Care Research Research Articles

Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants.

A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17-85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOE genotype had negligible impact on cognitive performance. Different cognitive domains had distinct genetic architectures, with one indicating brain region-specific activation of microglia and another with glycogen metabolism. Thus, the molecular and cellular mechanisms underpinning cognition are distinct from dementia risk loci, presenting different targets to slow down age-related cognitive decline. Participants can now be recalled stratified by genotype and cognitive phenotype for natural history and interventional studies of neurodegenerative and other disorders.

The times are changing: A primer on novel clinical trial designs and endpoints in critical care research.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Heterogeneity, Bayesian thinking, and phenotyping in critical care: A primer.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To familiarize clinicians with the emerging concepts in critical care research of Bayesian thinking and personalized medicine through phenotyping and explain their clinical relevance by highlighting how they address the issues of frequent negative trials and heterogeneity of treatment effect. The past decades have seen many negative (effect-neutral) critical care trials of promising interventions, culminating in calls to improve the field's research through adopting Bayesian thinking and increasing personalization of critical care medicine through phenotyping. Bayesian analyses add interpretive power for clinicians as they summarize treatment effects based on probabilities of benefit or harm, contrasting with conventional frequentist statistics that either affirm or reject a null hypothesis. Critical care trials are beginning to include prospective Bayesian analyses, and many trials have undergone reanalysis with Bayesian methods. Phenotyping seeks to identify treatable traits to target interventions to patients expected to derive benefit. Phenotyping and subphenotyping have gained prominence in the most syndromic and heterogenous critical care disease states, acute respiratory distress syndrome and sepsis. Grouping of patients has been informative across a spectrum of clinically observable physiological parameters, biomarkers, and genomic data. Bayesian thinking and phenotyping are emerging as elements of adaptive clinical trials and predictive enrichment, paving the way for a new era of high-quality evidence. These concepts share a common goal, sifting through the noise of heterogeneity in critical care to increase the value of existing and future research. The future of critical care medicine will inevitably involve modification of statistical methods through Bayesian analyses and targeted therapeutics via phenotyping. Clinicians must be familiar with these systems that support recommendations to improve decision-making in the gray areas of critical care practice.

Differential Privacy Protections in 2020 U.S. Decennial Census Data Do Not Impede Measurement of Racial and Ethnic Disparities.

Census data are vital to health care research but must also protect respondents' confidentiality. The 2020 decennial Census employs a new Differential Privacy framework; this study examines its effect on the accuracy of an important tool for measuring health disparities, the Bayesian Improved Surname and Geocoding (BISG) algorithm, which uses Census Block Group data to estimate race and ethnicity when self-reported data are unavailable. Using self-reported race and ethnicity data as our standard, we compared the accuracy of BISG estimates calculated using the original 2010 Census counts to the accuracy of estimates calculated using 2010 data but with 2020 Differential Privacy in place. The Differential Privacy methodology slightly decreases BISG accuracy for American Indian and Alaska Native people but has little effect for other groups, suggesting that the methodology will not impede health disparities research that employs BISG and similar methods.

The use of artificial neural networks and decision trees: Implications for health-care research

Abstract The use of decision trees and artificial neural networks (ANNs) in health-care research is widespread, as they enable health-care providers with the tools they need to make better medical decisions with their patients. ANNs specifically are extremely helpful in predictive research as they can provide investigators with knowledge about future trends and patterns. However, a major downside to ANNs is their lack of interpretability. Understandability of the model is important as it ensures the outcomes are true to the dataset’s original labels and are not impacted by algorithmic bias. In comparison, decision trees map out their entire process before providing the results, which leads to a higher level of trust in the model and the conclusions it supplies the investigators with. This is essential as many historical datasets lack equal and fair representation of all races and sexes, which might directly correlate to a lesser treatment given to females and individuals in minority groups. Here, we review existing work around the differences and connections between ANNs and decision trees with implications for research in health care.

Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia

IntroductionA significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and...

Palliative Care Research and Clinical Practice Priorities in the United States as Identified by an Interdisciplinary Modified Delphi Approach.

Background: Palliative care demands in the United States are growing amid a comparatively small workforce of palliative care clinicians and researchers. Therefore, determining research and clinical practice priorities is essential for streamlining initiatives to advance palliative care science and practice. Objectives: To identify and rank palliative care research and clinical practice priority areas through expert consensus. Design: Using a modified Delphi method, U.S. palliative care experts identified and ranked priority areas in palliative care research and clinical practice. Priorities were thematically grouped and analyzed for topic content and frequency; univariate analysis used the median of each priority item ranking, with a cutoff median of ≤8 indicating >76% agreement for an item's ranking. Results: In total, 27 interdisciplinary pediatric and adult palliative care experts representing 19 different academic institutions and medical centers participated in the preliminary survey and the first Delphi round, and 22 participated in the second Delphi round. The preliminary survey generated 78 initial topics, which were developed into 22 priority areas during the consensus meeting. The top five priorities were (1) access to palliative care, (2) equity in palliative care, (3) adequate financing of palliative care, (4) provision of palliative care in primary care settings, and (5) palliative care workforce challenges. Conclusions: These expert-identified priority areas provide guidance for researchers and practitioners to develop innovative models, policies, and interventions, thereby enriching the quality of life for those requiring palliative care services.

Palliative care interventional research in general practice: a narrative review of factors affecting research conduct.

The majority of palliative care provision occurs in general practice, yet only 9% of palliative care clinical trials were conducted in this setting. Evidence from hospital and specialist settings is not readily transferable to general practice, as the population, context and care processes are vastly different. Conducting interventional palliative care research in general practice settings is subject to many challenges and barriers. This narrative review aims to describe the factors influencing the conduct of interventional research in general practice settings for patients with palliative care needs. A narrative review was performed to identify factors affecting the conduct of palliative care interventional studies in general practice. A literature search of MEDLINE was conducted on 26 September 2023, and data were synthesised utilising a narrative approach. Sixteen articles were identified. Five thematic groupings were identified from the literature that affected the interventions: factors related to health care professionals (HCPs), patients and carers, general practices, health systems, and research design. HCPs and practices were focused on providing clinical care and struggled to incorporate research into their workload. Staff and patients often had negative perceptions in palliative care combined with limited research experience, often resulting in unwillingness to engage in interventions and gatekeeping. Engaging with general practice staff to design, participate and champion research were key facilitators of successful interventions. Palliative care interventions in general practice are invariably complex and challenging, yet acutely needed to address the care needs of patients in the community setting. Working together with patients, carers and clinicians to design and implement interventions appropriate for general practice settings is fundamental to their success.

Person-centred care (PCC) research in Ghana: a scoping review protocol

IntroductionPerson-centred care (PCC) is provision of care that is respectful of and responsive to individual patient preferences, needs and values, and ensures that patient values guide all clinical decisions. While...

Understanding engagement in diet and dementia prevention research among British South Asians: a short report of findings from a patient and public involvement group.

Dementia is a global public health challenge. Evidence suggests that individuals from South Asian communities are an at-risk group for dementia, partly as a result of early and cumulative exposure to known dementia risk factors, such as obesity and type 2 diabetes. There needs to be more culturally appropriate community engagement to increase awareness of dementia and identify better strategies to encourage participation in dementia-related research. We aimed to better understand the barriers and facilitators towards engaging with, and participating in, diet and dementia related research among British South Asians. This was achieved using a public and patient involvement (PPI) approach. A community-based, engagement event involving information sharing from experts and roundtable discussions with South Asian communities (n = 26 contributors) was held in June 2023 in Newcastle-upon-Tyne, UK. Collaboration from preidentified PPI representatives (n = 3) informed the content and structure of PPI activities, as well as recruitment. Data were synthesised using template analysis, a form of codebook thematic analysis. This involved deductively analysing data using relevant a priori themes, which were expanded upon, or modified, via inductive analysis. The findings highlighted the importance of trust, representation and appreciation of cultural barriers as facilitators to engagement in diet and dementia risk reduction research. Consideration of language barriers, time constraints, social influences and how to embed community outreach activities were reported as driving factors to maximise participation. This PPI work will inform the design and co-creation of a culturally adapted dietary intervention for brain health in accordance with the Medical Research Council and National Institute for Health and Care Research guidance for developing complex interventions.

Development of family resource indicators for people with schizophrenic disorder in community by modified Delphi method in Beijing, China

IntroductionMost people with schizophrenia in China are supported by their family members in community. The patient’s family is confronted with severe care burden and pressure, which directly affects the caregiver’s...

Classification of Documented Goals of Care Among Hospitalized Patients with High Mortality Risk: a Mixed-Methods Feasibility Study.

The ability to classify patients' goals of care (GOC) from clinical documentation would facilitate serious illness communication quality improvement efforts and pragmatic measurement of goal-concordant care. Feasibility of this approach remains unknown. To evaluate the feasibility of classifying patients' GOC from clinical documentation in the electronic health record (EHR), describe the frequency and patterns of changes in patients' goals over time, and identify barriers to reliable goal classification. Retrospective, mixed-methods chart review study. Adults with high (50-74%) and very high (≥ 75%) 6-month mortality risk admitted to three urban hospitals. Two physician coders independently reviewed EHR notes from 6months before through 6months after admission to identify documented GOC discussions and classify GOC. GOC were classified into one of four prespecified categories: (1) comfort-focused, (2) maintain or improve function, (3) life extension, or (4) unclear. Coder interrater reliability was assessed using kappa statistics. Barriers to classifying GOC were assessed using qualitative content analysis. Among 85 of 109 (78%) patients, 338 GOC discussions were documented. Inter-rater reliability was substantial (75% interrater agreement; Cohen's kappa = 0.67; 95% CI, 0.60-0.73). Patients' initial documented goal was most frequently "life extension" (N = 37, 44%), followed by "maintain or improve function" (N = 28, 33%), "unclear" (N = 17, 20%), and "comfort-focused" (N = 3, 4%). Among the 66 patients whose goals' classification changed over time, most changed to "comfort-focused" goals (N = 49, 74%). Primary reasons for unclear goals were the observation of concurrently held or conditional goals, patient and family uncertainty, and limited documentation. Clinical notes in the EHR can be used to reliably classify patients' GOC into discrete, clinically germane categories. This work motivates future research to use natural language models to promote scalability of the approach in clinical care and serious illness research.

Considerations of quality: examining theoretical perspectives informing infant and toddler pedagogy in Aotearoa/New Zealand

ABSTRACT With the growing participation of infants and toddlers in group care settings ongoing examination and research into what constitutes quality education and care for this age group is paramount. Theories and approaches espoused in Aotearoa/New Zealand’s mandated early childhood curriculum Te Whāriki: He whāriki mātauranga mo ngā mokopuna o Aotearoa. Early childhood curriculum (Ministry of Education, 2017) were examined to ascertain how they could inform quality pedagogy and practice with infants and toddlers. The research used an integrative literature review methodology to investigate the theoretical underpinnings of this curriculum and how these aligned to quality pedagogy for infants and toddlers. Evidence emerging from the research found many similarities between the pedagogical practices related to each theory and alignment with quality experiences for infants and toddlers. Moving forward it is suggested that an increased depth of knowledge of theories and their relationship to pedagogy for infants and toddlers would enhance teaching practice. The review also recommends that further research should be undertaken into how kaiako conceptualise and enact educational theory in infant and toddler ECEC settings.

Abstract PO5-05-14: Survival in Young Women with De Novo or Recurrent Metastatic Breast Cancer

Abstract Background. Approximately 12,000 women aged 40 years or younger are diagnosed with breast cancer every year in the United States alone. Limited data exist regarding survival in young women with metastatic breast cancer (MBC), particularly when considering modern tumor subtyping and treatment, though previous studies have suggested that patients presenting with MBC at diagnosis (de novo stage IV) have better prognosis than those who develop recurrent MBC after initial diagnosis of stage 0-III disease. We sought to determine survival rates in young patients with MBC stratified by disease presentation (de novo versus recurrent) and subtype. Methods. The Young Women’s Breast Cancer Study (YWS) is a multicenter, prospective cohort which enrolled 1,302 women diagnosed with stage 0-IV breast cancer at age ≤40 from 13 North American academic and community-based sites from 2006-2016. The current median follow-up is 10.1 (range 0.4-16.3) years. Histopathology slides were centrally reviewed for 97% of the participants, and clinical tumor molecular subtypes have been detailed. In the recurrent group, receptors were obtained from the initial breast surgery. Descriptive analyses were used to characterize patients with de novo or recurrent MBC, including demographic and disease characteristics, and survival rates. Overall survival was estimated using the Kaplan-Meier method and compared by log-rank test between those who presented with de novo and relapsed disease overall and within tumor subtypes. Results. Among 246 patients included in this analysis, 74.0% (n=182) had recurrent MBC and 26.0% (n=64) had de novo MBC. Most patients were white (n=208, 84.6%), while 6.9% were Asian (n=17), 4.5% Black (n=11), 0.8% Native American (n=2), 0.8% multiracial (n=2) and 2.4% other/unknown (n=6). A total of 4.5% of patients were Hispanic (n=11). Median age at diagnosis of de novo MBC was 37 years and 40 years for diagnosis of metastasis in the recurrent group. Median disease-free interval was 3.23 (range 0.32 – 13.84) years for the recurrent MBC group. Among all patients with MBC, most (55.7%, n=137) had estrogen receptor (ER) and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, whereas 17.9% (n=44) had ER and/or PR-positive HER2-positive, 7.3% (n=18) had ER/PR-negative HER2-positive, and 18.7% (n=46) had triple-negative tumors. A greater proportion of participants (43.8%, n=28) had HER2-positive disease in the de novo group than in the recurrent group (18.7%, n=34), P=< 0.0001. A total of 10.9% (n=7) of de novo patients had a germline BRCA mutation, compared to 13.7% (n=25) in the recurrent group. Median survival was 5.09 (95% CI: 3.74 – 6.38) years in the de novo group and 2.63 (95% CI: 1.98 – 3.21) years in the recurrent MBC group (P=0.0004). When stratifying by subtype, survival among patients with de novo ER and/or PR-positive HER2-positive disease was longer than among patients with recurrent disease (P=0.0149), whereas there were no statistically significant differences in survival between the de novo and recurrent disease groups in other disease subtypes (Table 1). Conclusion. Survival in young women with MBC is highly heterogeneous and varies substantially by tumor subtype and disease presentation. Those with de novo ER and/or PR-positive HER2-positive subtype appear to have better outcomes than those with recurrent MBC with the same subtype. These findings can inform patient care and potential future research to improve outcomes for young patients with MBC. Table 1: Median survival by disease presentation and subtype * 1 patient with recurrent MBC was not included because the initial diagnosis was DCIS MBC: metastatic breast cancer; OS: overall survival; CI: confidence interval; ER: estrogen receptor; PR: progesterone receptor; HER2: human epidermal growth factor receptor 2 Citation Format: Leticia Varella, Yue Zheng, Shoshana Rosenberg, Gregory Kirkner, Craig Snow, Kathryn Ruddy, Rulla Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia Borges, Steven Come, Laura Collins, Ellen Warner, Kate Dibble, Eric Winer, Ann Partridge. Survival in Young Women with De Novo or Recurrent Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-14.

Pitfalls and possibilities of using Root SedLine for continuous assessment of EEG waveforms-based metrics in intensive care research.

The Root SedLine Device is used for continuous electroencephalography (cEEG) based sedation monitoring in intensive care patients. The cEEG traces can be collected for further processing and calculation of relevant metrics not already provided. Depending on the device settings during acquisition, the acquired traces may be distorted by max/min values cropping or high digitization error. We aimed to systematically assess the impact of those distortions on metrics used for clinical research in the field of neuromonitoring.
Approach: A 16h cEEG acquired using the Root SedLine Device at the optimal screen settings was analyzed. Cropping and digitization error effects were simulated by consecutive reduction of the maximum cEEG amplitude by 2µV or by reducing the vertical resolution. Metrics were calculated within ICM+ using minute-by-minute data including total power, alpha delta ratio, and 95% spectral edge frequency. Data were analyzed by creating violin-plots or box-plots.
Main Results: Cropping led to a continuous reduction in total and band power leading to corresponding changes in variability thereof. Relative power and alpha delta ratio were less affected. Changes in resolution led to relevant changes. While total power and power of low frequencies were rather stable, power of higher frequencies increased with reducing resolution. 
Significance: Care must be taken when acquiring and analyzing cEEG waveforms from Root SedLine for clinical research. In order to retrieve good quality metrics, the screen settings must be kept within the central vertical scale while pre-processing techniques must be applied to exclude unacceptable periods.
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Progress towards universal health coverage and inequalities in infant mortality: an analysis of 4·1 million births from 60 low-income and middle-income countries between 2000 and 2019

Expanding universal health coverage (UHC) might not be inherently beneficial to poorer populations without the explicit targeting and prioritising of low-income populations. This study examines whether the expansion of UHC between 2000 and 2019 is associated with reduced socioeconomic inequalities in infant mortality in low-income and middle-income countries (LMICs). We did a retrospective analysis of birth data compiled from Demographic and Health Surveys (DHSs). We analysed all births between 2000 and 2019 from all DHSs available for this period. The primary outcome was infant mortality, defined as death within 1 year of birth. Logistic regression models with country and year fixed effects assessed associations between country-level progress to UHC (using WHO's UHC service coverage index) and infant mortality (overall and by wealth quintile), adjusting for infant-level, mother-level, and country-level variables. A total of 4 065 868 births to 1 833 011 mothers were analysed from 177 DHSs covering 60 LMICs between 2000 and 2019. A one unit increase in the UHC index was associated with a 1·2% reduction in the risk of infant death (AOR 0·988, 95% CI 0·981-0·995; absolute measure of association, 0·57 deaths per 1000 livebirths). An estimated 15·5 million infant deaths were averted between 2000 and 2019 because of increases in UHC. However, richer wealth quintiles had larger associated reductions in infant mortality from UHC (quintile 5 AOR 0·983, 95% CI 0·973-0·993) than poorer quintiles (quintile 1 0·991, 0·985-0·998). In the early stages of UHC, UHC expansion was generally beneficial to poorer populations (ie, larger reductions in infant mortality for poorer households [infant deaths per 1000 per one unit increase in UHC coverage: quintile 1 0·84 vs quintile 5 0·59]), but became less so as overall coverage increased (quintile 1 0·64 vs quintile 5 0·57). Since UHC expansion in LMICs appears to become less beneficial to poorer populations as coverage increases, UHC policies should be explicitly designed to ensure lower income groups continue to benefit as coverage expands. UK National Institute for Health and Care Research.

Assessing the impact of Canadian primary care research and researchers: Citation analysis.

To describe the citation impact and characteristics of Canadian primary care researchers and research publications. Citation analysis. Canada. A total of 266 established Canadian primary care researchers. The 50 most cited primary care researchers in Canada were identified by analyzing data from the Scopus database. Various parameters, including the number of publications and citations, research themes, Scopus h index, content analysis, journal impact factors, and field-weighted citation impact for their publications, were assessed. Information about the characteristics of these researchers was collected using the Google search engine. On average, the 50 most cited primary care researchers produced 51.1 first-author publications (range 13 to 249) and were cited 1864.32 times (range 796 to 9081) over 29 years. Twenty-seven publications were cited more than 500 times. More than half of the researchers were men (60%). Most were clinician scientists (86%) with a primary academic appointment in family medicine (86%) and were affiliated with 5 universities (74%). Career duration was moderately associated with the number of first-author publications (0.35; P=.013). Most research focused on family practice, while some addressed health and health care issues (eg, continuing professional education, pharmaceutical policy). Canada is home to a cadre of primary care researchers who are highly cited in the medical literature, suggesting that their work is of high quality and relevance. Building on this foundation, further investments in primary care research could accelerate needed improvements in Canadian primary care policy and practice.

The association between disability and mortality: a mixed-methods study

Globally, 1·3 billion people have a disability and are more likely to experience poor health than the general population. However, little is known about the mortality or life expectancy gaps experienced by people with disabilities. We aimed to undertake a systematic review and meta-analysis of the association between disability and mortality, compare these findings to the evidence on the association of impairment types and mortality, and model the estimated life expectancy gap experienced by people with disabilities. We did a mixed-methods study, which included a systematic review and meta-analysis, umbrella review, and life expectancy modelling. For the systematic review and meta-analysis, we searched MEDLINE, Global Health, PsycINFO, and Embase for studies published in English between Jan 1, 2007, and June 7, 2023, investigating the association of mortality and disability. We included prospective and retrospective cohort studies and randomised controlled trials with a baseline assessment of disability and a longitudinal assessment of all-cause mortality or cause-specific mortality. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. We did a random-effects meta-analysis to calculate a pooled estimate of the mortality rate ratio for people with disabilities compared with those without disabilities. We did an umbrella review of meta-analyses examining the association between different impairment types and mortality. We used life table modelling to translate the mortality rate ratio into an estimate of the life expectancy gap between people with disabilities and the general population. The systematic review and meta-analysis is registered with PROSPERO, CRD42023433374. Our search identified 3731 articles, of which 42 studies were included in the systematic review. The meta-analysis included 31 studies. Pooled estimates showed that all-cause mortality was 2·24 times (95% CI 1·84-2·72) higher in people with disabilities than among people without disabilities, although heterogeneity between the studies was high (τ2=0·28, I2=100%). Modelling indicated a median gap in life expectancy of 13·8 years (95% CI 13·1-14·5) by disability status. Cause-specific mortality was also higher for people with disabilities, including for cancer, COVID-19, cardiovascular disease, and suicide. The umbrella review identified nine meta-analyses, which showed consistently elevated mortality rates among people with different impairment types. Mortality inequities experienced by people with disabilities necessitate health system changes and efforts to address inclusion and the social determinants of health. National Institute for Health and Care Research, Rhodes Scholarship, Indonesia Endowment Funds for Education, Foreign, Commonwealth and Development Office (Programme for Evidence to Inform Disability Action), and the Arts and Humanities Research Council.

Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Теоретические предпосылки изучения ФЕ-терминов и их вариантов в английском языке делового общения

This article studies theoretical material in the field of phraseology and terminology of business English, placing special emphasis on the variability of phraseological units and terms. The paper presents an analytical review of recent and relevant dissertations, monographs and research articles on business phraseology and terminology as well as variability thereof. The lexical composition of business language and the role of phraseological units in it are examined. The review lists a number of articles explaining the trend towards phraseologization of numerous terms used in business communication. Further, the paper studies current views on the structure of the meaning of the term and examines three main approaches to the definition of the term. Special attention is paid to the motivation of terms and lack of motivation of phraseological terms. The process of terms becoming phraseological units and vice versa is investigated, as well as the transfer of existing phraseological terms into a new phraseological-semantic field; terms describing these processes are considered. Further, the review mentions academic works looking into ways of enriching the terminology of modern business English with new phraseological terms, which include metaphorical and metonymic interpretations of the prototype. In addition, studies into phraseological variation are presented, analysing the concept of phraseological variant and its typological classifications; works on terminological variation are listed. The phenomenon of variation is considered in terms of both expression and content. The review of existing scholarly works confirms the need for further careful research into phraseological terms and their variants.