full-field ERG is normal, a multifocal ERG will distinguish macular dystrophies. Fundus autofluorescence, near-infrared autofluorescence and high resolution optical coherence tomography improve the early diagnosis because morphological alterations can be detected prior to their ophthalmoscopic visibility. In addition, these non-invasive imaging techniques reveal new phenomena which are important for the differential diagnosis and follow-up of retinal dystrophies as well as for an improved understanding of their pathogenesis. Routine molecular genetic diagnosis is available for an increasing number of retinal dystrophies. A succinct clinical diagnosis is a prerequisite to allow selection of the gene(s) to be analysed. If genetic testing is indicated, a human geneticist should be involved for counselling of the patient and possibly further family members and initiation of the necessary steps for DNA testing. CONCLUSION: The combination of electrophysiological testing, retinal imaging and molecular genetic analysis allows a differentiated diagnosis of inherited retinal dystrophies and an individual counselling of patients. If inherited retinal dystrophies are suspected, a detailed examination in a retinal centre specialised on inherited retinal dystrophies is recommended.

[Clinical manifestations of functional disturbances of the retinal pigment epithelium]. / Klinische Manifestationen von Funktionsstörungen des retinalen Pigmentepithels.

The retinal pigment epithelium (RPE) serves a variety of different functions and impairment of these functions can lead to a multitude of different diseases of the posterior segment of the eye. The RPE plays an important role as an ion and fluid pump for the reabsorption of subretinal fluid in retinal detachment. On the other hand, defects in this pump function and in the outer blood-retinal barrier formed by the RPE, lead to fluid retention in inflammatory diseases. Metaplasia of RPE cells to myofibroblasts can lead to proliferative vitreoretinopathy and tractive retinal detachment. Early age-related maculopathy is caused by disturbances of phagocytosis and metabolism of the RPE. Imbalance of the physiological equilibrium between vasoproliferative and vasoinhibitory factors secreted by the RPE is probably involved in the development of atrophic or neovascular forms of advanced age-related macular degeneration. Mutations in the different steps involved in regeneration of the visual pigment (visual cycle) may lead to retinal dystrophy. Finally, immunoregulatory properties of the RPE are responsible for the phenomenon of immunological privilege, which may facilitate clinical interventions such as gene therapy and RPE transplantation.

[Evolution of health-related self-help. Experience from 40 years of work in self-help]. / Entwicklungslinien der Gesundheitsselbsthilfe. Erfahrungen aus 40 Jahren BAG SELBSTHILFE.

The characterization of health-related self-help often includes social demands, which indicate that the knowledge on this healthrelated self-help is very small. On the basis of 40 years experience in self-help, the article traces different lines of evolution in health-related self-help. The article describes the development of self-help structures and their success. It illustrates the association between self-help and self-help organisations. It demonstrates the social legitimation of work in self-help. Finally, the article describes current challenges for the work in health-related self-help. Based on the evidence of theses new challenges, for example, the increased significance of rare diseases, the growing scientific foundation of health care or the discussions on the different offers for health-related information and consultation, the article demonstrates the future trends in health-related self-help.