Copenhagen University Hospital Rigshospitalet Research Articles

Routine Use of [64Cu]Cu-DOTATATE PET/CT in a Neuroendocrine Tumor Center: Referral Patterns and Image Results of 2,249 Consecutive Scans.

The role of somatostatin receptor (SSTR) PET/CT, using 68Ga-based tracers or [64Cu]Cu-DOTATATE (64Cu-DOTATATE), in the management of patients with neuroendocrine neoplasm (NEN) is guided by appropriate use criteria (AUC). In this study, we performed systematic analyses of referral patterns and image findings of routine 64Cu-DOTATATE PET/CT scans to support AUC development. Methods: We included all clinical routine 64Cu-DOTATATE PET/CT scans performed between April 10, 2018 (start of clinical use), and May 2, 2022, at Copenhagen University Hospital-Rigshospitalet. We reviewed the referral text and image report of each scan and classified the indication according to clinical scenarios as listed in the AUC. Results: In total, 1,290 patients underwent 2,249 64Cu-DOTATATE PET/CT scans. Monitoring of patients with NEN seen both on conventional imaging and on SSTR PET without clinical evidence of progression was the most common indication (defined as "may be appropriate" in the AUC) and accounted for 703 (31.3%) scans. Initial staging after NEN diagnosis ("appropriate" in the AUC) and restaging after curative-intent surgery ("may be appropriate" in the AUC) accounted for 221 (9.8%) and 241 (10.7%) scans, respectively. Selection of patients eligible for peptide receptor radionuclide therapy ("appropriate" in the AUC) and restaging after peptide receptor radionuclide therapy completion ("appropriate" in the AUC) accounted for 95 (4.2%) and 115 (5.1%) scans, respectively. The number of scans performed for indications not defined in the AUC was 371 (16.5%). Image result analysis revealed no disease in 669 scans (29.7%), stable disease in 582 (25.9%), and progression in 461 (20.5%). In 99 of the 461 (21.5%) scans, progression was detected on PET but not on CT. Conclusion: Our study provided real-life data that may contribute to support development of 64Cu-DOTATATE/SSTR PET/CT guidelines including AUC. Some scenarios listed as "may be appropriate" in the current AUC were frequent in our data. Monitoring of patients with NEN without clinical evidence of progression was the most frequent indication for 64Cu-DOTATATE PET/CT, in which disease progression was detected in more than one third, and a large proportion was visible by PET only. We therefore conclude that this scenario could potentially be classified as appropriate.

Prognostic genomic alterations in patients undergoing liver resection for hepatocellular carcinoma

IntroductionGenetic mutations and amplifications found in hepatocellular carcinoma (HCC) have a potentially prognostic impact. The aim of this study was to investigate the prognostic value of mutations and amplifications in HCC from patients that were liver resected.MethodsPatients liver resected for HCC at Copenhagen University Hospital Rigshospitalet between May 2014 and January 2018 were included. DNA from freshly frozen tumour tissue was investigated with TruSight Oncology 500. Mutations and amplifications were correlated with disease-free survival and overall survival using multivariate Cox regression to assess the effect on prognosis.ResultsOf the 51 patients included, 88% were male and the median age was 69 years. Most patients had a single tumour (84%) with no vascular invasion (67%) in a non-cirrhotic liver (76% with fibrosis, 24% with cirrhosis). The median follow-up was 37 months. Patients with a MYC amplification (8%) were significantly younger than the remaining patients. Furthermore, they had a significantly shorter overall survival (15 months (95% CI: 0.0–31.6) vs. 59 months (95% CI: 34.4–83.6), p = < 0.001) and disease-free survival (8 months (95% CI: 4.6–11.4) vs. 19 months (95% CI: 12.3–25.7), p = 0.03). However, only overall survival remained statistically significant in the adjusted analysis. Furthermore, all patients with an ARID1A mutation (6%) had microvascular invasion and significantly larger tumours than the patients without ARID1A mutation.ConclusionMYC amplifications had a prognostic influence on survival, whereas ARID1A gene mutations were correlated with microvascular invasion. These may serve as prognostic biomarkers and should be validated in large, independent cohort.

Outcome of combined cataract surgery and iris prosthesis implantation in iris melanoma patients previously treated with iridocyclectomy: A national retrospective non-comparative case series.

To examine complications, visual outcomes, photic patient-reported symptoms, corneal morphology, IOL tilt, and intraocular pressure after implantation of an intraocular lens (IOL) and iris prosthesis (IP) following iridocyclectomy. Patients with previous iridocyclectomy treated with an IOL and IP at the Copenhagen University Hospital Rigshospitalet between 2007 and 2018 were included in this national retrospective non-comparative case series. The assessment encompassed BCVA, PRO questionnaire, corneal topography, and anterior segment OCT. 45 patients were included. Eight of 45 patients were previously treated with ruthenium-106 brachytherapy in conjunction with iridocyclectomy. Six of 45 patients developed endothelial dysfunction four of whom had received ruthenium-106 brachytherapy. Five of 45 patients had subluxation of the IOL/IP complex due to incomplete zonula apparatus. BCVA improved for all patients after lens surgery. 26 patients participated in the invited follow-up examination. 19 of 26 (73%) reported none or mild photic symptoms after IP instalment. Five (19%) reported ongoing severe photic symptoms. The corneal astigmatism significantly increased after iridocyclectomy but did not change after lens surgery. Implantation of an IOL and IP is a safe procedure, alleviating photic symptoms in most patients. It comes with higher risk of complications due to a more demanding procedure and larger surgical traumas from previous treatments. Ruthenium-106 brachytherapy increases the complication risk. Corneal astigmatism is induced by iridocyclectomy but does not change after lens surgery.

Motivation towards first trimester screening for preeclampsia among pregnant women in Denmark: A cross-sectional questionnaire study.

The aim of this cross-sectional questionnaire study was to investigate motivation to participate in a possible new screening for preeclampsia in the first trimester of pregnancy among Danish pregnant women through a questionnaire based on Theory of Planned Behavior developed for this specific purpose. The new screening combines maternal characteristics with mean arterial pressure, uterine artery pulsatility index and biochemical markers to predict the risk of preeclampsia, whereas the current Danish screening uses maternal characteristics alone. Participation was offered to a proportion of women attending a first or a second trimester screening scan at two University Hospitals in Copenhagen. The questionnaire was set up in REDCap® and answers were entered directly into the database, which was accessed via a QR-code. We invited 772 pregnant women to participate in the questionnaire survey between November 2021 and April 2022 at Copenhagen University Hospital Rigshospitalet (study site one) (n = 238) and Copenhagen University Hospital Hvidovre (study site two) (n = 534). The response rate was 71.8% (171/238) at study site one and 33.9% (181/534) at study site two. A total of 352 women were included in the study (total participation rate 45.6%). Most women had a positive attitude towards preeclampsia screening in pregnancy, and 99.4% said they would participate in a risk assessment for preeclampsia if given the opportunity. A total of 97.4% answered "yes" to whether a first trimester preeclampsia screening should be offered to all pregnant women in Denmark. Positive motivation to participate in preeclampsia screening was correlated with having a network with a positive attitude towards preeclampsia screening. The results of this study indicate that Danish pregnant women have a positive attitude towards participation in a first trimester screening for preeclampsia. This observation might be useful in relation to possible future implementation in Denmark.

Lack of an association between first-trimester concentration of mid-regional pro-atrial natriuretic peptide and risk of early-onset preeclampsia

We examined the heart failure biomarker mid-regional pro-atrial natriuretic peptide during the first trimester of pregnancy in relation to early-onset preeclampsia <34 weeks. This case-control study included 34 women with singleton pregnancies with a preeclampsia diagnosis and delivery before 34 weeks of gestation who had attended the routine first-trimester ultrasound scan at 11-13+6 weeks of gestation between August 2010 and October 2015 at the Copenhagen University Hospital Rigshospitalet, Denmark, and 91 uncomplicated singleton pregnancies matched by time of the routine first-trimester blood sampling at 8-13+6 weeks. Descriptive statistical analyses were performed for maternal characteristics and obstetric and medical history for the case versus the control group. Concentrations of mid-regional pro-atrial natriuretic peptide, placental growth factor, soluble fms-like tyrosine kinase-1, and pregnancy-associated plasma protein A between early-onset preeclampsia cases and the control group were compared using Students t-test and the Mann-Whitney U test. Biochemical marker concentrations were converted into multiples of the expected median values after adjustment for gestational age. Mid-regional pro-atrial natriuretic peptide levels were not significantly different between early-onset preeclampsia cases and the control group in the first trimester of pregnancy. As expected, both placental growth factor and pregnancy-associated plasma protein A levels were significantly lower in early-onset preeclampsia, whereas soluble fms-like tyrosine kinase-1 levels were not statistically significantly different. The maternal first-trimester concentration of mid-regional pro-atrial natriuretic peptide, a peptide with multiple biological functions including a relation to cardiovascular disease, was not significantly different in women with early-onset preeclampsia.

Annals On Call - Subclinical Coronary Atherosclerosis.

Web Exclusives6 June 2023Annals On Call - Subclinical Coronary AtherosclerosisFREERobert M. Centor, MD, and Klaus Fuglsang Kofoed, MD, PhD, DMScRobert M. Centor, MDHuntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Search for more papers by this author, and Klaus Fuglsang Kofoed, MD, PhD, DMScDepartment of Cardiology and Department of Radiology, Copenhagen University Hospital–Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (K.F.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/A22-0011 CME/MOC SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this episode of Annals On Call, Dr. Centor discusses subclinical atherosclerosis and the risk for myocardial infarction with Dr. Klaus Fuglsang Kofoed.Annals articles discussed include...Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort. A Prospective Observational Cohort Study: https://www.acpjournals.org/doi/10.7326/M22-3027About Annals On CallAnnals On Call focuses on a clinically influential article published in Annals of Internal Medicine. Dr. Robert Centor shares his own perspective on the material and interviews topic area experts to discuss, debate, and share diverse insights about patient care and health care delivery.For more information on Annals On Call and for more episodes, visit go.annals.org/OnCall. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Robert M. Centor, MD; Klaus Fuglsang Kofoed, MD, PhD, DMScAffiliations: Huntsville Regional Medical Campus, University of Alabama Birmingham School of Medicine, Birmingham, Alabama (R.M.C.)Department of Cardiology and Department of Radiology, Copenhagen University Hospital–Rigshospitalet, and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (K.F.K.)Disclosures: All relevant financial relationships have been mitigated. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=A22-0011.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures.This article was published at Annals.org on 6 June 2023. Nextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSubclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort Andreas Fuchs , Jørgen Tobias Kühl , Per Ejlstrup Sigvardsen , Shoaib Afzal , Andreas Dehlbæk Knudsen , Mathias Bech Møller , Martina Chantal de Knegt , Mathias Holm Sørgaard , Børge Grønne Nordestgaard , Lars Valeur Køber , and Klaus Fuglsang Kofoed Metrics Latest ePublished: 6 June 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.Loading ...

Specific thresholds of quantitative pupillometry parameters predict unfavorable outcome in comatose survivors early after cardiac arrest

AimQuantitative pupillometry is the guideline-recommended method for assessing pupillary light reflex for multimodal prognostication in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). However, threshold values predicting an unfavorable outcome have been inconsistent across studies; therefore, we aimed to identify specific thresholds for all quantitative pupillometry parameters. MethodsComatose post-OHCA patients were consecutively admitted to the cardiac arrest center at Copenhagen University Hospital Rigshospitalet from April 2015 to June 2017. The parameters of quantitatively assessed pupillary light reflex (qPLR), Neurological Pupil index (NPi), average/max constriction velocity (CV/MCV), dilation velocity (DV), and latency of constriction (Lat) were recorded on the first three days after admission. We evaluated the prognostic performance and identified thresholds achieving zero percent false positive rate (0% PFR) for an unfavorable outcome of 90-day Cerebral Performance Category (CPC) 3–5. Treating physicians were blinded for pupillometry results. ResultsOf the 135 post-OHCA patients, the primary outcome occurred for 53 (39%) patients.On any day during hospitalization, a qPLR < 4%, NPi < 2.45, CV < 0.1 mm/s, and an MCV < 0.335 mm/s predicted 90-day unfavorable neurological outcome with 0% FPR (95%CI: 0–0%), with sensitivities of 28% (17–40%), 9% (2–19%), 13% (6–23%), and 17% (8–26%), respectively on day 1. ConclusionWe found that specific thresholds of all quantitative pupillometry parameters, measured at any time following hospital admission until day 3, predicted a 90-day unfavorable outcome with 0% FPR in comatose patients resuscitated from OHCA. However, at 0% FPR, thresholds resulted in low sensitivity. These findings should be further validated in larger multicenter clinical trials.

AI-Powered Respiratory and Circulatory Distress Monitoring System Alerts to Potential Complications Post-Discharge

The Pulse| January 2023 AI-Powered Respiratory and Circulatory Distress Monitoring System Alerts to Potential Complications Post-Discharge Catlin Nalley Catlin Nalley Search for other works by this author on: This Site PubMed Google Scholar ASA Monitor January 2023, Vol. 87, 22. https://doi.org/10.1097/01.ASM.0000911760.87237.ab Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Search Site Citation Catlin Nalley; AI-Powered Respiratory and Circulatory Distress Monitoring System Alerts to Potential Complications Post-Discharge. ASA Monitor 2023; 87:22 doi: https://doi.org/10.1097/01.ASM.0000911760.87237.ab Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: patients' rooms, vital signs, denmark, surgical procedures, operative After a major surgery, there is an approximately 30% risk for serious adverse events during the first 30 postoperative days, and postoperative complications are ranked as the third most likely cause of death worldwide. “These numbers are not due to complications occurring in the OR, PACU, or ICU, but mainly in the general ward, where nurses are responsible for high patient volumes and infrequent intermittent manual vital sign monitoring result in late detection of complications and failure to rescue,” said Eske Kvanner Aasvang, MD, DMSci, Professor and Chief Consultant, Department of Anesthesiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark. Despite decades of use, international standards for track-and-trigger systems, such as the National Early Warning Score (NEWS), have not been proven to have any effect on morbidity or mortality. Recognizing this, Dr. Aasvang and his colleague Christian S. Meyhoff, MD, PhD, Professor and Chief Consultant, Department of Anesthesia and Intensive Care, Copenhagen University... You do not currently have access to this content.

Palliative Treatment of Esophageal Cancer Using Calcium Electroporation.

Calcium electroporation (CaEP) is a novel cancer therapy wherein high intracellular calcium levels, facilitated by reversible electroporation, trigger tumor necrosis. This study aimed to establish safety with CaEP within esophageal cancer. Patients with non-curable esophageal cancer were included at Copenhagen University Hospital Rigshospitalet in 2021 and 2022. In an outpatient setting, calcium gluconate was injected intratumorally followed by reversible electroporation applied with an endoscopic electrode. The primary endpoint was the prevalence of adverse events, followed by palliation of dysphagia. All patients were evaluated with CT and upper endoscopies up to two months after treatment. The trial was registered at ClinicalTrials.gov (NCT04958044). Eight patients were treated. One serious adverse event (anemia, requiring a single blood transfusion) and three adverse events (mild retrosternal pain (two) and oral thrush (one)) were registered. Initially, six patients suffered from dysphagia: two reported dysphagia relief and four reported no change. From the imaging evaluation, one patient had a partial response, three patients had no response, and four patients had progression. Six months after treatment, the patient who responded well was still in good condition and without the need for further oncological treatment. CaEP was conducted in eight patients with only a few side effects. This study opens the way for larger studies evaluating tumor regression and symptom palliation.

A characterization of trauma laparotomies in a scandinavian setting: an observational study

BackgroundDespite treatment advances, trauma laparotomy continuous to be associated with significant morbidity and mortality. Most of the literature originates from high volume centers, whereas patient characteristics and outcomes in a Scandinavian setting is not well described. The objective of this study is to characterize treatments and outcomes of patients undergoing trauma laparotomy in a Scandinavian setting and compare this to international reports.MethodsA retrospective study was performed in the Copenhagen University Hospital, Rigshospitalet (CUHR). All patients undergoing a trauma laparotomy within the first 24 h of admission between January 1st 2019 and December 31st 2020 were included. Collected data included demographics, trauma mechanism, injuries, procedures performed and outcomes.ResultsA total of 1713 trauma patients were admitted to CUHR of which 98 patients underwent trauma laparotomy. Penetrating trauma accounted for 16.6% of the trauma population and 66.3% of trauma laparotomies. Median time to surgery after arrival at the trauma center (TC) was 12 min for surgeries performed in the Emergency Department (ED) and 103 min for surgeries performed in the operating room (OR). A total of 14.3% of the procedures were performed in the ED. A damage control strategy (DCS) approach was chosen in 18.4% of cases. Our rate of negative laparotomies was 17.3%. We found a mortality rate of 8.2%. The total median length of stay was 6.1 days.ConclusionThe overall rates, findings, and outcomes of trauma laparotomies in this Danish cohort is comparable to reports from similar Western European trauma systems.

How Adolescents and Young Adults with Cancer Experience an Age-Appropriate Intervention When Undergoing Treatment in Adult Surgery Clinics: A Qualitative Study.

Purpose: Despite growing international attention, few interventions specifically target adolescents and young adults (AYAs) with cancer even though appropriate interventions may improve care delivery during cancer treatment. The study's purpose was to explore how AYAs with cancer experience an age-appropriate intervention when undergoing treatment in adult surgery clinics. Methods: Twenty AYAs with cancer, aged 18-29 years, from five surgery clinics at Copenhagen University Hospital Rigshospitalet participated in an intervention consisting of three main components: care provided by trained youth coordinator nurses (YCNs) to the greatest extent possible; a 1-hour one-on-one conversation with a YCN during hospitalization; and a postdischarge phone call. Semistructured interviews were used to collect data, which were analyzed in a stepwise process based on inductive content analysis. Results: Three themes were identified: a beacon in the dark; from patient to person; and the caring check-up. Participants felt safe and experienced a sense of presence and a caring environment in a significant and trusting relationship with YCNs, which encouraged them to share thoughts, feelings, and needs they previously had kept silent about. The one-on-one conversations helped them begin reflecting and in emotional processing and the postdischarge phone call was perceived as a caring check-up. Conclusions: The study shows how an age-appropriate intervention was experienced overall as meaningful for the participants hospitalized in adult surgery clinics, but more research is required to further examine the significance and effect of interventions that target AYAs with cancer.

Postgraduate Interprofessional Case-Based Learning in Childhood Cancer: A Feasibility Study.

Simple SummaryIn childhood cancer healthcare, interprofessional education involves multiple healthcare professionals with general and specific knowledge and skills. However, few interprofessional education programs exist in childhood cancer. This feasibility study assesses the acceptability, demand, practicality, and implementation of postgraduate interprofessional case-based learning for healthcare professionals from 13 different occupational groups working with children and adolescents with cancer. The study design is interventional, with subjective and objective assessment measures. Outcome measures provide sufficient information to inform a randomized controlled trial. Results from this feasibility study could be useful in the planning, design, and evaluation of postgraduate interprofessional education in other settings.This paper presents a feasibility study assessing the acceptability, demand, implementation, and practicality of postgraduate interprofessional case-based learning in childhood cancer at Copenhagen University Hospital—Rigshospitalet. Healthcare professionals included nurses, doctors, social workers, physiotherapists, occupational therapists, pharmacists, pharmacologists, dieticians, nursing assistants, and professionals with a supportive function (teachers, secretaries, priests, and daycare workers). All participated in a postgraduate interprofessional case-based learning session. Feasibility was assessed using Bowen’s focus areas of acceptability, demand, implementation, and practicality. Before and after the intervention session, three measurement tools were used 2–3 weeks before participation and 3–4 weeks after participation to collect data: Assessment of Interprofessional Team Collaboration Scale, Readiness for Interprofessional Learning Scale, and Safety Attitudes Questionnaire. Representing 13 occupational groups, 49 participants completed the case-based learning sessions, indicating acceptability and practicality. The pre- and post-intervention questionnaires were completed by 79% of the participants, 88% of whom rated the professional content as good or very good. A change over time was detected on all three scales measuring mean difference post-intervention scores. The outcome measures can be used to assess the effect of the intervention. Postgraduate interprofessional case-based learning in childhood cancer is feasible in terms of acceptability, demand, implementation, and practicality. Implementation requires leadership commitment at all levels.

Smartphone App to Self-Monitor Nausea During Pediatric Chemotherapy Treatment: User-Centered Design Process

BackgroundNausea and vomiting are common and distressing side effects for children receiving chemotherapy. Limited evidence is available to guide antiemetic recommendations; therefore, prospective and reliable evaluation of antiemetic efficacy is needed. Smartphone apps can be used to effortlessly and precisely collect patient-reported outcomes in real time.ObjectiveOur objective was to develop a smartphone app to monitor nausea and vomiting episodes in pediatric cancer patients aged 0 to 18 years and to test its usability and adherence to its use.MethodsWe used a user-centered design process and the evolutionary prototype model to develop and evaluate the app. Multidisciplinary group discussions and several rounds of patient feedback and modification were conducted. We translated the validated Pediatric Nausea Assessment Tool to assess nausea severity in children aged 4 to 18 years. The child’s own term for nausea was interactively incorporated in the nausea severity question, with response options expressed as 4 illustrative faces. Parent-reported outcomes were used for children aged 0 to 3 years. Reminders were sent using push notifications in order to ensure high response rates. Children aged 0 to 18 years who were undergoing chemotherapy were recruited from the Department of Pediatric Oncology at Copenhagen University Hospital Rigshospitalet to evaluate the app.ResultsThe app’s most important function was to record nausea severity in children. After assistance from a researcher, children aged 4 to 18 years were able to report their symptoms in the app, and parents were able to report symptoms for their children aged 0 to 3 years. Children (n=20, aged 2.0-17.5 years) and their parents evaluated the app prospectively during a collective total of 60 chemotherapy cycles. They expressed that the app was user-friendly, intuitive, and that the time spent on data entry was fair. The response rates were on average 92%, 93%, and 80% for the day before, the first day of, and the next 3 days after chemotherapy, respectively. Researchers and clinicians were able to obtain an overview of the patient’s chemotherapy dates and responses through a secure and encrypted web-based administrative portal. Data could be downloaded for further analysis.ConclusionsThe user-friendly app could be used to facilitate future pediatric antiemetic trials and to refine antiemetic treatment during chemotherapy.

Fetal fraction of cell-free DNA in pregnancies after fresh or frozen embryo transfer following assisted reproductive technologies.

Is the fetal fraction (FF) of circulating cell-free DNA (cfDNA) affected in pregnancies following ART treatment with either fresh or frozen embryo transfer (ET) compared with natural conception? This study shows a significant reduction in the FF in ART patients compared with naturally conceived pregnancies, which seems to be more pronounced after fresh ET compared with frozen ET. Non-invasive prenatal testing (NIPT) is based on cfDNA in maternal blood, of which about 10% is of placental origin and thus represents the fetal karyotype. Validation studies have demonstrated a high sensitivity, specificity and positive predictive value of NIPT for the detection of fetal trisomy 21, 18 and 13. Nevertheless, the FF of cfDNA is an important factor for NIPT test accuracy. Several studies have found a reduction in FF for pregnancies following ART in comparison with natural conception. However, knowledge on how the FF is affected in ART pregnancies after fresh ET compared with frozen ET is very limited. The study was designed as a case-control study. A total of 54 women with an ongoing pregnancy following ART treatment were included. After exclusion for different reasons, statistical analyses were based on 23 NIPT samples from pregnant women treated with fresh ET and 26 NIPT samples from pregnant women treated with frozen-thawed ET in a modified natural cycle. Women were included between February 2018 and November 2018. The results were compared with a control group of 238 naturally conceived pregnancies with a high-risk result from the combined first trimester screening (cFTS). The study included women from the Fertility Clinics at Copenhagen University Hospital Hvidovre and Copenhagen University Hospital Rigshospitalet. Blood samples for NIPT analysis were drawn between 11 + 0 and 14 + 2 weeks of gestation and were all analyzed at the NIPT Center at Copenhagen University Hospital Hvidovre. The NIPT-test was performed by massive-parallel whole-genome sequencing. The FF was determined using the SeqFF algorithm. We found a reduction in FF in ART patients compared with naturally conceived pregnancies, and the reduction was more pronounced for ART pregnancies after fresh ET (mean FF = 0.049) compared with frozen ET (mean FF = 0.063) (multivariate analysis adjusted for maternal BMI, P = 0.02). Another multivariate analysis, adjusted for BMI and multiples of median (MoM) values for pregnancy-associated plasma protein-A (PAPP-A), demonstrated a significantly reduced FF for ART pregnancies (mean FF = 0.056) compared with naturally conceived pregnancies (mean FF = 0.072) (P < 0.0001). We found that FF was significantly reduced with increasing maternal BMI (P < 0.0001) and with decreasing MoM values of PAPP-A (P = 0.003). A limitation of our study design was the relatively small sample size. Another limitation was that the control group was not matched with the ART-treated women. The majority of the women from the control group had a high risk from cFTS, thereby their biochemical markers were diverging. However, the biochemical markers for the ART-treated women with fresh or frozen ET were not divergent within the subgroups. Concurrent with other studies demonstrating a reduced FF for singleton pregnancies after ART treatment compared with naturally conceived pregnancies, we found a reduction in FF between the two groups. This is one of the first studies to examine FF in ART pregnancies after fresh ET compared with frozen ET, hence the existing knowledge is limited. We find that FF is even more reduced in pregnancies following fresh ET compared with frozen ET, which might possibly reflect the predisposition of being small for gestational age after fresh ET compared with natural cycle frozen ET. The study was supported by the A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal (the A.P. Møller Foundation for General Purposes). All authors declare no conflicts of interest. NA.

P4668Risk of valvular heart disease in bromocriptine-treated women with hyperprolactinaemic disorders

Abstract Background Systematic echocardiographic screening is currently recommended for patients with hyperprolactinemic disorders treated with dopamine agonists, due to a perceived risk of cardiac valve regurgitation as observed in patients with Parkinson's disease. The dopamine agonist bromocriptine is used frequently in hyperprolactinemia patients, but its relation to cardiac valve disease remain uncertain. Purpose To determine the incidence of valvular heart disease in bromocriptine-treated women with hyperprolactinaemic disorders compared with matched controls from background population. Methods In nationwide Danish registries, we identified patients with hyperprolactinaemic disorders treated with bromocriptine between 1995–2017. Patients were matched 1:5 with population controls based on age and sex using incidence density sampling. We estimated the risk of valvular heart disease defined as admission and/or outpatient clinic visits. Incidence rates, cumulative incidence curve and adjusted cox-proportional hazard models were used to assess outcomes. Results A total of 23883 female bromocriptine users and 119415 controls were included. Median age was 29.9 years (Q1-Q3 26.4–33.8). Both groups had few comorbidities, 218 (0.9%) patients and 787 (0.7%) controls with hypertension, 160 (0.7%) patients and 629 (0.5%) controls with diabetes, 408 (1.7%) patients and 1305 (1.1%) controls were beta-blocker users. During a mean follow-up of 19 years 106 (0.44%) patients and 416 (0.35%) controls were diagnosed with valvular heart disease. Incidence rates were 0.254 per 1000 patient years (PY) in bromocriptine users (95% CI 0.21–0.31) and 0.198 per 1000 PY in the control cohort (95% CI 0.18–0.22). Overall, the cumulative incidence of valvular heart disease was 0.6% (95% CI 0.48–0.73) among patients and 0.5% (95% CI 0.4–0.51) among controls; P=0.03 (figure 1a). In adjusted analysis bromocriptine users still had a significant higher risk of valvular heart disease (hazard ratio=1.32, 95% CI 1.06–1.64, P=0.01). Incidence of valvular heart disease Conclusion The use of bromocriptine in younger and otherwise healthy women with hyperprolactinaemic disorders, were associated with a low absolute risk of cardiac valve disease. Still risk was approximately 30% higher compared with age- and sex matched controls. Our study suggests a low clinical yield of echocardiographic screening in this patient population. Acknowledgement/Funding Internal grant, Copenhagen University Hospital Rigshospitalet

Pregnancy Loss and Cancer Risk: A Nationwide Observational Study

BackgroundCancer is the second leading cause of death worldwide. Few studies have investigated if recurrent pregnancy loss is associated with an increased risk of cancer. We aimed to assess whether pregnancy loss is associated with later cancer development. MethodsWe identified all invasive cancers after age 40, among all Danish women born between January 1957 and December 1972, ensuring a full reproductive history. Cases were matched by birth year 1:10 to cancer-free controls. Women were followed until the end of 2017. The number of pregnancy losses (miscarriages or still births) was correlated to long-term cancer risk using conditional logistic regression, providing odds ratios for specific cancers with different numbers of pregnancy losses, all adjusted for age, education, and other potential confounders. FindingsThe study included 28,785 women with cancer (mean age 48.7 [SD 5.0]) and 283,294 matched controls (mean age 48.6 [SD 5.0]). We found no overall association between pregnancy loss and later development of 11 site-specific types of cancer or cancer overall. Taking the sequence of pregnancy losses into account, primary recurrent pregnancy loss (three consecutive pregnancy losses without prior live birth) was associated with later overall cancer by an odds ratio of 1.27 (1.04–1.56). Secondary recurrent pregnancy loss showed no association to cancer. InterpretationPregnancy loss was not associated with later cancer development. Women with primary recurrent pregnancy loss had a borderline significant association to later cancer overall, this may be a chance finding. FundingOle Kirk's Foundation and Copenhagen University Hospital Rigshospitalet's Research Grant.

Appointed by young people – a qualitative study on young patients recruiting hospital staff in Denmark

There is a lack of knowledge about young peoples'wishes for the qualifications including skills and personal traits of hospital staff during the recruitment process. The aim of this qualitative study was to explore which qualifications, skills and personal traits young people prefer when recruiting hospital staff. A Youth Recruitment Committee (YRC) consisting of four young people performed six job interviews in parallel to conventional job interviews at Copenhagen University Hospital Rigshospitalet, Denmark. The interviews with the candidates and the subsequent YRC deliberation were observed and recorded, and data were analyzed using thematic analysis. Four main themes with matching sub-themes emerged from the data: (1) Personality (appearance and commitment), (2) Professional skills (approach, mentality and activities), (3) Project management (skills and experience), (4) Communication (during the interview and experiential approach to youth). It was important to the YRC that the candidate had professional experience working with young people as well as being a skilled project manager. The YRC also assessed the candidates´ communication during the interview. By inviting young people in as a separate recruitment committee, their perspectives and preferences were noted without interference from professionals. Our findings are in line with previous research regarding young peoples´ preferences on youth-friendly health services. Furthermore, this approach made it possible to evaluate candidates´ communication skills with young people as they were assessed during the job interviews.

OK-432 Treatment of Early Fetal Chylothorax: Pregnancy Outcome and Long-Term Follow-Up of 14 Cases

Background: The treatment options for fetal chylothorax include thoracocentesis, thoracoamniotic shunting, and pleurodesis using OK-432. Knowledge on the long-term outcomes after treatment with OK-432 is limited. Objective: The aim of this study was to assess the long-term outcomes of children treated in utero with OK-432. Methods: We performed follow-up on pregnancies and children treated in utero with OK-432 between 2003 and 2009 at Copenhagen University Hospital Rigshospitalet for pleural effusions at gestational age (GA) 16⁺⁰–21⁺⁶ weeks. Anamnestic information, physical examination, pulmonary function test, neuropediatric examination, and intelligence testing using the Wechsler Intelligence Scale were used for evaluation. Results: Fourteen cases, all chylothorax, were treated with OK-432. None had preterm premature rupture of membranes (PPROM), and the median GA at delivery was 38⁺⁵ (24⁺⁴–41⁺⁵) weeks. Twelve children were eligible for follow-up. The median age at follow-up was 11.4 (7.8–13.8) years. Pulmonary function was normal in all children and the mean full-scale IQ did not differ from that of normal children. Four children had a diagnosed medical condition, attention deficit disorder, or genetic syndrome. The remaining children had normal follow-up. Conclusion: Children treated with OK-432 have comparable survival rates and long-term neurodevelopmental outcomes to those treated with thoracoamniotic shunts. There seems to be a lower risk of procedure-related PPROM.

Initiating transitional care for adolescents with cystic fibrosis at the age of 12 is both feasible and promising.

Adolescence is a vulnerable period in cystic fibrosis, associated with declining lung function. This study described, implemented and evaluated a transition programme for adolescents. We conducted a single centre, nonrandomised and noncontrolled prospective programme at the cystic fibrosis centre at Copenhagen University Hospital Rigshospitalet from 2010 to 2011, assessing patients aged 12-18 at baseline and after 12 months. Changes implemented included staff training on communication, a more youth-friendly feel to the outpatient clinic, the introduction of youth consultations partly alone with the adolescent, and a parents' evening focusing on cystic fibrosis in adolescence. Lung function and body mass index (BMI) were measured monthly and adolescents were assessed for their readiness for transition and quality of life at baseline and 12 months. We found that 40 (98%) of the eligible patients participated and youth consultations were successfully implemented with no dropouts. The readiness checklist score increased significantly over the one-year study period, indicating increased readiness for transfer and self-care. Overall quality of life, lung function and BMI remained stable during the study period. A well-structured transition programme for cystic fibrosis patients as young as 12 years of age proved to be both feasible and sustainable.

The outcome of antenatal ultrasound diagnosed anomalies of the kidney and urinary tract in a large Danish birth cohort

ObjectiveAntenatal ultrasound diagnosed anomalies of the kidney and urinary tract (AUDAKUT) are reported in 0.3%–5% on prenatal ultrasound (US) and 0.3%–4.5% on postnatal US. The anterior-posterior diameter of the renal...