International Panel Research Articles

Standardizing eligibility and patient selection for Pressurized Intraperitoneal Aerosol Chemotherapy: A Delphi consensus statement

IntroductionPressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a procedure for minimally invasive drug administration in patients with peritoneal metastasis. Previous studies have emphasized the importance of uniformity in treatment protocols and standardization of this practice. This study aimed to reach a consensus on eligibility, patient selection, and choice of chemotherapy for PIPAC. MethodsA three-round modified Delphi study was conducted. A steering group formulated a list of baseline statements, addressing the objectives. The steering group consisted of seven expert surgical and medical oncologists. Available evidence and published key opinions were critically reviewed. An international expert panel scored those statements on a 4-point Likert scale. The statements were submitted electronically and anonymously. Consensus was reached if the agreement rate was ≥75%. A minimum Cronbach's alpha of >0.8 was set. ResultsForty-five (45/58; 77.6%) experts participated and completed all rounds. Experts were digestive surgeons (n = 28), surgical oncologists (n = 7), gynecologists (n = 5), medical oncologists (n = 4), and one clinical researcher. Their assessment of 81 preliminary statements in the first round resulted in 41 consolidated statements. In round two, consensus was reached on 40 statements (40/41; 97.6%) with a consensus of ≥80% for each individual statement. In the third round, 40 statements were unanimously approved as definitive. The choice of first- and second-line chemotherapy remained controversial and could not reach consensus. ConclusionsThis International Delphi study provides practical guidance on eligibility and patient selection for PIPAC. Ongoing trial data and long-term results that could contribute to the further standardization of PIPAC are eagerly awaited.

Pangenome-Wide Association Study and Transcriptome Analysis Reveal a Novel QTL and Candidate Genes Controlling both Panicle and Leaf Blast Resistance in Rice

Cultivating rice varieties with robust blast resistance is the most effective and economical way to manage the rice blast disease. However, rice blast disease comprises leaf and panicle blast, which are different in terms of resistance mechanisms. While many blast resistant rice cultivars were bred using genes conferring resistance to only leaf or panicle blast, mining durable and effective quantitative trait loci (QTLs) for both panicle and leaf blast resistance is of paramount importance. In this study, we conducted a pangenome-wide association study (panGWAS) on 9 blast resistance related phenotypes using 414 international diverse rice accessions from an international rice panel. This approach led to the identification of 74 QTLs associated with rice blast resistance. One notable locus, qPBR1, validated in a F4:5 population and fine-mapped in a Heterogeneous Inbred Family (HIF), exhibited broad-spectrum, major and durable blast resistance throughout the growth period. Furthermore, we performed transcriptomic analysis of 3 resistant and 3 sensitive accessions at different time points after infection, revealing 3,311 differentially expressed genes (DEGs) potentially involved in blast resistance. Integration of the above results identified 6 candidate genes within the qPBR1 locus, with no significant negative effect on yield. The results of this study provide valuable germplasm resources, QTLs, blast response genes and candidate functional genes for developing rice varieties with enduring and broad-spectrum blast resistance. The qPBR1, in particular, holds significant potential for breeding new rice varieties with comprehensive and durable resistance throughout their growth period.

International guidelines for intratumoral and intranodal injection of NBTXR3 nanoparticles in head and neck cancers.

An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration. The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections. An independent 3-member reading committee reviewed the recommendations. After two rounds of voting, strong consensus was obtained on all recommendations. Intratumoral and intranodal injection was deemed feasible. NBTXR3 volume calculation, choice of patients, preparation and injection procedure, potential side effects, post injection, and post treatment follow-up were described in detail. Best practices for the injection of NBTXR3 were defined, thus enabling international standardization of intratumoral nanoparticle injection.

Modelling of on-farm greenhouse gas emissions from dual-purpose meat and wool sheep production in different geographical regions of Norway

The whole-farm model, HolosNorSheep, was developed to estimate net greenhouse gas emissions from dual purpose sheep production in Norway. The model adopted a cradle-to-farm gate system boundary and is based on the International Panel on Climate Change methodology and includes direct emissions from enteric and manure methane (CH4; GWP100=27), direct and indirect nitrous oxide (N2O; GWP100=273) from manure and soils, direct carbon dioxide (CO2) emissions from energy use and indirect CO2 emissions from the production of input factors. Soil carbon balance is calculated using the ICBM-model. Emission intensities (CO2-eq/kg product) for sheep carcass and greasy wool, was estimated for five geographical regions of Norway (East, West, South, Mid and North). The geographical regions varied considerably in climate, feed resources, days on pasture and herd/farm management. Estimated emission intensities per kg carcass and greasy wool varied from 23.5 to 19.9 (Mid region) to 26.8 and 22.8 kg CO2-eq (North region) respectively. The difference between the Mid and North region was mainly due to higher CO2 and N2O emissions from use of fuel and N-fertilizer in the North, where a short growth season, and thus reduced grass yields, are compensated by using greater land area. Based on the distribution of sheep in the regions, and the emission intensities in each region, weighted average emission intensities per kg carcass and greasy wool were estimated as 25.1 and 23.3 kg CO2-eq, respectively. Five alternative methods for the allocation of the co-products were compared with the amounts allocated to greasy wool ranging from 0 % when using no allocation (i.e., all emissions allocated to the sheep carcass), 11 % for economic allocation, 12 % for mass allocation, 19 % for biophysical allocation based on energy requirement up to 31 % for allocation based on protein mass. The emission intensity for wool was highly sensitive to the allocation method used (range from 0 to 61 kg CO2-eq per kg greasy wool), while the effect on sheep carcass was lower (range 19 to 28 kg CO2-eq per kg carcass). For production systems where meat is the main product, as in Norway, allocation should be based on biophysical allocation based on energy requirement.

Brachytherapy for rhabdomyosarcoma: Survey of international clinical practice and development of guidelines

Background and purposeThe purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines. Materials and methodsAn international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel’s clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented. ResultsThe survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined. ConclusionsConsensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS).

Social Activities and Risk of Dementia in Community-Dwelling Older People: Gender-Specific Findings From a Prospective Cohort Study.

This study examines thegender-specific associations between a wide range of social activities and dementia risk. A prospective cohort study was conducted involving community-dwelling older Australians (≥70 years) without significant cognitive impairment at enrolment. During the first year of enrolment, we assessed 25 self-reported social activities covering various aspects, including support from relatives and friends, community participation, social interactions with surroundings, and loneliness. Dementia diagnosis followed DSM-IV criteria, adjudicated by an international expert panel. To estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between social activities and dementia, we performed Cox proportional hazards models, adjusting for age, educational attainment, baseline global cognition, and depressive symptoms. Among 9,936 participants who completed all social activity questionnaires (median [IQR] age: 73.4 [71.6-77.1] years; 47.4% men), dementia was diagnosed in 3.8% of men (n = 181/4,705) and 2.6% of women (n = 138/5,231) over a median 6.4 years (IQR: 5.3-7.6, range: 0.2-10.1) follow-up. Gender-specific relationships emerged: caregiving for a person with illness/disability in women (HR: 0.65, 95% CI: 0.42-0.99), and having ≥9 relatives feeling close to call for help in men (HR: 0.56, 95% CI: 0.33-0.96; reference <9 relatives) were associated with reduced dementia risk. Unexpectedly, in women, having ≥5 friends with whom they felt comfortable discussing private matters were associated with a greater dementia risk (HR: 1.69, 95% CI: 1.10-2.59; reference ≤2 friends). Imputed models further identified that babysitting/childminding was associated with lower dementia risk in men (HR: 0.75, 95% CI: 0.56-0.99). No other social activities showed significant associations with dementia. This study provides evidence of social activities influencing dementia risk. Further investigations are required to uncover the mechanisms driving these observed relationships.

The management of heart failure cardiogenic shock: an international RAND appropriateness panel

BackgroundObservational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF.MethodsA 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1–3 as inappropriate, 4–6 as uncertain and as 7–9 appropriate).ResultsOf the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS.ConclusionThis study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines.

French-Language Adaptation of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)

ObjectivesThis study aimed to adapt the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) protocol for perceptual voice assessment to the French language. The primary objective was to achieve consensus among an international panel of voice experts on the content of the adapted protocol. MethodsTo ensure the relevance and robustness of the French CAPE-V protocol, this study employed a systematic Delphi method and involved an international panel primarily comprising speech therapists and lecturers from France and Belgium. The multi-stage process included an initial panel size of 15 experts. Three rounds of online questionnaires, integrating both quantitative and qualitative data collection, were conducted. Participants provided feedback and ratings on various protocol elements until consensus was reached. Adaptations targeted the choice of task stimuli (sustained vowel, sentence reading, semi-spontaneous speech), of the rating scales, and vocal quality terminology. ResultsThe Delphi process achieved consensus on all elements of the adapted CAPE-V protocol. Notably, the sustained vowel task saw consensus in favor of the vowel /a/. Sentence adaptations achieved substantial agreement, with the final set unanimously approved. The simple Visual Analog Scale (VAS) emerged as the preferred rating scale. Agreement on terms for describing vocal qualities marked a crucial step in establishing a shared vocabulary among French-speaking voice experts. ConclusionsThe study successfully adapted the CAPE-V protocol for perceptual voice assessment to the French language through a systematic Delphi process. The final protocol closely resembles the original English version, maintaining its structure and core objectives. Consensus on sustained vowel tasks, sentence adaptations, rating scales, and vocal quality terminology indicates the relevance and robustness of the adapted protocol. Ongoing validation studies in France demonstrate the potential clinical utility of the adapted CAPE-V in French-speaking contexts, representing a significant step toward standardized and validated voice assessment tools for clinicians and researchers globally.

Quality Appraisal in Systematic Literature Reviews of Studies Eliciting Health State Utility Values: Conceptual Considerations.

The increasing number of studies that generate health state utility values (HSUVs) and the impact of HSUVs on cost-utility analyses make a robust tailored quality appraisal (QA) tool for systematic reviews of these studies necessary. This study aimed to address conceptual issues regarding QA in systematic reviews of studies eliciting HSUVs by establishing a consensus on the definitions, dimensions and scope of a QA tool specific to this context. A modified Delphi method was used in this study. An international multidisciplinary panel of seven experts was purposively assembled. The experts engaged in two anonymous online survey rounds. After each round, the experts received structured and controlled feedback on the previous phase. Controlled feedback allowed the experts to re-evaluate and adjust their positions based on collective insights. Following these surveys, a virtual face-to-face meeting was held to resolve outstanding issues. Consensus was defined a priori at all stages of the modified Delphi process. The response rates to the first-round and second-round questionnaires and the virtual consensus meeting were 100%, 86% and 71%, respectively. The entire process culminated in a consensus on the definitions of scientific quality, QA, the three QA dimensions-reporting,relevance and methodologicalquality-and the scope of a QA tool specific to studies that elicit HSUVs. Achieving this consensus marks a pivotal step towards developing a QA tool specific to systematic reviews of studies eliciting HSUVs. Future research will build on this foundation, identify QA items, signalling questions and response options, and develop a QA tool specific to studies eliciting HSUVs.

Treatment of Multiple Sclerosis with Cladribine Tablets: Literature Review and the Guidance of the Lithuanian Association of Neurologists

Cladribine is a disease-modifying drug used for the treatment of the highly active relapsing-remitting form of multiple sclerosis. Cladribine is a purine nucleoside analogue which selectively targets lymphocyte subpopulations involved in the pathogenesis of multiple sclerosis, and therefore it is classified as an immune reconstitution therapy drug. Two short courses of cladribine tablets given over two years significantly reduce the multiple sclerosis relapse rate and disability progression. For most patients, the effect persists in the third and the fourth year. This makes cladribine convenient for patients with multiple comorbidities, difficulties in adhering to their prescribed treatment regimen, those planning a pregnancy, or those for whom long-term immunosuppression is undesirable. Cladribine tablets are denoted by good safety characteristics, with the most prominent adverse effect being lymphopenia, which does not lead to an increased risk of infections other than Herpes zoster.However, in clinical practice, there are a number of issues related both to the initial administration of cladribine tablets and the strategy of treatment in different clinical situations during the first-to-fourth years of treatment, and particularly after the fourth year. Although there are no contraindications for additional courses of cladribine tablets, the product information does not provide detailed guidance on their continued use. During more than five years after the approval of the medicinal product, the new clinical trial data and the Real-World Evidence (RWE) on the efficacy and safety of cladribine tablets have become available, based on which, several national and international expert panels, as well as the Lithuanian Association of Neurologists, have issued guidance on the use of cladribine tablets reviewed in this article. Upon reactivation of the disease, additional courses of cladribine tablets or other disease-modifying therapies may be prescribed, depending on various factors related to the severity of the relapse, patient characteristics, and previously used medications. If the patient’s condition remains stable after the fourth year, extension of the treatment-free period with the structured monitoring approach could be appropriate.

Advancing Expertise in the Understanding of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Masterclass Event Summary

A masterclass initiated, organised, and funded by UCB, sought to advance understanding and expertise of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). MOGAD is a rare central nervous system (CNS) inflammatory disorder. It has only relatively recently been characterised as a separate entity to similar demyelinating conditions, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Differentiating MOGAD from MS and NMOSD can be challenging, but is essential to ensure a correct diagnosis in order to guide effective treatment and management. An increase in the availability of cell-based assays (CBA) for detection of autoantibodies directed against myelin oligodendrocyte glycoprotein (MOG) over the last decade has provided healthcare professionals with an important new diagnostic tool. However, the approach has limitations in terms of sensitivity and specificity, meaning results must be considered alongside clinical characteristics and neuroimaging. A proposed diagnostic pathway by the international MOGAD panel, published in March 2023, sets out the core clinical demyelinating events that could suggest MOGAD, when MOG-IgG testing may be appropriate, and when supporting clinical or MRI features are required to confirm a diagnosis. These consensus criteria are now being evaluated by centres around the world. This article will summarise the talks given by key opinion leaders from across Europe and the USA during the educational event. They discussed the pathology and presentation of MOGAD, how to integrate imaging into diagnostic pathways, and current management approaches. They also looked at possible future directions, in terms of novel treatment approaches.

Evaluation of the Vitek 2 system for antifungal susceptibility testing of Candida auris using a representative international panel of clinical isolates: overestimation of amphotericin B resistance and underestimation of fluconazole resistance.

Although the Vitek 2 system is broadly used for antifungal susceptibility testing of Candida spp., its performance against Candida auris has been assessed using limited number of isolates recovered from restricted geographic areas. We therefore compared Vitek 2 system with the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method using an international collection of 100 C. auris isolates belonging to different clades. The agreement ±1 twofold dilution between the two methods and the categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints and Vitek 2-specific wild-type upper limit values (WT-ULVs) were determined. The CLSI-Vitek 2 agreement was poor for 5-flucytosine (0%), fluconazole (16%), and amphotericin B (29%), and moderate for voriconazole (61%), micafungin (67%), and caspofungin (81%). Significant interpretation errors were recorded using the CDC breakpoints for amphotericin B (31% CA, 69% major errors; MaEs) and fluconazole (69% CA, 31% very major errors; VmEs), but not for echinocandins (99% CA, 1% MaEs for both micafungin and caspofungin) for which the Vitek 2 allowed correct categorization of echinocandin-resistant FKS1 mutant isolates. Discrepancies were reduced when the Vitek 2 WT-ULV of 16 mg/L for amphotericin B (98% CA, 2% MaEs) and of 4 mg/L for fluconazole (96% CA, 1% MaEs, 3% VmEs) were used. In conclusion, the Vitek 2 system performed well for echinocandin susceptibility testing of C .auris. Resistance to fluconazole was underestimated whereas resistance to amphotericin B was overestimated using the CDC breakpoints of ≥32 and ≥2 mg/L, respectively. Vitek 2 minimun inhibitory concentrations (MICs) >4 mg/L indicated resistance to fluconazole and Vitek 2 MICs ≤16 mg/L indicated non-resistance to amphotericin B.

Equity zombies in Canada’s blue economy: a critical feminist analysis for equitable policy implementation

IntroductionOcean equity is a key aim of blue economy frameworks globally and is a pillar of the international High Level Panel for A Sustainable Ocean Economy. However, the Panel offers only a general definition of ocean equity, with limited guidance for countries. Canada, as a party to the High Level Panel’s blue economy agenda, is developing its own blue economy strategy, seeking to reshape its ocean-based industries and advocate for new ones. How equity will be incorporated across scales is not yet known but has implications for how countries like Canada will develop their ocean-based industries. This raises important questions, including what are Canada’s equity commitments in relation to its blue economy and how will they be met? Currently, the industries identified in Canada’s emerging blue economy narratives are governed through both federal and provincial legislation and policies. These will shape how equity is implemented at different scales.MethodsIn this paper, we examine how the term equity is defined in relevant federal and provincial legislation and look to how understandings of equity found in critical feminist, environmental justice, and climate justice scholarship could inform policy and its implementation within Canada’s blue economy. We focus on two industries that are important for Canada’s blue economy: offshore oil and marine salmon aquaculture in the Canadian province of Newfoundland and Labrador. We investigate how existing legislation and policy shapes the characterization, incorporation, and implementation of equity in these industries.Results and discussionOur analysis highlights how a cohesive approach to ocean equity across the scales of legislation and policy is needed to ensure more robust engagement with social and environmental equity issues in blue economy discourse and implementation.

Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients

BackgroundAcquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. MethodsCREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5–2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. ResultsRecruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL−1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). ConclusionCyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FundingFrench Ministry of Health.ClinicalTrials.gov number: NCT01808911.

Adapting prescribing criteria for amyloid-targeted antibodies for adults with Down syndrome.

Prior authorization criteria for Federal Drug Administration (FDA) approved immunotherapeutics, among the class of anti-amyloid monoclonal antibodies (mAbs), established by state drug formulary committees, are tailored for adults with late-onset Alzheimer's disease. This overlooks adults with Down syndrome (DS), who often experience dementia at a younger age and with different diagnostic assessment outcomes. This exclusion may deny DS adults access to potential disease-modifying treatments. To address this issue, an international expert panel convened to establish adaptations of prescribing criteria suitable for DS patients and parameters for access to Centers for Medicare & Medicaid Services (CMS) registries. The panel proposed mitigating disparities by modifying CMS and payer criteria to account for younger onset age, using alternative language and assessment instruments validated for cognitive decline in the DS population. The panel also recommended enhancing prescribing clinicians' diagnostic capabilities for DS and initiated awareness-raising activities within healthcare organizations. These efforts facilitated discussions with federal officials, aimed at achieving equity in access to anti-amyloid immunotherapeutics, with implications for national authorities worldwide evaluating these and other new disease-modifying therapeutics for Alzheimer's disease.

Mortality of the Danish Nationwide AQP4 Antibody-Seropositive Neuromyelitis Optica Spectrum Disorder Patient Cohort.

We aimed to evaluate the mortality of patients with AQP4 antibody-seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) in Denmark compared with that in the general population. We identified patients with AQP4-Ab+ NMOSD fulfilling the 2015 International Panel for Neuromyelitis Optica Diagnosis (IPND) criteria from multiple sources (laboratories and the Danish Multiple Sclerosis Registry). We obtained detailed information about patients from hospital records and about the general population matched on age, sex, and calendar year from Statistics Denmark. We calculated standardized mortality ratio (SMR), excess number of deaths per 1,000 person-years (EDR), and life expectancies compared with those of the matched general population. We examined predictive factors of mortality and the cause of death. Of 66 patients with AQP4-Ab+ NMOSD between 2008 and 2020, 15 died. Overall, the SMR was 2.54 (95% CI 1.47-4.09), and the EDR was 16.8 (95% CI 4.6-34.3). The median life expectancy for patients with AQP4-Ab+ NMOSD was 64.08 years (95% CI 53.02-83.9), compared with 83.07 years for the general population. Risk of death over time was increased in the patient population with a hazard ratio (HR) of 2.22 (1.34-3.68; p = 0.002). The cause of death was directly related to NMOSD in 93% of the cases. The age at disease onset was an independent predictor of death (HR 1.042; 95% CI 1.006-1.079; p = 0.02). AQP4-Ab+ NMOSD is associated with increased mortality and shorter life expectancy compared with that in the general population, underlining the need for highly effective treatment approaches.

Can successful female STEM graduates contribute to narrowing the gender pay gap in the EU?

AbstractDrawing upon contemporary research, this paper examines whether there is a relationship of STEM (science, technology, engineering and maths) bachelor and master graduates to the gender pay gap (GPG) in the 27 EU Member states in 2013–2020 using a novel cross‐sectional data set based on the 2013 International Standard Classification of Education (ISCED). International panel data were analysed with the dynamic modelling fixed effects method and compared with the results received from the cross‐sectional analysis executed with the help of Bayesian model averaging methods. Our findings suggest that STEM education plays a significant role in forming the GPG. We can see a negative, robust and statistically significant effect of bachelor‐ and master‐level female STEM graduates on the GPG and a positive statistically significant effect of bachelor‐ and master‐level male STEM graduates on the GPG. The permanently lower women‐to‐men ratio in STEM education and those employed in high‐end sectors of science and technology can be one of the drivers of the persistent GPG in developed countries.

Vasa previa in singleton pregnancies: diagnosis and clinical management based on an international expert consensus

BackgroundThere are limited data to guide the diagnosis and management of vasa previa. Currently, what is known is largely based on case reports or series and cohort studies. Objective(s): To systematically collect and classify expert opinions and achieve consensus on the diagnosis and clinical management of vasa previa using focus group discussions (FGD) and a Delphi technique. Study DesignA four-round FGD and a three-round Delphi survey of an international panel of experts on vasa previa were conducted. Experts were selected based on their publication record on vasa previa. First, we convened an FGD panel of 20 experts and agreed on which issues were unresolved in the diagnosis and management of vasa previa. A three-round anonymous electronic survey was then sent to the full expert panel. Survey questions were presented on the diagnosis and management of vasa previa that the experts were asked to rate on a 5-point Likert scale (from strongly disagree = 1 to strongly agree = 5). Consensus was defined as a median score of 5. Following responses to each round, any statements that had median scores of 3 or less were deemed to have had no consensus and excluded. Statements with a median score of 4 were revised and re-presented to the experts in the next round. Consensus and non-consensus statements were then aggregated. ResultsSixty-eight international experts were invited to participate in the study, of which 57 participated. Experts were from 13 countries on five continents and have contributed to over 80% of published cohort studies on vasa previa, as well as national and international society guidelines. Completion rates were 84%, 93%, 91% for the first, second, and third rounds, respectively, and 71% completed all three rounds. The panel reached a consensus on 26 statements regarding the diagnosis and key points of management of vasa previa, including: 1) While there is no agreement on a distance between the fetal vessels and the cervical internal os to define vasa previa, the definition should not be limited to a 2 cm distance; 2) All pregnancies should be screened for vasa previa with routine examination for placental cord insertion and a color Doppler sweep of the region over the cervix at the second-trimester anatomy scan; 3) When a low-lying placenta or placenta previa is found in the second trimester, a transvaginal ultrasound with Doppler should be performed at around 32 weeks to rule out vasa previa; 4) Outpatient management of asymptomatic patients without risk factors for preterm birth is reasonable; 5)Asymptomatic patients with vasa previa should be delivered by scheduled cesarean between 35- and 37-weeks of gestation; and 6) There was no agreement on routine hospitalization, avoidance of intercourse, or use of 3-dimensional ultrasound for diagnosis of vasa previa. ConclusionsThrough FGD and a Delphi process, an international expert panel reached consensus on the definition, screening, clinical management, and timing of delivery in vasa previa, which could inform the development of new clinical guidelines.

PRECISE Version 2: Updated Recommendations for Reporting Prostate Magnetic Resonance Imaging in Patients on Active Surveillance for Prostate Cancer

Background and objectiveThe Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations standardise the reporting of prostate magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer. An international consensus group recently updated these recommendations and identified the areas of uncertainty. MethodsA panel of 38 experts used the formal RAND/UCLA Appropriateness Method consensus methodology. Panellists scored 193 statements using a 1–9 agreement scale, where 9 means full agreement. A summary of agreement, uncertainty, or disagreement (derived from the group median score) and consensus (determined using the Interpercentile Range Adjusted for Symmetry method) was calculated for each statement and presented for discussion before individual rescoring. Key findings and limitationsParticipants agreed that MRI scans must meet a minimum image quality standard (median 9) or be given a score of ‘X’ for insufficient quality. The current scan should be compared with both baseline and previous scans (median 9), with the PRECISE score being the maximum from any lesion (median 8). PRECISE 3 (stable MRI) was subdivided into 3-V (visible) and 3-NonV (nonvisible) disease (median 9). Prostate Imaging Reporting and Data System/Likert ≥3 lesions should be measured on T2-weighted imaging, using other sequences to aid in the identification (median 8), and whenever possible, reported pictorially (diagrams, screenshots, or contours; median 9). There was no consensus on how to measure tumour size. More research is needed to determine a significant size increase (median 9). PRECISE 5 was clarified as progression to stage ≥T3a (median 9). Conclusions and clinical implicationsThe updated PRECISE recommendations reflect expert consensus opinion on minimal standards and reporting criteria for prostate MRI in AS.

Codesign of Lynch ChoicesTM : Using implementation science to create a clinically deliverable patient decision support website to transform cancer genetics care pathways.

Resources including Patient Decision Aids (PtDA) are useful and valued by patients and clinicians to provide information and complement shared decision-making. Despite their promise, few PtDA exist for patients with genetic cancer susceptibility facing difficult decisions about risk management. We aimed to fill this gap, partnering with patients to codesign Lynch ChoicesTM , a PtDA website for families with Lynch Syndrome. In addition to a Patient Reference Panel, we purposively invited an international stakeholder panel including charities, public bodies, clinical and academic experts. Implementation strategies and frameworks were employed to optimise translation of research findings to improve care. Patient/stakeholder suggestions were incorporated in a transparent Table of Changes and prioritised using the Person-Based Approach throughout planning and codesign of Lynch ChoicesTM . An interactive stakeholder meeting was convened to identify barriers and facilitators to clinical implementation of the PtDA. Patient and stakeholder partnerships drove the direction of the research throughout codesign, resulting in several iterative refinements to the PtDA prior to roll out including the addition of illustrations/videos, clearer presentation of cancer risks and increased accessibility for lower literacy. Barriers and facilitators identified from stakeholders were used to create an implementation process map. Creating an effective, engaging PtDA is not enough. Systematic uptake in real world clinical practice, with its resource limitations, is needed to optimise benefit to patients and clinicians. Assessment of speed and breadth of dissemination and usage will be collected to further evidence the benefit of embedding implementation science methods from the outset to translate research findings into clinical practice.