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BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) occurs due to acquired mutations in bone marrow progenitor cells. CHIP confers a 2-fold risk of atherosclerotic cardiovascular disease. However, there are limited data regarding specific cardiovascular phenotypes. The purpose of this study was to define the coronary artery disease phenotype of the CHIP population-based on coronary angiography. METHODS: We recruited 1142 patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed DNA sequencing to determine CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and angiography phenotypes. RESULTS: We found that 18.4% of patients undergoing coronary angiography had a CHIP mutation. Those with CHIP had a higher risk of having obstructive left main (odds ratio, 2.44 [95% CI, 1.40-4.27]; P=0.0018) and left anterior descending (odds ratio, 1.59 [1.12-2.24]; P=0.0092) coronary artery disease compared with non-CHIP carriers. We additionally found that a specific CHIP mutation, ten eleven translocase 2 (TET2), has a larger effect size on left main stenosis compared with other CHIP mutations. CONCLUSIONS: This is the first invasive assessment of coronary artery disease in CHIP and offers a description of a specific atherosclerotic phenotype in CHIP wherein there is an increased risk of obstructive left main and left anterior descending artery stenosis, especially among TET2 mutation carriers. This serves as a basis for understanding enhanced morbidity and mortality in CHIP.
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BACKGROUND: Patients in intensive care units (ICU) are at an increased risk of pressure injuries. In ICUs, specialised support surfaces are an intervention often used to prevent pressure injuries. This systematic review and meta-analysis aimed to ascertain the effectiveness of different specialised support surface modes for preventing pressure injuries to adult ICU patients. METHODS: Ovid MEDLINE, Ovid Embase, EBSCO CINAHL, PEDro, Cochrane Library, Clinicaltrials.gov and eligible paper references were searched for appropriate studies. Studies were included if they investigated both dynamic support surface modes low-air-loss (LAL) and alternating pressure (AP), involved adult ICU patients (≥18 years old), and investigated pressure injury incidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Mixed Methods Appraisal Tool (MMAT) checklists were used for reporting and quality assessment. Risk ratios (RRs) with 95 % Confidence Intervals (CIs) were used to summarise pressure injury incidence. The pooled RR was calculated with the random-effects model using the Mantel-Haenszel method. Further secondary analysis examined length of stay (LoS) and severity of illness. RESULTS: The four included studies involved 3,308 patients. These studies were heterogeneous in design. When AP surface mode was compared with LAL surface mode, there was no significant difference in the occurrence of pressure injury (8.9 % versus 10.9 %, RR 0.64). Mattress mode also had no direct association with length of stay and severity of illness. CONCLUSION: This systematic review and meta-analysis found no significant difference in the effectiveness of LAL and AP support surface modes in preventing pressure injuries in adult ICU patients. IMPLICATIONS FOR CLINICAL PRACTICE: Clinicians should remember that mattresses are just one element within strategies to prevent pressure injuries in ICUs. The equivocal findings of this systematic review highlight the complexity of preventing pressure injuries and underscore the importance of holistic nursing care.
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Unidades de Cuidados Intensivos , Úlcera por Presión , Humanos , Úlcera por Presión/prevención & control , Unidades de Cuidados Intensivos/organización & administración , Lechos/normasRESUMEN
Cobb syndrome is a rare neurocutaneous disease characterized by multiple spinal vascular anomalies and vascular skin lesions affecting the corresponding dermatome. We present a case of a 12-year-old boy with history of spinal arteriovenous malformation (AVM) extending from T4-T5 status post partial embolization 3 years ago and hyperpigmented patch overlying his thoracic back region presenting with 2 days of back pain and lower extremity numbness and weakness. He had multiple Type III AVMs within the spinal and paraspinal tissues involving the T4-T7 vertebral elements, most extensively T4 and T5. The largest aneurysm located at the confluence of the main AVM nidus was a 4â mm anterior spinal artery aneurysm, which was embolized with partial embolization of the main AVM nidus, resulting in complete aneurysm occlusion. This report provides valuable insight on the natural history, recurrence risk, and treatment options of Cobb syndrome to aid in early diagnosis and improve outcomes.
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INTRODUCTION: Cyberattacks on healthcare organisations are becoming increasingly common and represent a growing threat to patient safety. The majority of breaches in cybersecurity have been attributed to human error. Intensive care departments are particularly vulnerable to cyberattacks. The aim of this study was to investigate cybersecurity awareness, knowledge and behaviours among critical care staff. METHODS: This was a multi-site cross-sectional survey study administered to critical care staff. Cybersecurity awareness was evaluated using the validated HAIS-Q instrument. Knowledge and behaviours were evaluated by direct questioning and scenario-based multiple-choice questions. Free text options were also offered to respondents. Thematic analysis was performed on free text sections. RESULTS: Median scores of 12-15 in each of the HAIS-Q focus areas were achieved, indicating high levels of cybersecurity awareness among critical care staff. However, self-reported confidence in cybersecurity practices, especially identifying signs of cybersecurity breaches and reporting cybersecurity incidents, were relatively low. Participants responses to the scenarios demonstrated a lack of knowledge and awareness of some of the mechanisms of cyberattacks. Barriers to safe cybersecurity practices among staff that emerged from the qualitative analysis included: a lack of training and education; heavy workloads and staff fatigue; perceived lack of IT support and poor IT infrastructure. CONCLUSION: Critical care staff appear to have a high-level cybersecurity awareness. However, in practice safe cybersecurity practices are not always followed. ICU departments and hospitals must invest in the human aspect of cybersecurity to strength their cyber-defences and to protect patients.
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Atención a la Salud , Hospitales , Humanos , Estudios Transversales , Seguridad Computacional , Cuidados CríticosRESUMEN
Established in 2006, the Irish Longitudinal Study on Ageing (TILDA) investigates the health, economic and social circumstances of a nationally-representative sample of people aged fifty years and older in a series of biennial data collection waves. Irish newspapers have been reporting the results of TILDA for over a decade and a half, and their texts represent reports of scientific research distilled through the pen of journalists. In their totality, their texts constitute a public discourse on ageing and health. Using critical discourse analysis, we examined the discourse within the texts of a purposive sample of two national daily newspapers. As sites of public discourse, newspapers reflect social life and are influential in forming and legitimating public attitudes. Like other sites of discourse, their language-in-use is contextually located, is rarely neutral and may employ strategies to discursively construct, sustain and privilege particular social identities, including ageing identities. Discursively constructed as 'ageing well', our analysis of newspaper texts revealed a discernible meta-discourse on ageing and health in which ageing was framed as a life course stage that may be cultivated, diligently self-nurtured and exploited for its positive aspects. When considered in light of literature on health and social inequalities, the consequences of this broadly positive ageing discourse can, somewhat perversely, frame older adults in unintended negative ways, including homogenising them and attributing to them capacities for ageing well that they may not possess. Discursively constructing older adults as a social and economic resource can also impose unrealistic expectations on them and may legitimise exploitation and demonstrate how normative ideologies of ageism and ableism are conveyed through legitimising language. Despite these potentially unintended consequences, the available media resources associated with TILDA may represent one of the most important contributions of the study, in terms of informing positive public attitudes towards ageing.
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Envejecimiento , Opinión Pública , Humanos , Anciano , Estudios Longitudinales , Factores Socioeconómicos , Proyectos de InvestigaciónRESUMEN
PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2 and vascular endothelial growth factor (VEGF) A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend (T&E)-based regimen with up to every-16-week dosing in the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss (best-corrected visual acuity [BCVA] of 25-73 letters) due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg every 8 weeks. The T&E up to every-16-week dosing regimen was based on central subfield thickness (CST) and BCVA change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE and RHINE (n = 940 and 951, respectively), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92, 96, and 100 average) with faricimab every 8 weeks (YOSEMITE and RHINE, +10.7 letters and +10.9 letters, respectively) or T&E (+10.7 letters and +10.1 letters, respectively) were comparable with aflibercept every 8 weeks (+11.4 letters and +9.4 letters, respectively). The median number of study drug injections was lower with faricimab T&E (YOSEMITE and RHINE, 10 and 11 injections, respectively) versus faricimab every 8 weeks (15 injections) and aflibercept every 8 weeks (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was improved further during year 2, with > 60% of patients receiving every-16-week dosing and approximately 80% receiving every-12-week or longer dosing at week 96. Almost 80% of patients who achieved every-16-week dosing at week 52 maintained every-16-week dosing without an interval reduction through week 96. Mean CST reductions were greater (YOSEMITE/RHINE weeks 92/96/100 average: faricimab every 8 weeks -216.0/-202.6 µm, faricimab T&E -204.5/-197.1 µm, aflibercept every 8 weeks -196.3/-185.6 µm), and more patients achieved absence of DME (CST < 325 µm; YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 87%-92%/88%-93%, faricimab T&E 78%-86%/85%-88%, aflibercept every 8 weeks 77%-81%/80%-84%) and absence of intraretinal fluid (YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 59%-63%/56%-62%, faricimab T&E 43%-48%/45%-52%, aflibercept every 8 weeks 33%-38%/39%-45%) with faricimab every 8 weeks or T&E versus aflibercept every 8 weeks through year 2. Overall, faricimab was well tolerated, with a safety profile comparable with that of aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to every 16 weeks were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2 and VEGF-A inhibition to promote vascular stability and to provide durable efficacy for patients with DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Inhibidores de la Angiogénesis , Retinopatía Diabética , Inyecciones Intravítreas , Edema Macular , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Humanos , Edema Macular/tratamiento farmacológico , Edema Macular/fisiopatología , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/fisiopatología , Retinopatía Diabética/diagnóstico , Agudeza Visual/fisiología , Método Doble Ciego , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/uso terapéutico , Angiopoyetina 2/antagonistas & inhibidores , Estudios de Seguimiento , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
Cancer is a global public health problem, but its exact prevalence in people with intellectual disabilities is still uncertain. This population, with limited health skills and complex health needs, faces many challenges in cancer prevention, screening, timely diagnosis and treatment. Furthermore, they are often underrepresented in general cancer prevention and screening policies across Europe, leading to widened disparities in health outcomes and premature mortality. Thus, unified national and local policies are needed to reduce inequalities and promoting a pan-European inclusion of people with intellectual disabilities. Our goal is to raise public awareness of this issue, including the involvement of people with intellectual disabilities, and promote engagement from relevant stakeholders. The COST Action 'Cancer- Understanding Prevention in Intellectual Disabilities' (CUPID) project will address health inequalities faced by people with intellectual disabilities in relation to cancer, and support the development of policy recommendations specifically tailored to their unique cognitive and healthcare needs, having a positive long-term impact on quality of life.
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BACKGROUND: COVID-19 accelerated the adoption of remote working in which employers' obligations for employees' health and well-being extended into the home. This paper reports on a systematic review of the health impacts of remote working within the context of COVID-19 and discusses the implications of these impacts for the future role of the occupational health nurse. METHOD: The review protocol was registered with PROSPERO (CRD42021258517) and followed the PRISMA guidelines. The review covered 2020-2021 to capture empirical studies of remote working during the COVID-19 pandemic, their physical and psychological impacts and mediating factors. RESULTS: Eight hundred and thirty articles were identified. After applying the inclusion criteria, a total of 34 studies were reviewed. Most studies showed low to very low strength of evidence using the GRADE approach. A minority of studies had high strength of evidence. These focused on the reduced risk of infection and negative effects in terms of reduced physical activity, increased sedentary activity, and increased screen time. CONCLUSION/APPLICATION TO PRACTICE: The synergy of work and personal well-being with the accelerated expansion of remote working suggests a more active role in the lives of workers within the home setting on the part of occupational health nurses. That role relates to how employees organize their relationship to work and home life, promoting positive lifestyles while mitigating adverse impacts of remote working on personal well-being.
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COVID-19 , Salud Laboral , Humanos , Teletrabajo , Pandemias , Salud MentalRESUMEN
FOXJ1 is expressed in ciliated cells of the airways, testis, oviduct, central nervous system and the embryonic left-right organizer. Ablation or targeted mutation of Foxj1 in mice, zebrafish and frogs results in loss of ciliary motility and/or reduced length and number of motile cilia, affecting the establishment of the left-right axis. In humans, heterozygous pathogenic variants in FOXJ1 cause ciliopathy leading to situs inversus, obstructive hydrocephalus and chronic airway disease. Here, we report a novel truncating FOXJ1 variant (c.784_799dup; p.Glu267Glyfs*12) identified by clinical exome sequencing from a patient with isolated congenital heart defects (CHD) which included atrial and ventricular septal defects, double outlet right ventricle (DORV) and transposition of the great arteries. Functional experiments show that FOXJ1 c.784_799dup; p.Glu267Glyfs*12, unlike FOXJ1, fails to induce ectopic cilia in frog epidermis in vivo or to activate the ADGB promoter, a downstream target of FOXJ1 in cilia, in transactivation assays in vitro. Variant analysis of patients with heterotaxy or heterotaxy-related CHD indicates that pathogenic variants in FOXJ1 are an infrequent cause of heterotaxy. Finally, we characterize embryonic-stage CHD in Foxj1 loss-of-function mice, demonstrating randomized heart looping. Abnormal heart looping includes reversed looping (dextrocardia), ventral looping and no looping/single ventricle hearts. Complex CHDs revealed by histological analysis include atrioventricular septal defects, DORV, single ventricle defects as well as abnormal position of the great arteries. These results indicate that pathogenic variants in FOXJ1 can cause isolated CHD.
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Cardiopatías Congénitas , Defectos de los Tabiques Cardíacos , Síndrome de Heterotaxia , Transposición de los Grandes Vasos , Humanos , Masculino , Factores de Transcripción Forkhead/genética , Atrios Cardíacos , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/patología , Transposición de los Grandes Vasos/genéticaRESUMEN
BACKGROUND: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score". METHODS: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. RESULTS: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. CONCLUSIONS: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
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COVID-19 , Pandemias , Humanos , Adulto , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Evaluación de Resultado en la Atención de Salud , Análisis Factorial , PsicometríaRESUMEN
Heterotaxy is a disorder with complex congenital heart defects and diverse left-right (LR) patterning defects in other organ systems. Despite evidence suggesting a strong genetic component in heterotaxy, the majority of molecular causes remain unknown. Established genes often involve a ciliated, embryonic structure known as the left-right organizer (LRO). Herein, we focus on genetic discoveries in heterotaxy in the past two years. These include complex genetic architecture, novel mechanisms regulating cilia formation, and evidence for conservation of LR patterning between distant species. We feature new insights regarding established LR signaling pathways, bring attention to heterotaxy candidate genes in novel pathways, and provide an extensive overview of genes previously associated with laterality phenotypes in humans.
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Tipificación del Cuerpo , Síndrome de Heterotaxia , Tipificación del Cuerpo/genética , Cilios/metabolismo , Síndrome de Heterotaxia/genética , Humanos , Fenotipo , Transducción de Señal/genéticaRESUMEN
Background: The COVID-19 global pandemic is a harbinger of a future destabilised world driven by climate change, rapid mass migration, food insecurity, state failures and epidemics. A significant feature fuelling this destabilised world is networked misinformation and disinformation (referred to as an infodemic), particularly in the area of health. Aims: To describe the interactive dynamic of climate change; mass population movement; famine; state failure and epidemic disease, analyse developments over the year 2020-2021 and discuss their relationship to an infodemic about disease and public health responses and how this should be addressed in the future. Methods: Using the concept of 'the Five Horsemen' of epochal change and network theory to guide a narrative review. Results: Concepts of epidemiology are reflected in how misinformation is spread around the world. Health care services and personnel face threats as a result that make it more difficult to manage pan global health risks effectively. Conclusions: Heath care professionals at an individual and organisational level need to counter infodemic networks. Health care professionals who consistently spread misinformation should have their licence to practice withdrawn.
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BACKGROUND: Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC) is more limited. METHODS: We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC. Patients were classified into three groups based on first-line therapy: ICI-based therapy (monotherapy or combination), vascular endothelial growth factor (VEGF) inhibitor monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. The primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used the Kaplan-Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates. RESULTS: We identified a total of 1145 patients with metastatic nccRCC. The most common subtype was papillary RCC (54.9%). For first-line therapy, 74.3% received VEGF monotherapy, 15% received mTOR monotherapy, and 10.7% received ICI-based therapy. Median OS in the ICI group was 28.6 months, versus 16.4 months in the VEGF group and 12.2 months in the mTOR group. Median TTF in the ICI group was 6.9 months, versus 5.0 months in the VEGF group and 3.9 months in the mTOR group. ORR was 27.2% in the ICI group, 14.5% in the VEGF group, and 9% in the mTOR group. After adjusting for the IMDC risk group, histological subtype, and age, the hazard ratio for OS was 0.57 (95% CI 0.42-0.78, p < 0.0001) for ICI versus VEGF and 0.50 (95% CI 0.36-0.71, p < 0.0001) for ICI versus mTOR. CONCLUSIONS: In advanced nccRCC, first-line ICI-based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results should be confirmed in prospective randomised trials.
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Carcinoma de Células Renales , Neoplasias Renales , Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma de Células Renales/patología , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/patología , Estudios Retrospectivos , Serina-Treonina Quinasas TOR , Resultado del Tratamiento , Factor A de Crecimiento Endotelial VascularRESUMEN
AIM: This article aims to outline the key concepts in hybrid warfare and cyberattack to better inform nurse managers in their strategic contribution to the defence of critical digital infrastructure. BACKGROUND: Hybrid warfare often targets a nation's critical digital infrastructure including that of health services. Hybrid warfare against national health services, primarily through cyberattack, is likely to increase in a more destabilized and conflictual international environment. EVALUATION: Key literature, reports and assessments on hybrid warfare, advanced persistent threats and cyberattack referenced to health services were analysed. KEY ISSUE: Health services are a key element of a nation's critical digital infrastructure and as such are a strategic target in hybrid warfare. Cyberattack through exploiting clinicians', such as nurses, online susceptibilities is a key route of attack. Nurse managers, to be effective planners, need to be fully informed about the context and specific nature of cyberattack. CONCLUSION(S): Articles about the relationship between hybrid warfare and cyberattack on health services digital infrastructure are rarely aimed at nurse managers. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers need to be fully informed about the geopolitical nature of cyberattacks if they are to be fully consulted and listened to in response planning in defence of health services' digital infrastructure.
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Enfermeras Administradoras , Servicios de Salud , HumanosRESUMEN
Somatic mutations in hematopoietic stem cells are common with aging and can result in expansion of clones harboring mutations, termed clonal hematopoiesis. This results in an increased risk of blood cancers but has also been linked with chronic inflammatory disease states. In recent years, clonal hematopoiesis has been established to have a causative role in atherogenesis and cardiovascular disease. Additionally, as the effector cells have been identified to be immune cells, there is ongoing interest in assessing whether dysregulated immune function plays a role in other chronic inflammatory conditions such as rheumatologic disease. Here, we summarize current understanding of clonal hematopoiesis with a focus on cardiovascular disease and inflammation while outlining the potential, yet unexplored, relationship between clonal hematopoiesis and autoimmune disease. Hematopoietic stem cells (HSCs) continually regenerate blood cells. Acquisition of a somatic mutation that provides a selective advantage, a driver mutation, can result in clonal expansion. Clonal hematopoiesis of indeterminate potential, where somatic mutations in certain cancer-associated genes result in clonal expansion in the absence of overt malignancy, can result in atherosclerotic cardiovascular disease in multiple vascular beds, inflammation, and may also contribute to the pathogenesis of autoimmune disease. Many questions remain unanswered regarding the relationship between clonal hematopoiesis and inflammatory disorders.
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Aterosclerosis , Enfermedades Autoinmunes , Enfermedades Cardiovasculares , Aterosclerosis/genética , Enfermedades Cardiovasculares/genética , Hematopoyesis Clonal/genética , Humanos , Inflamación/genéticaRESUMEN
PURPOSE: Randomized controlled trials (RCTs) are the cornerstone of delivering sustained improvements in cancer outcome. To inform radiation therapy research policy and prioritization, we analyze the radiation therapy RCT landscape including comparison with trials of systemic therapies over the same period, with a specific focus on funding and disparities across income settings. METHODS AND MATERIALS: This retrospective cohort study identified all phase 3 RCTs evaluating anticancer therapies published from 2014 to 2017. RCTs were classified according to anticancer modality and country of origin. Descriptive statistics were used to compare key characteristics of radiation therapy RCT studies according to study design characteristics, tumor types evaluated, types of intervention appraised, treatment intent and main funding sources. RESULTS: The study cohort included 694 RCTs of which 64 were radiation therapy RCTs (9%) compared with 601 systemic therapy RCTs (87%). Among all radiation therapy RCTs, 47% of them focused on 2 areas of evaluation: (1) combining radiation therapy with systemic agents (25%) and (2) changes in dose fractionation (22%). The most common cancers studied were head and neck (22%), lung (22%), and breast (14%), with cervical cancer trials representing only 3% of the cohort. Among the radiation therapy RCTs, 33% of them met their primary endpoint, and 62% assessed interventions in the curative setting compared with 31% in systemic therapy RCTs. For their country locations, 77% of radiation therapy RCTs took place in high-income countries, 13% in low-and-middle-income countries, and 11% in both high-income and low-and-middle-income countries. For funding, 17% of radiation therapy RCTs received funding from industry compared with 79% of systemic therapy RCTs. CONCLUSIONS: This study highlights the need for greater investment in radiation therapy RCTs and the need to look at the disparities in conducting RCTs globally. The study emphases the urgent need for more capacity building for cancer clinical trials in low-and-middle-income countries and more sustainable funding sources.
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Neoplasias , Humanos , Neoplasias/radioterapia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody. METHODS: YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593). FINDINGS: 3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]). INTERPRETATION: Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema. FUNDING: F Hoffmann-La Roche.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Anticuerpos Biespecíficos/administración & dosificación , Retinopatía Diabética/tratamiento farmacológico , Edema/tratamiento farmacológico , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Angiopoyetina 2/antagonistas & inhibidores , Anticuerpos Biespecíficos/efectos adversos , Retinopatía Diabética/diagnóstico , Método Doble Ciego , Esquema de Medicación , Edema/etiología , Femenino , Humanos , Inyecciones Intravítreas , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/efectos de los fármacos , Masculino , Persona de Mediana Edad , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/efectos de los fármacosRESUMEN
BACKGROUND: The EU promotes 'Open Science' as a public good. Complementary to its implementation is Citizen Science, which redefines the relationship between the scientific community, civic society and the individual. Open Science and Citizen Science poses challenges for the substance use and addictions research community but may provide positive opportunities for future European addiction research. This paper explores both current barriers and potential facilitators for the implementation of Open Science and Citizen Science in substance use and addictions research. METHODOLOGY: A scoping review was used to examine barriers and facilitators identified in the substance use and addiction research literature for the adoption of Open Science and Citizen Science. RESULTS: 'Technical' facilitators included the pre-registration of study protocols; publication of open-source datasets; open peer review and online tools. 'Motivational' facilitators included enhanced reputation; embracing co-creation; engaged citizenship and gamification. 'Economic' facilitators included the use of free tools and balanced remuneration of crowdworkers. 'Political' facilitators included better informed debates through the 'triple helix' approach and trust-generating transparency. 'Legal' facilitators included epidemiologically informed law enforcement; better policy surveillance and the validation of other datasets. 'Ethical' facilitators included the 'democratisation of science' and opportunities to explore new concepts of ethics in addiction research. CONCLUSION: Open Science and Citizen Science in substance use and addictions research may provide a range of benefits in relation to the democratisation of science; transparency; efficiency and the reliability/validity of data. However, its implementation raises a range of research integrity and ethical issues that need be considered. These include issues related to participant recruitment; privacy; confidentiality; security; cost and industry involvement. Progressive journal policies to support Open Science practices; a shift in researcher norms; the use of free tools and the greater availability of methodological and ethical standards are likely to increase adoption in the field.