Reports Non-financial Support Research Articles

Assessing couples' preferences for fresh or frozen embryo transfer: a discrete choice experiment.

What are couples' preferences for fresh embryo transfer versus freezing of all embryos followed by frozen embryo transfer and the associated clinical outcomes that may differentiate them? Couples' preferences are driven by anticipated chances of live birth, miscarriage, neonatal complications, and costs but not by the differences in the treatment process (including delay of embryo transfer linked to frozen embryo transfer and risk of ovarian hyperstimulation syndrome (OHSS) associated with fresh embryo transfer). A policy of freezing all embryos followed by transfer of frozen embryos results in livebirth rates which are similar to or higher than those following the transfer of fresh embryos while reducing the risk of OHSS and small for gestational age babies: it can, however, increase the risk of pre-eclampsia and large for gestational age offspring. Hence, the controversy continues over whether to do fresh embryo transfer or freeze all embryos followed by frozen embryo transfer. We used a discrete choice experiment (DCE) technique to survey infertile couples between August 2018 and January 2019. We asked IVF naïve couples attending a tertiary referral centre to independently complete a questionnaire with nine hypothetical choice tasks between fresh and frozen embryo transfer. The alternatives varied across the choice occurrences on several attributes including efficacy (live birth rate), safety (miscarriage rate, neonatal complication rate), and cost of treatment. We assumed that a freeze-all strategy prolonged treatment but reduced the risk of OHSS. An error components mixed logit model was used to estimate the relative value (utility) that couples placed on the alternative treatment approaches and the attributes used to describe them. Willingness to pay and marginal rates of substitution between the non-cost attributes were calculated. A total of 360 individual questionnaires were given to 180 couples who fulfilled the inclusion criteria, of which 212 were completed and returned Our study population included 3 same sex couples (2 females and 1 male) and 101 heterosexual couples. Four questionnaires were filled by one partner only. The response rate was 58.8%. Couples preferred both fresh and frozen embryo transfer (odds ratio 27.93 and 28.06, respectively) compared with no IVF treatment, with no strong preference for fresh over frozen. Couples strongly preferred any IVF technique that offered an increase in live birth rates by 5% (P = 0.006) and 15% (P < 0.0001), reduced miscarriage by 18% (P < 0.0001) and diminished neonatal complications by 10% (P < 0.0001). Respondents were willing to pay an additional £2451 (95% CI 604 - 4299) and £761 (95% CI 5056-9265) for a 5 and 15% increase in the chance of live birth, respectively, regardless of whether this involved fresh or frozen embryos. They required compensation of £5230 (95% CI 3320 - 7141) and £13 245 (95% CI 10 110-16 380) to accept a 10 and 25% increase in the risk of neonatal complications, respectively (P < 0.001). Results indicated that couples would be willing to accept a 1.26% (95% CI 1.001 - 1.706) reduction in the live birth rate for a 1% reduction in the risk of neonatal complications per live birth. Older couples appeared to place less emphasis on the risk of neonatal complications than younger couples. DCEs can elicit intentions which may not reflect actual behaviour. The external validity of this study is limited by the fact that it was conducted in a single centre with generous public funding for IVF. We cannot rule out the potential for selection or responder bias. If a strategy of freeze all was to be implemented it would appear to be acceptable to patients, if either success rates can be improved or neonatal complications reduced. Live birth rates, neonatal complication rates, miscarriage rates, and cost are more likely to drive their preferences than a slight delay in the treatment process. The results of this study have important implications for future economic evaluations of IVF, as they suggest that the appropriate balance needs to be struck between success and safety. A holistic approach incorporating patient preferences for expected clinical outcomes and risks should be taken into consideration for individualized care. No external funding was sought for this study. A.M. is the chief investigator of the randomized controlled trial 'Freeze all'. S.B. is an Editor in Chief of Human Reproduction Open. The other co-authors have no conflicts of interest to declare. Graham Scotland reports non-financial support from Merck KGaA, Darmstadt, Germany, outside the submitted work. N/A.

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Freezing All Embryos Versus Fresh Embryo Transfer in In-Vitro Fertilisation – a Multicentre Randomised Controlled Trial in the UK (E-Freeze)

Background: Embryos created following in-vitro fertilisation (IVF) are usually replaced within the uterus within a few days (fresh embryo transfer). It has been suggested that elective freezing of all embryos followed by transfer at a later date (freeze-all) could make treatment safer and more effective. The aim of this trial was to compare the clinical and cost-effectiveness of a strategy of freeze-all versus fresh embryo transfer. Methods: A two arm, non-blinded, parallel group pragmatic randomised trial was conducted across 18 IVF clinics in the UK. Couples undergoing IVF, where the woman was <42 years of age were randomised (1:1 allocation ratio) to either freeze-all or a fresh embryo transfer, provided they had at least 3 good quality embryos. The primary outcome was healthy baby rate (term singleton live birth with appropriate weight for gestation) (ISCTRN: 61225414). Findings: Between 2016 and 2019, 619 couples were randomised (309 to freeze-all and 310 to fresh transfer). Of these, 307 and 309 couples in the freeze-all and fresh transfer arms were included in the primary analysis. There was no evidence of a statistically significant difference in outcomes in the freeze-all group compared to the fresh embryo transfer group: healthy baby rate {20.3 % (62/307) versus 24.4% (75/309); Risk Ratio (RR), 95% Confidence Interval (CI): 0.84, 0.62 to 1.15}]; ovarian hyperstimulation (3.6% versus 8.1%; RR, 99% CI: 0.44, 0.15 to 1.30); live birth rate (28.3% versus 34.3%; RR, 99% CI 0.83, 0.65 to 1.06), and miscarriage (14.3% versus 12.9%; RR 99% CI: 1.09, 0.72 to 1.66). Adherence to allocation was poor in the freeze-all group. The freeze-all approach was more costly and was unlikely to be cost-effective in a UK NHS context. Interpretation: This study provides no evidence to support the adoption of a routine policy of freezing all embryos in preference to fresh embryo transfer in order to improve infant outcomes. Clinical Trial Registration Details: The trial was registered with the International Standard Randomised Controlled Trial Register (ISRCTN61225414) as was conducted as per published protocol. Funding Information: NIHR HTA, UK (13/115/82). Declaration of Interests: PH, JK, report receipt of funding from NIHR, during the conduct of the study. JB, CC,EJ, KS report receipt of funding from NIHR, during the conduct of the study and outside the submitted work. AM reports grants from NIHR personal fees from Merck Serono, personal fees from Ferring, and Cooks, outside the submitted work. SB reports grants from NIHR HTA, during the conduct of the study and remuneration from Oxford University Press for role as Editor in Chief of Human Reproduction Open. DB reports grants from NIHR, during the conduct of the study; grants from European Commission, grants from Diabetes UK, grants from NIHR, grants from ESHRE, grants from MRC, outside the submitted work. YC reports personal fees from Merck Serono, personal fees from Ferring, outside the submitted work. EJ reports membership of the HTA Commissioning Board (2013–16), the NIHR HTA General Board (2016–17) and is a member of the NHS England and NIHR partnership programme (2019 to present). RM reports other private practice fees from Manchester Fertility, personal fees from Merck, personal fees from Ferring, personal fees from Gedeon Richter, outside the submitted work. GS reports non-financial support and other from Merck KGaA, Darmstadt, Germany, outside the submitted work. ST reports personal fees from CooperSurgical International, personal fees from Parallabs, outside the submitted work. Other Authors’ Competing Interests: None declared. Ethics Approval Statement: The E-Freeze trial protocol was approved by the North of Scotland Research Ethics Service (NoSRES) Committee (Study Ref: 15/NS/0114). Local approval and site-specific assessments were obtained from each participating site.

VStore: A Novel Virtual Reality Assessment of Functional Cognition

Background: Cognitive deficits are present in a number of neuropsychiatric disorders including, Alzheimer’s disease, schizophrenia and depression. Assessments used to measure cognition in these disorders are time-consuming, burdensome, and lack ecological validity. To address these limitations, we developed a novel virtual reality shopping task – VStore. This study aims to establish the validity of VStore compared to the established computerised cognitive battery, Cogstate. Methods:104 healthy volunteers aged 20-79 completed the assessments. Main VStore outcomes included: 1) verbal recall of 12 grocery items, 2) time to collect items, 3) time to select items on a self-checkout machine, 4) time to make the payment, 5) time to order coffee, and 6) total completion time. To establish concurrent validity, bivariate correlations were performed between VStore outcomes and Cogstate tasks measuring attention, processing speed, verbal and visual learning, working memory, executive function, and paired associate learning. Construct validity analysis was also performed to examine which cognitive domains best predicted VStore performance. Finally, two ridge regression models were built using VStore outcomes in the first, and Cogstate outcomes in the second model as predictors of biological age to compare their sensitivity to age-related cognitive decline. Findings: We found moderate correlations between VStore and Cogstate outcomes. VStore Total Time was best explained by tasks measuring working memory and paired associate learning, in addition to age and technological familiarity, accounting for 46% of the variance. Finally, with λ = 5·16, the model fitting selected five parameters for VStore when predicting biological age (MSE = 185·8, SE= 19·34). With λ = 9·49 for Cogstate, the model fitting selected eight tasks (MSE = 226·8, SE = 23·48). Interpretation: These findings suggest that VStore is a promising assessment that engages standard cognitive domains and is sensitive to age-related cognitive decline. Funding Statement: Medical Research Council – Doctoral Training Partnership, King’s College London. Declaration of Interests: LP reports non-financial support from Vitae VR Ltd., during the conduct of the study. Authors SSS and EM created VStore, with contributions from LAP and technical development from VitaeVR Ltd. King’s College London has licensed its rights in VStore to VitaeVR Ltd. Authors LAP, EM, and SSS are entitled to a share of any revenues King’s College London may receive from commercialisation of VStore by VitaeVR Ltd. The other authors have no conflict of interest to declare. Ethics Approval Statement: Ethical approval was granted by the Psychiatry, Nursing and Midwifery Research Ethics Committee, King’s College London (LRS-16/17-4540). Informed consent was obtained.

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Remdesivir for the Treatment of Hospitalised Patients with COVID-19 (DisCoVeRy): A Randomised, Controlled, Open-Label Trial

Prognostic Indicators and Outcomes of Hospitalised COVID-19 Patients with Neurological Disease: A Systematic Review and Individual Patient Data Meta-Analysis

Background: Neurological COVID-19 disease has been reported widely, but often without using standard case definitions or detailed diagnostic work up. Several meta-analyses, based on such reports, describe the neurological diagnoses but give little information on outcomes and risk factors.Methods: We conducted an individual patient data meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute, and extracted aggregate data from published reports. We analysed features associated with poor outcome (moderate to severe sequelae or death, 3-6, on the modified Rankin scale) using multivariable models. Findings: We identified 381 studies (31 unpublished) describing 4443 patients with COVID-19 and neurological disease: 83 of these provided IPD for 1979 (45%) patients. Encephalopathy (978 [49%]) and cerebrovascular events (506 [26%]), were the most common diagnoses in the IPD database and aggregate data. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41] overall), and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-Dimer. Overall, 30-day mortality was 30% (27-32). The hazard of death was reduced for patients in the WHO European region, but increased in low- and lower-middle-income countries. Interpretation: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission. Funding This study was funded by the UK Medical Research Council’s Global Effort on COVID-19 Programme (MR/V033441/1); UK National Institute for Health Research (NIHR)-funded Global Health Research Group on Acute Brain Infections (17/63/110); and the NIHR Health Protection Research Unit in Emerging and Zoonotic Infections (NIHR200907), at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford (Grant Nos. IS-HPU-1112-10117 and NIHR200907).Declaration of Interests: BS reports a grant from UKRI/DHSC Global Effort on COVID-19 Research (Medical Research Council) and non-financial support from UK National Institute for Health Research Global Health Research Group on Brain Infections. SL and TS are supported by a grant from the EU Zika Preparedness Latin American Network consortium (ZikaPLAN). ZikaPLAN has received funding from the EU's Horizon 2020 research and innovation programme under grant agreement number 734584. LCG reports non-financial support from Pfizer, non-financial support from Gilead. LB reports grants from GlaxoSmithKline, Research England and Wellcome Trust. AMBM reports grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico CNPq/Brazil, and São Paulo Research Foundation FAPESP/Brazil. AP reports personal fees from ZAMBON, UCB , BIOMARIN, and ABBvie pharma. TS was an adviser to the GlaxoSmithKline Ebola Vaccine programme, chaired a Siemens Diagnostics clinical advisory board, and advises the WHO Brain Health Unit Forum on Neurology and COVID-19; TS has also previously filed a patent for a test for bacterial meningitis based on a blood test (GB 1606537.7, April 14, 2016), and has grants from the UK Medical Research Council and National Institute for Health Research. All other authors declare no conflict of interest

Chronic Obstructive Pulmonary Disease (Japanese Version).

In the Clinic4 August 2020Chronic Obstructive Pulmonary Disease (Japanese Version)Wassim W. Labaki, MD, MS and Sharon R. Rosenberg, MD, MSWassim W. Labaki, MD, MSUniversity of Michigan, Ann Arbor, Michigan (W.W.L.)Search for more papers by this author and Sharon R. Rosenberg, MD, MSNorthwestern University, Chicago, Illinois (S.R.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/IsTranslatedFrom_AITC202008040_Japanese SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Editors' Note: This article (available in PDF format) is the translated Japanese version of In the Clinic: Chronic Obstructive Pulmonary Disease (Labaki WW, Rosenberg SR. Chronic Obstructive Pulmonary Disease. Ann Intern Med. 2020;173:ITC17-ITC32. doi:10.7326/AITC202008040. Author, Article, and Disclosure InformationAuthors: Wassim W. Labaki, MD, MS; Sharon R. Rosenberg, MD, MSAffiliations: University of Michigan, Ann Arbor, Michigan (W.W.L.)Northwestern University, Chicago, Illinois (S.R.R.)Funding Source: American College of Physicians.Acknowledgment: The authors thank Michael R. Littner, MD, author of the previous version of this In the Clinic.Disclosures: Dr. Labaki, ACP Contributing Author, reports nonfinancial support from Pulmonx and personal fees from Konica Minolta outside the submitted work. Dr. Rosenberg, ACP Contributing Author, has nothing to disclose. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-0505.With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians. The patient information page was written by Monica Lizarraga from the Patient and Interprofessional Partnership Initiative at the American College of Physicians.In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/guidelines/. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoChronic Obstructive Pulmonary Disease Wassim W. Labaki and Sharon R. Rosenberg Metrics 4 August 2020Volume 173, Issue 3Page: JITC17-JITC32KeywordsBronchodilatorsChronic obstructive pulmonary diseaseDyspneaEmphysemaExerciseForced expiratory volume in the first second of expirationLungsMortalityOxygenThorax ePublished: 16 May 2023 Issue Published: 4 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association.

Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association.

Prognosis of patients with sickle cell disease and COVID-19: a French experience

Prognosis of patients with sickle cell disease and COVID-19: a French experience

COVID-19 and Cushing's syndrome: recommendations for a special population with endogenous glucocorticoid excess

COVID-19 and Cushing's syndrome: recommendations for a special population with endogenous glucocorticoid excess

Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology.

Acute Kidney Injury in COVID-19: Emerging Evidence of a Distinct Pathophysiology.

Correspondence

*Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland †Institute for Research in Ophthalmology, Foundation for Ophthalmology Development, Poznań, Poland ‡Hygeia Clinic, Gdańsk, Poland A. Grzybowski reports non-financial support from Alcon, personal fees and non-financial support from Valeant, grants from Zeiss, personal fees and non-financial support from Santen, outside the submitted work. P. Kanclerz reports non-financial support from Visim and Optopol Technology. The authors have no proprietary interest within the presented subject.

Rheumatic disease and COVID-19: initial data from the COVID-19 Global Rheumatology Alliance provider registries.

Author(s): Gianfrancesco, Milena A; Hyrich, Kimme L; Gossec, Laure; Strangfeld, Anja; Carmona, Loreto; Mateus, Elsa F; Sufka, Paul; Grainger, Rebecca; Wallace, Zachary; Bhana, Suleman; Sirotich, Emily; Liew, Jean; Hausmann, Jonathan S; Costello, Wendy; Robinson, Philip; Machado, Pedro M; Yazdany, Jinoos; COVID-19 Global Rheumatology Alliance Steering Committee

Sound Science before Quick Judgement Regarding RAS Blockade in COVID-19.

There has been much speculation in journals as well as social and traditional media about a link between popularly used classes of drugs that inhibit the renin-angiotensin system (RAS) and novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) infection or coronavirus

A UK-wide British Society of Thoracic Imaging COVID-19 imaging repository and database: design, rationale and implications for education and research

A UK-wide British Society of Thoracic Imaging COVID-19 imaging repository and database: design, rationale and implications for education and research

Selinexor in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (SADAL): A Single-Arm Multinational Phase 2 Trial

Background: Relapsed or refractory diffuse large B‑cell lymphoma (RR DLBCL) is an aggressive cancer with a median survival of less than 6 months. The SADAL trial aims to assess the response to the oral selective inhibitor of nuclear export (SINE) selinexor in patients with RR DLBCL who have no therapeutic options of demonstrated clinical benefit. Methods: SADAL was a multicenter, open-label Phase 2b study conducted at 59 sites globally. Patients 18 years with previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously diagnosed indolent lymphoma, and having received at least two prior therapies were enrolled. Germinal center B-cell (GCB) or non-GCB tumor subtype and double/triple expressor status were determined by immunohistochemistry and double/triple hit status was determined by cytogenetic assays. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The primary outcome was overall response rate (ORR) by central radiologic review. A modified intent-to-treat population was used for all efficacy endpoints. Findings: 127 patients were enrolled from October 21, 2015 through November 2, 2019. The ORR was 28.3% (95% CI: 20.7%, 37.0%), including complete response in 15 (11.8%) and partial response in 21 (16.5%) patients. Median overall survival (OS) was 9.1 months (95% CI: 6.6, 15.1) with longer OS observed in responding patients. Responses were observed across different subgroups regardless of age, gender, prior therapy, DLBCL subtype, refractory status or prior ASCT therapy. Adverse events were generally reversible and managed with dose modifications and/or standard supportive care. Interpretation: In both GCB- and non-GCB DLBCL subtypes, single agent oral selinexor induced durable responses which were associated with longer survival. Selinexor may be a new oral, non-cytotoxic treatment option for patients with RR DLBCL after two lines of chemo-immunotherapy. Trial Registration: This trial is registered at ClinicalTrials.gov, NCT02227251. Funding Statement: This study (NCT02227251) was funded by Karyopharm Therapeutics Inc, Newton, Massachusetts, USA, which provided all study materials. Declaration of Interests: NK reports research support from Verastem, Gilead, Celgene, and Roche, as well as honoraria from Gilead, Janssen, and Karyopharm. FC reports personal fees from Takeda, Gilead, and Janssen, outside the submitted work. MC reports personal fees from Celgene, Gilead, Janssen, Karyopharm, Novartis, Roche, Sandoz, and Servier outside the submitted work. GF reports personal fees from Karyopharm and Roche, outside the submitted work. AG reports personal fees and honoraria from AstraZeneca, personal fees and board membership from Cota and Kite/Gilead, personal fees from Janssen, Celgene, Acerta, and research funding from Constellation, Bayer, CALBG, Genentech, Hoffman-La Roche, MD Anderson, Morphosys, Pharmacyclics, and the University of Nebraska, outside the submitted work. OC reports grants, personal fees, and non-financial support from Roche, personal fees and non-financial support from Takeda, BMS, Amgen, Janssen, Abbvie, grants and personal fees from Gilead, and personal fees from Merck, outside the submitted work. BH reports grants and personal fees from Karyopharm, outside the submitted work. UJ reports personal fees from Karyopharm, during the conduct of the study; grants and personal fees from AbbVie, Celgene, Gilead, Janssen, Novartis, Roche, Takeda, Amgen, Miltenyi, and BMS, outside the submitted work. JMS reports honoraria from Roche, Janssen, Gilead, Celgene, Novartis outside the submitted work. MS reports personal fees from Karyopharm during the conduct of the study, and personal fees from Amgen, Abbvie, Gilead, Takeda, Celgene, Pharmacyclics, Astellas, Verastem, Merck, Novartis, Genentech, and Seattle Genetics, outside the submitted work. TPV reports honoraria from WinMedica, Astellas, and Gilead, honoraria, advisory board membership and research support from Takeda, honoraria and advisory board membership from Roche, Bristol, Genesis, and Novartis, advisory board membership at Janssen, honoraria and research support from Merck and Amgen, and research support from Pfizer and Karyopharm. AJ reports personal fees from Karyopharm Therapeutics during the conduct of the study. YL reports personal fees from Karyopharm Therapeutics, outside the submitted work. HC, YL, XM, KC, DM, HW, JS, JRS, SS, and MK are employees of Karyopharm. AJ is a consultant for Karyopharm. MK and SS are stockholders of Karyopharm. SS holds patents (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents (PCT/US12/048319, 499/2012, PI20102724, and 2012000928) on hydrazide-containing nuclear transport modulators and uses. All other authors declare no competing interests. Ethics Approval Statement: The institutional review board or independent ethics committee at each study center approved the protocol, and the study was performed in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and the principles of the Declaration of Helsinki.

Prevalence and Risk Factors of Infection in the Representative COVID-19 Cohort Munich

Background: Population-based studies investigating the dynamics of the SARS-CoV-2 pandemic are needed. Here, we report on baseline findings from April through June 2020 of a prospective cohort study in Munich, Germany.Methods: We drew a representative sample of 2994 private households. The 5313 participating household members 14 years and older completed questionnaires and provided blood samples. SARS-CoV-2 seropositivity was defined as Roche N pan-Ig ≥ 0·4218. We adjusted the prevalence for the sampling design, sensitivity, and specificity. We investigated risk factors for SARS-CoV-2 seropositivity and geospatial transmission patterns by generalized linear mixed models and permutation tests.Findings: Seropositivity for SARS-CoV-2 specific antibodies was 1·82% (95% confidence interval (CI) 1·28-2·37%) as compared to 0·46% PCR-positive cases officially registered in Munich. Loss of the sense of smell or taste was associated with seropositivity (odds ratio (OR) 47·4; 95% CI 7·2-307·0) and infections clustered within households. Participants suffering from respiratory allergies (OR 2·7; 95% CI 0·9-8·6) and working in high-risk jobs (OR 2·0; 95% CI 0·5-6·7) showed non-significantly increased odds for SARS-CoV-2 seropositivity.Interpretation: Applying a validated assay, we demonstrate a low SARS-CoV-2 seroprevalence in the Munich population 14 years and older towards the end of the first pandemic wave. However, we noted official sub-registration at this early stage of the pandemic.Funding: Bavarian State Ministry of Science and the Arts, University Hospital of LMU Munich, Helmholtz Centre Munich, University of Bonn, and University of Bielefeld.Declaration of Interests: FF, TF, DM, LO, and VT report grants from the Bavarian State Ministry of Science and the Arts during the conduct oft he study. TF reports grants from the University Hospital of LMU Munich, Helmholtz Center Munich, University of Bonn, University of Bielefeld, and German Ministry for Education and Research during the conduct of the study. JH reports grants from the German Federal Ministry of Education and Research during the conduct of the study. MH and AW report personal fees and non-financial support, LO and MP report non-financial support from Roche Diagnostics. MH, LO, MP, and AW report non-financial support from Euroimmun, Viramed, and Mikrogen. MH, MP, and AW report grants, non-financial support, and other from German Center for Infection Research (DZIF). FF, MH, LO, MP, VT, and AW report grants and non-financial support from the Government of Bavaria. MH, LO, MP, and AW report non-financial support from BMW, Mercedes Benz, Munich Police, and Accenture. MH and AW report personal fees and non-financial support from Dr. Box Betrobox during the conduct of the study. LO and MP report non-financial support from Dr. Box Betrobox. MH and AW have a patent Sample System for Sputum Diagnostics of SARS-CoV-2 pending. DM reports to be a a sub-investigator on a Phase I SARS-CoV-2 vaccine trial and on a Phase I rabies vaccine trial, both sponsored by CureVac AG. MP and AW report non-financial support from Dr. Becker MVZ. VT reports support from CureVac AG outside the submitted work. AW reports personal fees and other from Haeraeus Sensors. AW reports non-financial support from Bruker Daltronics outside the submitted work. AW is involved in other different patents and companies not in relation with the serology of SARS-CoV-2. All other authors report nothing to disclose.Ethics Approval Statement: Prior to study initiation, this study had been approved by therespective Institutional Review Board.

Type 1 Diabetes in 2017 - Global Estimates of Incident and Prevalent Cases in Children and Adults

Background: Data on type 1 diabetes incidence and prevalence are limited, particularly for adults. This study aims to estimate global numbers of incident and prevalent cases of type 1 diabetes in 2017 for all age groups by country and areas defined by income and region. Methods: Incidence rates of type 1 diabetes in children from existing literature were used and extrapolated to adults using available data on adult to child incidence ratios. Age-specific incidence rates were applied to population estimates to obtain incident case numbers. Duration of diabetes was estimated from available data and adjusted using differences in childhood mortality between countries. Prevalent case numbers were derived by modelling the relationship between prevalence, incidence, and disease duration. Findings: Global numbers of incident and prevalent cases were estimated to be 234,710 and 9,004,610, respectively. High income countries, with 17% of the global population, account for 49% of global incident cases and 52% of prevalent cases. Asia has the largest number of incident (32%) and prevalent (31%) cases and the largest proportion of the population (60%). Globally, the prevalent cases were 6%, 35%, 43%, and 6% in the age groups 0-14, 15-39, 40-64, and 65+ years, respectively. Interpretation: Globally type 1 diabetes represents about 2% of the estimated total cases of diabetes, ranging from less than 1% in certain Pacific countries to more than 15% in Northern European populations. This study provides information for development of health care and policy approaches to manage type 1 diabetes. Funding Statement: The study was funded by the US Centers for Disease Control and Prevention, through grant 5NU2GGH001235-05-00 of the WHO-CDC Cooperative Agreement, and by The Leona M. and Harry B. Helmsley Charitable Trust as part of the ACCISS Study. Declaration of Interests: AG and SMH report grants from the Institute of Applied Economics and Health Research, Copenhagen, Denmark outside the submitted work. SW reports non-financial support from Novo Nordisk, outside the submitted work. All other authors declare no competing interests.

Comparing Dynamics and Determinants of SARS-CoV-2 Transmissions Among Health Care Workers of Adult and Paediatric Settings in Central Paris

Background: From the start of the pandemic, health-care workers (HCW) have paid a heavy toll to the coronavirus desease-19 (COVID-19) outbreak. Routes of transmission however remain to be fully understood. Methods: This prospective study compared two settings of a tertiary-care university hospital located in central Paris: a 1,500-bed adult and a 600-bed paediatric setting, accounting for a total of 13,278 employees. From February 24th until April 10th, 2020, all symptomatic HCW were screened for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on a nasopharyngeal swab. HCW screened positive were prospectively questioned by phone on their profession, symptoms, occupational and non-occupational exposures to SARS-CoV-2. Findings: Among 1344 symptomatic HCW tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no death have been reported. Most HCW (70%) had patient-facing occupational activities and 22% in COVID-19 dedicated units. The total number of HCW cases peaked on week 13 (March 23rd, 2020) then decreased slowly until April 10th, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking for all hospital staff and personal protective equipment (PPE) for direct care to COVID-19 patients). Attack rates were of 3 · 2% and 2 · 3% in the adult and paediatric settings, respectively (p=0 · 0022). In the adult setting, HCW more frequently reported exposure to COVID-19 patients without PPE (25% versus 15%, p=0 · 046). In both settings, report of contacts with children attending out-of-home care facilities dramatically decreased all over the study period. Interpretation: In central Paris, implementation of universal masking, reinforcement of hand hygiene, social distancing and PPE with medical masks for patients’ care allowed protection of HCW and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities. Funding Statement: None.Declaration of Interests: AC reports personal fees and non-financial support from Janssen Cilag, outside the submitted work. RG reports personal fees and other from Sanofi, personal fees from MSD, personal fees from Eumedica, personal fees from Pfizer, personal fees from Frezenius, personal fees from Cubist, personal fees from Correvio, personal fees from Astellas, outside the submitted work. PF reports personal fees and nonfinancial support from MSD France, personal fees from ViiV Healthcare, non-financial support from Gilead Science, personal fees and non-financial support from Janssen Cilag, personal fees from Medtronic SAS, non-financial support from Astellas, non-financial support from GSK, outside the submitted work. MLV reports non-financial support from Biomerieux, non-financial support from Diasorin, outside the submitted work. OL reports personal fees from Pfizer, personal fees from Astellas, personal fees from MSD, personal fees from Gilead, outside the submitted work. SK reports research grants from bioMérieux, personal fees from Accelerate Diagnostics, bioMérieux, MSD and Menarini, and travel expenses from bioMérieux, Astellas, MSD and Pfizer, outside the submitted work. All other authors declare no conflict of interests. Ethics Approval Statement: This study was approved by the Ethical Review Committee for publications of the Cochin university Hospital (CLEP) (N°: AAA-2020-08012). According to French policy, a non-opposition statement was obtained for all participants, meaning that all had received written detailed information on the objectives of the study and were free to request withdrawal of their consent for participation at any time.

Recommendations for the surgical treatment of endometriosis. Part 2: deep endometriosis.

STUDY QUESTIONHow should surgery for endometriosis be performed?SUMMARY ANSWERThis document provides recommendations covering technical aspects of different methods of surgery for deep endometriosis in women of reproductive age.WHAT IS KNOWN ALREADYEndometriosis is highly prevalent and often associated with severe symptoms. Yet compared to equally prevalent conditions, it is poorly understood and a challenge to manage. Previously published guidelines have provided recommendations for (surgical) treatment of deep endometriosis, based on the best available evidence, but without technical information and details on how to best perform such treatment in order to be effective and safe.STUDY DESIGN, SIZE, DURATIONA working group of the European Society for Gynaecological Endoscopy (ESGE), ESHRE and the World Endometriosis Society (WES) collaborated on writing recommendations on the practical aspects of surgery for treatment of deep endometriosis.PARTICIPANTS/MATERIALS, SETTING, METHODSThis document focused on surgery for deep endometriosis and is complementary to a previous document in this series focusing on endometrioma surgery.MAIN RESULTS AND THE ROLE OF CHANCEThe document presents general recommendations for surgery for deep endometriosis, starting from preoperative assessments and first steps of surgery. Different approaches for surgical treatment are discussed and are respective of location and extent of disease; uterosacral ligaments and rectovaginal septum with or without involvement of the rectum, urinary tract or extrapelvic endometriosis. In addition, recommendations are provided on the treatment of frozen pelvis and on hysterectomy as a treatment for deep endometriosis.LIMITATIONS, REASONS FOR CAUTIONOwing to the limited evidence available, recommendations are mostly based on clinical expertise. Where available, references of relevant studies were added.WIDER IMPLICATIONS OF THE FINDINGSThese recommendations complement previous guidelines on management of endometriosis and the recommendations for surgical treatment of ovarian endometrioma.STUDY FUNDING/COMPETING INTEREST(S)The meetings of the working group were funded by ESGE, ESHRE and WES. Dr Roman reports personal fees from ETHICON, PLASMASURGICAL, OLYMPUS and NORDIC PHARMA, outside the submitted work; Dr Becker reports grants from Bayer AG, Volition Rx, MDNA Life Sciences and Roche Diagnostics Inc. and other relationships or activities from AbbVie Inc., and Myriad Inc, during the conduct of the study; Dr Tomassetti reports non-financial support from ESHRE, during the conduct of the study; and non-financial support and other were from Lumenis, Gedeon-Richter, Ferring Pharmaceuticals and Merck SA, outside the submitted work. The other authors had nothing to disclose.TRIAL REGISTRATION NUMBERna