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BACKGROUND AND AIMS: Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS: A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS: Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS: This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment. ispartof: GASTROINTESTINAL ENDOSCOPY vol:94 issue:6 pages:1059-1068 ispartof: location:United States status: published

ObjectiveTo explore impacts of the COVID-19 pandemic on patterns of sickness absence among staff employed by the National Health Service (NHS) in England.MethodsWe analysed prospectively collected, pseudonymised data on 959,356 employees who were continuously employed by NHS trusts during 1 January 2019 to 31 July 2020, comparing the frequency of new sickness absence in 2020 with that at corresponding times in 2019.ResultsAfter exclusion of episodes directly related to COVID-19, the overall incidence of sickness absence during the initial 10 weeks of the pandemic (March-May 2020) was more than 20% lower than in corresponding weeks of 2019, but trends for specific categories of illness varied. Marked increases were observed for asthma (122%), infectious diseases (283%) and mental illness (42.3%), while reductions were apparent for gastrointestinal problems (48.4%), genitourinary/gynaecological disorders (33.8%), eye problems (42.7%), injury and fracture (27.7%), back problems (19.6%), other musculoskeletal disorders (29.3%), disorders of ear, nose and throat (32.7%), cough/flu (24.5%) and cancer (24.1%). A doubling of new absences for pregnancy-related disorders during 18 May to 19 July of 2020 was limited to women with earlier COVID-19 sickness absence.ConclusionsVarious factors will have contributed to the large and divergent changes that were observed. The findings add to concerns regarding delays in diagnosis and treatment of cancers, and support a need to plan for a large backlog of treatment for many other diseases. Further research should explore the rise in absence for pregnancy-related disorders among women with earlier COVID-19 sickness absence.1. What is already known about this subject?Historically, rates of sickness absence among the NHS workforce in England have been relatively high but stable. Reports of a marked increase during the first wave of the COVID-19 pandemic have not distinguished between different categories of underlying illness.2. What are the new findings?During the first wave of COVID-19, incidence of sickness-absence changed markedly when compared to the previous year, with major increases for some categories of illness, and large declines for many others, including cancer.3. How might this impact on policy or clinical practice in the foreseeable future?The findings support a need to plan for effects from delayed diagnosis and treatment of cancer, and to manage a large backlog of treatment for many other diseases.

Összefoglaló. Bevezetés: Mivel hazánkban a sclerosis multiplex gyakoriságáról, valamint életkori és nemi jellegzetességeiről az elmúlt évtizedekben – egészen 2020-ig – csak regionális jellegű felmérések készültek egy-egy centrum betegforgalma alapján, az újonnan diagnosztizált és már ismert betegek országos koreloszlásáról és annak időbeli változásairól nincsenek ismereteink. Célkitűzés: Jelen munkánkban több mint 14 000 beteg adatainak elemzésével a prevalens és incidens betegek koreloszlásának változását vizsgáljuk 2004–2016 során, és eredményeinket összevetjük az elmúlt évtizedekben közölt hazai adatokkal. Módszer: Munkacsoportunk az egészségbiztosítási pénztár anonimizált NEUROHUN adatbázisát elemezte, amely tartalmazza a 2004 és 2016 között az összes hazai, államilag finanszírozott, a fekvő- és járóbeteg-szakellátásból neurológiai diagnózissal jelentett esetet. A sclerosis multiplex BNO-kódjának előfordulása alapján korábban létrehoztuk a betegség adminisztratív definícióját, és megbecsültük a sclerosis multiplex országos prevalenciáját és incidenciáját. Eredmények: A prevalens betegek átlagéletkora 2015-ben 47,9 év, ugyanebben az évben az incidens betegek átlagéletkora 37,4 év volt. Vizsgálatunk szerint a prevalens betegek átlagéletkora szignifikánsan – évente egyötöd–egyharmad évvel (pKövetkeztetés: Eredményeink szerint az újonnan diagnosztizált sclerosis multiplexes páciensek átlagosan egyre fiatalabbak, és a prevalens betegek között is egyre fiatalabb korosztályok a legnépesebbek, de a javuló túlélés és a hosszabb élettartam miatt a prevalens betegek átlagéletkora összességében valószínűleg fokozatosan emelkedik. Orv Hetil. 2021; 162(19): 746–753. Summary. Introduction: The nationwide age and gender distribution of newly diagnosed and prevalent multiple sclerosis patients has been unknown in Hungary, as until 2020 only regional studies had been reported about the frequency and age characteristics of subjects with multiple sclerosis, based on single-center patient registries. Objective: In the present study with the analysis of over 14 000 patients, we describe the changes in age distribution of prevalent and incident subjects between 2004 and 2016 and compare our results with the data published on the subject during the last decades in Hungary. Method: We have analyzed the pseudonymized NEUROHUN database provided by the single-payer National Health Insurance Fund, that contains each claim submitted by public hospitals and outpatient services for neurologic diseases between 2004 and 2016. Using the ICD10-code of multiple sclerosis, we have previously established the administrative definition of the illness and estimated its prevalence and incidence in the country. Results: The mean age of prevalent patients was 47.9 years in 2015, whereas in the same year the mean age of incident cases was 37.4 years. The average age of prevalent patients shows a significant rise – with an annual increase of one fifth–one third year (pConclusion: Our results suggest that though new patients are younger year-by-year and the most populous age groups are also younger, altogether the average age of prevalent subjects continuously increases, probably due to the longer survival and lifespan of patients with multiple sclerosis. Orv Hetil. 2021; 162(19): 746–753.

Background: The aim of this study was to examine the correlation between the risk of increasing kyphosis as well as collapse of the osteoporotic vertebral body fractures and the intensity of the bone edema in magnetic resonance imaging (MRI) scans. Inclusion criteria included the following: age >18 years and osteoporotic vertebral body fracture grade I–IV according to OF classification. Exclusion criteria included the following: other pathological fractures due to primary tumors or metastasis, OF grade V fractures, and AO type B or C fractures. Methods: This was a retrospective study from pseudonymized data of a tertiary spine center. No additional imaging were performed. Measurements of bisegmental kyphosis angle of the fracture for involvement of both endplates and monosegmental angle for involvement of 1 endplate, as well as vertebral body height loss in initial radiographs and at follow-ups after 3 and 6 months have been performed. Also, the initial signal intensity of the vertebral body edema was measured using integrated tool of the DICOM viewer (Impax V6.5 Agfa, Brentford, UK) in addition to the signal intensity of the cerebrospinal fluid (CSF) as reference for T1, T2, and separate target illumination radar (STIR) sequences of the MRI scans. A quotient from the signal intensity of the vertebral body edema and the reference (CSF) has been generated. Patients have been divided to 4 groups according to the ratio ( 3) and compared in regards to the results of the degree of kyphosis and vertebral collapse at follow-ups and final examination. The statistical analysis was performed using linear regression using statistic software SPSS version 26. Results and Conclusions: Forty-four patients have been included: 9 males and 35 females with an average age of 71.5 years. The analysis showed a significant correlation between the increasing kyphosis at follow-ups and the quotient of the signal intensity for STIR and T2 weighing with P = .002 (SD ±2.664) for STIR and P = .001 (SD ±1.616) for T2 sequences. Furthermore, there was only a correlation between the intensity ratio and kyphosis for STIR weighting at last examination (P = .017; SD ±1.360). There was no correlation between the height loss and the signal intensity. Level of Evidence: Level 2

Objectives Preoperative planning of lung resection extent is decisive for preoperative functional work-up and selection for multimodal treatment. It is mainly based on preoperative chest CT. We aimed at evaluating chest CT adequacy to predict the extent of lung resection and hypothesized a relation with CT interpreters’ level of experience. Materials and Methods A pseudonymized CT library was built from patients who had curative intent lung resection for centrally located NSCLC. CT library was interpreted by 20 thoracic surgery residents or attendings. Interpreters were blinded to intraoperative findings and scored one point when lung resection was adequately planned. Points were summed up in a score from 0 to 20. Interpreters’ experience was evaluated through nine variables: age, position (resident vs. attending), years of experience in evaluating chest CTs, number of anatomic resections and sleeve resections attended as first assistant or performed as surgeon in presence of a teaching assistant or as main surgeon/teaching assistant. Variables characterizing interpreters’ experience were divided into equal sized groups. Independent sample T-test and one-way ANOVA/Tukey post hoc tests were used to compare scores between groups. Results CT library included 20 patients. Lung resections were lobectomy (n = 7, 35 %), sleeve lobectomy (n = 10, 50 %), sleeve bilobectomy (n = 2, 10 %), pneumonectomy (n = 1, 5%). Twenty interpreters scored a median of 10 (4–14). Attending surgeons had significantly higher mean scores (11.2 ± 1.3) compared to residents (7.7 ± 2.3, p = 0.001). All scores were significantly different between groups related to interpreters’ levels of experience, except for interpreters’age. Conclusion Preoperative CT evaluation for predicting intraoperative lung resection for centrally located NSCLC strongly depends on interpreters’ experience.

Introduction The majority of pediatric surgeons and hepatologists recommend the centralization of biliary atresia (BA) treatment within experienced liver units. We aimed to investigate whether voluntary self-restriction and acceptance of the need for this change in practice changed the BA referral policy in Germany during the last decade. Materials and Methods In cooperation with pediatric surgeons, gastroenterologists or hepatologists, and pediatric liver transplant units, the 2-year follow-up data of infants with BA born in Germany between 2010 and 2014 were collected using www.bard-online.com or pseudonymized data transfer. Results were compared with our previous analysis of the outcome data of infants with BA born between 2001 and 2005 in Germany. Result Overall, 173 infants with BA were identified, of whom 160 underwent Kasai portoenterostomy (KPE; 92.5%) and 13 (7.5%) underwent primary liver transplantation at 21 German centers. At 2-year follow-up, overall survival was 87.7% (vs. 81.9% in 2001–2005 [p = 0.19]), survival with native liver post-KPE was 29.2% (vs. 22.8% in 2001–2005 [p = 0.24]), and jaundice-free survival with native liver post-KPE was 24.0% (vs. 20.1% in 2001–2005 [p = 0.5]). Compared with the 2001–2005 analysis, all criteria showed improvement but the differences are statistically not significant. Conclusion Our observation shows that KPE management requires improvement in Germany. Centralization of BA patients to German reference liver units is not yet mandatory. However, European and national efforts with regard to the centralization of rare diseases support our common endeavor in this direction.

Background Learning from routine healthcare data is important for the improvement of the quality of care. Providing feedback on clinicians’ performance in comparison to their peers has been shown to be more efficient for quality improvements. However, the current methods for providing feedback do not fully address the privacy concerns of stakeholders. Methods The paper proposes a distributed architecture for providing feedback to clinicians on their clinical performances while protecting their privacy. The indicators for the clinical performance of a clinician are computed within a healthcare institution based on pseudonymized data extracted from the electronic health record (EHR) system. Group-level indicators of clinicians across healthcare institutions are computed using privacy-preserving distributed data-mining techniques. A clinician receives feedback reports that compare his or her personal indicators with the aggregated indicators of the individual’s peers. Indicators aggregated across different geographical levels are the basis for monitoring changes in the quality of care. The architecture feasibility was practically evaluated in three general practitioner (GP) offices in Norway that consist of about 20,245 patients. The architecture was applied for providing feedback reports to 21 GPs on their antibiotic prescriptions for selected respiratory tract infections (RTIs). Each GP received one feedback report that covered antibiotic prescriptions between 2015 and 2018, stratified yearly. We assessed the privacy protection and computation time of the architecture. Results Our evaluation indicates that the proposed architecture is feasible for practical use and protects the privacy of the patients, clinicians, and healthcare institutions. The architecture also maintains the physical access control of healthcare institutions over the patient data. We sent a single feedback report to each of the 21 GPs. A total of 14,396 cases were diagnosed with the selected RTIs during the study period across the institutions. Of these cases, 2924 (20.3%) were treated with antibiotics, where 40.8% (1194) of the antibiotic prescriptions were narrow-spectrum antibiotics. Conclusions It is feasible to provide feedback to clinicians on their clinical performance in comparison to peers across healthcare institutions while protecting privacy. The architecture also enables monitoring changes in the quality of care following interventions.

Introduction: Approximately 1 out of 4 stroke patients suffers ischemic stroke secondary to atrial fibrillation (AF). Although indicated, withholding of anticoagulants for secondary prevention is a widespread phenomenon. Objective: We examined the longitudinal change of recommendation and prescription of secondary preventive anticoagulation in AF patients in an acute stroke center setting focusing on the impact of the introduction of direct oral anticoagulants (DOACs) and the change of national stroke prevention guidelines. Methods: Consecutive patients admitted with an acute cerebrovascular ischemic event underwent regular diagnostic work-up. Pseudonymized clinical data were entered into the institution’s stroke registry. In those patients with AF, discharge letters were collected and evaluated for temporal trends and affecting factors of recommended and prescribed antithrombotic secondary medication at the time of discharge from hospital. Results: Of 7,175 patients admitted between January 2009 and December 2018, 1,812 (25.3%) suffered stroke caused by AF. Frequency of patients with recommended anticoagulation increased within the observation period from 66.7 to 95.8% (per year; adjusted odds ratio [OR], 1.309; confidence interval [CI], 1.153–1.486). Independently from this time trend, DOAC approval (adjusted OR, 4.026; CI 1.962–8.265) and guideline change (adjusted OR, 2.184; CI, 1.006–4.743) were associated with an increasing frequency of recommendation for anticoagulation. The rate of patients already receiving recommended anticoagulation for secondary prevention at discharge increased from 42.1 to 62.5%. Introduction of DOACs was not associated with this trend, and guideline change was even associated with decreasing frequency of anticoagulated patients at hospital discharge (adjusted OR, 0.641; CI, 0.414–0.991). Fear of early intracerebral bleeding was the most common reason for withholding anticoagulation (37%) at hospital discharge and stayed stable during the observation period. Conclusions: Changing national guidelines with discard of contraindications for anticoagulation and the introduction of DOACs led to a broader recommendation of oral anticoagulation. However, both, new guidelines and DOACs, were not found to be associated with an increasing percentage of patients discharged from our hospital already on recommended anticoagulant prevention. This might be explained by the decreasing length of hospital stay during the study period and a missing evidence of early bleeding risk of DOACs in patients with acute brain infarction. Evidence-based data to close this therapeutic gap are needed.

In Germany, the incidence of cervical cancer, a disease caused by human papillomaviruses (HPV), is higher than in neighboring European countries. HPV vaccination has been recommended for girls since 2007. However, it continues to be significantly less well received than other childhood vaccines, so its potential for cancer prevention is not fully realized.To find new starting points for improving vaccination rates, we analyzed pseudonymized routine billing data from statutory health insurers in the PRÄZIS study in the federal state Saarland serving as a model region. We show that lowering the HPV vaccination age to 9 years led to more completed HPV vaccinations already in 2015. Since then, HPV vaccination rates and the proportion of 9-to 11-year-old girls among HPV-vaccinated females have steadily increased. However, HPV vaccination rates among 15-year-old girls in Saarland remained well below 50% in 2019. Pediatricians vaccinated the most girls overall, with a particularly high proportion at the recommended vaccination age of 9-14 years, while gynecologists provided more HPV catch-up vaccinations among 15-17-year-old girls, and general practitioners compensated for HPV vaccination in Saarland communities with fewer pediatricians or gynecologists. We also provide evidence for a significant association between attendance at the U11 or J1 medical check-ups and HPV vaccination. In particular, participation in HPV vaccination is high on the day of U11. However, obstacles are that U11 is currently not funded by all statutory health insurers and there is a lack of invitation procedures for both U11 and J1, resulting in significantly lower participation rates than for the earlier U8 or U9 screenings, which are conducted exclusively with invitations and reminders.Based on our data, we propose to restructure U11 and J1 screening in Germany, with mandatory funding for U11 and organized invitations for HPV vaccination at U11 or J1 for both boys and girls.

Background Atrial fibrillation is a cardiac arrhythmia commonly encountered in a primary care setting. Current screening is limited to pulse palpation and ECG confirmation when an irregular pulse is found. Paroxysmal atrial fibrillation will, however, still be difficult to pick up. With the advent of smartphones, screening could be more cost-efficient by making use of simple applications, lowering the need for intensive screening to discover (paroxysmal) atrial fibrillation. Methods/design This cluster randomized trial will examine the effect of using a smartphone-based application such as FibriCheck® on the detection rate of atrial fibrillation in a Flemish general practice population. This study will be conducted in 22 primary care practices across the Flanders region of Belgium and will last 12 months. Patients above 65 years of age will be divided in control and intervention groups on the practice level. The control group will be subjected to standard opportunistic screening only, while the intervention group will be prescribed the FibriCheck® app on top of this opportunistic screening. The difference in detection rate between control and intervention groups will be calculated at the end of the study. We will use the online platform INTEGO for pseudonymized data collection and analysis, and risk calculation. Discussion Smartphone applications might offer a way to cost-effectively screen for (paroxysmal) atrial fibrillation in a primary care setting. This could open the door for the update of future screening guidelines. Trial registration ClinicalTrials.gov NCT04545723. Registered on September 10, 2020.

Summary Background The German programme for skin cancer screening was established in 2008 with the aim of reducing skin cancer mortality. However, the effectiveness and risk–benefit ratio of the programme remain unclear. Objectives To compare the mortality rates of patients with melanoma who participate in a screening programme to those who do not. Methods A retrospective cohort study, based on pseudonymized health insurance data of 1 431 327 individuals from Saxony, Germany, was conducted for the period 2010–2016. Patients with prevalent and incident melanoma were defined based on diagnosis, medical procedures and prescriptions. Patients who underwent screening and had a first diagnosis of melanoma within 2 years of screening were assigned to the intervention group. Relative survival and Cox regression were used to assess potential differences in mortality. Results We identified 4552 individuals with prevalent and 2475 individuals with incident melanoma. The percentage of screening participants (n = 1801) who had locoregional (4·2% vs. 13·5%) and/or distant metastases (4·3% vs. 8·0%), or who were treated with systemic anticancer therapies (11·6% vs. 21·8%) was lower vs. nonparticipants (n = 674). Screening participants had significantly better survival rates. The unadjusted Cox model gave a hazard ratio (HR) of 0·37 [95% confidence interval (CI) 0·30–0·46]. After adjusting for named confounders, the effect remained (HR 0·62, 95% CI 0·48–0·80). Conclusions Patients who participated in the screening programme had lower mortality than those who had not undergone screening. However, these findings may result from a healthy screen bias and/or overdiagnosis associated with screening, and not from the screening itself.

Background Few longitudinal studies investigate predictors of substance use incidence among immigrants. The current study describes substance use disorders in immigrants to Sweden, focusing on drinking culture in the country of origin and socioeconomic status (SES), and how these intersect with generational status to influence risk. Methods Using pseudonymized Swedish population registry data, we track onset of alcohol use disorder and drug use disorder in a longitudinal study of 815,778 first-generation immigrants and 674,757 second-generation immigrants from 64 countries over a 6-year period. Cox regression analysis estimated risks of alcohol and drug use disorders in second-generation immigrants compared to first-generation, and moderation analyses assessed interactions of generational status with country-of-origin per capita alcohol consumption and SES. Results Immigrants and second-generation immigrants originating from countries with high levels of alcohol consumption had higher risks for alcohol and drug use disorders. Immigrants with high SES had lower risks for alcohol and drug use disorders. The interaction between generational status and country-of-origin alcohol consumption was significant for drug use disorder (not for alcohol use disorder), with drug use disorder risk for second-generation immigrants being highest for those from countries with the lowest level of country-of-origin per capita alcohol consumption. The interaction between generational status and SES was significant for alcohol use disorder, with low-SES second-generation immigrants showing markedly higher risk than first-generation immigrants with comparable SES. Conclusions Among immigrants in Sweden, second-generation immigrants are at increased risk of developing alcohol and drug use disorders, particularly if they have lower SES. Policy and community attention to these high-risk subgroups in immigrant communities is warranted.

Real-world data are crucial to continuously improve the management of patients with rheumatic and musculoskeletal diseases (RMDs). The German RheumaDatenRhePort (RHADAR) registry encompasses a network of rheumatologists and researchers in Germany providing pseudonymized real-world patient data and allowing timely and continuous improvement in the care of RMD patients. The RHADAR modules allow automated anamnesis and adaptive coordination of appointments regarding individual urgency levels. Further modules focus on the collection and integration of electronic patient-reported outcomes in between consultations. The digital RHADAR modules ultimately allow a patient-centered adaptive approach to integrated medical care starting as early as possible in the disease course. Such a closed-loop system consisting of various modules along the whole patient pathway enables comprehensive and timely patient management in an unprecedented manner.

Background The impact of the COVID-19 outbreak and lockdown in liver transplant (LT) patients remains unknown. The aim of this cross-sectional study was to assess the consequences of the COVID-19 pandemic on the physical and mental health of LT patients during the lockdown period. Methods Between August and October 2020 a Web-based questionnaire was emailed to 238 LT patients undergoing regular follow-up at our unit. This pseudonymized survey explored demographic and lifestyle variables (i.e. eating and physical habits), disruptions in routine medical care, and different dimensions of mental health, COVID-19-related mood and coping (worries/anxiety, depression, insomnia, fear of Covid, resilience, etc.), and health perception using different validated instruments. Results 48.7% (116 of 238) LT recipients accepted to participate, 104 of whom gave their consent to publish the data. The median age was 63 years. Up to 39.4% presented worrying scores indicating moderate/severe generalized anxiety disorder (GAD), whereas 25.5% exhibited moderate/severe insomnia and only 10.5% moderate/severe depression. Forty patients (38.5%) gained weight, 24% experienced a worsening in their eating habits and 63.4% referred to practice less or much less exercise during the lockdown. Only 25% perceived a worsening in the control of their chronic comorbidities. Missed medical appointments (0.9%) or worsening adherence to therapy (1.9%) were exceptional. Conclusions COVID-19 lockdown has negatively impacted the mental and physical health of LT patients. Long-term consequences remain unclear.

The three-armed cluster-randomized trial ARena (sustainable reduction of antibiotic-induced antimicrobial resistance) aimed to foster appropriate antibiotic use and reduce overprescribing in German ambulatory care to counter antibiotic resistance. Multi-faceted interventions targeted primary care physicians, teams and patients. This study examined the effectiveness of the implementation program. ARena was conducted in 14 primary care networks with 196 practices. All arms received data-based feedback on antibiotics prescribing and quality circles. Arms II and III received different add-on components each. Primary outcome examined is the prescribing rate for systemic antibiotics for cases with non-complicated acute infections (upper respiratory tract, bronchitis, sinusitis, tonsillitis, otitis media). Secondary outcomes refer to the prescribing of quinolones and guideline-recommended antibiotics. Based on pseudonymized quarterly claims data, mixed logistic regression models examined pre-post intervention antibiotic prescribing rate changes and compared to matched standard care. A significant rate reduction (arm I 11.7%, arm II 9.9%, arm III 12.7%) and significantly lower prescribing rates were observed for all arms (20.1%, 18.9% and 23.6%) compared to matched standard care (29.4%). Fluoroquinolone prescribing was reduced in all intervention arms and rates for recommended substances generally increased. No significant post-interventional difference between intervention arms was detected. Findings indicate implementation program impact compared to standard care.

Objectives Maternal obesity during pregnancy is associated with adverse intrauterine events and fetal outcomes and may increase the risk of obesity and metabolic disease development in offspring. Higher parity, regardless of socioeconomic status, is associated with increased maternal body mass index (BMI). In this study, we examined the relationship between parity, maternal obesity, and fetal outcomes in a large sample of mother-neonate pairs from Lower Saxony, Germany. Methods This retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony’s statewide quality assurance initiative. 448,963 cases were included. Newborn outcomes were assessed in relation to maternal BMI and parity. Results Maternal obesity was associated with an increased risk of placental insufficiency, chorioamnionitis, and fetal distress while giving birth. This effect was present across all parity groups. Fetal presentation did not differ between BMI groups, except for the increased risk of high longitudinal position and shoulder dystocia in obese women. Maternal obesity was also associated with an increased risk of premature birth, low arterial cord blood pH and low 5-min APGAR scores. Conclusions Maternal obesity increases the risk of adverse neonatal outcomes. There is a positive correlation between parity and increased maternal BMI. Weight-dependent fetal risk factors increase with parity, while parity-dependent outcomes occur less frequently in multipara. Prevention and intervention programs for women planning to become pregnant can be promising measures to reduce pregnancy and birth complications.

Highlights • Children’s understanding of epilepsy reflects their lived experiences. • Parents are key information gatekeepers and shape children’s understanding. • Children face challenges in being meaningfully involved in healthcare decisions., Purpose To use a qualitative research approach to determine children’s understandings of epilepsy and their epilepsy treatment. Methods Children aged 7–16 years with physician-confirmed active epilepsy (i.e., having had an epileptic seizure in the past year and or currently taking antiepileptic drugs (AEDs), and not known to have an intellectual disability, were invited to participate. Children had semi-structured interviews separately on two occasions. Between the first and second interviews, an observation of a routine epilepsy clinic appointment of individual children was conducted, and was then discussed during the second interview. Participatory research tools were used in both child interviews to facilitate discussions. Interviews were audio recorded and transcribed, pseudonymized and entered into NVivo (version 12, QSR International). Data were analyzed using a thematic approach. Results Twenty-three children of mean age 10.1 years (range 8–14), mean duration of epilepsy of 4.6 years (range 2–10) were enrolled. Twelve were 12 female; 7 had focal, 14 had generalized, and 2 had combined epilepsy; 20 were on monotherapy; and 16 had tried previous AEDs. All had an initial (first) interview; 20 were observed during a clinic appointment and had a second interview. Five broad themes emerged: understanding of epilepsy; understanding of seizures; understanding of medication; understanding of children’s role in clinical appointments; influences on children’s understanding. Children spoke about what epilepsy meant by describing the physical sensations of having a seizure or through the act of taking medication. Children described the role they had, or felt they should have, but reported challenges in being meaningfully involved in clinical appointments. While healthcare professionals were initial information nodes, epilepsy information from parents appeared to be more significant for children. Conclusions The perspectives of children with epilepsy are valuable for clinicians to understand; assumptions should not be made that children’s views can be accessed via parents. Clinicians need to be constantly aware of children’s views and ways of understanding and communicating about their epilepsy. To support this, the research – drawing on children’s words, meanings, and stories – was used to inform an easily accessible, gender-neutral, animation about epilepsy that provides information about the condition, seizures, and medication (https://youtu.be/MO7xXL2ZXP8).

BackgroundRecord linkage is increasingly used in health research worldwide. Combining the patient information available in healthcare, administrative and clinical databases broadens the research perspectives, particularly for chronic diseases. Recent guidelines highlight the need for transparency on the used record linkage processes and the extracted data to be used by researchers.MethodsTherefore, the aim of this study was to describe the deterministic iterative approach used to link the French Epidemiology and Information Network (REIN), a French national End-Stage Renal Disease registry, with the Système National des Données de Santé (SNDS), a French nationwide medico-administrative healthcare database.ResultsAmong the 22,073 patients included in the REIN registry who started renal replacement therapy between 2014 and 2015 in France, 19,223 (87.1%) were matched with patients in the SNDS database. Comparison of matched and unmatched patients confirmed the absence of any major selection bias. Then, the record linkage was evaluated using the comorbidity status (diabetes).ConclusionsThis fast and efficient method of record linkage with pseudonymized data and without unique and direct identifier might inspire other research teams. It also opens the path for new research on chronic kidney disease.

Background:Early diagnosis and reliable differentiation between rheumatic diseases (RMDs) are crucial to start an adequate therapy and prevent irreversible damage. Since finger joints are commonly affected in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), imaging of the peripheral skeleton is an essential step of diagnosis at a rheumatologist. High resolution peripheral quantitative computed tomography (HR-pQCT) allows an even more detailed and three-dimensional (3D) illustration of the peripheral bone than conventional radiographs. Segmented scans contain further information, such as the density, microstructure, and shape of the bones, which can be further analyzed by neural networks.Objectives:We hypothesize that, based on the shape of the second metacarpophalangeal (MCP) joint from HR-pQCT images, a neural network can be trained to differentiate between RA, PsA, and healthy controls and to reveal regions in the bone shape characteristic for the diseases.Methods:HR-pQCT images of MCP joints from patients with classified CCP positive RA, classified PsA, and healthy controls with low motion artifacts and appropriate scan region were selected as reported previously [3]. Scans were performed as part of the clinical routine and patients gave their informed consent to use pseudonymized data (Ethics approval 334_16B). Based on the assumption that pathognomonic changes develop over time, only images were used, where the period between classification and imaging exceeded one year.Based on previous work [4], a pixel-wise mask of the second metacarpal bone was generated using a neural network based on the HR-pQCT scans of patients. Supervised auto-encoder [1] networks were used to predict the correct class given the bone mask only. For the neural network experiment, the patient scans were split on a patient-level into training (70%), validation (20%), and testing (10%). Guided backpropagation [2] was used as a method to investigate the regions influencing the class prediction most.Results:In total, images of 331 patients were included in the experiments. The evaluation of the model on the 33 test cases yielded a high accuracy for the healthy control with 94%, RA patients with 84%, and PsA patients with 89%. An area under the receiver operator curve of 91% could be achieved. The regions of the bone mask influencing the network´s decision most are highlighted exemplary in Figure 1.Figure 1.Visualization of the HR-pQCT slices with gradient maps. Higher values (red) represent regions that had a stronger contribution to the classification result. The HR-pQCT images are displayed for reference only. (a) Healthy patient, (b) RA diagnosed patient, and (c) PsA diagnosed patient. The first row shows the single slices with the highest values corresponding to the 3D bone masks in the second row.Conclusion:For the first time, a neural network-based approach successfully provides a differential diagnosis of RA and PsA based only on the shape of the second MCP in HR-pQCT images. The evaluation of the test set suggests that high curvatures of the bone surface in the joint region significantly influence the prediction of the network, suggesting an in-depth investigation of these regions for patients affected by RA and PsA. Based on these promising findings, we aim to extend the approach to seronegative RA as well as early RA and PsA.References:[1]Le, L. et al. (2018). Supervised autoencoders: Improving generalization performance with unsupervised regularizers. In Advances in Neural Information Processing Systems.[2]Springenberg, J. T. et al. (2015). Striving for simplicity: The all convolutional net. 3rd International Conference on Learning Representations, ICLR 2015 - Workshop Track Proceedings.[3]Simon, D. et al. (2017). Age- and Sex-Dependent Changes of Intra-articular Cortical and Trabecular Bone Structure and the Effects of Rheumatoid Arthritis. Journal of Bone and Mineral Research, 32(4), 722–730.[4]Folle, L. et al. (2021). Fully Automatic Bone Mineral Density Measurements using Deep Learning. Manuscript submitted for publication.Acknowledgements:This work was supported by the emerging field initiative (project 4 Med 05 “MIRACLE”) of the University Erlangen-Nürnberg and MASCARA - Molecular Assessment of Signatures Characterizing the Remission of Arthritis grant 01EC1903A.Disclosure of Interests:Lukas Folle: None declared, Chang Liu: None declared, David Simon Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Timo Meinderink: None declared, Anna-Maria Liphardt Consultant of: Mylan/Meda Pharma, Grant/research support from: Novartis, Gerhard Krönke Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Georg Schett Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Andreas Maier: None declared, Arnd Kleyer Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Novartis, Lilly

Background Evaluating the completeness of tuberculosis (TB) notification data is important for monitoring of TB surveillance systems. We conducted an inventory study to calculate TB underreporting in Germany in 2013–2017. Methods Acquisition of two pseudonymized case-based data sources (national TB notification data and antibiotic resistance surveillance data) was followed by two-source Capture-recapture (CRC) analysis, as case-based data from a third source was unavailable. Aggregated data on consumption of a key anti-TB drug (pyrazinamide [PZA]) was compared to an estimated need for PZA based on TB notification data to obtain an independent underreporting estimation. Additionally, notified TB incidence was compared to TB rate in an aggregated health insurance fund dataset. Results CRC and PZA-based approaches indicated that between 93 and 97% (CRC) and between 91 and 95% (PZA) of estimated cases were captured in the national TB notification data in the years 2013–2017. Insurance fund dataset did not indicate TB underreporting on the national level in 2017. Conclusions Our results suggest that more than 90% of estimated TB cases are captured within the German TB surveillance system, and accordingly the TB notification rate is likely a good proxy of the diagnosed TB incidence rate. An increase in underreporting and discrepancies however should be further investigated.

Background The aim of this study is to investigate the potential impact of prostate magnetic resonance imaging (MRI) -related interreader variability on a population-based randomized prostate cancer screening trial (ProScreen). Methods From January 2014 to January 2018, 100 men aged 50–63 years with clinical suspicion of prostate cancer (PCa) in Helsinki University Hospital underwent MRI. Nine radiologists individually reviewed the pseudonymized MRI scans of all 100 men in two ProScreen trial centers. All 100 men were biopsied according to a histological composite variable comprising radical prostatectomy histology (N = 38) or biopsy result within 1 year from the imaging (N = 62). Fleiss’ kappa (κ) was used to estimate the combined agreement between all individual radiologists. Sample data were subsequently extrapolated to 1000-men subgroups of the ProScreen cohort. Results Altogether 89% men of the 100-men sample were diagnosed with PCa within a median of 2.4 years of follow-up. Clinically significant PCa (csPCa) was identified in 76% men. For all PCa, mean sensitivity was 79% (SD ±10%, range 62–96%), and mean specificity 60% (SD ±22%, range 27–82%). For csPCa (Gleason Grade 2–5) MRI was equally sensitive (mean 82%, SD ±9%, range 67–97%) but less specific (mean 47%, SD ±20%, range 21–75%). Interreader agreement for any lesion was fair (κ 0.40) and for PI-RADS 4–5 lesions it was moderate (κ 0.60). Upon extrapolating these data, the average sensitivity and specificity to a screening positive subgroup of 1000 men from ProScreen with a 30% prevalence of csPCa, 639 would be biopsied. Of these, 244 men would be true positive, and 395 false positive. Moreover, 361 men would not be referred to biopsy and among these, 56 csPCas would be missed. The variation among the radiologists was broad as the least sensitive radiologist would have twice as many men biopsied and almost three times more men would undergo unnecessary biopsies. Although the most sensitive radiologist would miss only 2.6% of csPCa (false negatives), the least sensitive radiologist would miss every third. Conclusions Interreader agreement was fair to moderate. The role of MRI in the ongoing ProScreen trial is crucial and has a substantial impact on the screening process.

Background Infectious diseases, such as HCV infection, HBV infection and syphilis, put a huge burden on public health. Accurate and fast testing is required for clinical usage. Objectives This study aimed to evaluate the clinical performance of Elecsys® Anti−HCV II, Elecsys® HBsAg II and Elecsys® Syphilis using samples from routine diagnosis in China. Methods Specificity was tested in approximately 3000 unselected pseudonymized samples from routine clinical patients for each assay. Sensitivity of HCV and HBsAg assays was tested in 2 seroconversion panels, respectively. Results The 3 investigational assays on cobas e 801 were showed to have excellent sensitivity and specificity which is comparable to existing assays. Conclusion They are suitable for routine clinical diagnostic use, including pre-operative assessment in China.

Background The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) and Public Health England (PHE) have successfully worked together on the surveillance of influenza and other infectious diseases for over 50 years, including three previous pandemics. With the emergence of the international outbreak of the coronavirus infection (COVID-19), a UK national approach to containment has been established to test people suspected of exposure to COVID-19. At the same time and separately, the RCGP RSC’s surveillance has been extended to monitor the temporal and geographical distribution of COVID-19 infection in the community as well as assess the effectiveness of the containment strategy. Objectives The aims of this study are to surveil COVID-19 in both asymptomatic populations and ambulatory cases with respiratory infections, ascertain both the rate and pattern of COVID-19 spread, and assess the effectiveness of the containment policy. Methods The RCGP RSC, a network of over 500 general practices in England, extract pseudonymized data weekly. This extended surveillance comprises of five components: (1) Recording in medical records of anyone suspected to have or who has been exposed to COVID-19. Computerized medical records suppliers have within a week of request created new codes to support this. (2) Extension of current virological surveillance and testing people with influenza-like illness or lower respiratory tract infections (LRTI)—with the caveat that people suspected to have or who have been exposed to COVID-19 should be referred to the national containment pathway and not seen in primary care. (3) Serology sample collection across all age groups. This will be an extra blood sample taken from people who are attending their general practice for a scheduled blood test. The 100 general practices currently undertaking annual influenza virology surveillance will be involved in the extended virological and serological surveillance. (4) Collecting convalescent serum samples. (5) Data curation. We have the opportunity to escalate the data extraction to twice weekly if needed. Swabs and sera will be analyzed in PHE reference laboratories. Results General practice clinical system providers have introduced an emergency new set of clinical codes to support COVID-19 surveillance. Additionally, practices participating in current virology surveillance are now taking samples for COVID-19 surveillance from low-risk patients presenting with LRTIs. Within the first 2 weeks of setup of this surveillance, we have identified 3 cases: 1 through the new coding system, the other 2 through the extended virology sampling. Conclusions We have rapidly converted the established national RCGP RSC influenza surveillance system into one that can test the effectiveness of the COVID-19 containment policy. The extended surveillance has already seen the use of new codes with 3 cases reported. Rapid sharing of this protocol should enable scientific critique and shared learning. International Registered Report Identifier (IRRID) DERR1-10.2196/18606

Smart Breath Analyzers were developed as sensing terminals of a telemedicine architecture devoted to remote monitoring of patients suffering from Chronic Obstructive Pulmonary Disease (COPD) and home-assisted by non-invasive mechanical ventilation via respiratory face mask. The devices based on different sensors (CO2/O2 and Volatile Organic Compounds (VOCs), relative humidity and temperature (R.H. &amp, T) sensors) monitor the breath air exhaled into the expiratory line of the bi-tube patient breathing circuit during a noninvasive ventilo-therapy session, the sensor raw signals are transmitted pseudonymized to National Health Service units by TCP/IP communication through a cloud remote platform. The work is a proof-of-concept of a sensors-based IoT system with the perspective to check continuously the effectiveness of therapy and/or any state of exacerbation of the disease requiring healthcare. Lab tests in controlled experimental conditions by a gas-mixing bench towards CO2/O2 concentrations and exhaled breath collected in a sampling bag were carried out to test the realized prototypes. The Smart Breath Analyzers were also tested in real conditions both on a healthy volunteer subject and a COPD suffering patient.

The Dutch Parelsnoer Institute-Cerebrovascular accident (CVA) Study is part of the Parelsnoer Institute (PSI), initiated in 2007 by the Netherlands Federation of University Medical Centers (NFU). PSI is a cooperation of all eight Dutch University Medical Centers (UMCs) and aims at building large prospectively collected datasets with uniformly and standardized storage of biomaterials for complex diseases. Currently, PSI covers 18 disease-specific cohorts called ‘Pearls’, and this number is still growing. One of these cohorts is the Stroke or CVA Pearl. For each of the cohorts, PSI offers the UMCs an infrastructure and standard procedures for storing the specific biomaterials in their certified biobanks. Clinical data are stored in a central database after being pseudonymized to ensure patient privacy. For the Parelsnoer Institute-CVA Study, blood for genetic analysis, serum and plasma are collected according to nationally agreed standards. Currently (November 2017) the Stroke Pearl has stored blood samples with prospectively obtained clinical data of around 6000 patients in all UMCs combined. Blood samples and data are available for all researchers with a methodologically valid research proposal. Funding statement: PSI was founded in 2007 with a five year grant from the Dutch Government. From 2011 until now PSI is funded and facilitated by the Netherlands Federation of University Medical Centers (NFU) and its member institutions, independent of external funds. Additional funds from governmental sources, industry sponsors and charity are used for the analysis on the existing data and the expansion of PSI with new diseases.

Background: The COVID-19 pandemic and associated public health measures affect healthcare seeking behaviour, access to healthcare, test strategies, disease notification and workload at public health authorities, but may also lead to a true change in transmission dynamics. We aimed to assess the impact of the pandemic and associated public health measures on other notifiable infectious diseases under surveillance in Germany. Methods: We included 32 nationally notifiable diseases categories with case numbers >100/year in 2016-2019. We used quasi-Poisson regression analysis on a weekly aggregated time-series incorporating trend and seasonality, to compute the relative change in case numbers during week 2020-10 to 2020-32 (pandemic), in comparison to week 2016-01 to 2020-09. Findings: During week 2020-10 to 2020-32, 216,825 COVID-19 cases, and 162,942 (-35%) cases of other diseases, were notified. Case numbers decreased across all ages and notification categories (all p

Background:Incidence estimates of PsA in Norway have varied from 6.9/100,000 person-years (pyrs) in Northern Norway to 41.3/100,000 pyrs in Central Norway, and point prevalence estimates have ranged from 1.3 to 6.9 per 1,000 adult inhabitants1,2, while nationwide epidemiologic data on PsA in Norway have been lacking.Objectives:To estimate prevalence, incidence and use of disease-modifying antirheumatic drugs (DMARDs) among PsA patients in Norway.Methods:The Norwegian Cardio-Rheuma register includes pseudonymized data from the total Norwegian population ≥18 years of age during 2008-2017, identified from the National Population register. Demographic and socioeconomic data were retrieved from Statistics Norway. Data on public or private somatic specialized care episodes were collected from the Norwegian Patient register (NPR) [ICD-10 codes for diagnoses and medical procedure codes for biologic DMARD infusions]. Information on dispensed DMARD prescriptions was captured from the Norwegian Prescription Database. Based on NPR data, PsA cases were defined as persons fulfilling three criteria: 1) 1st episode with ICD-10 code M07.0-M07.3 or L40.5 as main or contributory diagnosis (index date), 2) 2nd episode with code M07.0-M07.3 or L40.5 within 2-year period following index date, 3) an episode in internal medicine or rheumatology clinic with recorded M07.0-M07.3 or L40.5 within 2 years from index date. Years 2008-2010 served as a look-back period to identify prevalent PsA cases. To estimate pyrs at risk, we calculated number of individuals aged ≥ 18 years living in Norway on the 1st of January of each year 2011-2015 multiplied by one year (prevalent PsA cases excluded). Age- and sex-standardized incidence rates were calculated with 5-year age groups using the Norwegian adult population on January 1st 2015 as the standard.Results:During the look-back period 2008-2010, 7,697 cases fulfilled the PsA definition. In total, 6,183 incident PsA cases were identified during 2011-2015 (incidence 32/100,000 pyrs, 28 among men and 35 among women). Based on a sensitivity analysis comprising 5,065 PsA cases with no dispensed DMARD prescriptions ≥12 months before index date, incidence was slightly lower (26/100,000 pyrs). Patient characteristics and DMARD use are shown in Table 1. The incidence was highest among those aged 50-59 years in both sexes (Figure 1). PsA incidence was lower among those with higher education level (crude/age- and sex-standardized incidence per 100,000 pyrs for those below upper secondary education 34/38, upper secondary or post-secondary non-tertiary education 36/36, higher education 26/25). Point prevalence of PsA was 3.3/1,000 adult inhabitants on January 1st 2016.Table 1.Characteristics and treatment penetration of incident PsA patients 2011-2015AllExcluding cases with DMARDs >1 yr prior to index dateN61835065Women, n (%)3442 (55.7)2783 (54.9)Age at index date, median (IQR)50.5 (40.7 - 59.8)49.9 (40.2 - 59.3)Use of DMARDs after index date, n (%)12 months24 months12 months24 months Any conventional DMARD3706 (59.9)4048 (65.4)2894 (57.1)3184 (62.9) Methotrexate3313 (53.6)3650 (59.0)2638 (52.1)2933 (57.9) Sulfasalazine440 (7.1)586 (9.5)330 (6.5)457 (9.0) Any biologic DMARD842 (13.6)1197 (19.4)485 (9.6)771 (15.2) TNF-inhibitors810 (13.1)1154 (18.7)477 (9.4)758 (15.0) Oral glucocorticoids1773 (28.7)2240 (36.2)1449 (28.6)1807 (35.7) Any DMARD or glucocorticoids4365 (70.6)4742 (76.7)3384 (66.8)3725 (73.5)Conclusion:Our estimate of PsA incidence and prevalence are in the mid-range compared to studies from smaller regions in Norway. Methotrexate was initiated for more than half of PsA cases within one year from index date, whereas 19% had used biologic DMARDs within two years.References:[1]Hoff M, Gulati A, Romundstad P et al. Prevalence and incidence rates of psoriatic arthritis in central Norway: data from the Nord-Trondelag health study. Ann Rheum Dis 2015;74:60-64.[2]Nossent J & Gran J. Epidemiological and clinical characteristics of psoriatic arthritis in northern Norway. Scand J Rheumatol 2009; 8:251-5.Acknowledgements:This work has been supported by a research grant from FOREUM Foundation for Research in Rheumatology.Disclosure of Interests:Anne Kerola Speakers bureau: Boehringer-Ingelheim, Consultant of: Pfizer, Gilead and Boehringer-Ingelheim, Joseph Sexton: None declared, Silvia Rollefstad: None declared, Grunde Wibetoe: None declared, Cynthia S. Crowson: None declared, Espen Haavardsholm: None declared, Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi, Consultant of: AbbVie, Amgen, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, Grant/research support from: research funding to Diakonhjemmet Hospital from AbbVie, Amgen, BMS, MSD, Pfizer and UCB, Anne Grete Semb Speakers bureau: AbbVie, Bayer, Lilly, Novartis, Sanofi, Consultant of: Sanofi, Grant/research support from: Collaborative research support from Lilly, outside the submitted work.

ZusammenfassungEntscheidungen im Gesundheitswesen sollten sich auf verlässliche und aktuelle Daten stützen. Da solche Daten besonders aus dem ambulanten Sektor kaum vorhanden und/oder nur schwer und zeitverzögert zugänglich sind, soll das neu eingerichtete BeoNet-Register (BNR) die medizinische Versorgungsrealität und -qualität des ambulanten Sektors mithilfe von Routinedaten aus der elektronischen Patientenakte (eP) abbilden. Diese „real-world“-Daten sollen mit Primärerhebungen verknüpft eine breite Datenbasis zur Beantwortung von Fragen der Praxis, der Versorgungsforschung und Ökonomie bilden. Interessierte Praxisinhaber verpflichten sich zu einer längerfristigen Teilnahme an dem 2-phasigen Projekt (Pilot- und Roll-Out-Phase). Informationen der eP der Praxen werden pseudonymisiert, verschlüsselt und über standardisierte Schnittstellen zeitnah, vollständig und longitudinal in die Datenbank (DB) des BNR übertragen, ohne den Praxisbetrieb zu stören. Dafür wird die Behandlungsdatentransfer-Schnittstelle (BDT) als gemeinsamer Nenner unterschiedlicher Arztinformationssysteme genutzt. Die kompilierten Variablen beinhalten Informationen zur Praxis, Stammdaten des Patienten und medizinische Parameter inklusive Angaben zu Diagnose, Therapie und Überweisungen. Ergänzt werden sie durch zusätzliche erhobene ‚patient-reported outcomes‘. Datenerhebung und Datenschutz unterliegen strengen Anforderungen, die im Rahmen des Datenschutzkonzeptes und des Ethikantrages festgelegt und für alle Forscher bindend sind. Retrospektive Auswertungen seit der Einführung der eP sowie Analysen des aktuellen Erkrankungsspektrums des hausärztlichen, pneumologischen und pädiatrischen ambulanten Sektors sind möglich. Derzeit befinden sich 98 497 Patienten-IDs aus Hannover, München und Heidelberg nebst zugehörigen Informationen in der BNR- DB. Die BNR-Daten sind umfangreicher und detaillierter als die Abrechnungsdaten der Krankenkassen. (Semi-) automatisierte Daten- Prüfroutinen und regelmäßige Feedback-Berichte sowie Datenanalysen sind implementiert und werden kontinuierlich erweitert. Während der Pilotphase wurden 2 Anwendungsbeispiele des BNR erarbeitet. Hier wird das COPD-Projekt vorgestellt, dass die Inanspruchnahme von medizinischen Leistungen in Verbindung mit der Lebensqualität Betroffener analysiert. Die Roll-Out-Phase des Projektes startet 2016. Die Datenbasis des BNR für retro- und prospektive Querschnitts- und Längsschnittstudien wird Deutschlandweit und fortlaufend ausgeweitet.

Aims The Myocardial Ischaemia National Audit Project (MINAP) collects data from admissions in England, Wales, and Northern Ireland with Type 1 myocardial infarction (T1 MI). The project aims to improve clinical care through the audit process and to provide powerful high-resolution data for research. Methods and results MINAP collects data spanning 130 data fields covering the course of patient care, from the moment the patient calls for professional help through to hospital discharge and rehabilitation. Data are entered by clinicians and clerical staff within hospitals, and pseudonymized records are uploaded centrally to the National Institute for Cardiovascular Outcomes Research (NICOR), hosted by Barts Health NHS Trust, London, UK. Two hundred and six hospitals submit over 92 000 new cases to MINAP annually. Approximately 1.5 million patient records are currently held in the database. Patient demographics, medical history, clinical assessment, investigations, treatments, drug therapy prior to admission, during hospital stay, and at discharge are collected. Data completeness of three key data fields (age, admission blood pressure, and heart rate) is over 91%. Vital status following hospital discharge is obtained via linkage to data from the United Kingdom Office for National Statistics. An annual report is compiled using these data, with individual hospital summary data included. Datasets are available to researchers by application to NICOR. Conclusion MINAP is the largest single healthcare system heart attack registry, and includes data from hospitalizations with T1 MI in England, Wales, and Northern Ireland. It includes high-resolution data across the patient pathway and is a powerful tool for quality improvement and research.

Background: In a randomized controlled trial, compared with standard care alone in breast cancer, acupuncture as a prophylactic treatment did not show better quality of life or fewer side effects of chemotherapy (NCT01727362 [clinicaltrials.gov]). The aim of the qualitative part of this mixed methods study was to better understand the subjective perspectives of the patients regarding quality of life during chemotherapy and the perceived effects of acupuncture. Methods: In a nested retrospective qualitative study, semi-structured telephone interviews were conducted with 5 responders and 5 non-responders (defined by the outcome of the primary parameter FACT-B) who were randomly selected from both study arms. The interviews were digitally recorded, pseudonymized, transcribed, and then deductively and inductively analyzed according to Qualitative Content Analysis using MAXQDA® software. Results: A total of 20 patients were included in the qualitative part of the study. In both groups, most women stated that their quality of life was surprisingly better than what they had expected before starting the chemotherapy. All patients of the acupuncture group experienced the acupuncture treatments as relaxing and beneficial, mentioning a friendly setting, and empathic attitude of the therapist. Most of these patients stated that the acupuncture treatment reduced chemotherapy-induced side effects. The patients reported that acupuncture was supportive for coping with the disease in a salutogenic way. For all patients, finding strategies to cope with life-threatening cancer and the side effects of chemotherapy was essential, for example, keeping a positive attitude toward life, selecting social contacts, and staying active as much as possible. Conclusions: Patients in the acupuncture group reported positive effects on psychological and physical well-being after receiving the study intervention. For all patients, having coping strategies for cancer seemed to be more important than reducing side effects. Therefore, further studies should focus more on coping strategies and reducing acute side effects.

Cancer is one of the widest spread diseases in human society. Therefore, the need has grown to monitor, evaluate, and predict its development. Cancer registries address this problem by collecting data on cancer cases, striving for high quality, accuracy, and completeness. One of the basic challenges in this context is the linkage of data from multiple sources. In order to link new cancer records with existing ones, the cancer registries typically use an algorithm referred to as record linkage. Although the algorithm has automated a significant amount of the linking process, there still is a certain percentage of records that cannot be linked automatically. This study addresses the problem of reducing the need of manually matching records with machine learning methods. The particular challenge is caused by pseudonymization of the data. The main contribution is thus finding ways to encode the—pseudonymized—data, i.e., feature extraction so that it can be interpreted by a classifier. Three classifiers (neural network, support vector machines, decision tree) manage to achieve at least 93% classification rate on a dataset of 73 000 cancer records extracted from the inventory of a cancer registry. In addition, ensemble techniques boost the performance further to over 95%. We present an in-depth discussion of the experimental results from a perspective of applying the classification-based record linkage in real practice. Two scenarios of translating to practice will be outlined with a potential of reducing the human workload by an order of magnitude of hundreds of hours.

SummaryBackground In Germany a nationwide melanoma screening programme for adults aged ≥ 35 years was introduced in July 2008. Evidence on utilization and effects is limited. Objectives To examine the uptake and effects of the German nationwide screening programme. Methods This analysis is based on pseudonymized outpatient routine data of a German health insurance company covering data of > 2 million individuals from Saxony for the years 2005–2012. Cases of melanoma and nonmelanoma skin cancer (NMSC) were identified using an algorithm based on the International Classification of Diseases, 10th Revision. Cross-sectional and longitudinal analyses were applied to determine the utilization of the screening programme and effects on skin cancer incidence and disease severity as a proxy for prognosis. Results Overall, 38·0% of eligible persons (≥ 35 years) were screened at least once between July 2008 and December 2012. The annual participation rate was 12·4%. Out of 533 393 persons screened, melanoma and NMSC were diagnosed in 0·3% and 2·5%, respectively. The 6-month melanoma incidence per 100 000 insured persons decreased from 12·8 before screening introduction (January to June 2008) to 10·2 after introduction (July to December 2008). NMSC incidence increased from 173·8 to 175·5 per 100 000. The numbers of screening participants receiving interferon alpha and/or being diagnosed with lymph node and/or distant metastasis (8·6%, 5·9%, 1·5%, respectively) were lower than in nonparticipants (11·2%, 8·5%, 3·5%). These differences were not significant. Conclusions The results suggest that the introduction of a generic skin cancer screening programme in Germany was not associated with significant changes in incidence. No firm conclusions regarding the effects of skin cancer screening on prognosis can be drawn. Longer follow-up and linkage with clinical registry data are necessary to clarify the effect of screening participation on incidence and prognosis.

Objective Surgery in patients with highly eloquent glioblastoma (GB) remains challenging. The aim of this study was to evaluate influence of use of intraoperative magnetic resonance imaging (iMRI) on extent of resection (EOR), clinical outcome, and survival in patients with preoperatively intended subtotal resection of GB. Methods Retrospective assessment was performed in 3 neurosurgical centers (2008–2013). All patients with primary GB, unilocular growth, and adjuvant radiochemotherapy in whom subtotal resection was intended were included. Imaging data were pseudonymized and volumetrically assessed by a central reviewer. Clinical outcome was evaluated based on complications, new permanent neurologic deficits, and survival. Based on subtraction of potential EOR (as defined by reviewer) from effective EOR, EOR change (ΔEOR) was calculated for each case. We calculated multivariate linear regressions to assess influence on effective EOR and ΔEOR, binary regressions to assess influence on complications and new permanent neurologic deficits, and Cox regression models to assess survival. Results Assessment included 70 patients. In iMRI group, a significantly lower ΔEOR (4% vs. 22%, P = 0.008) was found. In linear regression model controlling for age, tumor volume, neurophysiologic mapping, and iMRI, only iMRI influenced ΔEOR significantly (P = 0.03, odds ratio 0.27). In binary regression model controlling for age, tumor volume, effective EOR, neurophysiologic mapping, and iMRI, none of the variables showed a significant difference concerning complications and new permanent neurologic deficits. Overall survival was significantly influenced by age (P = 0.03, odds ratio 1.02) and iMRI (P = 0.026, odds ratio 0.51). Conclusions Maximum safe resection is an important prognostic factor for patients with eloquent GBs. iMRI seems to be a relevant tool to achieve this goal.

Objectives Aircraft, road, and rail traffic noise can cause sleep disturbances. Since night work and shorter sleep durations have been linked to increased risks of breast cancer, we examined if 24-hour, or day- or night-time traffic noise exposure may also increase the risk of breast cancer. Methods To investigate the noise-related risks of breast cancer, the pseudonymized insurance records of three large statutory health companies (2005–2010) for women aged ≥40 years living in the region surrounding the Frankfurt international airport were analyzed with address-specific acoustic data representing aircraft, road, and rail-traffic noise. Noise exposure among women with incident breast cancer (N=6643) were compared with that of control subjects (N=471 596) using logistic regression and adjusting for age, hormone replacement therapy, education and occupation (only available for 27.9%), and a regional proportion of persons receiving long-term unemployment benefits as an ecological indicator of socioeconomic level. Analyses were also stratified according to estrogen receptor (ER) status. Results An increased odds ratio (OR) was observed for ER negative (ER-) tumors at 24-hour aircraft noise levels 55–59 dB [OR 55–59 dB 1.41, 95% confidence interval (CI) 1.04–1.90] but not for ER positive (ER+) breast cancers (OR 55–59 dB 0.95, 95% CI 0.75–1.20). Clear associations between road and rail traffic noise were not observed. Conclusions The results indicate increased aircraft noise may be an etiologic factor for ER- breast cancers. However, information regarding potential confounding factors was largely unattainable. Further research is required to understand how environmental noise may be involved in the pathogenesis of ER- breast cancers.

Background The datanetwork Rheuma 4.0 (DNR_4.0) is a consortium of 5 internistic-rheumatologic specialized practices. Patient data that were collected routinely will be pooled pseudonymized (e.g. via RheumaDok) and will be made available to answer numerous healthcare- and scientific research questions. Methods The participating centres document the following data in specific rheumatologic data documentation systems (RheumaDok, Emil, DocuMed.rh). These data will be routed automatically to the data base of the DNR_4.0 via a prespecified interface and can be used for certain research areas: Diagnosis (by rheumatologist (R), anamnesis (R), medication (R), morning stiffness (R, patient (P)), scores like RADAI (R, P), DAS28 (R), BASDAI (P), BASFI (P), quality of life (R, P). Also prespecified laboratory measures (R) like ESR, CRP etc. can be collected automatically. Patient reported Outcomes (PROs) that were entered via mobile applications like RheumaLive and AxSpALive can be collected in certain intervalls and be sent encrypted into the medical office data base. The data entered by patients will be screened by the rheumatologist or nurse and will be stored in the underlying data base. Clinical data that are collected during regular F2F-appointments will be stored together with the PROs according to a specific period of time. Results The datanetwork Rheuma 4.0 (DNR_4.0) is an association of 5 internistic-rheumatologic specialized practices. By the automated documentation of PROs (patient) and medical measures (rheumatologist) in an underlying data base, scientific and health care real worl data can be collected without extra workload or time requirements. These data are specific and different from data collected by other centres. In principal, the extension of the group to increase the number of participating centres is easily possible because the interface is an “open system”. This allows to build an automised collecting, big and representative data base. Now pooled data sets of 18.000 patients are available in the data base. In a first step, quality and the completeness of the existing data sets will be evaluated and the daily documentation routines will be described. Anonymised statistical analysis of the pooled data sets of the rheumatologic centres will allow to gain knowledge in respect to health care research of the own working group and external interested parties like research groups, sick funds, insurance companies and companies. Conclusions The german biologic registry Rabbit and the “Core documentation” data base deliver valid data about the safety and efficacy of rheumatologic medication. The datanetwork Rheuma 4.0 will make a valuable contribution – especially in conjunction with apps of patient9s self management like RheumaLive and AxSpALive – to health care research, therapeutic strategies and clinical questions from daily practice. Acknowledgements RheumaLive and AxSpALive werde developed by Starhealth GmbH on behalf of UCB Pharma GmbH. Disclosure of Interest S. Kleinert Speakers bureau: UCB, F. Schuch Speakers bureau: UCB, S. Spathling-Mestekemper Speakers bureau: UCB, M. Feuchtenberger Speakers bureau: UCB, C. Kuhn: None declared, M. Welcker Speakers bureau: UCB

Background If rheumatoid arthritis (RA) is not in remission or at least low disease under methotrexate (MTX), leflunomide is an approved conventional synthetic DMARD, which is commonly used in some countries. Objectives To investigate in a real life situation whether patients with RA benefit from instituting leflunomide after methotrexate. Methods The clinical data of all RA patients who had at least once received leflunomide, and who agreed to the pseudonymized analysis of their data (approved by the local ethics committee), were analyzed from the time of leflunomide initiation on to the time of stopping leflunomide or the last visit in 2015, which ever came first. Results In total, 145 RA patients treated with leflunomide were identified. Of these, 87 received leflunomide after MTX had failed as a first line DMARD, and 8 received leflunomide as a first line DMARD. 50 patients had another first line therapy. Of the first line leflunomide patients 3 (38%) were still on leflunomide at the last visit, as compared to 7 of the 44 patients (16%) who were switched from MTX to leflunomide, and 0 of the 27 patients in whom leflunomide was added to MTX (p Conclusions Leflunomide constitutes a longer term option for a subgroup of RA patients with contraindications to MTX or after MTX failure. After one year, leflunomide had led to sustained acceptable disease control in approximately one third of the patients, but only in one in five under leflunomide combined with MTX. These results are supportive of the EULAR recommendations that patients should be switched to a second conventional DMARD in the absence of predictors of bad outcome only. If leflunomide is initiated, the patients need to be followed closely for potential secondary loss of efficacy. Disclosure of Interest None declared

BACKGROUND: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria.METHODS: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria.RESULTS: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate.CONCLUSION: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.

Osteoporosis-related hip fractures represent a substantial cause of mortality and morbidity in industrialized countries like Austria. Identification of groups at high risk for mortality after hip fracture is crucial for health policy decisions. To determine in-hospital, long-term, and excess mortality after osteoporosis-related hip fracture in Austrian patients, we conducted a retrospective cohort analysis of pseudonymized invoice data from Austrian social insurance authorities covering roughly 98 % of the entire population. The data set included 31,668 subjects aged 50 years and above sustaining a hip fracture between July 2008 and December 2010 with follow-up until June 2011, and an age-, gender-, and regionally matched control population without hip fractures (56,320 subjects). Kaplan-Meier and Cox hazard regression analyses served to determine unadjusted and adjusted mortality rates: Unadjusted all-cause 1-year mortality amounted to 20.2 % (95 % CI: 19.7-20.7 %). Males had significantly higher long-term, in-hospital, and excess mortality rates than females, but younger males exhibited lower excess mortality than their female counterparts. Advanced age correlated with increased long-term and in-hospital mortality, but lower excess mortality. Excess mortality, particularly in males, was highest in the first 6 months after hip fracture, but remained statistically significantly elevated throughout the observation period of 3 years. Longer hospital stay per fracture was correlated with mortality reduction in older patients and in patients with more subsequent fractures. In conclusion, more efforts are needed to identify causes and effectively prevent excess mortality especially in male osteoporosis patients.

Introduction: One of the most challenging problems for physicians in ambulatory care, especially general practitioners (GPs)/ family physicians, is supervising their patients’ medication. Especially for older patients, who often suffer from different chronic conditions at the same time and regularly take five or more drugs, it is a challenge to find a good balance between overuse and underuse and to prevent adverse drug reactions and interactions. Policy context and objective: There are different guidelines and classification systems to assess the extent of over-, under- and misuse of drugs in a patient population. In Germany exist e.g. PRISCUS or FORTA [1], which help providers in monitoring and optimizing the drug therapy for their patients. In the Integrated Care Model Gesundes Kinzigtal [2] both systems where tested and discussed. The physicians of a regional quality circle concerning safe drug treatment preferred FORTA as they felt it provided more detailed information which pharmaceutical medications to prefer in what order and which to avoid for specific conditions or comorbidities. The objective is to show how the FORTA classification can be used to benchmark different practices by calculating a condition-overarching FORTA-Score and how it furthermore provides information for each practice how to improve their drug management in the future. Targeted population: The FORTA classification is used for all patients of 65 years and above. Based on claims data patients are attributed to a GP practice when they received at least 50% of their medical treatments from that practice. Afterwards the diagnoses of each patient are cross-checked with related drug treatments rating each combination included in the FORTA classification system from rank A to D. Diagnoses and prescriptions are assessed taking into account the practices’ own services as well as diagnoses and prescriptions from other providers. Highlights: Physicians who participate in the Integrated Care System Gesundes Kinzigtal show a reduced FORTA-Score over time and have a lower mean value compared to non-participating physicians. Nevertheless there is a big variation within the different participating practices. Some benchmark reports as well as detailed information concerning pseudonymized individual cases for the discussions in the quality circles will be shown in the presentation. Transferability: The algorithm of the FORTA classification was translated into SQL-based computer programme queries which could more or less easily be transfered to other populations provided that diagnoses and prescription information is accessible. The reports for the physicians of the quality circles in Gesundes Kinzigtal use a very innovative visualization concept with sparklines to monitor developments over time and reports can easily be entered by physicians using their web browser. Conclusions: The FORTA classification system provides helpful information for the managers of the Integrated Care System Gesundes Kinzigtal as well as for the physicians concerning the developments in safe drug treatment for older patients. The FORTA systems gives advices what prescriptions for specific conditions for older patients should be left out or need to be exchanged. Combining the clinically approved classification system with a data analysis algorithm and a simple but effective information system enables quality circles working on safe drug treatment to optimize care management for whole populations. References: 1- Kuhn-Thiel AM., Weis C., Wehling M. Consensus Validation of the FORTA (Fit fOR The Aged) List: A Clinical Tool for Increasing the Appropriateness of Pharmacotherapy in the Elderly. Drugs & Aging 31 (2):201:131-140. Available from: http://link.springer.com/article/10.1007%2Fs40266-013-0146-0). 2- Hildebrandt H., Schulte T., Stunder B. Triple Aim in Germany: Improving Population Health, Integrating Health Care and Reducing Costs of Care – Lessons for the UK? Journal of Integrated Care 20 (4): 2012:205-222.

Total thyroidectomy is increasingly used as a surgical approach for many thyroid conditions. Subsequently, postoperative hypocalcaemia is observed with increasing frequency, often resulting in prolonged hospital stay, increased use of resources, reduced quality of life and delayed return to work. The administration of vitamin D is essential in the therapy of postoperative hypocalcaemia; calcitriol is most commonly used. What has not been examined so far is whether and how routine preoperative vitamin D prophylaxis using calcitriol can help to prevent postoperative hypocalcaemia. This study evaluates routine preoperative calcitriol prophylaxis for all patients who are to undergo a total thyroidectomy, compared with the current standard of post-treatment, i.e., selective vitamin D treatment for patients with postoperative hypocalcaemia. This clinical observational (minimal interventional clinical trial) trial is a multicentre, prospective, randomized superiority trial with an adaptive design. Datasets will be pseudonymized for analysis. Patients will be randomly allocated (1:1) to the intervention and the control groups. The only intervention is 0.5 μg calcitriol orally twice a day for 3 days prior to surgery. For the primary endpoint measure (number of patients with hypocalcaemia), hypocalcaemia is defined as serum calcium of less than 2.1 mmol/l on any day during the postoperative course; this measure will be analyzed using a Chi-square test comparing the two groups. Secondary endpoint measures, such as number of days to discharge, quality of life, and economic parameters will also be analyzed. By virtue of the direct comparison of clinically and economically relevant endpoints, the efficacy as well as efficiency of preoperative calcitriol prophylaxis of hypocalcaemia will be clarified. These results should be available 24 months after the first patient has been enrolled. The results will be used to inform a revised practice parameter guideline of whether or not to recommend preoperative calcitriol for all patients in whom total thyroidectomy is planned. Deutsches Register Klinischer Studien, DRKS00005615 (Feb.12.2016).

Purpose: Although the carcinogenic effect of ionizing radiation is well known, knowledge gaps persist on the health effects of low-dose radiation, especially in children. The cancer incidence rate in a cohort of 92,957 children diagnosed using X-rays in the years 1976-2003 in the radiology department of a large university clinic was studied. Materials and Methods: Individual radiation doses per examination were reconstructed using an algorithm taking into account the dose area product and other exposure parameters together with conversion factors computed specifically for the equipment and protocols used in the radiology department. Incident cancer cases in the period 1980-2006 were identified via record linkage to the German Childhood Cancer Registry using pseudonymized data. Results: A total of 87 cancers occurred in the cohort between 1980 and 2006: 33 leukemia, 13 lymphoma, 10 brain tumors, and 31 other tumors. The standardized incidence ratio (SIR) for all cancers was 0.99 (95 % CI: 0.79 1.22). A dose-response relationship was not observed for all cancers, leukemia and lymphoma or solid tumors. The cancer risks for boys and girls did not differ. Conclusion: No increase in the cancer incidence risk in relation to very low doses of diagnostic ionizing radiation was observed in this study. However, the results are compatible with a broad range of risk estimates. (orig.)

Neoplastic involvement of cerebrospinal fluid (CSF) and meninges is a relatively rare and highly heterogeneous disease. Only few randomized studies investigated different treatment strategies and achived no conclusive results. New prospective studies with homogeneous entities are difficult to establish and some initiatives failed recently. Therefore, an open, multicentric registry may be an adequate alternative for a prospective documentation and analysis of a large number of cases of neoplastic meningitis from different primary neoplasms. To enable an easy multicentric access, an internet-based database was chosen. Secutrial is a professional database which enables pseudonymized registration of clinical courses and meets all reuqirements for the protection of personal data. Predefined routines allow for an immediate analysis of data like survival or toxicity including the most recently documented data. The internet-based access enables a multicentric, international documentation of cases of neoplastic meningitis. Analysis of these data may allow conclusions on efficacy and toxicity of different treatment strategies in the separate tumor entities. The configuration of the database allows for a separate documentation of the course of primary neoplasm, systemic and solid central nervous system metastases as well as neoplastic meningitis. Also, complications of the disease and toxicity of treatment can be documented. By such, the database is able to discriminate between different causes of clinical deterioration and death. Operative, medical treatment and radiotherapy can be assessed as well as results of radiological, histological and cytological examniations including diagnostic and prognostic markers. The system is flexible enough to enable the addition of newly established items like biomarkers if needed. Dicomm data of radiological examniations can be upoaded and shared if needed and biobanking organized. The results of tumor boards can be documented as well. Since multicentric prospective trials are difficult to perform for this rare and heterogeneous disease, an internet based registry appears to be an adequate alternative to collect data on treatment results. We think that the structure and content of the database presented here provides an adequate tool to collect and analyse a large number of cases with neoplastic meningitis.

As a result of the aging population and medical advances resulting in falling mortality for ischemic heart diseases, the incidence of heart failure is likely to continue to increase in the years to come. This will pose a challenge to both funders and service providers (1, 2). The rate of new cases of heart failure is 10 per 1000 individuals aged over 65 years (3). In addition to considerable morbidity, heart failure is also associated with an unfavorable prognosis and thus high disease-related mortality. Overall, 52.3% of all heart failure patients die within five years of their initial diagnosis (3). Heart failure is a major disease in Germany and is the third most common cause of death, accounting for around 49 000 cases in 2008 (4). In 2009 it was also—aside from normal newborns—the most common main diagnosis in German hospitals (363 700 cases) (ICD-10 I50) (5). Furthermore, disease progression is characterized by frequent hospital readmissions: 23% of hospitalized patients are readmitted as inpatients within 30 days of their first hospital stay, and the six-month hospital readmission rate is as high as 44 to 50% (6– 8). The direct costs of heart failure in Germany have risen constantly in recent years and in 2008 reached the record sum of €3.2 billion, which was 1.2% of all Germany’s health care expenditure. Approximately 45% (€1.45 billion) of disease costs are inpatient hospital care costs (9). This study shows that a case management program for heart failure patients can reduce the number of hospital stays and readmissions. This can also lead to savings in inpatient treatment costs. The study also analyzed the extent to which participation in a case management program affects mortality. Clinical heterogeneity (e.g. of the primary data on the study groups) is a significant variable in clinical field studies in particular. According to Gartlehner et al. (10), the patient-related heterogeneity of a clinical picture can lead to variation in the results obtained and to statistical heterogeneity. This effect can be greater than the estimated random error (10). The CorBene field data provides information on the medical care of heart failure patients who receive routine treatment in cardiology and primary-care practices. This means that in the future patient-related medical data from routine care will have to be matched with pseudonymized data of individuals with statutory health insurance. This will make it possible to investigate data on routine care continually. Data quality poses a particular challenge in this context, in terms of completeness and plausibility of content.

HEALTH RELATED QUALITY OF LIFE AND DEVICE-ACCEPTANCE IN PATIENTS WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS AND TELEMONITORING Florian Leppert, Johannes Siebermair, Stefan Kaab, Wolfgang Greiner OBJECTIVES: Telemedical systems (TMS) and data management for implantable cardioverter-defibrillators (ICD) promise to reduce costs and optimize patient care. Depressive symptoms are common among patients with an ICD and the health related quality of life (HRQoL) is affected by the underlying disease and the implanted device, respectively. TMS might improve the HRQoL of patients and ICDs acceptance due to a closer monitoring and, thereby, an increased level of perceived safety. In this study, changes in the level of depression, HRQoL and device acceptance over a period of six months after ICD-implantation were investigated. METHODS: In this randomized controlled trial, 161 (80.7% male; age: 64,1 ± 14,6; 82% with coronary disease, 11% with dilated cardiomyopathy) patients with an ICD were randomized at the day of implantation into intervention (n=82) or control group (n=79). Patients in the intervention group were equipped with a telemonitoring system that transferred device data (e.g. critical events, status of battery, heart function) from the patients’ home to the medical practitioner via internet. The control group received regular care. Patients were asked to fill out three questionnaires (the generic EQ-5D, the depression specific Hospital Anxiety and Depression Scale (HADS) and the device specific Florida Patient Acceptance Survey (FPAS)); the follow-up period was six month, with postal surveys on a monthly basis (7 times in total). Collected data were analyzed in a pseudonymized manner. Datasets with missing values were filled by applying the Expectation-Maximization (EM) method. RESULTS: Nine patients dropped out before survey completion at month six for different reasons (e.g. draw back consent or death). Of the remaining 152 patients 140 patients filled out at least two sets of questionnaires and were included in the analyses. After six months the mean improvement in the health related quality of life (EQ-5D-Index) in the telemonitoring group was 10.7 points compared to baseline (p=.006) while the mean change in HRQoL in the control group was 5.5 points (p=.138). FPAS and HADS-D showed small but non-significant advantage for the telemonitoring group concerning acceptance and level of depression, respectively. CONCLUSIONS: Preliminary results suggest that telemonitoring systems have the ability to improve the health related quality of life of patients with implantable cardioverter-defibrillators. Results on effects towards the level of depression and anxiety and the enhancement of ICDs acceptance are also promising. Since ICDs are used in chronic heart diseases a longer follow-up period seems to be required to validate the effects.

Objective To investigate the potential of MRI for lung nodule detection in a high-risk population in comparison to low-dose CT. Methods 49 participants (31 men, 18 women, 51–71 years) of the German Lung Cancer Screening and Intervention Trial (LUSI) with a cancer-suspicious lung lesion in CT were examined with non-contrast-enhanced MRI of the lung at 1.5T. Data were pseudonymized and presented at random order together with 30 datasets (23 in men, 7 in women, 18–64 years) from healthy volunteers. Two radiologists read the data for the presence of nodules. Sensitivity and specificity were calculated. Gold standard was either histology or long-term follow-up. Contrast-to-Noise-Ratio (CNR) was measured for all detected lesions in all MRI sequences. Results Average maximum diameter of the lesions was 15mm. Overall sensitivity and specificity of MRI were 48% (26/54) and 88% (29/33) compared to low-dose CT. Sensitivity of MRI was significantly higher for malignant nodules (78% (12.5/16)) than for benign ones (36% (13.5/38); P =0.007). There was no statistically significant difference in sensitivity between nodules (benign and malignant) larger or smaller than 10mm ( P =0.7). Inter observer agreement was 84% ( κ =0.65). Lesion-to-background CNR of T2-weighted single-shot turbo-spin-echo was significantly higher for malignant nodules (89±27) than for benign ones (56±23; P =0.002). Conclusion The sensitivity of MRI for detection of malignant pulmonary nodules in a high-risk population is 78%. Due to its inherent soft tissue contrast, MRI is more sensitive to malignant nodules than to benign ones. MRI may therefore represent a useful test for early detection of lung cancer.

Background There is limited evidence regarding the safety of pharmacologic treatments during pregnancy. With the increasing number of new medications available for the treatment of rheumatic and autoimmune diseases, there is a growing need for systematic collection of prospective real-world data on drug safety in pregnancy and lactation. Objectives To determine the safety of various drug treatments during pregnancy and the influence of the underlying rheumatic disease on outcome and child development. Methods The Rhekiss register is designed as a prospective nationwide, web-based longitudinal observational cohort study. Pregnant patients with confirmed diagnose of inflammatory rheumatic disease are eligible to be enrolled until the 20th week of pregnancy regardless of drug treatment. Rheumatologists as well as patients report three times during pregnancy (each trimester) and semi-annually after birth until the child9s 2nd birthday. Patients can use the online documentation system remote or in the practice. Information on all given drug treatments, details on the course of the maternal disease, the development of the pregnancy, maternal or fetal complications during pregnancy, pregnancy outcomes, and child development during the first two years of life are collected. At baseline, sociodemographic parameters, prior pregnancies, and comorbidities are reported. The register is designed as uniform platform with specific modules for various inflammatory rheumatic diseases. Only pseudonymized data are used, data security issues conform with regulatory authorities have been implemented. It can be easily extended and translated to other languages. Results The register started on 15th of September 2015. Until end of January 2016, 106 rheumatologists in outpatient clinic or private practices signed up for participation. Among these, 28 units recruited patients so far. 99 patients were enrolled until end of January. Of these, 26 had rheumatoid arthritis, 26 systemic lupus erythematosus, 17 other connective tissue diseases, 9 juvenile idiopathic arthritis, 8 spondyloarthritis, 7 psoriatic arthritis, 4 autoinflammatory syndromes and 2 systemic vasculitis. Mean age of the patients was 31.1 (± 5.1) years, mean disease duration 6.5 (± 8.2) years. Mean disease activity, assessed by the rheumatologist on a numeric rating scale from 0–10, was 2.6 (± 2.1) over all diagnoses. On a disease severity scale ranging from 1 to 5 (highest grade), two thirds of the patients were reported as grade 2 or 3. Conclusions The German pregnancy register Rhekiss was initiated to fill the knowledge gap on the course and outcomes of pregnancies in patients with rheumatic diseases as well as on the current use and the safety of treatments during pregnancy and lactation. The fast uptake of patients shows that there is a substantial need for and a high interest in real-life data to guide treatment decisions. Rhekiss can be easily extended and translated to other languages. At the time of the EULAR congress, data on the first seven months of the register will be available for presentation. Disclosure Rhekiss is a collaborative project of the DRFZ Berlin and the Rheumazentrum Rhein-Ruhr e.V. Dusseldorf, jointly funded by both institutions. Disclosure of Interest None declared

One additional benefit of the post mortem external examination is to collect valid information about cause of death and to set up a national mortality register. To date, the only German federal state to have established a mortality index for the purpose of epidemiological studies is the city of Bremen (1). Up until now, national epidemiological mortality follow-ups have only been feasible by requesting pseudonymized death certificates from the local public health departments. Because in some German federal states death certificates only need to be kept for a limited period of time (10 years), significant data losses, especially in the case of historical cohorts, may be assumed when follow-ups are based on the individual collection of death certificates (2). To provide reliable follow-up information, not only the death certificate needs to be correctly completed, but the underlying cause of death must also be coded with the correct ICD. Coding is done by coders in the state statistical offices who work according to official coding rules (3). Most coders do not have any specific medical training or education. They learn the coding rules in seminars and regular refresher courses. Notwithstanding, even among experienced coders, differences in coding behaviour arise because of the complexity of the applied rules and the erratic quality of death certificates. In particular, when death certificate entries are ambiguous, coders have to try to interpret the underlying cause of death. This was confirmed in our experience of mortality studies in which coders carried out the reference coding of the cause of death from death certificates. In addition to the specific medical qualification for carrying out post mortem external examinations as proposed in the current political debate, an automated multicausal coding of causes of death, comparable to the existing IRIS program (4), should be required. This would ensure valid, reproducible coding of causes of death. With the concurrent establishment of a national mortality register, an intensification of epidemiological research using mortality data should be expected in Germany, which should also reveal implausibilities in the determination of causes of death. This should also contribute to improved data quality in the cause of death statistics.

Background In advanced-stage indolent lymphoma, therapeutic approaches may vary from watch and wait, antibody monotherapy, immunochemotherapy, or dose-intensified consolidation up to allogeneic strategies. In this nationwide survey, representative hematologic/oncologic centers monitored current treatment strategies in indolent lymphoma in general practice. Methods Four hundred ninety-five centers involved in the treatment of indolent lymphoma including university hospitals, community hospitals, and oncologists in practice were identified and contacted. Thirteen percent of centers provided information on 741 patients, which corresponds to 10% of the expected national prevalence. Detailed data on 576 unselected patients from 46 representative centers (2 university hospitals, 25 community hospitals, and 19 oncologists in practice) for whom a treatment decision took place in the fourth quarter of 2006 (start, change, or end of therapy) were included in this analysis. Data were verified by monitoring the pseudonymized patient documents. Results Median age was 67 years (range, 17 to 95 years) and 65% of patients were 60 years of age or older. Concomitant disease was frequent with cardiac disease (29%), hypertension (28%), diabetes (11%), and renal impairment (7%) being the most typical combinations. Histologies included 39% follicular lymphoma, 26% chronic lymphocytic leukemia (CLL), 10% marginal zone, 9% mantle cell lymphoma (MCL), and 16% other. Only 10% of the overall patient population were treated within these studies. The aim of initial therapy was curative in 35%, and physicians aimed at improved survival in 62% and palliation only in 54% of patients. Radiation (10%), antibody monotherapy (4%), chemotherapy (33%), and combined immunochemotherapy (31%) were the most frequent approaches. Applied chemotherapies included cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) (46%), fludarabine combinations (F/FC/FCM: 15%), chlorambucil (14%), CVP/COP (9%) and bendamustin (4%). Maintenance was used in 12% and autologous/allogeneic stem cell consolidation were rarely applied (both in 3% of patients). At first relapse, combined approaches including immunochemotherapy (49%), maintenance therapy (16%), and autologous/allogeneic transplantation (14%/4%) were more frequently administered. As expected, different treatment strategies and response rates were observed in follicular lymphoma (FL), MCL, and CLL. Interestingly, supportive measures including antibiotics (34%), erythrocyte transfusions (32%), granulocyte colony-stimulating factor (22%), immunoglobulines (19%), antifungal drugs (13%), and erythropoetin (10%) were frequently applied even in first-line therapy. Overall response was 83% (FL: 97%, MCL: 95%, CLL: 74%) with a 39% complete response (FL 63%, MCL 54%, CLL 15%) rate. Discussion In this population-based survey, patients characteristics differed significantly from published study cohorts as did clinical strategies and therapeutic approaches. Thus, clinically more relevant studies in medically compromised patients are urgently warranted.

Neoplastic involvement of cerebrospinal fluid (CSF) and meninges is a relatively rare and highly heterogeneous disease. Only few randomized studies investigated different treatment strategies and achived no conclusive results. New prospective studies with homogeneous entities are difficult to establish and some initiatives failed recently. Therefore, an open, multicentric registry may be an adequate alternative for a prospective documentation and analysis of a large number of cases of neoplastic meningitis from different primary neoplasms. To enable an easy multicentric access, an internet-based database was chosen. Secutrial is a professional database which enables pseudonymized registration of clinical courses and meets all requirements for the protection of personal data. Predefined routines enable an immediate analysis of data like survival or toxicity including the most recently documented data. The internet-based access enables a multicentric, international documentation of cases of neoplastic meningitis. Analysis of these data may allow for conclusions on efficacy and toxicity of different treatment strategies in the separate tumor entities. The configuration of the database provides a separate documentation of the course of primary neoplasm, systemic and central nervous system metastases as well as neoplastic meningitis. Operative, medical treatment and radiotherapy can be assessed as well as results of radiological, histological and cytological examinations including diagnostic and prognostic markers. Also, complications of the disease and toxicity of treatment can be documented. By such, the database is able to discriminate between different causes of clinical deterioration and death. The system is flexible enough to enable the addition of newly established items like biomarkers if needed. Dicomm data of radiological examinations can be uploaded and shared if needed and biobanking organized. The results of tumor boards can be documented as well. Since multicentric prospective trials are difficult to perform for this rare and heterogeneous disease, an internet based registry appears to be an adequate alternative to collect data on treatment results. We think that the structure and content of the database presented here provides an adequate tool to collect and analyse a large number of cases with neoplastic meningitis. Disclosures: Strik: Mundipharma: Consultancy, Honoraria, Speakers Bureau; Medac: Consultancy, Honoraria; Micromet: Consultancy.

Most patients with Whipple’s disease have rheumatic symptoms. The aim of our prospective, questionnaire-based, non-interventional clinical study was to assess whether these symptoms are useful in guiding the differential diagnosis to the rheumatic disorders. Forty patients with Whipple’s disease, followed by 20 patients for validation and 30 patients with rheumatoid-, 21 with psoriatic-, 15 with palindromic- and 25 with axial spondyloarthritis were recruited for the present investigation. Patients with Whipple’s disease and patients with rheumatic disorders were asked to record rheumatic symptoms on pseudonymized questionnaires. The data obtained were subjected to multiple logistic regression analysis. Episodic pain with rapid onset, springing from joint to joint was most common in patients with palindromic arthritis and second most common and somewhat less conspicuous in Whipple’s disease. Continuous pain in the same joints predominated in patients with rheumatoid-, psoriatic-, and axial spondyloarthritis. Multiple logistic equations resulted in a predicted probability for the diagnosis of Whipple’s disease of 43.4 ± 0.19% (M ± SD) versus a significantly lower probability of 23.8 ± 0.19% (M ± SD) in the aggregate of patients with rheumatic disorders. Mean area under the curve (AUC) ± SD was 0.781 ± 0.044, 95% CI 0.695–0.867, asymptotic significance p