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1.
Blood ; 135(11): 791-803, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-31932844

RESUMO

The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations. Primary and adaptive resistance to venetoclax-based combinations was most commonly characterized by acquisition or enrichment of clones activating signaling pathways such as FLT3 or RAS or biallelically perturbing TP53. Single-cell studies highlighted the polyclonal nature of intratumoral resistance mechanisms in some cases. Among cases that were primary refractory, we identified heterogeneous and sometimes divergent interval changes in leukemic clones within a single cycle of therapy, highlighting the dynamic and rapid occurrence of therapeutic selection in AML. In functional studies, FLT3 internal tandem duplication gain or TP53 loss conferred cross-resistance to both venetoclax and cytotoxic-based therapies. Collectively, we highlight molecular determinants of outcome with clinical relevance to patients with AML receiving venetoclax-based combination therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Biologia Computacional/métodos , Resistencia a Medicamentos Antineoplásicos , Perfilação da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Nucleofosmina , Prognóstico , Retratamento , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Falha de Tratamento , Resultado do Tratamento
2.
Int J Behav Nutr Phys Act ; 19(1): 141, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36451168

RESUMO

BACKGROUND: Whole-of-school programs have demonstrated success in improving student physical activity levels, but few have progressed beyond efficacy testing to implementation at-scale. The purpose of our study was to evaluate the scale-up of the 'Internet-based Professional Learning to help teachers promote Activity in Youth' (iPLAY) intervention in primary schools using the RE-AIM framework. METHODS: We conducted a type 3 hybrid implementation-effectiveness study and collected data between April 2016 and June 2021, in New South Wales (NSW), Australia. RE-AIM was operationalised as: (i) Reach: Number and representativeness of students exposed to iPLAY; (ii) Effectiveness: Impact of iPLAY in a sub-sample of students (n = 5,959); (iii) Adoption: Number and representativeness of schools that received iPLAY; (iv) Implementation: Extent to which the three curricular and three non-curricular components of iPLAY were delivered as intended; (v) Maintenance: Extent to which iPLAY was sustained in schools. We conducted 43 semi-structured interviews with teachers (n = 14), leaders (n = 19), and principals (n = 10) from 18 schools (11 from urban and 7 from rural locations) to determine program maintenance. RESULTS: Reach: iPLAY reached ~ 31,000 students from a variety of socio-economic strata (35% of students were in the bottom quartile, almost half in the middle two quartiles, and 20% in the top quartile). EFFECTIVENESS: We observed small positive intervention effects for enjoyment of PE/sport (0.12 units, 95% CI: 0.05 to 0.20, d = 0.17), perceptions of need support from teachers (0.26 units, 95% CI: 0.16 to 0.53, d = 0.40), physical activity participation (0.28 units, 95% CI: 0.10 to 0.47, d = 0.14), and subjective well-being (0.82 units, 95% CI: 0.32 to 1.32, d = 0.12) at 24-months. Adoption: 115 schools received iPLAY. IMPLEMENTATION: Most schools implemented the curricular (59%) and non-curricular (55%) strategies as intended. Maintenance: Based on our qualitative data, changes in teacher practices and school culture resulting from iPLAY were sustained. CONCLUSIONS: iPLAY had extensive reach and adoption in NSW primary schools. Most of the schools implemented iPLAY as intended and effectiveness data suggest the positive effects observed in our cluster RCT were sustained when the intervention was delivered at-scale. TRIAL REGISTRATION: ACTRN12621001132831.


Assuntos
Internet , Instituições Acadêmicas , Humanos , Adolescente , Estudantes , Coleta de Dados , Prazer
3.
Rev Med Liege ; 77(3): 153-160, 2022 Mar.
Artigo em Francês | MEDLINE | ID: mdl-35258863

RESUMO

Medulloblastoma is a cerebellar grade IV tumour according to the WHO classification, mainly seen in children under the age of 15. This cancer can nevertheless occur in adults. We report the case of a 22-year-old patient with a medulloblastoma disseminated in the spine. The patient had a type 1 Arnold-Chiari malformation causing hydrocephalus treated by ventriculoperitoneal shunt. The current condition began with perineal and lower limb hypoesthesia, ataxic gait, erectile dysfunction and urinary incontinence. Subsequently, a predominant paraparesis of the right lower limb appeared. The patient was treated according to the PNET HR+5 protocol combining two courses of conventional chemotherapy followed by two courses of high-dose chemotherapy with autograft recovery. Given the excellent response, a proton therapy was then delivered to the whole cerebrospinal axis with boosts to the primary tumour sites. The case of this young adult patient shows on the one hand an atypical presentation, and on the other hand underlines, in the absence of a specific therapeutic strategy established for adults, the importance of collaboration between the adult and pediatric oncology departments, with management integrating innovations such as proton therapy and molecular typing.


Le médulloblastome est une tumeur cérébelleuse de grade IV selon l'Organisation Mondiale de la Santé, principalement observée chez les enfants de moins de 15 ans. Ce cancer peut néanmoins survenir chez l'adulte. Nous rapportons le cas d'un patient de 22 ans présentant un médulloblastome disséminé au niveau du rachis. Le patient est porteur d'une malformation d'Arnold-Chiari de type 1 provoquant une hydrocéphalie traitée par dérivation ventriculo-péritonéale. L'affection actuelle a débuté par une hypoesthésie du périnée et des membres inférieurs, une démarche ataxique, un trouble érectile et des troubles vésico-sphinctériens. Par la suite est apparue une paraparésie prédominant au membre inférieur droit. Le patient a été traité selon le protocole pédiatrique PNET HR+5 combinant deux cures de chimiothérapie conventionnelle suivies de deux cures de chimiothérapie à haute dose avec rattrapage par autogreffe. Vu l'excellente réponse, une protonthérapie a été administrée sur l'axe cérébrospinal avec surdosages sur les sites primaires de la tumeur. Le cas de ce jeune adulte illustre, d'une part, une présentation atypique et d'autre part, souligne, en l'absence de stratégie thérapeutique spécifique établie pour l'adulte, l'importance de la collaboration entre les services d'Oncologie adulte et pédiatrique, la prise en charge intégrant les innovations telles que la protonthérapie et le typage moléculaire.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Adulto , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/patologia , Neoplasias Cerebelares/cirurgia , Criança , Humanos , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/terapia , Adulto Jovem
4.
BJOG ; 128(8): 1282-1291, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33539617

RESUMO

OBJECTIVE: To study genetic variants and their function within genes coding for complement receptors in pre-eclampsia. DESIGN: A case-control study. SETTING: Pre-eclampsia is a common vascular disease of pregnancy. The clearance of placenta-derived material is one of the functions of the complement system in pregnancy. POPULATION: We genotyped 500 women with pre-eclamptic pregnancies and 190 pregnant women without pre-eclampsia, as controls, from the FINNPEC cohort, and 122 women with pre-eclamptic pregnancies and 1905 controls from the national FINRISK cohort. METHODS: The functional consequences of genotypes discovered by targeted exomic sequencing were explored by analysing the binding of the main ligand iC3b to mutated CR3 or CR4, which were transiently expressed on the surface of COS-1 cells. MAIN OUTCOME MEASURES: Allele frequencies were compared between pre-eclamptic pregnancies and controls in genetic studies. The functional consequences of selected variants were measured by binding assays. RESULTS: The most significantly pre-eclampsia-linked CR3 variant M441K (P = 4.27E-4, OR = 1.401, 95% CI = 1.167-1.682) displayed a trend of increased adhesion to iC3b (P = 0.051). The CR4 variant A251T was found to enhance the adhesion of CR4 to iC3b, whereas W48R resulted in a decrease of the binding of CR4 to iC3b. CONCLUSIONS: Results suggest that changes in complement-facilitated phagocytosis are associated with pre-eclampsia. Further studies are needed to ascertain whether aberrant CR3 and CR4 activity leads to altered pro- and anti-inflammatory cytokine responses in individuals carrying the associated variants, and the role of these receptors in pre-eclampsia pathogenesis. TWEETABLE ABSTRACT: Genetic variants of complement receptors CR3 and CR4 have functional consequences that are associated with pre-eclampsia.


Assuntos
Antígeno CD11b/genética , Integrina alfaXbeta2/genética , Antígeno de Macrófago 1/genética , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/imunologia , Antígenos CD18/metabolismo , Citocinas/biossíntese , Feminino , Genótipo , Humanos , Integrina alfaXbeta2/metabolismo , Antígeno de Macrófago 1/metabolismo , Mutação , Fagocitose , Gravidez
5.
Appl Opt ; 60(8): 2288-2303, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690328

RESUMO

The advanced radiographic capability (ARC) laser system, part of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory, is a short-pulse laser capability integrated into the NIF. The ARC is designed to provide adjustable pulse lengths of ∼1-38ps in four independent beamlets, each with energies up to 1 kJ (depending on pulse duration). A detailed model of the ARC lasers has been developed that predicts the time- and space-resolved focal spots on target for each shot. Measurements made to characterize static and dynamic wavefront characteristics of the ARC are important inputs to the code. Modeling has been validated with measurements of the time-integrated focal spot at the target chamber center (TCC) at low power, and the space-integrated pulse duration at high power, using currently available diagnostics. These simulations indicate that each of the four ARC beamlets achieves a peak intensity on target of up to a few 1018W/cm2.

6.
J Intellect Disabil Res ; 65(5): 464-488, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33719112

RESUMO

BACKGROUND: Classroom-based active breaks can help typically developing children reduce sitting, increase physical activity and improve cognitive functions and on-task behaviour. Yet, this strategy has not been tested in children with intellectual disability (ID) - a population who are insufficiently active. This study aimed to investigate the effects of a 5-week active breaks intervention on cognitive functions and on-task behaviour in schoolchildren with ID. METHODS: Twenty-four children, aged between 8 and 12 years (37.5% girls), were recruited. Children's cognitive functions (response inhibition, lapses of attention, interference and working memory) were measured at baseline and end of trial using computer-based tests. Sitting, standing and movement patterns were assessed with inclinometers, and on-task behaviour was directly observed in the classroom before and after active breaks, at baseline, mid-trial and end of trial. Linear mixed models were used to investigate the intervention effects on cognitive functions and sedentary patterns; generalised linear mixed models were used to analyse on-task behaviour data. RESULTS: A significant time × group interaction was found for working memory favouring the intervention (B = 11.56, 95% confidence interval [1.92, 21.21]). No significant effects were found in relation to the other measures of children's cognition or on-task behaviour. Stepping time and bouts of sitting were positively affected. CONCLUSIONS: Classroom-based active breaks can increase physical activity and reduce sedentary behaviour in children with ID and might also benefit their working memory. Further research is required to clarify the effects on cognition and to investigate whether this strategy has other benefits in this population.


Assuntos
Deficiência Intelectual , Criança , Cognição , Feminino , Humanos , Masculino , Projetos Piloto , Instituições Acadêmicas , Comportamento Sedentário
7.
Rev Med Liege ; 76(4): 232-238, 2021 Apr.
Artigo em Francês | MEDLINE | ID: mdl-33830685

RESUMO

As the prevalence of cancers increases with age, some elderly patients are confronted with multiple tumoural pathologies. The clinical case of a 70-year-old patient with adenocarcinoma of the breast and multiple myeloma complicated by severe renal failure illustrates the complexity of oncogeriatric management. The geriatric assessment makes it possible to detect frailty and provides assistance in the development of a personalized care plan while respecting the quality of life.


Comme la prévalence des cancers augmente avec l'âge, certains patients âgés se trouvent confrontés à plusieurs pathologies tumorales. Ce cas clinique d'une patiente de 70 ans, avec un adénocarcinome du sein et un myélome multiple compliqué d'une insuffisance rénale sé-vère, illustre la complexité de la prise en charge oncogériatrique. En effet, l'évaluation gériatrique permet de dépister la fragilité et apporte une aide à l'élaboration d'un plan de soins personnalisé en respectant la qualité de vie.


Assuntos
Neoplasias da Mama , Fragilidade , Mieloma Múltiplo , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Avaliação Geriátrica , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Qualidade de Vida
8.
Osteoarthritis Cartilage ; 27(7): 1011-1017, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30922982

RESUMO

BACKGROUND: Data on the economic consequences of hip and knee osteoarthritis (OA) are scarce. We aimed to estimate the annual direct and indirect costs for patients followed for hip and/or knee OA in the Knee and Hip Osteoarthritis Long term Assessment (KHOALA) cohort. METHODS: The KHOALA cohort, set up from 2007 to 2009, is a French multicenter study of 878 individuals with symptomatic knee/hip OA who were 40-75 years old. Resources used were collected annually for 5 years. Costs were assigned by using official sources and expressed in 2018 euros per patient. RESULTS: The mean annual total costs per patient over the 5-year study period were 2,180 ± 5,305€. The mean annual direct medical costs per patient were 2,120 ± 5,275€ and mean annual indirect costs per patient 180 ± 1,735€ for people of working age. Costs increased slightly over the study period. Drugs were the largest cost share, representing over 50% of all direct costs. However, the proportion attributable to OA drugs accounted for only 10.5% of drug costs. The second cost share was hospitalizations; hip and knee prosthetic surgery accounted for 27% of surgery hospitalization costs. Health professional visits were the third cost share, accounting for 3% of direct medical costs. The median costs induced could be as high as 2 billion €/year (IQR 0.7-4.3) in France. CONCLUSION: Hip and knee OA costs were substantial and increased over the study period in France. However, the costs attributable to OA represented only a small fraction of overall costs.


Assuntos
Custos de Cuidados de Saúde/estatística & dados numéricos , Osteoartrite do Quadril/economia , Osteoartrite do Joelho/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adulto , Idoso , Artroplastia de Quadril/economia , Artroplastia de Quadril/estatística & dados numéricos , Artroplastia do Joelho/economia , Artroplastia do Joelho/estatística & dados numéricos , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/terapia , Osteoartrite do Joelho/terapia
9.
Lupus ; 27(10): 1679-1686, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30016929

RESUMO

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH ( n = 253; 96%) or low-dose aspirin ( n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41-17.96); p=.016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.


Assuntos
Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/tratamento farmacológico , Aspirina/efeitos adversos , Fibrinolíticos/efeitos adversos , Heparina de Baixo Peso Molecular/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia Pós-Parto/induzido quimicamente , Adulto , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Cesárea/efeitos adversos , Quimioterapia Combinada , Feminino , França , Humanos , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/terapia , Hemorragia Pós-Parto/diagnóstico , Hemorragia Pós-Parto/terapia , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
10.
Chemotherapy ; 63(2): 90-94, 2018 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-29621772

RESUMO

Advances in the systemic treatment of stage IV colorectal cancer with liver metastases has offered improved survival rates for patients who otherwise face a dismal prognosis. However, a pathologically complete response (PCR) to chemotherapy for colorectal liver metastases is still rare, and its significance is not fully understood. In this case report, we describe a patient who achieved PCR after neoadjuvant immunotherapy with pembrolizumab and a left hepatectomy using an ex vivo resection technique.

11.
Occup Med (Lond) ; 68(9): 631-634, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30412248

RESUMO

BACKGROUND: Sedentary behaviour (SB) in the form of uninterrupted sitting constitutes a risk factor for chronic disease that is independent of the risks associated with insufficient physical activity (PA). However, little is known about employee and manager health beliefs concerning SB and PA. AIMS: We assess health beliefs of desk-based workers concerning PA and SB accrued at work versus during leisure. We ask whether recreational PA attenuates the perceived ill-health effects of prolonged occupational SB, and compare attitudes of employees and managers to interventions aimed at reducing/interrupting workplace sitting. METHODS: Two hundred and twenty-two desk-based employees and 121 managers located in Melbourne, Australia, rated the healthiness of vignettes describing combinations of uninterrupted sitting, sitting with breaks, light PA and moderate-to-vigorous PA accumulated at work and during leisure time. Participants also responded to open-ended questions concerning the implications of reducing workplace sitting. RESULTS: Mixed-model ANOVA revealed that the presence of leisure-time PA greatly diminished the perceived detrimental effects to health of workplace sitting. Subsequent thematic analysis of qualitative data further revealed that participants' concerns with SB were primarily musculoskeletal and workplace performance rather than chronic health. CONCLUSIONS: Employees and their managers do not rate uninterrupted sitting as being unhealthy when it is presented to them in the form of an 'active couch potato' lifestyle (a person who meets minimum PA recommendations but spends much of their work time and non-PA time sitting). We recommend that interventions targeting workplace SB take into account the contextual nature of health beliefs.


Assuntos
Exercício Físico/psicologia , Comportamentos Relacionados com a Saúde , Local de Trabalho/normas , Adulto , Análise de Variância , Atitude Frente a Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional/normas , Comportamento Sedentário , Vitória , Local de Trabalho/psicologia
12.
Rheumatol Int ; 37(7): 1203-1206, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28447208

RESUMO

Antisynthetase syndrome is a heterogeneous idiopathic inflammatory myopathy. Anti-Jo1 is the most common antibody found in this condition. Dermatomyositis is known to be associated with malignancy, but the association between antisynthetase syndrome and malignancy is not clearly established. We report a case of an association of squamous cell carcinoma of the lung and anti-Jo1 antisynthetase syndrome. A 67-year-old man presented with polyarthritis, muscle weakness of the pelvic girdle, "mechanic's hands," and weight loss. A diagnosis of antisynthetase syndrome was considered based on the clinical features and the presence of anti-Jo1 antibodies. Positron emission tomography was performed because of weight loss and revealed a pulmonary hypermetabolic lesion. Histological findings revealed squamous cell carcinoma. The patient underwent lobectomy and is currently free of symptoms with regular monitoring. This unusual presentation of squamous cell carcinoma of the lung illustrates the need of a systematic approach to the diagnosis of antisynthetase syndrome. Positron emission tomography can be a useful imaging modality in the diagnosis of paraneoplastic syndromes associated with antisynthetase syndrome especially in the presence of warning signs/symptoms.


Assuntos
Anticorpos Antinucleares/sangue , Carcinoma de Células Escamosas/complicações , Neoplasias Pulmonares/complicações , Miosite/complicações , Idoso , Biomarcadores/sangue , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Miosite/sangue , Miosite/diagnóstico , Miosite/imunologia , Pneumonectomia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Ann Rheum Dis ; 75(6): 1108-13, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26048170

RESUMO

OBJECTIVES: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. METHODS: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. RESULTS: Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. CONCLUSIONS: In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.


Assuntos
Abatacepte/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Imunossupressores/efeitos adversos , Infecções Oportunistas/induzido quimicamente , Abatacepte/uso terapêutico , Adulto , Fatores Etários , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Comorbidade , Feminino , França/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/imunologia , Sistema de Registros , Fatores de Risco
14.
Osteoarthritis Cartilage ; 24(9): 1500-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27034093

RESUMO

OBJECTIVE: An overview of the economic consequences - overall costs as well as cost breakdown (direct and indirect) - of hip and knee osteoarthritis (OA) worldwide. METHODS: A systematic literature search of EMBASE, MEDLINE, Scopus and Cochrane databases for articles was performed independently by two rheumatologists who used the same predefined eligible criteria. Papers without abstracts and in languages other than English or French were excluded. Extracted costs were converted to an annual cost and to 2013 euros (€) by using the Consumer Price Index of the relevant countries and the 2013 Purchasing Power Parities between these countries and the European Union average. RESULTS: A total of 45 abstracts were selected, and 32 articles were considered for the review. The studied populations were heterogeneous: administrative, hospital and national health survey data. Annual total costs per patient ranged from 0.7 to 12 k€, direct costs per patient from 0.5 to 10.9 k€ and indirect costs per patient from 0.2 to 12.3 k€. The weighted average annual costs per patient living with knee and hip OA were 11.1, 9.5 and 4.4 k€ for total, direct and indirect costs, respectively. CONCLUSIONS: This review highlights the heterogeneity of studies and lack of methodologic consensus to obtain reliable cost-of-illness estimates for lower-limb OA. However, costs induced by the disease seem substantial and deserve to be more extensively explored.


Assuntos
Osteoartrite do Joelho , Efeitos Psicossociais da Doença , Inquéritos Epidemiológicos , Humanos , Articulação do Joelho , Osteoartrite do Quadril
15.
Lupus ; 25(12): 1365-8, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26945023

RESUMO

OBJECTIVES: The objective of this study was to assess the contribution of clinically significant antiphospholipid antibodies (aPL) to organ damage in systemic lupus erythematosus (SLE). METHODS: Patients with disease duration of less than 10 years and at least 5 years of follow-up were identified from two SLE registries. A clinically significant antiphospholipid antibody (aPL) profile was defined as: positive lupus anticoagulant, anticardiolipin IgG/M ≥ 40 G phospholipid units (GPL)/M phospholipid units (MPL), and/or anti-ß2-glycoprotein-I IgG/M ≥ 99th percentile on two or more occasions, at least 12 weeks apart. Organ damage was assessed by the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Univariate and multivariate analysis compared SLE patients with and without SDI increase during a 15-year follow-up. RESULTS: Among 262 SLE patients, 33% had a clinically significant aPL profile, which was associated with an increased risk of organ damage accrual during a 5-year follow-up in univariate analysis, and during a 15-year follow-up in the multivariate analysis adjusting for age, gender, race, disease duration at registry entry, and time. In the multivariate analysis, older age at diagnosis and male gender were also associated with SDI increase at each time point. CONCLUSION: A clinically significant aPL profile is associated with an increased risk of organ damage accrual during a 15-year follow-up in SLE patients.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Adulto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Índice de Gravidade de Doença , Adulto Jovem
16.
Health Law Can ; 36(4): 174-90, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27476246

RESUMO

This three-part paper presents practical holistic models of determining impairment and occupational disability with respect to common "own occupation" and "any occupation" definitions. The models consider physical, emotional and cognitive impairments in unison, and draw upon case law support for empirically based functional assessment of secondary cognitive symptoms arising from psychological conditions, including chronic pain disorders. Case law is presented, primarily in the context of Ontario motor vehicle accident legislation, to demonstrate how triers of fact have addressed occupational disability in the context of chronic pain; and interpreted the "own occupation" and "any occupation" definitions. In interpreting the definitions of "own occupation" and "any occupation", courts have considered various concepts, such as: work as an integrated whole, competitive productivity, demonstrated job performance vs. employment, work adaptation relative to impairment stability, suitable work, retraining considerations, self-employment, and remuneration/socio-economic status. The first segment of the paper reviews the above concepts largely in the context of pre-104 Income Replacement Benefit (IRB) entitlement, while the second segment focuses on post-104 IRB entitlement. In the final segment, the paper presents a critical evaluation of computerized transferable skills analysis (TSAs) in the occupational disability context. By contrast, support is offered for the notion that (neuro) psychovocational assessments and situational work assessments should play a key role in "own occupation" disability determination, even where specific vocational rehabilitation/retraining recommendations are not requested by the referral source (e.g., insurer disability examination).


Assuntos
Prática Clínica Baseada em Evidências , Modelos Teóricos , Saúde Ocupacional/legislação & jurisprudência , Avaliação da Capacidade de Trabalho , Transtornos Cognitivos/diagnóstico , Fraude/prevenção & controle , Seguro por Deficiência/economia , Ontário
17.
Langmuir ; 29(6): 1790-5, 2013 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-23305466

RESUMO

This article reports a one-step approach for the fabrication of highly uniform, spherical Ag particles with tailored dimensions ranging from 10 to 30 nm. Coated with silica shell, the high uniformity of the particles allows their spontaneous assembly into millimeter-long extended 3-D arrays with transverse dimensions of tens of micrometers, using a microfluidic evaporation-based process.

18.
Child Care Health Dev ; 39(1): 94-102, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22040271

RESUMO

BACKGROUND: Increasing children's participation in physical activity and decreasing time spent in sedentary behaviours is of great importance to public health. Despite living in disadvantaged neighbourhoods, some children manage to engage in health-promoting physical activity and avoid high levels of screen-based activities (i.e. watching TV, computer use and playing electronic games). Understanding how these children manage to do well and whether there are unique features of their home or neighbourhood that explain their success is important for informing strategies targeting less active and more sedentary children. The aim of this qualitative study was to gain in-depth insights from mothers regarding their child's resilience to low physical activity and high screen-time. METHODS: Semi-structured face-to-face interviews were conducted with 38 mothers of children who lived in disadvantaged neighbourhoods in urban and rural areas of Victoria, Australia. The interviews were designed to gain in-depth insights about perceived individual, social and physical environmental factors influencing resilience to low physical activity and high screen-time. RESULTS: Themes relating to physical activity that emerged from the interviews included: parental encouragement, support and modelling; sports culture in a rural town; the physical home and neighbourhood environment; child's individual personality; and dog ownership. Themes relating to screen-time behaviours encompassed: parental control; and child's individual preferences. CONCLUSIONS: The results offer important insights into potential avenues for developing 'resilience' and increasing physical activity and reducing screen-time among children living in disadvantaged neighbourhoods. In light of the negative effects of low physical activity and high levels of screen-time on children's health, this evidence is urgently needed.


Assuntos
Proteção da Criança , Mães/psicologia , Atividade Motora , Comportamento Sedentário , Populações Vulneráveis/psicologia , Adulto , Criança , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Relações Mãe-Filho , Áreas de Pobreza , Pesquisa Qualitativa , Características de Residência , População Rural , Esportes/psicologia , Televisão , População Urbana , Vitória , Jogos de Vídeo/psicologia
19.
Med Sci Sports Exerc ; 55(8): 1456-1464, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36924338

RESUMO

PURPOSE: Previous research has focused on device-based measures of activity compensation, with little understanding of how children perceive potential compensatory responses to activity or inactivity, or whether these change after periods of activity or inactivity. The aim of this study was (a) to explore the alignment between children's self-reported usual compensation and compensation recall after experimental conditions and (b) to examine sex differences. METHODS: In total, 360 children (47% boys) participated in at least one of three experimental conditions over 6 wk: (a) restricted physical activity (PA; indoor play), (b) imposed moderate- to vigorous-intensity PA (MVPA; sports class), and (c) imposed light-intensity PA (LPA; standing lesson). Before the first condition, children reported their "usual compensation" behavior to examples of restricted/imposed PA, and 2-3 d after each experimental condition, they completed a recall measure of their compensation after the condition. Multilevel regression models were conducted to determine whether children's perceptions of "usual compensation" score were associated with recalled compensation score after imposed or restricted PA. Additional models were fitted for sex-specific associations. RESULTS: Overall and among girls, the usual compensation score was positively associated with the compensatory recall score for the additional MVPA and LPA conditions ( P < 0.0005; e.g., they thought they would usually compensate for additional MVPA and then perceived that they compensated after additional MVPA). A negative association was seen in the restricted activity condition among girls ( P = 0.03). All associations in the boys' analyses were statistically nonsignificant. CONCLUSIONS: These findings suggest some alignment between children's self-reported usual compensation and compensation recall after imposed changes to routine activity. Future research should consider device-measured comparisons and identify characteristics of children at risk of activity compensation in future interventions.


Assuntos
Exercício Físico , Esportes , Humanos , Masculino , Criança , Feminino , Autorrelato , Comportamento Infantil
20.
Eur Rev Med Pharmacol Sci ; 27(9): 3993-4005, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37203823

RESUMO

OBJECTIVE: Coronary heart disease (CHD) is the most common cause of mortality and morbidity. Acute coronary syndrome (ACS) is the most advanced form of the CHD spectrum. The triglyceride-glucose index (TGI) and atherogenic plasma index (AIP) are associated with future cardiovascular events. This study investigated the association of these parameters with the severity of CAD and prognosis in the first-diagnosed ACS patients. PATIENTS AND METHODS: Our study was designed retrospectively, including 558 patients. Patients were divided into four subgroups: high and low TGI and high and low AIP. SYNTAX scores, in-hospital mortality, major adverse cardiac events (MACE), and survival were compared at 12-month follow-up. RESULTS: More three-vessel disease and higher SYNTAX scores have been detected in the high AIP and TGI groups. More MACEs have been observed in high AIP and TGI groups than low groups. AIP and TGI were found to be independent predictors for SYNTAX ≥23. While AIP has been found to be an independent risk factor for MACE, TGI has not been detected as an independent risk factor. In addition to AIP, age, three-vessel disease, and lower EF were the independent risk factors for MACE. Survival was lower in high TGP and AIP groups. CONCLUSIONS: AIP and TGI are costless bedside parameters that can be easily calculated. These parameters can predict the severity of CAD in first-diagnosed ACS patients. Besides, AIP is an independent risk factor for MACE. AIP and TGI parameters can guide our treatment in this patient population.


Assuntos
Síndrome Coronariana Aguda , Aterosclerose , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/diagnóstico , Síndrome Coronariana Aguda/diagnóstico , Triglicerídeos , Glucose , Estudos Retrospectivos , Fatores de Risco
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