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Importance: Return to work after breast cancer (BC) treatment depends on several factors, including treatment-related adverse effects. While cancer-related cognitive impairment is frequently reported by patients with BC, to date, no longitudinal studies have assessed its association with return to work. Objective: To examine whether cognition, assessed using objective and subjective scores, was associated with return to work 2 years after BC diagnosis. Design, Setting, and Participants: In a case series of the French Cancer Toxicities (CANTO) cohort, a study of patients with stage I to III BC investigated cognition from April 2014 to December 2018 (2 years' follow-up). Participants included women aged 58 years or younger at BC diagnosis who were employed or looking for a job. Main Outcomes and Measures: The outcome was return to work assessed 2 years after BC diagnosis. Objective cognitive functioning (tests), cognitive symptoms, anxiety, depression, and fatigue were prospectively assessed at diagnosis (baseline), 1 year after treatment completion, and 2 years after diagnosis. Multivariable logistic regression models were used to explain return to work status at year 2 according to each cognitive measure separately, adjusted for age, occupational class, stage at diagnosis, and chemotherapy. Results: The final sample included 178 women with BC (median age: 48.7 [range, 28-58] years), including 37 (20.8%) who did not return to work at year 2. Patients who returned to work had a higher (ie, professional) occupational class and were less likely to have had a mastectomy (24.1% vs 54.1%; P < .001). Return to work at year 2 was associated with lower overall cognitive impairment (1-point unit of increased odds ratio [1-pt OR], 0.32; 95% CI, 0.13-0.79; P = .01), higher working memory (1-pt OR, 2.06; 95% CI, 1.23-3.59; P = .008), higher processing speed (1-pt OR, 1.97; 95% CI, 1.20-3.36; P = .01) and higher attention performance (1-pt OR, 1.63; 95% CI, 1.04-2.64; P = .04), higher perceived cognitive abilities (1-pt OR, 1.12; 95% CI, 1.03-1.21; P = .007), and lower depression (1-pt OR, 0.83; 95% CI, 0.74-0.93; P = .001) at year 2 assessment. Return to work at year 2 was associated with several measures assessed at baseline and year 1: higher processing speed (1-pt OR, 2.38; 95% CI, 1.37-4.31; P = .003 and 1.95; 95% CI, 1.14-3.50; P = .02), higher executive performance (1-pt OR, 2.61; 95% CI, 1.28-5.75; P = .01, and 2.88; 95% CI, 1.36-6.28; P = .006), and lower physical fatigue (10-pt OR, 0.81; 95% CI, 0.69-0.95; P = .009 and 0.84; 95% CI, 0.71-0.98; P = .02). Conclusions and Relevance: In this case series study of patients with BC, return to work 2 years after diagnosis was associated with higher cognitive speed performance before and after BC treatment. Cognitive difficulties should be assessed before return to work to propose suitable management.
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Neoplasias de la Mama , Cognición , Reinserción al Trabajo , Humanos , Neoplasias de la Mama/psicología , Neoplasias de la Mama/complicaciones , Femenino , Reinserción al Trabajo/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Disfunción Cognitiva/etiología , Francia/epidemiología , Estudios Prospectivos , DepresiónRESUMEN
We report the mechanism of the iron-catalyzed oxidative α-amination of ketones with sulfonamides. Using linear free energy relationships, competition experiments, and identification of reaction intermediates, we have found that the mechanism of this reaction proceeds through rate-limiting electron transfer to 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) from an iron enolate in the process of forming an α-DDQ adduct. The adduct then serves as the electrophile for substitution with sulfonamide nucleophiles, accelerated by iron and additional DDQ. This mechanistic study rules out formation of an α-carbocation intermediate and purely radical mechanistic hypotheses.
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BACKGROUND: Long-term treatment-related toxicities, such as neurological and metabolic toxicities, are major issues in breast cancer. We investigated the interest of metabolomic profiling to predict toxicities. METHODS: Untargeted high-resolution metabolomic profiles of 992 patients with ER+/HER2- breast cancer from the prospective CANTO cohort were acquired (n=1935 metabolites). A residual-based modeling strategy with a discovery and validation cohort was used to benchmark machine learning algorithms, taking into account confounding variables. RESULTS: Adaptive LASSO has a good predictive performance, has limited optimism bias, and allows the selection of metabolites of interest for future translational research. The addition of low-frequency metabolites and non-annotated metabolites increases the predictive power. Metabolomics adds extra performance to clinical variables to predict various neurological and metabolic toxicity profiles. CONCLUSIONS: Untargeted high-resolution metabolomics allows better toxicity prediction by considering environmental exposure, metabolites linked to microbiota, and low-frequency metabolites.
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BACKGROUND: Genetic epilepsy diagnosis is increasing due to technological advancements. Although the use of molecular diagnosis is increasing, chromosomal microarray analysis (CMA) remains an important diagnostic tool for many patients. We aim to explore the role and indications of CMA in epilepsy, given the current genomic advances. METHODS: We obtained data from 378 epileptic described patients, who underwent CMA between 2015 and 2021. Different types of syndromic or nonsyndromic epilepsy were represented. RESULTS: After excluding patients who were undertreated or had missing data, we included 250 patients with treated epilepsy and relevant clinical information. These patients mostly had focal epilepsy or developmental and epileptic encephalopathy, with a median start age of 2 years. Ninety percent of the patients had intellectual disability, more than two thirds had normal head size, and 60% had an abnormal magnetic resonance imaging. We also included 10 patients with epilepsy without comorbidities. In our cohort, we identified 35 pathogenic copy number variations (CNVs) explaining epilepsy with nine recurrent CNVs enriched in patients with epilepsy, 12 CNVs related to neurodevelopmental disorder phenotype with possible epilepsy, five CNVs including a gene already known in epilepsy, and nine CNVs based on size combined with de novo occurrence. The diagnosis rate in our study reached 14% (35 of 250) with first-line CMA, as previously reported. Although targeted gene panel sequencing could potentially diagnose some of the reported epilepsy CNVs (34% [12 of 35]). CONCLUSIONS: CMA remains a viable option as the first-line genetic test in cases where other genetic tests are not available and as a second-line diagnostic technique if gene panel or exome sequencing yields negative results.
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The implementation and potential of ketogenic dietary therapies (KDTs) have changed over time. The organization of KDT services, the availability of multidisciplinary teams, resources and support for patients and families still vary widely around the world. This diversity is reflected by a lack of consistency in reported outcomes, optimization of using KDT and KDT compliance. To highlight the unmet needs for KDT services, the ERN EpiCARE Ketogenic Dietary Therapy Special Interest Group (KDT SIG) conducted an online survey on KDT implementation and utilization, addressing the following topics: Use and completeness of guidelines and protocols; assessment of compliance and outcome parameters, sustainability and inclusivity in daily life. Consistently reported unmet needs included the lack of psychological support and resources to measure and improve adherence to KDT, the lack of inclusion strategies, and shared guidelines and protocols adapting to specific needs. Future interventions should focus primarily on educational and informative measures together with creation of shared protocols for complex care. PLAIN LANGUAGE SUMMARY: This study provides the results of a survey compiled by clinicians and patients representatives belonging to ERN Epicare, designed to unravel unmet needs from both patients' and healthcare practitioners' perspectives during ketogenic dietary therapies (KDT) provision. Importantly, results show the need to create new shared protocols and guidelines meant for KDT use in complex care situations and to develop future strategies initiatives to support patients improving their social inclusivity.
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Dieta Cetogénica , Humanos , Encuestas y Cuestionarios , Epilepsia/dietoterapia , Necesidades y Demandas de Servicios de Salud , Evaluación de NecesidadesRESUMEN
Self-regulatory skills are increasingly recognized as critical early education goals, but few efforts have been made to identify all the features of the classroom that actually promote such skills. This study experiments with a new observational measure capturing three dimensions of the classroom environment hypothesized to influence self-regulation: classroom management, emotionally supportive interactions, and direct promotion of self-regulatory skills. These classroom dimensions were tested as predictors of change over the kindergarten year in both self-regulatory and academic skills in a sample of racially/ethnically-diverse low-income children in Tulsa, OK. Results showed that classroom management was associated with small gains in one of four measures of self-regulation, and four of six measures of academic skills. The other dimensions of the environment had weak or no associations with outcomes. These results indicate that further work is needed to refine both models and measures of the self-regulatory environment.
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When the COVID-19 pandemic forced school closures in the U.S. in March 2020, children's learning moved home and online, making school participation a challenge for many families, particularly those with low incomes. Although there is not a clear and agreed-upon digital analog for in-person school participation for young elementary students, existing research on young children's school attendance and engagement in non-pandemic times suggests that family characteristics broadly recognized to shape child development (e.g., parental depressive symptoms, household chaos), children's own characteristics (e.g., pre-COVID-19 academic skills; demographics), and logistical barriers with particular relevance to remote learning (e.g., internet access) may be determinants of remote learning participation. The current study explores the extent to which student participation during COVID-induced remote learning was predicted by family and child characteristics and logistical barriers by drawing on an existing study of diverse low-income students in Tulsa, OK who were in 1st grade when the pandemic emerged. We capitalize on unique, comprehensive, multi-informant data collected before and during COVID-19 to examine young children's participation in remote learning while controlling for pre-existing differences that might otherwise be confounded with both COVID-related stressors and obstacles to remote learning participation. Both family characteristics (e.g., parent depression, household chaos, single mother) and logistical barriers (e.g., internet and device access) predicted children's remote learning participation. Implications for school administrators and policymakers - with a focus on preparation for future disasters that may once again force school closures - are discussed.
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Background and Objectives: DNA polymerase subunit gamma (POLG) deficiency is likely the most frequent cause of nuclear-encoded mitochondrial disorders. POLG-related disorders reportedly constitute a spectrum of overlapping phenotypes from infancy to late adulthood. We retrospectively reviewed natural histories for 40 children carrying biallelic pathogenic POLG variants. Methods: The patients were identified by the French coordinating center for mitochondrial disorders (CARAMMEL), making this a large monocentric series on childhood-onset POLG deficiency. Results: Three patterns of clinical course and survival were observed, distinguished by main category of symptoms: neurologic, hepatic, and gastrointestinal. A total of 24 patients needed urgent neurointensive care for tonic-clonic seizures, myoclonic epilepsy, and status epilepticus, occasionally precipitated by valproate administration. Other neurologic symptoms included dystonia, cerebellar ataxia, and peripheral neuropathy. We report 6 POLG-deficient patients with polyradiculoneuropathy mimicking subacute Guillain-Barré syndrome and provide postgadolinium MRI evidence of diffuse cranial nerve root and cauda equina enhancement, suggesting these disorders have an inflammatory component. Children presenting with enteral nervous system involvement had vomiting, gastroparesis, and chronic intestinal pseudo-obstruction. They had later ages of onset and lived much longer. Primarily, hepatic presentations had the earliest onset and shortest survivals. Secondary hepatic failure was frequently precipitated by valproate administration given before diagnosis to patients with focal impaired awareness seizures or absence of seizures. These POLG deficiencies were often fatal, with age at death ranging from 3 months to 10 years, with a significant difference in survival between the 3 clinical forms; 6 of the 40 children did survive. No genotype-phenotype correlations were found for the 3 clinical course types. Discussion: The study demonstrates the prevalence of neurologic presentation and the extent of central, peripheral, and autonomous nervous system involvement in 60% of patients. Most of the patients with early onset and rapidly fatal hepatic failure did not live long enough to develop neurologic symptoms. The study revealed a new clinical form of POLG deficiency presenting with neurodigestive symptoms with longer lifespan. We also propose that POLG deficiency should be considered in children presenting with unexplained polyradiculoneuropathy, demyelinating neuropathy, and elevated CSF protein. Finally, valproate administration remains a notable cause of avoidable death in POLG-deficient patients.
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PURPOSE: Postdiagnosis exercise is associated with lower breast cancer (BC) mortality but its link with risk of recurrence is less clear. We investigated the impact and dose-response relationship of exercise and recurrence in patients with primary BC. METHODS: Multicenter prospective cohort analysis among 10,359 patients with primary BC from 26 centers in France between 2012 and 2018 enrolled in the CANcer TOxicities study, with follow-up through October 2021. Exercise exposure was assessed using the Global Physical Activity Questionnaire-16, quantified in standardized metabolic equivalent of task-hours per week (MET-h/wk). We examined the dose/exposure response of pretreatment exercise on distant recurrence-free interval (DRFI) for all patients and stratified by clinical subtype and menopausal status using inverse probability treatment weighted multivariable Cox models to estimate hazard ratios (HRs). RESULTS: For the overall cohort, the relationship between exercise and DRFI was nonlinear: increasing exercise ≥ 5 MET-h/wk was associated with an inverse linear reduction in DRFI events up to approximately 25 MET-h/wk; increasing exercise over this threshold did not provide any additional DRFI benefit. Compared with <5 MET-h/wk, the adjusted HR for DRFI was 0.82 (95% CI, 0.61 to 1.00) for ≥ 5 MET-h/wk. Stratification by subtype revealed the hormone receptor-/human epidermal growth factor receptor 2- (HR-/HER2-; HR, 0.59 [95% CI, 0.38 to 0.92]) and HR-/HER2+ (HR, 0.37 [95% CI, 0.14 to 0.96]) subtypes were preferentially responsive to exercise. The benefit of exercise was observed especially in the premenopausal population. CONCLUSION: Postdiagnosis/pretreatment exercise is associated with lower risk of DRFI events in a nonlinear fashion in primary BC; exercise has different impact on DRFI as a function of subtype and menopausal status.
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BACKGROUND: Prediction of outcomes remains an unmet need in candidates for LVADs. The development of right-heart failure portends an excess in mortality rates, but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap. METHODS: The ASSIST-ICD registry was used to test right ventriculoarterial coupling as a surrogate parameter at implantation for the prediction of all-cause mortality. RESULTS: The ratio of the tricuspid annular-plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (Pâ¯=â¯0.89), nor was the pulmonary artery pulsatility index (PAPi) (Pâ¯=â¯0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (P < 0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen levels, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65]; P < 0.01). CONCLUSION: Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.
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PURPOSE: Socioeconomic status (SES) influences the survival outcomes of patients with early breast cancer (EBC). However, limited research investigates social inequalities in their quality of life (QoL). This study examines the socioeconomic inequalities in QoL after an EBC diagnosis and their time trends. PATIENTS AND METHODS: We used data from the French prospective multicentric CANTO cohort (ClinicalTrials.gov identifier: NCT01993498), including women with EBC enrolled between 2012 and 2018. QoL was assessed using the European Organisation for Research and Treatment of Cancer QoL Core 30 questionnaire (QLQ-C30). summary score at diagnosis and 1 and 2 years postdiagnosis. We considered three indicators of SES separately: self-reported financial difficulties, household income, and educational level. We first analyzed the trajectories of the QLQ-C30 summary score by SES group. Then, social inequalities in QLQ-C30 summary score and their time trends were quantified using the regression-based slope index of inequality (SII), representing the absolute change in the outcome along socioeconomic gradient extremes. The analyses were adjusted for age at diagnosis, Charlson Comorbidity Index, disease stage, and type of local and systemic treatment. RESULTS: Among the 5,915 included patients with data on QoL at diagnosis and at the 2-year follow-up, social inequalities in QLQ-C30 summary score at baseline were statistically significant for all SES indicators (SIIfinancial difficulties = -7.6 [-8.9; -6.2], SIIincome = -4.0 [-5.2; -2.8]), SIIeducation = -1.9 [-3.1; -0.7]). These inequalities significantly increased (interaction P < .05) in year 1 and year 2 postdiagnosis, irrespective of prediagnosis health, tumor characteristics, and treatment. Similar results were observed in subgroups defined by menopausal status and type of adjuvant systemic treatment. CONCLUSION: The magnitude of preexisting inequalities in QoL increased over time after EBC diagnosis, emphasizing the importance of considering social determinants of health during comprehensive cancer care planning.
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Neoplasias de la Mama , Calidad de Vida , Factores Socioeconómicos , Humanos , Neoplasias de la Mama/terapia , Neoplasias de la Mama/psicología , Neoplasias de la Mama/economía , Femenino , Persona de Mediana Edad , Francia , Estudios Prospectivos , Anciano , Adulto , Clase Social , Encuestas y CuestionariosRESUMEN
PURPOSE: In this single-institution phase II investigator-initiated study we assessed the ability of MAPK and VEGF pathway blockade to overcome resistance to immunotherapy in microsatellite stable metastatic colorectal cancer (MSS mCRC). PATIENTS AND METHODS: Patients with MSS, BRAF wild-type mCRC who progressed on ≥2 prior lines of therapy received pembrolizumab, binimetinib, and bevacizumab until disease progression or unacceptable toxicity. After a safety run-in, patients were randomized to a 7-day run-in of binimetinib or simultaneous initiation of all study drugs, to explore whether MEK inhibition may increase tumor immunogenicity. The primary endpoint was objective response rate in all patients combined (ORR, by RECIST v1.1). RESULTS: Fifty patients received study drug treatment; 54% were male with median age 55 years (range 31-79). The primary endpoint, ORR, was 12.0% (95% confidence interval [CI] 4.5-24.3%), which was not statistically different than the historical control data of 5% (p=0.038, exceeding pre-specified threshold of 0.025). The disease control rate was 70.0% (95% CI 55.4-82.1%), median progression-free survival 5.9 months (95% CI 4.2-8.7 months), and median overall survival 9.3 months (95% CI 6.7-12.2 months). No difference in efficacy was observed between the randomized cohorts. Grade 3 and 4 adverse events were observed in 56% and 8% of patients, respectively; the most common were rash (12%) and increased aspartate aminotransferase (12%). CONCLUSION: Pembrolizumab, binimetinib, and bevacizumab failed to meet its primary endpoint of higher ORR compared to historical control data, demonstrated a high disease control rate, and demonstrated acceptable tolerability in refractory MSS mCRC.
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BACKGROUND: Inflammation could be related to cancer-related cognitive impairment (CRCI) and might be used as a predictive marker of long-term CRCI. We evaluated associations between inflammatory markers assessed at diagnosis of breast cancer and CRCI two years afterwards. METHODS: Newly diagnosed stage I-III patients with breast cancer from the French CANTO-Cog (Cognitive sub-study of CANTO, NCT01993498) were included at diagnosis (baseline). Serum inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10, TNFα, CRP) were assessed at baseline. Outcomes at year 2 post-baseline included overall cognitive impairment (≥ 2 impaired domains) and the following domains: episodic memory, working memory, attention, processing speed, and executive functions. Multivariable logistic regression models evaluated associations between markers and outcomes, controlling for age, education, and baseline cognitive impairment. RESULTS: Among 200 patients, the mean age was 54 ± 11 years, with 127 (64%) receiving chemotherapy. Fifty-three (27%) patients had overall cognitive impairment at both timepoints. Overall cognitive impairment at year 2 was associated with high (> 3 mg/L) baseline CRP (OR = 2.84, 95%CI: 1.06-7.64, p = 0.037). In addition, associations were found between high CRP and processing speed impairment (OR = 2.47, 95%CI:1.05-5.87, p = 0.039), and between high IL-6 and episodic memory impairment (OR = 5.50, 95%CI:1.43-36.6, p = 0.010). CONCLUSIONS: In this cohort, high levels of CRP and IL-6 assessed at diagnosis were associated with overall CRCI, processing speed and episodic memory impairments two years later. These findings suggest a potential inflammatory basis for long-term CRCI. CRP may represent an easily measurable marker in clinical settings and be potentially used to screen patients at greater risk of persistent CRCI.
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Neoplasias de la Mama , Disfunción Cognitiva , Inflamación , Humanos , Femenino , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/sangre , Neoplasias de la Mama/diagnóstico , Persona de Mediana Edad , Disfunción Cognitiva/sangre , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Inflamación/sangre , Adulto , Anciano , Biomarcadores/sangre , Pruebas Neuropsicológicas , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Citocinas/sangreRESUMEN
BACKGROUND: Fasting before coronary procedures is currently recommended to reduce complications despite the lack of scientific evidence. OBJECTIVES: The TONIC (Comparison Between Fasting and No Fasting Before Interventional Coronary Intervention on the Occurrence of Adverse Events) noninferiority trial investigated the safety and comfort of a nonfasting strategy (ad libitum food and drinks) vs traditional fasting (>6 hours for solid food and liquids) before coronary procedures. METHODS: In this monocentric, prospective, single-blind randomized controlled trial, 739 patients undergoing coronary procedures were included and randomized to a fasting or a nonfasting strategy. Emergency procedures were excluded. The primary endpoint was a composite of vasovagal reaction, hypoglycemia (defined by blood sugar ≤0.7 g/L), and isolated nausea and/or vomiting. Noninferiority margin was 4%. Secondary endpoints were contrast-induced nephropathy and patients' satisfaction. RESULTS: Among the 739 procedures (697 elective and 42 semiurgent), 517 angiographies, and 222 angioplasties (including complex and high-risk procedures) were performed. The primary endpoint occurred in 30 of 365 nonfasting patients (8.2%) vs 37 of 374 fasting patients (9.9%), demonstrating noninferiority (absolute between-group difference, -1.7%; 1-sided 95% CI upper limit: 1.8%). No food-related adverse event occurred, and contrast-related acute kidney injuries were similar between groups. Overall, procedure satisfaction and perceived pain were similar in both groups, but nonfasting patients reported less hunger and thirst (P < 0.01). In case of redo coronary procedures, most patients (79%) would choose a nonfasting strategy. CONCLUSIONS: The TONIC randomized trial demonstrates the noninferiority of a nonfasting strategy to the usual fasting strategy for coronary procedures regarding safety, while improving patients' comfort.
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Ayuno , Satisfacción del Paciente , Humanos , Ayuno/sangre , Masculino , Femenino , Estudios Prospectivos , Método Simple Ciego , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Factores de Tiempo , Factores de Riesgo , Intervención Coronaria Percutánea/efectos adversos , Angiografía Coronaria/efectos adversos , Hipoglucemia/inducido químicamente , Hipoglucemia/sangre , Síncope Vasovagal/etiología , Síncope Vasovagal/prevención & control , Glucemia/metabolismo , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Medición de RiesgoRESUMEN
Thrombosis remains one of the leading causes of death in the world. The history of anticoagulation has evolved considerably from non-specific drugs (i.e., heparins and vitamin K antagonists, VKA) to agents that directly target specific coagulation factors (i.e., argatroban, fondaparinux and direct oral anticoagulants, DOAC). Since the last decade, DOAC are widely used in clinical practice because of their ease to use, their favorable pharmacological profile and the fact that they do not require monitoring. However, despite having a better safety profile than vitamin K antagonist, their bleeding risk is not negligible. New anticoagulants targeting the contact phase of coagulation are currently being developed and could make it possible to prevent the risk of thrombosis without impairing hemostasis. Epidemiological and preclinical data on FXI deficiency make FXI a promising therapeutic target. The aim of this review is to summarize the results of the various clinical trials available that focus on FXI/FXIa inhibition, and to highlight the challenges that this new therapeutic class of anticoagulants will face.
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Anticoagulantes , Trombosis , Humanos , Anticoagulantes/farmacología , Coagulación Sanguínea/fisiología , Factor XI , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Vitamina KRESUMEN
BACKGROUND: Cardiogenic shock (CS) is the most severe form of acute heart failure. Discrepancies have been reported between sexes regarding delays, pathways and invasive strategies in CS complicating acute myocardial infarction. However, effect of sex on the prognosis of unselected CS remains controversial. OBJECTIVES: The aim was to analyze the impact of sex on aetiology, management and prognosis of CS. METHODS: The FRENSHOCK registry included all CS admitted in 49 French Intensive Care Units (ICU) and Intensive Cardiac Care Units (ICCU) between April and October 2016. RESULTS: Among the 772 CS patients included, 220 were women (28.5%). Women were older, less smokers, with less history of ischemic cardiac disease (20.5% vs 33.6%) than men. At admission, women presented less cardiac arrest (5.5 vs 12.2%), less mottling (32.5 vs 41.4%) and higher LVEF (30 ± 14 vs 25 ± 13%). Women were more often managed via emergency department while men were directly admitted at ICU/ICCU. Ischemia was the most frequent trigger irrespective of sex (36.4% in women vs 38.2%) but women had less coronary angiogram and PCI (45.9% vs 54% and 24.1 vs 31.3%, respectively). We found no major difference in medication and organ support. Thirty-day mortality (26.4 vs 26.5%), transplant or permanent assist device were similar in both sexes. CONCLUSION: Despite some more favorable parameters in initial presentation and no significant difference in medication and support, women shared similar poor prognosis than men. Further analysis is required to cover the lasting gap in knowledge regarding sex specificities to distinguish between differences and inequalities. NCT02703038.
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Sistema de Registros , Choque Cardiogénico , Humanos , Choque Cardiogénico/terapia , Choque Cardiogénico/mortalidad , Choque Cardiogénico/epidemiología , Femenino , Masculino , Anciano , Factores Sexuales , Francia/epidemiología , Persona de Mediana Edad , Unidades de Cuidados Intensivos/estadística & datos numéricos , PronósticoRESUMEN
This cohort study assesses quality-of-life trajectories up to 6 years after breast cancer diagnosis among individuals in France.
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Neoplasias de la Mama , Humanos , Femenino , Calidad de Vida , Medición de Resultados Informados por el PacienteRESUMEN
PURPOSE: To present a synthesis of evidence related to the factors influencing communication partners' use of augmentative and alternative communication with persons with severe/profound intellectual disability. MATERIALS AND METHODS: An integrative review guided by five steps; problem identification, literature search, data evaluation, data analysis and presentation was undertaken. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, nine databases were searched, 1,342 studies were screened against the eligibility criteria, and 15 studies underwent thematic analysis. RESULTS: Two themes emerged; (1) Achieving Meaningful Communication and (2) Communication Partners' Preparedness to Use Augmentative and Alternative Communication. Achieving meaningful communication was central to communication partners' use of augmentative and alternative communication and was two-fold. It involved identifying the persons' communication methods and encouraging them to communicate. Communication partners' preparedness also influenced their use of augmentative and alternative communication. This preparedness was impacted by communication partners' preconceived thoughts about and knowledge of augmentative and alternative communication, nurturing their belief in augmentative and alternative communication, and the interpersonal dynamic between network members. CONCLUSION: Communication partners' use of augmentative and alternative communication is influenced by multiple and complex factors. The findings contribute to the knowledge of the potential factors to be considered to prepare communication partners to use augmentative and alternative communication.
Multiple, complex factors influence communication partners of persons with severe/profound intellectual disability use of augmentative and alternative communication (AAC), which include communication partners' beliefs, attitudes, expectations, knowledge and resources such as training, support and time.To offer individuals with severe/profound intellectual disability opportunities to communicate, communication partners need to recognise their attempts and thus, their ability. Continuously being sensitive to the individuals' communication methods, whilst being cognisant that these methods can change may enhance communication partners' awareness and understanding of the individuals' communication attempts.Communication partners' need to feel prepared to use AAC. To feel prepared, they need to be aware of the potential benefits that AAC can offer the interaction and the long-term outcomes, develop their knowledge, and be surrounded by a supportive team dynamic.
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While constant speed gait is well understood, far less is known about how humans change walking speed. It is also unknown if the transition steps smoothly morph between speeds, or if they are unique. Using data from a prior study in which subjects transitioned between five speeds while walking on a treadmill, joint kinematic data were decomposed into trend and periodic components. The trend captured the time-varying nature of the gait, and the periodic component captured the cyclic nature of a stride. The start and end of the transition were found by detecting where the trend diverged from a ±2 standard deviation band around the mean of the pre- and post-transition trend. On average, the transition started within half a step of when the treadmill changed speed ( p << 0.001 for equivalence test). The transition length was 2 to 3 steps long. A predictive kinematic model was fit to the experimental data using Bezier polynomials for the trend and Fourier series for the periodic component. The model was fit using 1) only constant speed walking, 2) only speed transition steps, and 3) a random sample of five step types and then validated using the complement of the training data. Regardless of the training set, the model accurately predicted untrained gaits (normalized RMSE , normalized maximum error generally ). Because the errors were similar for all training sets, this implies that joint kinematics smoothly morph between gaits when humans change speed.
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Marcha , Velocidad al Caminar , Humanos , Fenómenos Biomecánicos , Caminata , Prueba de EsfuerzoRESUMEN
BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD. METHODS: A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment. RESULTS: The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3. CONCLUSION: Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy. PLAIN LANGUAGE SUMMARY: Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.