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Little is known about the impact of standardized imaging surveillance on anxiety levels and well-being of patients after endovascular aortic aneurysm repair (EVAR). We hypothesize that patient anxiety levels increase just before receiving the imaging results compared with standard anxiety levels. Methods: Prospective cohort study from November 2018 to May 2020 including post-EVAR patients visiting the outpatient clinics of 4 Dutch hospitals for imaging follow-up. The Patient-Reported Outcomes Measurement Information System (PROMIS) was used. Patients completed the PROMIS Anxiety v1.0 Short Form (SF) 4a, PROMIS-Global Health Scale v1.2, and PROMIS-Physical Function v1.2 SF8b at 2 time points: prior to the result of the imaging study (T1: pre-visit) and 6–8 months later (T2: reference measurement). Mean T-scores at T1 were compared to T2, and T2 to the general 65+ Dutch population. Results: Altogether 342 invited patients were eligible, 214 completed the first questionnaire, 189 returned 2 completed questionnaires and 128 patients did not participate. Out of 214 respondents, 195 were male (91.1%) and the mean (standard deviation) age was 75.2 (7.0) years. There were no significant differences between T1 and T2 in anxiety levels (0.48; 95% confidence interval[CI] -0.42–1.38), global mental health (0.27; 95% CI -0.79–0.84), global physical health (0.10; 95% CI -0.38–1.18) and physical function (0.53; 95% CI -0.26–1.32). Compared with the 65+ Dutch population, at T2 patients experienced more anxiety (3.8; 95% CI 2.96–5.54), had worse global physical health (-3.2; 95% CI -4.38 – -2.02) and physical function (-2.4; 95% CI -4.00 – -0.80). Global mental health was similar (-1.0; 95% CI -2.21 – 0.21). Conclusions: Post-EVAR patients do not experience more anxiety just before receiving surveillance imaging results than outside this period, but do suffer from more anxiety and worse physical outcomes than the 65+ Dutch population.

Objective: The aims of the present study were to examine the impact of type 2 endoleaks (T2EL) on overall survival and to determine the need for secondary intervention after endovascular aneurysm repair (EVAR). Methods: A multicentre retrospective cohort study in the Netherlands was conducted among patients with an infrarenal abdominal aortic aneurysm (AAA) who underwent EVAR between 2007 and 2012. The primary endpoint was overall survival for patients with (T2EL+) or without (T2EL-) a T2EL. Secondary endpoints were sac growth, AAA rupture, and secondary intervention. Kaplan–Meier survival and multivariable Cox regression analysis were used. Results: A total of 2 018 patients were included. The median follow up was 62.1 (range 0.1 – 146.2) months. No difference in overall survival was found between T2EL+ (n = 388) and T2EL- patients (n = 1630) (p =.54). The overall survival estimates at five and 10 years were 73.3%/69.4% and 45.9%/44.1% for T2EL+/T2EL- patients, respectively. Eighty-five of 388 (21.9%) T2EL+ patients underwent a secondary intervention. There was no difference in overall survival between T2EL+ patients who underwent a secondary intervention and those who were treated conservatively (p =.081). Sac growth was observed in 89 T2EL+ patients and 44/89 patients (49.4%) underwent a secondary intervention. In 41/44 cases (93.1%), sac growth was still observed after the intervention, but was left untreated. Aneurysm rupture occurred in 4/388 T2EL patients. In Cox regression analysis, higher age, ASA classification, and maximum iliac diameter were significantly associated with worse overall survival. Conclusion: No difference in overall survival was found between T2EL+ and T2EL- patients. Also, patients who underwent a secondary intervention did not have better survival compared with those who did not undergo a secondary intervention. This study reinforces the need for conservative treatment of an isolated T2EL and the importance of a prospective study to determine possible advantages of the intervention.

Aim of the study Patients with cancer might have an increased risk for severe outcome of coronavirus disease 2019 (COVID-19). To identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods This observational cohort study has been designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a nationwide collaboration of oncology physicians in the Netherlands. A questionnaire has been developed to collect pseudonymised patient data on patients’ characteristics, cancer diagnosis, and treatment. All patients with COVID-19 and a cancer diagnosis or treatment in the past 5 years are eligible. Results Between March 27th and May 4th, 442 patients were registered. For this first analysis, 351 patients were included of whom 114 patients died. In multivariable analyses, age ≥65 years (p, Highlights • Patients with cancer might have an increased risk for severe outcome of COVID-19. • This nationwide study investigated risk factors for fatal outcome of COVID-19. • Among 442 registered patients with cancer, 32.3% of patients died of COVID-19. • Haematological malignancy and lung cancer increased the risk of fatal outcome. • These results can guide treatment and vaccination decisions in patients with cancer.

Objective This study determined if partial sick leave was associated with a shorter duration of sick leave due to musculoskeletal disorders (MSD) based on routinely collected health data in Dutch sick-listed employees. Furthermore, the effect of timing of partial sick leave on sick leave duration was determined. Methods This cohort study consisted of 771 employees with partial sick leave and 198 employees with full-time sick leave who participated in an occupational health check, and had sick leave due to MSD for minimally 4 weeks and were diagnosed by an occupational physician. Multivariable linear regression models were performed to determine the effects of partial sick leave (unadjusted and adjusted for confounders and MSD diagnosis) and Kaplan–Meier curves were presented for visualization of return to work for different timings of starting partial sick leave. Furthermore, linear regression analysis were done in subsets of employees with different minimal durations of sick leave to estimate the effects of timing of partial sick leave. Results Initial results suggest that partial sick leave was associated with longer sick leave duration, also when adjusted for confounders and sick leave diagnosis. Secondary results which accounted for the timing of partial sick leave suggest that partial sick leave had no effect on the duration of sick leave. Conclusion Partial sick leave does not influence MSD sick leave duration in this study when accounting for the timing of partial sick leave.

IntroductionStrict imaging surveillance protocols to detect complications following endovascular aneurysm repair (EVAR) are common practice. However, controversy exists as to whether all EVAR patients need intense surveillance. The 2019 European Society for Vascular Surgery guidelines for management of abdominal aortic aneurysm (AAA) suggest that patients may be considered for limited follow-up with imaging if classified as ‘low risk’ for complications based on their initial postoperative imaging. The current study aims to investigate the intervention-free survival and overall survival stratified for patients with and without yearly imaging surveillance.Methods and analysisThe Observing a Decade of Yearly Standardised Surveillance in EVAR patients with Ultrasound or CT Scan study comprises a national multicentre retrospective cohort study in 17 medical centres. Consecutive patients with an asymptomatic or symptomatic infrarenal AAA who underwent EVAR between January 2007 and January 2012 will be included in this study with follow-up until December 2018. Clinical variables and all follow-up information will be retrieved in extensive data collection from the patient’s medical records. In addition, an e-survey was sent to vascular surgeons at the 17 participating centres to gauge their opinions regarding the possibility of safely reducing the frequency of imaging surveillance. Primary endpoints are intervention after EVAR and aneurysm-related mortality. The initial estimated sample size is 1997 patients.Ethics and disseminationThe study has been approved by the Medical Ethics Review Committee of the Amsterdam UMC, location Academic Medical Centre, Amsterdam, the Netherlands. Study findings will be disseminated via presentations at conferences and publications in peer-reviewed journal.Trial registration numberThe Netherlands Trial Registry, NL6953 (old: NTR28773).

Objective: What are the cost per live birth and the incremental cost of preventing a miscarriage with preimplantation genetic testing for aneuploidy (PGT-A) by polar body biopsy and array-based comprehensive genome hybridisation (aCGH) versus regular IVF/ICSI without PGT-A for infertility treatment in women 36–40 years of age?. Design: Decision tree model. Population: A randomised clinical trial on PGT-A (ESTEEM study). Methods: Two treatment strategies were compared: one cycle of IVF/ICSI with or without PGT-A. Costs and effects were analysed with this model for four different cost scenarios: high-, higher medium, lower medium and low-cost. Base case, sensitivity, threshold, and probabilistic sensitivity analyses were used to examine the cost-effectiveness implications of PGT-A. Results: PGT-A increased the cost per live birth by approximately 15% in the high-cost scenario to approximately 285% in the low-cost scenario. Threshold analysis revealed that PGT-A would need to be associated with an absolute increase in pregnancy rate by 6% to >39% or, alternatively, would need to be US$2,969 (high-cost scenario) to US$4,888 (low-cost scenario) cheaper. The incremental cost to prevent one miscarriage by PGT-A using the base case assumptions was calculated to be US$34,427 (high-cost scenario) to US$51,146 (low-cost scenario). A probabilistic sensitivity analysis showed cost-effectiveness for PGT-A from 1.9% (high-cost scenario) to 0.0% (low-cost scenario) of calculated samples. Conclusions: While avoiding unnecessary embryo transfers and miscarriages are important goals, patients and doctors need to be aware of the high-cost implications of applying PGT-A using aCGH on polar bodies. Tweetable abstract: PGT-A by polar body biopsy and comprehensive genome hybridisation increases cost per live birth and requires high financial spending per miscarriage averted.

Background: Caregivers of Parkinson’s disease (PD) patients provide important support during the pre- and postoperative phase of deep brain stimulation (DBS). High levels of caregiver burden have been reported after DBS. However, a comparison between preoperative and postoperative burden and associated factors has been insufficiently studied. Objective: To investigate the influence of DBS on caregiver burden, and to identify the differential impact of patient-related factors on caregiver burden before and after DBS. Methods: Consecutive patients referred for DBS eligibility screening or during one-year follow-up assessments were included. Caregiver burden was measured with the short Zarit Burden Interview (ZBI-12). Inverse Probability Weighting (IPW) was used to compare caregiver burden between preoperative and postoperative assessments. Results: We included 47 patients (24 screening, 23 follow-up) (median age 65 years, 29.4% female sex). DBS did not impact caregiver burden (screening: median ZBI-12 9.5 (IQR 3.25, 16.75); follow-up median ZBI-12 6 (IQR 4, 14); IPW-coefficient 0.57 (95% CI –2.75, 3.89)). Worse caregiver burden during DBS screening was associated with worse patient-related scores on depressive symptoms, anxiety, QoL, and impulsiveness. Worse scores on depressive symptoms, anxiety, apathy, postural-instability-gait-disorder, and QoL were associated with worse caregiver burden at one-year follow-up. Conclusion: DBS appears not associated with changes in caregiver burden. Various symptoms are valued differently between screening and follow-up assessments in terms of caregiver burden. Early recognition of caregivers “at risk” may improve guidance of patient-caregiver dyads throughout the DBS process.

Aim of the study: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted cancer care. In this study, clinical patient characteristics related to COVID-19 outcomes and advanced care planning, in terms of non-oncological treatment restrictions (e.g. do not-resuscitate codes), were studied in patients with cancer and COVID-19. Methods: The Dutch Oncology COVID-19 Consortium registry was launched in March 2020 in 45 hospitals in the Netherlands, primarily to identify risk factors of a severe COVID-19 outcome in patients with cancer. Here, an updated analysis of the registry was performed, and treatment restrictions (e.g. do-not-intubate codes) were studied in relation to COVID19 outcomes in patients with cancer. Oncological treatment restrictions were not taken into account. Results: Between 27th March 2020 and 4th February 2021, 1360 patients with cancer and COVID-19 were registered. Follow-up data of 830 patients could be validated for this analysis. Overall, 230 of 830 (27.7%) patients died of COVID-19, and 60% of the remaining 600 patients with resolved COVID-19 were admitted to the hospital. Patients with haematological malignancies or lung cancer had a higher risk of a fatal outcome than other solid tumours. No correlation between anticancer therapies and the risk of a fatal COVID-19 outcome was found. In terms of end-of-life communication, 50% of all patients had restrictions regarding life prolonging treatment (e.g. do-not-intubate codes). Most identified patients with treatment restrictions had risk factors associated with fatal COVID-19 outcome. Conclusion: There was no evidence of a negative impact of anticancer therapies on COVID-19 outcomes. Timely end-of-life communication as part of advanced care planning could save patients from prolonged suffering and decrease burden in intensive care units. Early discussion of treatment restrictions should therefore be part of routine oncological care, especially during the COVID-19 pandemic. 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Objectives Our objective was to evaluate the role of potential predictors in explaining spatial variation among diabetes hospitalization rates in Germany. Study design This was an ecological analysis using hospital routine data. Methods County-level hospitalization rates (n = 402) in 2015 were calculated based on the German Diagnosis Related Groups database. We used a funnel plot to identify counties with high hospitalization rates. To examine the impact of predictors such as socio-economic status or structure of primary care, we performed linear and logistic regression analyses. Results The crude hospitalization rate was 262 admissions per 100,000 population. In multivariable logistic models, we found the percentage of employees with academic degree (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.56–0.91), high hospital bed rate (4th quartile vs 1st quartile; OR: 2.73, CI: 1.03–7.24), and diabetes prevalence (OR: 1.49, CI: 1.17–1.90) to be significant predictors for high hospitalization rates. In multivariable linear models, the percentage of unemployed (regression coefficient b: 4.79, CI: 0.81–8.78) and rurality (b: 0.52, CI: 0.19–0.85) explained the variation in addition to predictors from logistic regression. Primary care structure was not a significant predictor in multivariable models. Conclusions The non-significant impact of primary care in adjusted models casts the use of diabetes hospitalizations as indicators for access and quality of primary care into doubt. Diabetes hospitalizations may rather reflect demand for care.

OBJECTIVE: The aim of this study was to develop a prediction model for the prognosis of sick leave due to low back pain (LBP). METHODS: This is a cohort study with 103 employees sick-listed due to non-specific LBP and spinal disc herniation. A prediction model was developed based on questionnaire data and registered sick leave data with follow up of 180 days. RESULTS: At follow up 31 (30.1%) employees were still sick-listed due to LBP. Forward selection procedure resulted in a model with: catastrophizing, musculoskeletal work load, and disability. The explained variance was 27.3%, calibration was adequate and discrimination was fair with area under the ROC-curve (AUC) = 0.761 (interquartile range [IQR]: 0.755-0.770). CONCLUSION: The prediction model of this study can adequately predict LBP sick leave after 180 days and could be used for employees sick listed due LBP.

BACKGROUND: Quality assurance for acute in-hospital care in Germany is based on compulsory comparisons between institutions, so-called external quality assurance (EQA). The effectiveness of EQA has not yet been adequately studied. The purpose of the QUASCH project, which is supported by the Innovation Fund of the Federal Joint Committee, is to investigate the association between EQA and health care outcomes, specifically with respect to stroke. METHODS: The analyses were based on data from 379 825 patients insured by the AOK health insurance fund who were acutely admitted to a hospital because of stroke over the period 2007–2017. Data on 47 659 patients were derived from EQA documentation in the state of Hesse, in which stroke EQA had already been introduced in 2003; data on the remaining 332 166 patients were from other federal states, where 117 734 of these patients had been treated under EQA conditions. The association of EQA with mortality over the period of observation was analyzed by multivariate Cox regression, with the following covariates: age, sex, comorbidities, time period of occurrence, nursing care level, type of stroke, socio-economic deprivation in the region of origin, and treatment in a stroke unit. RESULTS: Compared to treatment without EQA, mortality risk under EQA in the state of Hesse was significantly lower (hazard ratio [HR]: 0.93; 95% confidence interval: [0.92; 0.95]). The reduction in mortality risk with EQA was somewhat lower in the other federal states (HR: 0.96 [0.95; 0.97]). Treatment in a stroke unit was associated with a mortality risk that was lower still (HR: 0.86 [0.85; 0.87]). Mortality risk rose with age, comorbidities, and need for nursing care; it was lower in women and in persons whose stroke occurred in a later period. CONCLUSION: Quality assurance measures are associated with lower mortality risk after stroke. The concentration of care in specially qualified institutions is associated with stronger effects than EQA alone.

ObjectivesPatients in German ambulatory care frequently report patient safety problems (PSP). It is unclear whether patients report PSP back to their general practitioner (GP) or specialist in charge. This study reports on how patients respond to experienced PSP.DesignRetrospective cross-sectional study.SettingComputer-assisted telephone interviews (CATI) with randomly recruited citizens aged ≥40 years in Germany.Participants10 037 citizens ≥40 years. About 52% of the interviewees were female, 38% were between 60 and 79 years old and about 47% reported that they were chronically ill. A total of 2589 PSPs was reported.Primary and secondary measures/ResultsAccording to the respondents (n=1422, 77%, 95% CI: 74.7 to 79.1), 72% (95% CI: 70.2 to 73.7) of PSP were reported back to the GP in charge or to another GP/specialist. Further reactions were taken by 65% (95% CI: 62.5 to 67.5) of the interviewees: around 63% (95% CI: 62.5 to 66.2) of the reported PSP led to a loss of faith in the physician or to complaints. χ2 and binary logistic regression analyses show significant associations between the (a) reporting and (b) reaction behaviour and determinants like ‘medical treatment area’ ((a) χ2=17.13, p=0.009/(b) χ2=97.58, p=0.000), ‘PSP with/without harm’ ((a) χ2=111.84, p=0.000/(b) χ2=265.39, p=0.000) and sociodemographic characteristics when respondents are aged between 40 and 59 years ((a) OR 2.57/(b) OR 2.60) or have chronic illnesses ((a) OR 2.16/(b) OR 2.14).ConclusionThe data suggest that PSPs are frequently reported back to the GP or specialist in charge and have a significant serious impact on the physician–patient relationship. Much could be learnt from the patient reporting and reacting behaviour to prevent PSPs in ambulatory care.

Objective To assess the care for hypertension in Sierra Leone, by the use of a cascade-of-care approach, to identify where the need for healthcare system interventions is greatest. Methods Using data from a nationwide household survey on surgical conditions undertaken in 1.956 participants ≥18 years from October 2019 till March 2020, a cascade of care for hypertension consisting of four categories - hypertensive population, those diagnosed, those treated and those controlled - was constructed. Hypertension was defined as having a blood pressure ≥140/90mmHg, or self-reported use of antihypertensive medication. Logistic regression analysis was used to investigate factors associated with undiagnosed hypertension. Results The prevalence of hypertension was 22%. Male sex, age 18-34 years and living in a rural location were significantly associated with the odds of undiagnosed hypertension. Among those with hypertension, 23% were diagnosed, 11% were treated, and 5% had controlled blood pressure. The largest loss to care (77%) was between being hypertensive and receiving a diagnosis. There was no significant difference between men and women in the number of patients with controlled blood pressure. Adults aged 40 or older were observed to be better retained in care compared to those younger than 40 years of age. Conclusion There is a significant loss to care in the care cascade of hypertension in Sierra Leone. Our results suggests that increasing awareness of cardiovascular risk and risk factor screening for early diagnosis might have a large impact on hypertension care.

STUDY QUESTION Is fatigue a frequent symptom of endometriosis? SUMMARY ANSWER Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature. WHAT IS KNOWN ALREADY Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis. STUDY DESIGN, SIZE, DURATION The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background. PARTICIPANTS/MATERIALS, SETTING, METHODS Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios. MAIN RESULTS AND THE ROLE OF CHANCE Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease. LIMITATIONS, REASONS FOR CAUTION Women with asymptomatic endometriosis cannot be excluded in the control group which would lead to underestimation of our results. The study's design allows no evaluation of causal effects. WIDER IMPLICATIONS OF THE FINDINGS As fatigue is experienced by numerous women with endometriosis, it needs to be addressed in the discussion of management and treatment of the disease. In addition to treating endometriosis, it would be beneficial to reduce insomnia, depression, pain and occupational stress in order to better manage fatigue. STUDY FUNDING/COMPETING INTEREST(s) There was no additional funding received for this study and no conflict of interest. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT 02511626.

Background The Framingham score is commonly used to estimate the risk of cardiovascular disease (CVD). This study investigated whether work-related variables improve Framingham score predictions of sickness absence due to CVD. Methods Eleven occupational health survey variables (descent, marital status, education, work type, work pace, cognitive demands, supervisor support, co-worker support, commitment to work, intrinsic work motivation and distress) and the Framingham Point Score (FPS) were combined into a multi-variable logistic regression model for CVD sickness absence during 1-year follow-up of 19 707 survey participants. The Net Reclassification Index (NRI) was used to investigate the added value of work-related variables to the FPS risk classification. Discrimination between participants with and without CVD sickness absence during follow-up was investigated by the area under the receiver operating characteristic curve (AUC). Results A total of 129 (0.7%) occupational health survey participants had CVD sickness absence during 1-year follow-up. Manual work and high cognitive demands, but not the other work-related variables contributed to the FPS predictions of CVD sickness absence. However, work type and cognitive demands did not improve the FPS classification for risk of CVD sickness absence [NRI = 2.3%; 95% confidence interval (CI) −2.7 to 9.5%; P = 0.629]. The FPS discriminated well between participants with and without CVD sickness absence (AUC = 0.759; 95% CI 0.724–0.794). Conclusion Work-related variables did not improve predictions of CVD sickness absence by the FPS. The non-laboratory Framingham score can be used to identify health survey participants at risk of CVD sickness absence.

RLIM, also known as RNF12, is an X-linked E3 ubiquitin ligase acting as a negative regulator of LIM-domain containing transcription factors and participates in X-chromosome inactivation (XCI) in mice. We report the genetic and clinical findings of 84 individuals from nine unrelated families, eight of whom who have pathogenic variants in RLIM (RING finger LIM domain-interacting protein). A total of 40 affected males have X-linked intellectual disability (XLID) and variable behavioral anomalies with or without congenital malformations. In contrast, 44 heterozygous female carriers have normal cognition and behavior, but eight showed mild physical features. All RLIM variants identified are missense changes co-segregating with the phenotype and predicted to affect protein function. Eight of the nine altered amino acids are conserved and lie either within a domain essential for binding interacting proteins or in the C-terminal RING finger catalytic domain. In vitro experiments revealed that these amino acid changes in the RLIM RING finger impaired RLIM ubiquitin ligase activity. In vivo experiments in rlim mutant zebrafish showed that wild type RLIM rescued the zebrafish rlim phenotype, whereas the patient-specific missense RLIM variants failed to rescue the phenotype and thus represent likely severe loss-of-function mutations. In summary, we identified a spectrum of RLIM missense variants causing syndromic XLID and affecting the ubiquitin ligase activity of RLIM, suggesting that enzymatic activity of RLIM is required for normal development, cognition and behavior.

Objective: A downside of Deep Brain Stimulation (DBS) for Parkinson's Disease (PD) is that cognitive function may deteriorate postoperatively. Electroencephalography (EEG) was explored as biomarker of cognition using a Machine Learning (ML) pipeline.Methods: A fully automated ML pipeline was applied to 112 PD patients, taking EEG time-series as input and predicted class-labels as output. The most extreme cognitive scores were selected for class differentiation, i.e. best vs. worst cognitive performance (n = 20 per group). 16,674 features were extracted per patient; feature-selection was performed using a Boruta algorithm. A random forest classifier was modelled; 10-fold cross-validation with Bayesian optimization was performed to ensure generalizability. The predicted class-probabilities of the entire cohort were compared to actual cognitive performance.Results: Both groups were differentiated with a mean accuracy of 0.92; using only occipital peak frequency yielded an accuracy of 0.67. Class-probabilities and actual cognitive performance were negatively linearly correlated (b =-0.23 (95% confidence interval (-0.29,-0.18))).Conclusions: Particularly high accuracies were achieved using a compound of automatically extracted EEG biomarkers to classify PD patients according to cognition, rather than a single spectral EEG feature.Significance: Automated EEG assessment may have utility for cognitive profiling of PD patients during the DBS screening. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

People with intellectual disabilities have a lower life expectancy and more frequent comorbidities than the general population and have unmet health needs. Insufficient medical care is suspected to be one reason, for which little data is available in Germany. The study therefore focuses on the question of how people with intellectual disabilities make use of medical care, including screening and preventive measures.In a cross-sectional study in 3 workshops for people with intellectual disabilities, the use of health care was surveyed by means of questionnaires from their relatives. The evaluation was carried out descriptively and by means of inferential statistics comparing participants with the general population as well as within the group of participants for socio-demographic differences.Almost all 181 participants (participation rate 19.3%) had a family doctor. In comparison to the general population, the participants made more frequent use of the services of general practitioners and the care provided by numerous other specialist areas. They made less frequent use of screening for colon, breast, cervix and prostate and more frequent use for skin cancer and general check-up. Dental check-ups and preventive measures showed no difference. Participants living in institutional settings made more use of the regular services than those living with relatives or alone. Participants with a migration background were less aware of care services.The results do not show any indications of a general undersupply of health care. Participation in cancer screening with more complex examinations should be encouraged, especially for people with mental disabilities living alone or with relatives. Those with a migration background and their families should be specifically informed.Menschen mit geistiger Behinderung weisen eine geringere Lebenserwartung und häufigere Komorbidität als die Allgemeinbevölkerung sowie ungedeckte Gesundheitsbedarfe auf. Als ein Grund wird eine unzureichende medizinische Versorgung vermutet, wozu in Deutschland wenige Daten vorliegen. Die Studie widmet sich deshalb der Frage, wie Menschen mit geistiger Behinderung die medizinische Versorgung einschließlich Vorsorge und präventive Angebote in Anspruch nehmen.Querschnittstudie in 3 Werkstätten für Menschen mit geistiger Behinderung. Von Angehörigen wurde die Inanspruchnahme der Gesundheitsversorgung per Fragebogen erhoben. Die Auswertung erfolgte deskriptiv und inferenzstatistisch im Vergleich zur Allgemeinbevölkerung sowie innerhalb der Teilnehmenden auf soziodemografische Unterschiede.Fast alle 181 Teilnehmer (Teilnahmequote 19,3%) haben einen Hausarzt. Im Vergleich zur Allgemeinbevölkerung nehmen die Teilnehmer die hausärztliche und die Versorgung durch zahlreiche andere Facharztgebiete häufiger in Anspruch. Die Krebsvorsorge für Dickdarm, Brust, Gebärmutterhals und Prostata nehmen sie seltener, für Haut und den Check-up öfter in Anspruch. Bei Zahnarztkontrollen und Maßnahmen der Gesundheitsförderung zeigt sich kein Unterschied. Teilnehmer aus Wohnheimen nehmen die Regelangebote mehr in Anspruch als die bei Angehörigen oder alleine Lebenden. Teilnehmer mit Migrationshintergrund kennen die Versorgungsangebote weniger gut.Hinweise auf eine generelle gesundheitliche Unterversorgung zeigen die Ergebnisse nicht. Die Teilnahme an der Krebsvorsorge mit aufwändigeren Untersuchungen sollte gefördert werden, insbesondere für die allein oder bei Angehörigen lebenden Menschen mit geistiger Behinderung; Menschen mit Migrationshintergrund und ihre Angehörigen sollten gezielt informiert werden.

Background Early morbidity and mortality are low after endovascular abdominal aneurysm repair (EVAR), but secondary interventions and late complications are common. The aim of the present multicenter cohort study is to detail the frequency and indication for interventions after EVAR and the impact on long-term survival. Methods A retrospective multicenter cohort study of secondary interventions after elective EVAR for an infrarenal abdominal aortic aneurysm was conducted. Consecutive patients (n = 349) undergoing EVAR between January 2007 and January 2012 were analyzed, with long-term follow-up until December 2018. Those requiring intervention were classified in accordance with the indications and specific nature of the intervention and treatment. The primary study end point was overall survival classified for patients with and without intervention. Kaplan-Meier analysis was used to estimate overall survival for those who did and who did not undergo secondary interventions. Univariable and multivariable Cox regression were performed to identify independent variables associated with mortality. Results Some 56 patients (16%) underwent 72 secondary interventions after EVAR during a median (interquartile range) follow-up period of 53.2 months (60.1). Some 45 patients (80.4%) underwent one intervention. Indications for intervention included mainly endograft kinking/outflow obstruction and type II endoleak. An endovascular technique was used in 40.3% of interventions. Median time to secondary intervention was 24.1 months. In 93 patients with abnormalities on imaging, no intervention was performed mainly because the abnormality had disappeared on follow-up imaging (43%). Kaplan-Meier curves showed no difference in survival for patients with and without secondary interventions (P = 0.153). Age (hazard ratio [HR]: 1.089, 95% confidence interval [CI]: 1.063–1.116), ASA classification (ASA III, IV HR: 1.517, 95% CI: 1.056–2.178) were significantly related to mortality. Conclusions Secondary intervention rates are still considerable after EVAR. Endograft kinking/outflow obstruction and endoleak type II are the most common indications for a secondary intervention. Secondary interventions did not adversely affect long-term overall survival after EVAR.

The response to levodopa (LR) is important for managing Parkinson's Disease and is measured with clinical scales prior to (OFF) and after (ON) levodopa. The aim of this study was to ascertain whether an ambulatory wearable device could predict the LR from the response to the first morning dose. The ON and OFF scores were sorted into six categories of severity so that separating Parkinson's Kinetigraph (PKG) features corresponding to the ON and OFF scores became a multi-class classification problem according to whether they fell below or above the threshold for each class. Candidate features were extracted from the PKG data and matched to the class labels. Several linear and non-linear candidate statistical models were examined and compared to classify the six categories of severity. The resulting model predicted a clinically significant LR with an area under the receiver operator curve of 0.92. This study shows that ambulatory data could be used to identify a clinically significant response to levodopa. This study has also identified practical steps that would enhance the reliability of this test in future studies.

Background In 2004, the Federal Joint Committee, supreme decision-making body in German healthcare, introduced minimum volume requirements (MVRQs) as a quality instrument. Since then, MVRQs were implemented for seven hospital procedures. This study evaluates the effect of a system-wide intermission of MVRQ for total knee arthroplasty (TKA), demanding 50 annual cases per hospital. Methods An uncontrolled before–after study based on federal-level data including the number of hospitals performing TKA, and TKA cases from the external hospital quality assurance programme in Germany (2004–2017). Bi- and multivariate analyses based on hospital-level secondary data of TKA cases and TKA quality indicators extracted from hospital quality reports in Germany (2006–2014). Results The number of TKAs performed in Germany decreased by 11% after suspending the TKA-MVRQ in 2011, and rose by 13% after its reintroduction in 2015. The number of hospitals with less than 50 cases rose from 10 to 25% and their case share from 2 to 5.5% during suspension. Change in hospital volume after the suspension of TKA-MVRQ was not associated with hospital size, ownership, or region. All four evaluable quality indicators increased significantly in the year after their first public reporting. Compared to hospitals meeting the TKA-MVRQ, three indicators show slight but statistically significant better quality in hospitals below the TKA-MVRQ. Conclusions In Germany, TKA-MVRQs seem to induce in-hospital caseload adjustments rather than foster regional inter-hospital case transfers as intended.

Objective Although subthalamic Deep Brain Stimulation (STN DBS) is proven effective in improving symptoms of Parkinson's Disease (PD), previous literature demonstrates a discrepancy between objective improvement and patients' perception thereof. We aimed to examine whether postoperative stimulation challenge tests (SCT) alters patients' satisfaction after STN DBS for PD. Methods Fifty-four PD patients underwent preoperative levodopa challenge tests and were routinely invited for SCT 1-2 years postoperatively. SEverity of predominantly Nondopaminergic Symptoms in PD (SENS-PD) scores quantified non-dopaminergic disease severity. Motor functioning was quantified using Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III scores; a ratio between conditions ON and OFF (preoperative Med-ON vs. Med-OFF, and postoperative Med-ON/Stim-ON vs. Med-OFF/Stim-OFF) reflected treatment benefit. ‘Global Impression of Change’ (GIC) and ‘Global Satisfaction with Surgery’ (GSS) Likert scales were filled out before and immediately after SCT. Results Postoperative Med-ON/Stim-ON severity was lower than preoperative ON severity. Disease severity scores were not different between assessments. GIC and GSS scores were higher after SCT versus before (GIC: Z = -3.80, r = 0.37, subjects indicating maximum scores before SCT: 32.1%, after SCT: 57.1%; GSS: Z = -3.69, r = 0.35, maximum scores before SCT: 25.0%, after SCT: 46.4%). Higher non-dopaminergic disease severity was associated with lower GIC and GSS scores (GIC: OR 1.2 (95%CI 1.0–1.3); GSS: OR 1.2 (95%CI 1.1–1.3), while motor-scores and magnitude of DBS-effects were not. Conclusion SCT improves patients’ satisfaction and is recommended especially in case of suboptimal subjective valuations. This information should be considered in clinical practice and in the context of clinical trials.

Adverse childhood experiences (ACE) have a significant effect on psychological and physical child development and represent a risk factor for interpersonal difficulties.This study aims to investigate the association between ACE, in particular physical, sexual, emotional abuse and neglect, and partnership quality during adulthood in women.This study is a secondary analysis of a retrospective multi-center study evaluating risk factors and quality of life in women with and without endometriosis, a chronic, disabling gynecological disease. The investigation includes 533 consenting adult women (159 with ACE and 374 women without) recruited from various hospitals in Switzerland, Austria and Germany.To evaluate the association between ACE and partnership, a questionnaire including the Childhood Trauma Questionnaire and a validated partnership questionnaire were used.Altogether, 29.8 % (N = 159) women experienced maltreatment in childhood, 9.7 % (N = 52) of them more than one type. Women who went through ACE showed a lower level of happiness (P = 0.013) and of quality of partnership (P = 0.001) as well as a higher number of conflict areas (P0.001). Emotional (P = 0.03; 95 % CI=-1.27,-0.070) and sexual abuse (P = 0.01; 95 % CI=-1.765,-0.197) had the strongest association with reduced partnership quality.Our study showed a significant association between ACE, in particular sexual and emotional abuse, and reduced partnership quality. As the quality of partnership is a key factor in the quality of life, improvement in social support with a special focus on intimate relationships should be part of the strategy to address the consequences of ACE already during childhood/adolescence.

Purpose. The impact of an out-of-hours laparoscopic cholecystectomy on outcome is controversial. We sought to determine the association between an out-of-hours procedure and postoperative complications within 90 days. Methods. Between 2014 and 2016, 1553 laparoscopic cholecystectomies were performed. Therapeutic, operative, and outcome data were prospectively collected and analyzed. We defined out of hours as during weekends, national holidays, and daily between 5PM and 8AM. Results. Most patients operated on were female (n=988; 63.6%) and the majority of procedures were electives (n=1341; 86.3%). Although all procedures were performed with a laparoscopic intent, 42 (2.7%) were converted to open procedure. In total, 145 (9.3%) procedures were out of hours, all nonelective, and in most cases for acute cholecystitis (n=111; 7.1%). Overall, there were 212 complications in 191 patients (12.3%), most (n=153; 9.9%) classified as minor. The conversion rate in the out-of-hours group was significantly higher (9.7% vs 2.0%; p p; p=0.069). Conclusion. An out-of-hours laparoscopic cholecystectomy was not found to be an independent risk factor for developing postoperative morbidity and time of day should therefore only be a relative contraindication.

Sharply defined radiolucencies on a panoramic radiograph are often interpreted as cystic laesions. In some cases, however, it appears to be another condition, or an anatomical variation. In the present case, involving 2 healthy patients, 1 or more sharply defined lucencies were seen in the lateral parts of the mandible. After exploration, in both cases, an empty cavity was found without epithelial lining, which is pathognomonic for a simple bone cyst. Multiple occurrences are uncommon.Een scherp begrensde radiolucentie op een panoramische röntgenopname worden vaak geduid als een cysteuze laesie. In sommige gevallen blijkt echter sprake te zijn van een andere aandoening, dan wel een anatomische variatie. In de voorliggende casus werden bij 2 gezonde patiënten 1 of meerdere scherp begrensde radiolucenties in de zijdelingse delen van de mandibula gezien. Na exploratie werd in beide gevallen een lege holte aangetroffen zonder epitheliale bekleding dat pathognomonisch is voor een simpele beencyste. Multipel voorkomen is ongewoon.

Assisted reproduction has become a standard treatment for prospective parents who cannot conceive children normally because one or both partners are subfertile or infertile owing to congenital birth defects, childhood infection, cancer therapy or accidents. In vitro fertilisation, often in combination with intracytoplasmic sperm injection (ICSI), offers these patients a safe and efficient option to have children. The development of new technologies has further expanded the application of assisted reproductive technologies (ART) to help patients with inherited mutations for severe diseases—such as cystic fibrosis, Huntington or Duchenne muscular dystrophy—who have a high risk that their children would inherit a devastating disease and either die at young age and/or suffer greatly throughout life. Many couples who prefer to become the genetic parents of a disease‐free child can now achieve this by either prenatal diagnosis (PND) and selective termination of pregnancy or preimplantation genetic diagnosis (PGD) and selective transfer of embryos without the disease‐causing mutations. Whatever their choice, couples or individuals who carry disease‐causing mutations need genetic and reproductive counselling to inform them about the disease and its causes and its recurrence risk and discuss the options for having healthy children. After counselling, couples need to take an autonomous decision to refrain from having children, to adopt, to opt for gamete donation or to use ART with PND or PGD. In the 1960s, it became possible to obtain amniotic fluid for genetic analysis of the embryo's genome. Amniocentesis is commonly performed at the 16th week of pregnancy when there is sufficient amniotic fluid to take a sample of about 20 ml for cell culture. It was first done blindly, which means that the puncture site was located by external palpation of the uterus. In the 1970s, ultrasound scanning became available, which drastically improved safety as the gynaecologist can see the puncture needle on …

We report on the first PGD performed for the m.14487 T>C mitochondrial DNA (mtDNA) mutation in the MT-ND6 gene, associated with Leigh syndrome. The female carrier gave birth to a healthy baby boy at age 42. This case adds to the successes of PGD for mtDNA mutations.

The aim of this study was to analyze the clinical relevance of sensor-based daily life chair rise performance measured in old people. A pendant-sensor was worn during standardized tests and in daily life to detect chair rise transfers and analyze transfer peak power. Linear correlations between mean, median, 25th, and 75th percentile transfer peak powers in daily life and mean peak power in standardized tests were evaluated with Pearson correlation (r). Associations between transfer peak powers in different experiments and outcomes of a clinical mobility test [timed-up-and-go (TUG)], a test of limitation in activities [Groningen activity restriction scale (GARS)], and a frailty test [Groningen frailty indicator (GFI)] were evaluated with Spearman correlation (rho). Twenty-five old people (70-85 years) participated in the study. The results showed that chair rise peak powers assessed based upon one-week of daily life activities significantly correlated with peak power measured in standardized tests (r: [0.66, 0.74], p

Recently, American colleagues called for a systematic collection of anonymized data on how many embryos and foetuses are deselected per institution per year, and for which conditions. These authors argued that if this information would be reported to a government agency or international body, the information would provide a baseline against which jurisdiction-specific trends in selection could be assessed. People who have disabilities, together with other key stakeholders, laypeople and experts, would then be in a position to assess the social impact of human selecting technologies and to make recommendations for action to mitigate negative effects as appropriate. However, such a systematic data collection does already exist in the Netherlands and has been in place for more than 30 years. It was first introduced to monitor the practise of prenatal diagnosis by the eight licence holders sending in all data to the Minister of Public Health, Welfare and Sports. Later, the same method was expanded to preimplantation genetic diagnosis. For 8 years, these data have been discussed in the parliament, which shows that the practice of embryo selection can indeed be kept under democratic control, albeit retrospectively.

Patients with advanced Parkinson's Disease (PD) may be eligible for Deep Brain Stimulation (DBS) in case of medication-related motor fluctuations or tremor refractory to oral medication. However, several PD symptoms are unresponsive to DBS and constitute relative contra-indications for DBS. Patients referred for DBS undergo an eligibility screening during which motor functioning and contra indications for surgery are assessed. During this pre-screening the potential benefits and drawbacks of surgery are discussed, together with patients' expectations of the results of DBS. Unrealistic expectations on the benefits of DBS may contribute to reduced patient satisfaction and poor clinical outcomes after surgery. The aim of this multicenter study (289 patients) was to assess the reasons for rejection after an outpatient-based pre-screening visit for DBS referrals, with particular emphasis on the role of patient expectations of DBS. The most frequent reason contributing to rejection was suboptimal oral treatment or satisfying symptom-control with oral medication (50% of rejections). Unrealistic expectations were identified in 38% of rejected patients and were the singular reason for rejection in 4%. Incorporating the assessment of unrealistic expectations increased the accuracy (Area Under the Curve) of determining DBS eligibility from 0.92 ((95% confidence interval (95%CI) 0.88-0.97) to 0.97 (95%CI 0.96-0.99). Patients' expectations of DBS are easily checked, and better education of patients and treating neurologists with regard to unrealistic expectations of this procedure may improve efficiency of referrals and avoid unnecessary stress and disappointments during screening.

Background It is unknown whether intraoperative testing during awake Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) can be used to postoperatively identify the best settings for chronic stimulation. Objective To determine whether intraoperative test stimulation is indicative of postoperative stimulation results. Methods Records of consecutive Parkinson's Disease patients who received STN DBS between September 2012 and December 2017 were retrospectively analyzed. The best depth identified after intraoperative stimulation via the microelectrode's stimulation tip was compared with the depth of the contact selected for chronic stimulation after a standard monopolar contact review. Moreover, thresholds for induction of clinical effects (optimal improvement of rigidity and induction of side-effects) were compared between stimulation at the postoperatively selected contact and at the corresponding intraoperative depth. Results Records of 119 patients were analyzed (mean (SD) age 60.5 (6.5) years, 31.9% female, 238 STNs). In 75% of cases, the postoperatively selected contact corresponded with the intraoperative depth with the largest therapeutic window or was immediately dorsal to it. Higher stimulation intensities were required postoperatively than intraoperatively to relieve rigidity (p = 0.002) and induce capsular side-effects (p = 0.016). Conclusion In the majority of cases, the postoperative contact for chronic stimulation was at a similar level or immediately dorsal with respect to the identified best intraoperative depth. Postoperatively, relief of rigidity and induction of capsular side-effects occur at higher stimulation intensities than during intraoperative test stimulation.

What are the specific characteristics of sexual activity in women with endometriosis compared with women without endometriosis?Multicentre case control study. Participants were recruited from university hospitals, district hospitals and doctor's offices in Germany, Switzerland and Austria. A total of 565 women with endometriosis were pair-matched to 565 control women by age and ethnic background. Diagnosis of endometriosis was confirmed by histology, and disease stage was classified according to American Society for Reproductive Medicine criteria. Data on sexuality were collected using selected questions from the Brief Index of Sexual Function and the Sexual History Form.Altogether, 69.1% of women with endometriosis and 77.8% of control women engaged in sexual activity during the month before the study period (P0.001). Overall, 42.3% of endometriosis-affected women and 30.5% of the control women desired a higher frequency of sexual activity (P0.001). Petting, foreplay and vaginal sexual intercourse were reported to be practised less often by women with endometriosis. Frequencies for masturbation, reciprocal masturbation, oral and anal sex were similar in both groups. Dyspareunia was negatively associated with sexual activity (OR 2.42, 95% CI 1.26 to 4.63), whereas chronic pain showed no association with sexual activity (OR 1.35, 95% CI 0.93, 1.96).Women with endometriosis have lower frequencies of petting, foreplay and vaginal sexual intercourse than control women; this difference has to be attributed, at least in part, to dyspareunia. Potentially pain-free sexual options are used to a limited degree. As endometriosis-affected women desire higher levels of sexual activity, sexual counselling should be included in medical support.

Though clinical trials for medical applications of dimethyl sulfoxide (DMSO) reported toxicity in the 1960s, later, the FDA classified DMSO in the safest solvent category. DMSO became widely used in many biomedical fields and biological effects were overlooked. Meanwhile, biomedical science has evolved towards sensitive high-throughput techniques and new research areas, including epigenomics and microRNAs. Considering its wide use, especially for cryopreservation and in vitro assays, we evaluated biological effect of DMSO using these technological innovations. We exposed 3D cardiac and hepatic microtissues to medium with or without 0.1% DMSO and analyzed the transcriptome, proteome and DNA methylation profiles. In both tissue types, transcriptome analysis detected >2000 differentially expressed genes affecting similar biological processes, thereby indicating consistent cross-organ actions of DMSO. Furthermore, microRNA analysis revealed large-scale deregulations of cardiac microRNAs and smaller, though still massive, effects in hepatic microtissues. Genome-wide methylation patterns also revealed tissue-specificity. While hepatic microtissues demonstrated non-significant changes, findings from cardiac microtissues suggested disruption of DNA methylation mechanisms leading to genome-wide changes. The extreme changes in microRNAs and alterations in the epigenetic landscape indicate that DMSO is not inert. Its use should be reconsidered, especially for cryopreservation of embryos and oocytes, since it may impact embryonic development.

The response to levodopa (LR) is important for managing Parkinson&rsquo, s Disease and is measured with clinical scales prior to (OFF) and after (ON) levodopa. The aim of this study was to ascertain whether an ambulatory wearable device could predict the LR from the response to the first morning dose. The ON and OFF scores were sorted into six categories of severity so that separating Parkinson&rsquo, s Kinetigraph (PKG) features corresponding to the ON and OFF scores became a multi-class classification problem according to whether they fell below or above the threshold for each class. Candidate features were extracted from the PKG data and matched to the class labels. Several linear and non-linear candidate statistical models were examined and compared to classify the six categories of severity. The resulting model predicted a clinically significant LR with an area under the receiver operator curve of 0.92. This study shows that ambulatory data could be used to identify a clinically significant response to levodopa. This study has also identified practical steps that would enhance the reliability of this test in future studies.

ObjectivesEndometriosis is a gynaecological disease most commonly causing severe and chronic pelvic pain as well as an impaired quality of life. The aim of this study was to investigate if and how endometriosis affects choices regarding professional life as well as the quality of daily working life.Design, setting and participantsIn the context of a multicentre case–control study, we collected data from 505 women with surgically/histologically confirmed diagnosis of endometriosis and 505 matched controls. Study participants were recruited prospectively in hospitals and doctors’ practices in Switzerland, Germany and Austria. Using a detailed questionnaire, the study investigated work–life and career choices of study participants.Main outcome measuresAssociations between endometriosis/disease symptoms and limitations in career development as well as ability to work.ResultsWomen with endometriosis were less often able to work in their desired profession than women from the control group (adjusted OR=1.84, 95% CI: 1.15 to 2.94, R2=0.029, p=0.001) and they had to take health-related limitations into consideration in their career decisions to a significantly higher degree than women in the control group (OR=4.79, 95% CI: 2.30 to 9.96, R2=0.063, p2=0.072, p2=0.087, pConclusionsEndometriosis is associated with impairment of professional life, in particular with regard to career choices. Further research to develop strategies to support endometriosis-affected women in realising professional opportunities is recommended.Trial registration numberNCT02511626; Pre-results.

The putative association between hormones and cognitive performance is controversial. While there is evidence that estradiol plays a neuroprotective role, hormone treatment has not been shown to improve cognitive performance. Current research is flawed by the evaluation of combined hormonal effects throughout the menstrual cycle or in the menopausal transition. The stimulation phase of a fertility treatment offers a unique model to study the effect of estradiol on cognitive function. This quasi-experimental observational study is based on data from 44 women receiving IVF in Zurich, Switzerland. We assessed visuospatial working memory, attention, cognitive bias, and hormone levels at the beginning and at the end of the stimulation phase of ovarian superstimulation as part of a fertility treatment. In addition to inter-individual differences, we examined intra-individual change over time (within-subject effects). The substantial increases in estradiol levels resulting from fertility treatment did not relate to any considerable change in cognitive functioning. As the tests applied represent a broad variety of cognitive functions on different levels of complexity and with various brain regions involved, we can conclude that estradiol does not show a significant short-term effect on cognitive function.

Contains fulltext : 167696.pdf (Publisher’s version ) (Open Access) Genomic imprinting is a mechanism in which gene expression varies depending on parental origin. Imprinting occurs through differential epigenetic marks on the two parental alleles, with most imprinted loci marked by the presence of differentially methylated regions (DMRs). To identify sites of parental epigenetic bias, here we have profiled DNA methylation patterns in a cohort of 57 individuals with uniparental disomy (UPD) for 19 different chromosomes, defining imprinted DMRs as sites where the maternal and paternal methylation levels diverge significantly from the biparental mean. Using this approach we identified 77 DMRs, including nearly all those described in previous studies, in addition to 34 DMRs not previously reported. These include a DMR at TUBGCP5 within the recurrent 15q11.2 microdeletion region, suggesting potential parent-of-origin effects associated with this genomic disorder. We also observed a modest parental bias in DNA methylation levels at every CpG analyzed across approximately 1.9 Mb of the 15q11-q13 Prader-Willi/Angelman syndrome region, demonstrating that the influence of imprinting is not limited to individual regulatory elements such as CpG islands, but can extend across entire chromosomal domains. Using RNA-seq data, we detected signatures consistent with imprinted expression associated with nine novel DMRs. Finally, using a population sample of 4,004 blood methylomes, we define patterns of epigenetic variation at DMRs, identifying rare individuals with global gain or loss of methylation across multiple imprinted loci. Our data provide a detailed map of parental epigenetic bias in the human genome, providing insights into potential parent-of-origin effects.

STUDY QUESTION: We wanted to probe the opinions and current practices on preimplantation genetic screening (PGS), and more specifically on PGS in its newest form: PGS 2.0? STUDY FINDING: Consensus is lacking on which patient groups, if any at all, can benefit from PGS 2.0 and, a fortiori, whether all IVF patients should be offered PGS. WHAT IS KNOWN ALREADY: It is clear from all experts that PGS 2.0 can be defined as biopsy at the blastocyst stage followed by comprehensive chromosome screening and possibly combined with vitrification. Most agree that mosaicism is less of an issue at the blastocyst stage than at the cleavage stage but whether mosaicism is no issue at all at the blastocyst stage is currently called into question. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: A questionnaire was developed on the three major aspects of PGS 2.0: the Why, with general questions such as PGS 2.0 indications; the How, specifically on genetic analysis methods; the When, on the ideal method and timing of embryo biopsy. Thirty-five colleagues have been selected to address these questions on the basis of their experience with PGS, and demonstrated by peer-reviewed publications, presentations at meetings and participation in the discussion. The first group of experts who were asked about 'The Why' comprised fertility experts, the second group of molecular biologists were asked about 'The How' and the third group of embryologists were asked about 'The When'. Furthermore, the geographical distribution of the experts has been taken into account. Thirty have filled in the questionnaire as well as actively participated in the redaction of the current paper. MAIN RESULTS AND THE ROLE OF CHANCE: The 30 participants were from Europe (Belgium, Germany, Greece, Italy, Netherlands, Spain, UK) and the USA. Array comparative genome hybridization is the most widely used method amongst the participants, but it is slowly being replaced by massive parallel sequencing. Most participants offering PGS 2.0 to their patients prefer blastocyst biopsy. The high efficiency of vitrification of blastocysts has added a layer of complexity to the discussion, and it is not clear whether PGS in combination with vitrification, PGS alone, or vitrification alone, followed by serial thawing and eSET will be the favoured approach. The opinions range from in favour of the introduction of PGS 2.0 for all IVF patients, over the proposal to use PGS as a tool to rank embryos according to their implantation potential, to scepticism towards PGS pending a positive outcome of robust, reliable and large-scale RCTs in distinct patient groups. LIMITATIONS, REASONS FOR CAUTION: Care was taken to obtain a wide spectrum of views from carefully chosen experts. However, not all invited experts agreed to participate, which explains a lack of geographical coverage in some areas, for example China. This paper is a collation of current practices and opinions, and it was outside the scope of this study to bring a scientific, once-and-for-all solution to the ongoing debate. WIDER IMPLICATIONS OF THE FINDINGS: This paper is unique in that it brings together opinions on PGS 2.0 from all different perspectives and gives an overview of currently applied technologies as well as potential future developments. It will be a useful reference for fertility specialists with an expertise outside reproductive genetics. LARGE SCALE DATA: none. STUDY FUNDING AND COMPETING INTERESTS: No specific funding was obtained to conduct this questionnaire.

Objective: Differences in disease progression in Parkinson disease (PD) have variously been attributed to 2 motor subtypes: tremor-dominant (TD) and postural instability and gait difficulty (PIGD)–dominant (PG). We evaluated the role of these phenotypic variants in severity and progression of nondopaminergic manifestations of PD and motor complications. Methods: Linear mixed models were applied to data from the Profiling Parkinson9s disease (PROPARK) cohort (n = 396) to evaluate the effect of motor subtype on severity and progression of cognitive impairment (Scales for Outcomes in Parkinson9s disease [SCOPA]–Cognition [SCOPA-COG]), depression (Hospital Anxiety and Depression Scale [HADS]), autonomic dysfunction (SCOPA–Autonomic [SCOPA-AUT]), excessive daytime sleepiness, psychotic symptoms (SCOPA–Psychiatric Complications [SCOPA-PC]), and motor complications. In first analyses, subtype as determined by the commonly used ratio of tremor over PIGD score was entered as a factor, whereas in second analyses separate tremor and PIGD scores were used. Results were verified in an independent cohort (Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP]; n = 365). Results: The first analyses showed that PG subtype patients had worse SCOPA-COG, HADS, SCOPA-AUT, SCOPA-PC, and motor complications scores, and exhibited faster progression on the SCOPA-COG. The second analyses showed that only higher PIGD scores were associated with worse scores for these variables; tremor score was not associated with severity or progression of any symptom. Analyses in the independent cohort yielded similar results. Conclusions: In contrast to PIGD, which consistently was associated with greater severity of nondopaminergic symptoms, there was no evidence of a benign effect of tremor. Our findings do not support the use of the TD subtype as a prognostic trait in PD. The results showed that severity of PIGD is a useful indicator of severity and prognosis in PD by itself.

Prematurely born children are at higher risk for long-term adverse motor and cognitive outcomes. The aim of this paper was to compare quantitative measures derived from electroencephalography (EEG) between extremely (EP) and very prematurely (VP) born children at 9–10 years of age. Fifty-five children born

Endometriosis affects various aspects of women's lives. We searched for predictors for patient satisfaction with medical support (PSwMS) in women with endometriosis. The study was designed as a multi-centre retrospective cohort study. We approached women with histologically confirmed endometriosis from 2010 until 2016, comparing women satisfied to women dissatisfied with medical support. We analysed data on characteristics of endometriosis, PSwMS and the influence of disease characteristics on PSwMS. Information on satisfaction with medical support was collected through a standardized questionnaire. After exclusion of 73 women because of inchoately filled in questionnaires, data from 498 women was evaluated. Altogether, it was observed that 54.6% (n = 272) of the study participants were satisfied with medical support and 45.4% (n = 226) were not. Feeling adequately informed by the time of diagnosis (p < 0.001), taking women's mental troubles seriously (p < 0.001) and supporting women in handling their pain (p < 0.001) were significantly associated with satisfaction. We found adequate information to be the most distinctive indicator for PSwMS. Further, acknowledging psychological distress and supporting women in handling their symptoms rather than to alleviate them, positively affect PSwMS. To achieve PSwMS, healthcare providers have to give adequate information on endometriosis and its management.

Hospitalizations and lower limb amputations related to diabetes mellitus (DM) are considered to be potentially avoidable. Appropriate outpatient care of diabetes prevents complications. Rates on potentially avoidable hospitalizations for diabetes are core indicators of the German diabetes surveillance program. International comparisons showed high hospitalization rates in Germany for both indicators.The objective of this analysis is to describe time trends on hospitalizations and inpatient lower limb amputations (major amputations) for DM. Furthermore, we analyze small area variations.Based on the German diagnosis related groups (DRGs) dataset we calculated age-standardized rates covering 2005-2015. Calculations rely on the Organisation for Economic Co-operation and Development (OECD) indicator definitions. Time trends are obtained by linear regression modelling. We also stratified into age groups and analyzed 2015 small-area variations using age-adjusted rates.Crude hospitalization rates were 310 admissions per 100,000 inhabitants in men (amputation rate: 15.6) and 216 admissions per 100,000 inhabitants in women (amputation rate: 7.1) in 2015. Age-adjusted hospitalizations and amputations rates in women decreased over time (10.3 and 1.2 cases per 100,000 inhabitants and year, respectively). In men, the amputation rate decreased significantly (1.5 cases per 100,000 inhabitants and year). We found higher rates for men than for women in almost all age categories. In eastern Germany and parts of Bavaria and North Rhine-Westphalia rates are particularly high.A decrease in hospitalization rates may indicate improvements in ambulatory diabetes care over time. Future studies should consider age-specific differences and small-area variations.

STUDY QUESTION Is maltreatment during childhood (MC), e.g. sexual abuse, physical abuse, emotional abuse and neglect, associated with diagnosis of endometriosis? SUMMARY ANSWER Childhood sexual abuse, emotional abuse/neglect and inconsistency experiences were associated with the diagnosis of endometriosis while no such association was found for physical abuse/neglect and other forms of maltreatment. WHAT IS KNOWN ALREADY Symptoms of endometriosis such as chronic pelvic pain, fatigue and depression, are correlated with MC, as are immune reactions linked to endometriosis. These factors support a case for a potential role of MC in the development of endometriosis. STUDY DESIGN, SIZE, DURATION The study was designed as a multicentre retrospective case-control study. Women with a diagnosis of endometriosis were matched to control women from the same clinic/doctor's office with regard to age (±3 years) and ethnic background. A total of 421 matched pairs were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with endometriosis and control women were recruited in university hospitals, district hospitals, and doctors' offices in Germany, Switzerland and Austria. A German-language version of the Childhood Trauma Questionnaire (CTQ) was used to evaluate MC. Diagnosis of endometriosis was confirmed histologically and classified according to ASRM criteria. MAIN RESULTS AND THE ROLE OF CHANCE Women with endometriosis reported significantly more often than control women a history of sexual abuse (20%/14%, P = 0.0197), emotional abuse (44%/28%, P < 0.0001), emotional neglect (50%/42%, P = 0.0123) and inconsistency experiences (53%/41%, P = 0.0007). No statistically significant differences could be demonstrated for physical abuse/neglect (31%/26%, P = 0.1738). Combinations of different abuse/neglect experiences were described significantly more often in women with endometriosis. Frequencies of other MC, i.e. violence against the mother (8%/7%, P = 0.8222), drug abuse in the family (5%/3%, P = 0.0943), mentally handicapped family members (1%/1%, P = 0.7271), suicidal intentions in the family (6%/4%, P = 0.2879) and family members in prison (1%/1%, P = 0.1597) were not statistically different in women with endometriosis and control women. LIMITATIONS, REASONS FOR CAUTION Some control women might present asymptomatic endometriosis, which would lead to underestimation of our findings. The exclusion of pregnant women may have biased the results. Statistical power for sub-analyses of physical abuse/neglect and sexual abuse was limited. WIDER IMPLICATIONS OF THE FINDINGS A link to MC needs to be considered in women with endometriosis. As there are effective strategies to avoid long-term consequences of MC, healthcare professionals should inquire about such experiences in order to be able to provide treatment for the consequences as early as possible. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER Endo_QoL NCT 02511626.

Male births exceed female births by 5-6% (for a sex ratio at birth of 1.05-1.06) while a women's life expectancy, on a global scale, is about 6 years longer. Thus within various age groups the male:female ratio changes over time. Until age 50 years men outnumber women; thereafter their numbers show a sharp decline. Consequently at age 80 years, there are many more women than men. An estimated 25% of this male excess mortality is due to biological causes, the rest being explained by behavioural, cultural and environmental factors. For both women and men, the main health risks related to lifestyle are smoking, alcohol, unhealthy diet and physical inactivity. In the year 2010, overweight (BMI: 25-29 kg/m(2)) and obesity (BMI:30 kg/m(2)) were responsible for over 3 million deaths, with similar relative risks in men and women for overweight and obesity. Smoking and alcohol are the major causes of the global gender gap in mortality. For women in some parts of the world however pregnancy is also hazardous. On a global scale, in 2013 about 300 000 deaths were related to pregnancy, with sub-Saharan Africa registering the highest maternal mortality: over 500 maternal deaths per 100 000 births. Additional woman's health risks arise from gender discrimination, including sex-selective abortion, violence against women and early child marriage. Providers should be aware of the effect that these risks can have on both reproductive and general health.

Research question Conventional treatments are often associated with adverse effects and endometriosis pain symptoms may reoccur despite treatment. Consequently, many women use complementary health approaches (CHA) and home remedies (HR) to relieve their pain. The aim of this study was to examine the frequency and the subjectively perceived efficacy of CHA/HR use by women affected by endometriosis. Design Retrospective evaluation using medical charts and a questionnaire. Women recruited in hospitals and in self-help groups were asked about the use of ‘topical heat’, ‘repose/relaxation’, ‘movement/massages’, ‘homeopathy/phytotherapy’, ‘acupuncture/traditional Chinese medicine (TCM)’ and ‘kinesiology/physiotherapy’. Results From a total of 574 women with a confirmed diagnosis of endometriosis, 359 (62.5%) applied some form of CHA/HR. Women suffering from fatiguing disease symptoms more often selected alternative therapies (odds ratio [OR] 3.14, 95% confidence interval [CI] 1.39–7.11, P = 0.006) compared with women without these characteristics. Furthermore, women dissatisfied with healthcare provided by their treating physician, more frequently (OR 2.30, 95% CI 1.19–4.45, P = 0.013) chose the aforementioned alternative strategies. Conclusion As conventional therapies may not be sufficiently effective, women's needs should be closely examined, and individual treatment options should be discussed and initiated by clinicians to provide the best comprehensive treatment possible for endometriosis.

STUDY QUESTION: Does preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening (CCS) of the first and second polar body to select embryos for transfer increase the likelihood of a live birth within 1 year in advanced maternal age women aged 36-40 years planning an ICSI cycle, compared to ICSI without chromosome analysis? SUMMARY ANSWER: PGT-A by CCS in the first and second polar body to select euploid embryos for transfer does not substantially increase the live birth rate in women aged 36-40 years. WHAT IS KNOWN ALREADY: PGT-A has been used widely to select embryos for transfer in ICSI treatment, with the aim of improving treatment effectiveness. Whether PGT-A improves ICSI outcomes and is beneficial to the patients has remained controversial. STUDY DESIGN, SIZE, DURATION: This is a multinational, multicentre, pragmatic, randomized clinical trial with intention-to-treat analysis. Of 396 women enroled between June 2012 and December 2016, 205 were allocated to CCS of the first and second polar body (study group) as part of their ICSI treatment cycle and 191 were allocated to ICSI treatment without chromosome screening (control group). Block randomization was performed stratified for centre and age group. Participants and clinicians were blinded at the time of enrolment until the day after intervention. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile couples in which the female partner was 36-40 years old and who were scheduled to undergo ICSI treatment were eligible. In those assigned to PGT-A, array comparative genomic hybridization (aCGH) analysis of the first and second polar bodies of the fertilized oocytes was performed using the 24sure array of Illumina. If in the first treatment cycle all oocytes were aneuploid, a second treatment with PB array CGH was offered. Participants in the control arm were planned for ICSI without PGT-A. Main exclusion criteria were three or more previous unsuccessful IVF or ICSI cycles, three or more clinical miscarriages, poor response or low ovarian reserve. The primary outcome was the cumulative live birth rate after fresh or frozen embryo transfer recorded over 1 year after the start of the intervention. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 205 participants in the chromosome screening group, 50 (24%) had a live birth with intervention within 1 year, compared to 45 of the 191 in the group without intervention (24%), a difference of 0.83% (95% CI: -7.60 to 9.18%). There were significantly fewer participants in the chromosome screening group with a transfer (relative risk (RR) = 0.81; 95% CI: 0.74-0.89) and fewer with a miscarriage (RR = 0.48; 95% CI: 0.26-0.90). LIMITATIONS, REASONS FOR CAUTION: The targeted sample size was not reached because of suboptimal recruitment; however, the included sample allowed a 90% power to detect the targeted increase. Cumulative outcome data were limited to 1 year. Only 11 patients out of 32 with exclusively aneuploid results underwent a second treatment cycle in the chromosome screening group. WIDER IMPLICATIONS OF THE FINDINGS: The observation that the similarity in birth rates was achieved with fewer transfers, less cryopreservation and fewer miscarriages points to a clinical benefit of PGT-A, and this form of embryo selection may, therefore, be considered to minimize the number of interventions while producing comparable outcomes. Whether these benefits outweigh drawbacks such as the cost for the patient, the higher workload for the IVF lab and the potential effect on the children born after prolonged culture and/or cryopreservation remains to be shown. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the European Society of Human Reproduction and Embryology. Illumina provided microarrays and other consumables necessary for aCGH testing of polar bodies. M.B.'s institution (UZBrussel) has received educational grants from IBSA, Ferring, Organon, Schering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speakers' fees from Organon, Serono Symposia and Merck. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott and Gedeon-Richter as well as personal fees from VitroLife, NMC Healthcare, ReprodWissen, BioSilu and ZIVA. W.V., C.S., P.M.B., V.G., G.A., M.D.,T.E.G., L.G., G.Ka., G.Ko., J. L., M.C.M., M.P., A. S., M. T., K.V., J.G. and K.S. declare no conflict of interest. TRIAL REGISTRATION NUMBER: NCT01532284. TRIAL REGISTRATION DATE: 7 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 25 June 2012.

Summary Background The National Association of Statutory Health Insurance Physicians develops quality indicators (QIs) for ambulatory care in Germany. This study explores the feasibility of a total of 48 QIs. Methods Cross-sectional observational study with primary data collection in writing from medical practices in 10 specialist fields of outpatient care. “Feasibility” covers 7 criteria for indicator assessment and data collection: applicability, availability, retrievability, complexity, relevance, reliability, and acceptance. A questionnaire consisting of 10 questions was used to evaluate these feasibility criteria for each indicator. Survey results were subjected to descriptive analysis. Results The analyzed sample comprises 103 participants who have been working as practice-based physicians for an average of 13 years. 40% only keep electronic medical records and 2% only paper records, and the rest uses both. The rating of QIs in the field-specific QI sets shows the following mean values: 67% of the participants consider the QIs assigned to them as corresponding to their practice care mandate. Data on these QIs deemed to be applicable are collected by 94% of respondents, documented by 91%, and by 51% electronically. 58% of the data required for the denominator, and 38% for the numerator are retrievable from the practice management system. The time required to access data on a QI is more than 30 minutes for 84% of respondents, and 67% consider the effort involved as unacceptable. The rating received was 61% for the relevance of QIs to the assessment of a practitioner's own quality of health care, 69% for the estimated reliability of data collection, and 58% for the acceptance of being evaluated via QIs. Conclusions In order to improve the feasibility of QI-based practice assessments it will be necessary to a) fine-tune the selection of QIs for the respective groups of specialist, b) to promote the use of computerized practice management systems, and c) integrate effective and user-friendly retrieval functions in the software. Another aspect to be explored is how the acceptance of QI-based practice evaluations can be improved in individual specialist fields.

OBJECTIVE:In Parkinson's Disease (PD), measures of non-dopaminergic systems involvement may reflect disease severity and therefore contribute to patient-selection for Deep Brain Stimulation (DBS). There is currently no determinant for non-dopaminergic disease severity. In this exploratory study, we investigated whether quantitative EEG reflects non-dopaminergic disease severity in PD.METHODS:Sixty-three consecutive PD patients screened for DBS were included (mean age 62.4 ± 7.2 years, 32% females). Relative spectral powers and the Phase-Lag-Index (PLI) reflecting functional connectivity were analysed on routine EEGs. Non-dopaminergic disease severity was quantified using the SENS-PD score and its subdomains; motor-severity was quantified using the MDS-UPDRS III.RESULTS:The SENS-PD composite score correlated with a spectral ratio ((δ + θ)/(α1 + α2 + β) powers) (global spectral ratio Pearson's r = 0.4, 95% Confidence Interval (95%CI) 0.1-0.6), and PLI in the α2 band (10-13 Hz) (r = -0.3, 95%CI -0.5 to -0.1). These correlations seem driven by the subdomains cognition and psychotic symptoms. MDS-UPDRS III was not significantly correlated with EEG parameters.CONCLUSIONS:EEG slowing and reduced functional connectivity in the α2 band were associated with non-dopaminergic disease severity in PD.SIGNIFICANCE:The described EEG parameters may have complementary utility as determinants of non-dopaminergic involvement in PD.

Background Endometriosis-associated pain and dyspareunia influence female sexuality, but little is known about men's experiences in affected couples. Aim To investigate how men partners experience sexuality in partnership with women with endometriosis. Methods A multi-center case-control study was performed between 2010 and 2015 in Switzerland, Germany, and Austria. 236 Partners of endometriosis patients and 236 partners of age-matched control women without endometriosis with a similar ethnic background were asked to answer selected, relevant questions of the Brief Index of Sexual Functioning and the Global Sexual Functioning questionnaire, as well as some investigator-derived questions. Outcomes We sought to evaluate sexual satisfaction of men partners of endometriosis patients, investigate differences in sexual activities between men partners of women with and without endometriosis, and identify options to improve partnership sexuality in couples affected by endometriosis. Results Many partners of endometriosis patients reported changes in sexuality (75%). A majority of both groups was (very) satisfied with their sexual relationship (73.8% vs 58.1%, P = .002). Nevertheless, more partners of women diagnosed with endometriosis were not satisfied (P = .002) and their sexual problems more strongly interfered with relationship happiness (P = .001) than in partners of control women. Frequencies of sexual intercourse (P < .001) and all other partnered sexual activities (oral sex, petting) were significantly higher in the control group. The wish for an increased frequency of sexual activity (P = .387) and sexual desire (P = .919) did not differ statistically between both groups. Clinical Translation There is a need to evaluate qualitative factors that influence sexual satisfaction in endometriosis patients. Conclusions This is one of the first studies to investigate male sexuality affected by endometriosis. The meticulous verification of diagnosis and disease stage according to operation reports and histology allows for a high reliability of diagnosis. Our men's response rate of almost 50% is higher compared to other studies. Recruiting men through their woman partner may have caused selection bias. The adjustment to the specific situation in endometriosis by selecting questions from the Brief Index of Sexual Functioning and Global Sexual Functioning and adding investigator-derived questions likely influenced the validity of the questionnaires. Despite the fact that both partners of endometriosis patients and of control women largely reported high sexual satisfaction, there are challenges for some couples that arise in the context of a sexual relationship when one partner has endometriosis. Challenges such as sexuality-related pain or a reduced frequency of sexual activities should be addressed by health care professionals to ameliorate any current difficulties and to prevent the development or aggravation of sexual dysfunction.