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Previous diffusion MRI studies have reported mixed findings on white matter microstructure alterations in obsessive-compulsive disorder (OCD), likely due to variation in demographic and clinical characteristics, scanning methods, and underpowered samples. The OCD global study was created across five international sites to overcome these challenges by harmonizing data collection to identify consistent brain signatures of OCD that are reproducible and generalizable. Single-shell diffusion measures (e.g., fractional anisotropy), multi-shell Neurite Orientation Dispersion and Density Imaging (NODDI) and fixel-based measures, were extracted from skeletonized white matter tracts in 260 medication-free adults with OCD and 252 healthy controls. We additionally performed structural connectome analysis. We compared cases with controls and cases with early (<18) versus late (18+) OCD onset using mixed-model and Bayesian multilevel analysis. Compared with healthy controls, adult OCD individuals showed higher fiber density in the sagittal stratum (B[SE] = 0.10[0.05], P = 0.04) and credible evidence for higher fiber density in several other tracts. When comparing early (n = 145) and late-onset (n = 114) cases, converging evidence showed lower integrity of the posterior thalamic radiation -particularly radial diffusivity (B[SE] = 0.28[0.12], P = 0.03)-and lower global efficiency of the structural connectome (B[SE] = 15.3[6.6], P = 0.03) in late-onset cases. Post-hoc analyses indicated divergent direction of effects of the two OCD groups compared to healthy controls. Age of OCD onset differentially affects the integrity of thalamo-parietal/occipital tracts and the efficiency of the structural brain network. These results lend further support for the role of the thalamus and its afferent fibers and visual attentional processes in the pathophysiology of OCD.
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Idade de Início , Encéfalo , Conectoma , Imagem de Tensor de Difusão , Transtorno Obsessivo-Compulsivo , Substância Branca , Humanos , Transtorno Obsessivo-Compulsivo/patologia , Substância Branca/patologia , Adulto , Masculino , Feminino , Conectoma/métodos , Imagem de Tensor de Difusão/métodos , Encéfalo/patologia , Pessoa de Meia-Idade , Imagem de Difusão por Ressonância Magnética/métodos , Adulto Jovem , Anisotropia , Teorema de Bayes , Estudos de Casos e Controles , AdolescenteRESUMO
BACKGROUND: Pseudomonas aeruginosa is a multidrug-resistant pathogen causing recalcitrant pulmonary infections in people with cystic fibrosis (pwCF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been developed that partially correct the defective chloride channel driving disease. Despite the many clinical benefits, studies in adults have demonstrated that while P. aeruginosa sputum load decreases, chronic infection persists. Here, we investigate how P. aeruginosa in pwCF may change in the altered lung environment after CFTR modulation. METHODS: P. aeruginosa strains (n = 105) were isolated from the sputum of 11 chronically colonized pwCF at baseline and up to 21 months posttreatment with elexacaftor-tezacaftor-ivacaftor or tezacaftor-ivacaftor. Phenotypic characterization and comparative genomics were performed. RESULTS: Clonal lineages of P. aeruginosa persisted after therapy, with no evidence of displacement by alternative strains. We identified commonly mutated genes among patient isolates that may be positively selected for in the CFTR-modulated lung. However, classic chronic P. aeruginosa phenotypes such as mucoid morphology were sustained, and isolates remained just as resistant to clinically relevant antibiotics. CONCLUSIONS: Despite the clinical benefits of CFTR modulators, clonal lineages of P. aeruginosa persist that may prove just as difficult to manage in the future, especially in pwCF with advanced lung disease.
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INTRODUCTION: Evaluating the quality of the care pathway for patients with chronic diseases, such as multiple sclerosis (MS), is an important issue. Process indicators are a recognized method for evaluating professional practices. However, these tools have been little developed in the field of MS, and few data are available. The aim of this study was to describe, retrospectively, with validated indicators, the quality of the care pathway in a population-based cohort of 700 patients with the first manifestations of the disease occurring between January 1, 2000 and December 31, 2001 and during the first 10 years of disease. METHOD: This assessment was based on 48 indicators specific to MS. The information required for the calculation of each indicator was collected from the source files of the 700 patients of the cohort. RESULTS: Data for the 10 years of follow-up were collected for 80% of the patients. In total, 36 indicators were calculated. These results reveal that there is room for improvement, particularly in terms of the initial assessment, access to ophthalmological evaluation, employment, obtaining an evaluation of the need for rehabilitation and access to such care. CONCLUSION: The results of this survey provide access to unprecedented new data in France, that professionals and patients can appropriate to improve the targeting of actions, to improve the quality of care further for patients with MS in France. We propose to continue this process by submitting, for discussion, a targeted list of updated indicators relating to changes in guidelines, and in issues concerning the quality of patient management.
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Esclerose Múltipla , Procedimentos Clínicos , França/epidemiologia , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Assessing the quality of care management for patients with a chronic disease such as multiple sclerosis (MS) is a major challenge for healthcare systems around the world. It needs to be carried out using tools that are recognized by professionals and patients alike, and should concern practices, systems, and scientific data. No such tools are currently available in Europe. The purpose of the present study was to develop indicators to contribute to assess the quality of care management for patients with MS in France. METHODS: An expert panel comprising 25 professionals from well known teams across France selected the indicators on the basis of consensus. In accordance with the Rand/UCLA Appropriateness Method, each expert had to agree with the recommendations, and there had to be agreement among the experts. RESULTS: The expert panel selected 48 indicators representing seven domains of care management for patients with MS: physical and rehabilitation medicine, disease progression, access to care, magnetic resonance imaging (MRI) management, relapse management, management of disease-modifying treatments, and management of the symptoms of disability progression. Some of these quality indicators (notably pertaining to MRI management) had not previously been identified in the literature. CONCLUSION: These indicators may allow professionals to comprehensively assess and compare their practices and cooperation, thereby contributing to improve the quality of care management for patients with MS in France.
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Esclerose Múltipla , Consenso , Europa (Continente) , França/epidemiologia , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Qualidade da Assistência à SaúdeRESUMO
BACKGROUND: Six monthly courses of mitoxantrone were approved in France in 2003 for patients with highly active multiple sclerosis (MS). OBJECTIVE: To report the 10-year clinical follow-up and safety of mitoxantrone as an induction drug followed by maintenance therapy in patients with early highly active relapsing-remitting MS (RRMS) and an Expanded Disability Status Scale (EDSS) score<4, 12months prior to mitoxantrone initiation. METHODS: In total, 100 consecutive patients with highly active RRMS from the Rennes EDMUS database received monthly mitoxantrone 20mg combined with methylprednisolone 1g for 3 (n=75) or 6months (n=25) followed by first-line disease-modifying drug (DMD). The 10-year clinical impact was studied through clinical activity, DMD exposure, and adverse events. RESULTS: Twenty-four percent were relapse-free over 10years and the mean annual number of relapses was 0.2 at 10years. The mean EDSS score remained significantly improved for up to 10years, changing from 3.5 at mitoxantrone initiation to 2.7 at 10years. The probability of disability worsening and improvement from mitoxantrone initiation to 10years were respectively 27% and 58%, and 13% converted to secondary progressive MS. Patients only remained untreated or treated with a first-line maintenance DMD for 6.5years in average. In our cohort, mitoxantrone was generally safe. No leukemia was observed and six patients developed neoplasms, including 4 solid cancers. CONCLUSION: Monthly mitoxantrone for 3 or 6months, followed by maintenance first-line treatment, may be an attractive therapeutic option for patients with early highly active RRMS, particularly in low-income countries.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Seguimentos , Humanos , Mitoxantrona/farmacologia , Mitoxantrona/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Crônica Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , RecidivaRESUMO
BACKGROUND: Studies have shown that oral high-dose methylprednisolone (MP) is non-inferior to intravenous MP in treating multiple sclerosis relapses in terms of effectiveness and tolerance. In order to assist with resource allocation and decision-making, its cost-effectiveness must also be assessed. Our objective was to evaluate the cost-utility of per os high-dose MP as well as the cost-savings associated with implementing the strategy. METHODS: A cost-utility analysis at 28 days was carried out using data from the French COPOUSEP multicenter, double-blind randomized controlled non-inferiority trial and the statutory health insurance reimbursement database. Costs were calculated using a societal perspective, including both direct and indirect costs. An incremental cost-effectiveness ratio was calculated and bootstrapping methods assessed the uncertainty surrounding the results. An alternative scenario analysis in which MP was administered at home was also carried out. A budgetary impact analysis was carried at five years. RESULTS: In the conditions of the trial (hospitalized patients), there was no significant difference in utilities and costs at 28 days. The incremental cost-effectiveness ratio was 15,360 per quality-adjusted life-year gained. If multiple sclerosis relapses were treated at home, oral MP would be more effective, less costly and associated with annual savings up to 25 million euros for the French healthcare system. CONCLUSIONS: Oral MP is cost-effective in the treatment of multiple sclerosis relapses and associated with major savings.
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Esclerose Múltipla , Análise Custo-Benefício , Humanos , Metilprednisolona/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , RecidivaRESUMO
OBJECTIVE: Increased autonomic arousal is a proposed risk factor for posttraumatic stress disorder (PTSD). Few studies have prospectively examined the association between physiological responses to acute psychological stress before a traumatic event and later PTSD symptoms. The present prospective study examined whether cardiovascular responses to an acute psychological stress task before the COVID-19 global pandemic predicted PTSD symptoms related to the ongoing pandemic. METHODS: Participants (n = 120) were a subsample of an ongoing research study. Phase 1 consisted of a 10-minute baseline and 4-minute acute psychological stress task with blood pressure and heart rate recorded throughout. Phase 2 was initiated 2 weeks after the COVID-19 pandemic declaration. Participants completed the Impact of Event Scale-Revised (IES-R) with respect to the ongoing pandemic. Hierarchical linear regression analyses were used to examine whether cardiovascular stress reactivity predicted COVID-19 PTSD symptoms. RESULTS: Heart rate reactivity significantly predicted IES intrusion (ß = -0.208, t = -2.28, p = .025, ΔR2 = 0.041, confidence interval = -0.021 to -0.001) and IES hyperarousal (ß = -0.224, t = -2.54, p = .012, ΔR2 = 0.047, confidence interval = -0.22 to - 0.003), but not IES avoidance (p = .077). These results remained statistically significant after adjustment for sex, socioeconomic status, baseline cardiovascular activity, neuroticism, race, ethnicity, body mass index, and adverse childhood experiences. There were no statistically significant associations between blood pressure and any of the Impact of Event Scale-Revised subscales (p values > .12). CONCLUSIONS: Diminished heart rate responses (i.e., lower physiological arousal) to acute psychological stress before the COVID-19 pandemic significantly predicted reported PTSD symptoms during the crisis.
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COVID-19/psicologia , Frequência Cardíaca/fisiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Estresse Psicológico/etiologia , COVID-19/complicações , Feminino , Humanos , Masculino , Pandemias/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/fisiopatologia , Inquéritos e Questionários , Texas/epidemiologia , Adulto JovemRESUMO
BACKGROUND: The ferroxidase zyklopen (Zp) has been implicated in the placental transfer of iron to the fetus. However, the evidence for this is largely circumstantial. OBJECTIVES: This study aimed to determine whether Zp is essential for placental iron transfer. METHODS: A model was established using 8- to 12-wk-old pregnant C57BL/6 mice on standard rodent chow in which Zp was knocked out in the fetus and fetal components of the placenta. Zp was also disrupted in the entire placenta using global Zp knockout mice. Inductively coupled plasma MS was used to measure total fetal iron, an indicator of the amount of iron transferred by the placenta to the fetus, at embryonic day 18.5 of gestation. Iron transporter expression in the placenta was measured by Western blotting, and the expression of Hamp1, the gene encoding the iron regulatory hormone hepcidin, was determined in fetal liver by real-time PCR. RESULTS: There was no change in the amount of iron transferred to the fetus when Zp was disrupted in either the fetal component of the placenta or the entire placenta. No compensatory changes in the expression of the iron transport proteins transferrin receptor 1 or ferroportin were observed, nor was there any change in fetal liver Hamp1 mRNA. Hephl1, the gene encoding Zp, was expressed mainly in the maternal decidua of the placenta and not in the nutrient-transporting syncytiotrophoblast. Disruption of Zp in the whole placenta resulted in a 26% increase in placental size (P < 0.01). CONCLUSIONS: Our data indicate that Zp is not essential for the efficient transfer of iron to the fetus in mice and is localized predominantly in the maternal decidua. The increase in placental size observed when Zp is knocked out in the entire placenta suggests that this protein may play a role in placental development.
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Ceruloplasmina , Placenta , Animais , Ceruloplasmina/genética , Feminino , Feto/metabolismo , Ferro/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Placenta/metabolismo , Placentação , GravidezRESUMO
Invasive predators are known to have negative consumptive and non-consumptive effects on native species, but few examples show how the abundance of native prey may influence an established invasive predator. We compared invasive brown treesnakes (Boiga irregularis; BTS) found in caves occupied by endangered Mariana swiftlets (Aerodramus bartschi) to snakes found in nearby forests and caves without birds to quantify how the abundance of native avian prey impacts BTS abundance and behavior on Guam. From 2011 to 2017 we removed 151 BTS in caves occupied by swiftlets and never observed BTS in caves without birds. Notable locations included snakes foraging near swiftlets and in holes that allowed cave access and escape from capture. Of 43 BTS with gut contents, 27 (63%) contained swiftlets. BTS in swiftlet-occupied caves had greater fat mass compared to forests, indicating access to swiftlets may increase body condition and promote reproduction. Number of ovarian follicles was significantly greater in female snakes from swiftlet-occupied caves compared to those from ravine, but not limestone forests; evidence of male BTS being more capable of reproduction was limited (i.e., fewer non-discernible but not significantly larger testes in snakes from caves). Assuming other limiting factors are considered, altering the functional response of predators through the modification of caves or interdiction lures to exclude or hinder the largest BTS could bolster swiftlet populations by increasing nesting refugia in currently-occupied caves and facilitate recolonization of historical caves.
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Colubridae , Aves Predatórias , Animais , Aves , Feminino , Florestas , Guam , Masculino , Comportamento PredatórioRESUMO
BACKGROUND: Most data regarding the use of disease-modifying therapies (DMTs) in multiple sclerosis (MS) comes from clinical series or regional databases that have a risk of recruitment bias. French health administrative data offers the significant advantage of being extensive in regards to both MS population coverage and DMT prescriptions. OBJECTIVES: To describe patterns of DMTs usage at the level of the entire French population of MS patients from 2010 to 2015. METHODS: MS patients were identified during a 6-year study period via the French national health data system (covering 97% of the general population) and characteristics of patients who received at least one treatment were compared to those that never received treatment over the indicated period. A state sequence analysis was performed to study in a longitudinal way MS patients who started DMTs in 2010 and then to classify them into groups of similar therapeutic patterns. DMTs were categorized into first-line, second-line and off-label use, and included untreated periods for at least six months. Groups that were obtained were described and compared using a multinomial logistic regression. RESULTS: A total of 112,415 patients with MS were identified, of whom 54.0% received at least one DMT over the 6 years. The probability of being treated significantly decreased with age. Comorbidities and physical limitations appeared to be more frequent in not treated patients than in treated patients. Significant differences were also found between the two groups regarding the use of healthcare services (hospitalizations and visits to general practitioner, neurologist and nurse). Based on the 6-year therapeutic sequences, a four-cluster typology was obtained on the 4,474 patients who started a DMT in 2010. The first group which consisted of more than half of the patients (57.0%) mainly used first-line DMTs. The second group (13.1%) represented patients with second-line DMTs whereas the third group (7.3%) was comprised of off-label users and the last group (22.6%) was composed of MS patients who received no or minimal treatments. Classification into one of these groups was associated with patient's age, long-term disease status, pregnancy occurrence, estimated level of disability, levels of care (visits to a neurologist, nurse and/or physiotherapist and hospital/rehabilitation stays) and occurrence of death. CONCLUSIONS: The exhaustive population-based dataset from the French national health data system gave the opportunity to provide a detailed description regarding the use of DMTs for MS at national level. The innovative method of state sequence analysis allowed obtaining four homogeneous groups of patients among thousands of longitudinal therapeutic sequences. The predominant place of first-line treatments was confirmed even if the type of first-line treatments has probably changed since 2015.
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Esclerose Múltipla , Bases de Dados Factuais , França/epidemiologia , Hospitalização , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologiaRESUMO
The Veterinary Internship and Residency Matching Program (VIRMP) recently revised its electronic standardized letter of reference (SLOR) to improve the quality and usefulness of the data obtained from it and to enhance the relevance of non-cognitive and cognitive candidate attributes assessed. We used a stepwise process including a broad survey of SLOR readers and writers, analysis of past SLORs, and a multi-wave iterative revision that included key stakeholders, such as residency and internship program directors from academia and private practice. Data from the SLOR survey and analysis of past SLOR responses identified opportunities to improve applicant differentiation, mitigate positive bias, and encourage response consistency. The survey and other analytics identified and confirmed performance domains of high relevance. The revised SLOR assesses four performance domains: knowledge base and clinical skills, stress and time management, interpersonal skills, and personal characteristics. Ratings within the revised SLOR are predominantly criterion-referenced to enhance discernment of candidate attributes contained within each domain. Questions assessing areas of strength and targeted mentoring were replaced with free-text boxes, which allow writers to comment on positive and neutral/negative ratings of attributes within domains. Minor revisions were made to certain questions to enhance readability, streamline responses, or address targeted concerns identified in the SLOR survey or stakeholder review. The revised SLOR was deployed in the 2020 VIRMP; data from a survey of writers (n = 647) and readers (n = 378) indicate that the redesign objectives were achieved.
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Educação em Veterinária , Internato e Residência , Animais , Competência Clínica , Seleção de Pessoal , Inquéritos e QuestionáriosRESUMO
AIM: To determine whether outcomes for people with diabetes undergoing elective surgery improve following the introduction of innovations in the peri-operative care pathway. METHODS: Following a baseline audit of 185 people with diabetes listed for elective surgery (July to December 2017) with a length of stay > 24 hours, a number of changes in practice were implemented. These included dissemination of a 'diabetes peri-operative passport' to participants preoperatively, formation of a diabetes surgery working group, recruitment of surgical diabetes champions and the roll-out of surgical diabetes study days. Crucial was recruitment of a diabetes peri-operative nurse, whose role included engaging and educating others and supporting individuals throughout their peri-operative diabetes care. Records of 166 individuals listed for surgery during the implementation period (July to December 2018) were then audited using the same methodology. RESULTS: The availability of a recent HbA1c measurement significantly increased (63% vs 92%; P ≤ 0.001). The mean HbA1c of those seen for optimizations by the diabetes peri-operative nurse significantly decreased [84 mmol/mol (9.8%) vs 62 mmol/mol (7.8%); P ≤ 0.001]. Recurrent hypoglycaemia significantly decreased (7.0% vs 0.6%; P = 0.002) and the mean number of hyperglycaemic events in people experiencing hyperglycaemia almost halved (3.0 vs 1.7; P=0.007). The mean length of hospital stay significantly decreased (4.8 vs 3.3 days; P=0.001) and, crucially, 30-day readmissions did not increase (12% vs 9%; P=0.307). Postoperative complications significantly decreased (28% vs 16%; P=0.008), including a composite of dysglycaemic complications, poor wound healing, wound infection and other infections (12% vs 5.4%; P=0.023). CONCLUSION: The new pathway improved important peri-operative outcomes for people with diabetes undergoing elective surgery with the potential for cost savings. These findings could have important implications for peri-operative care on a wider scale.
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Diabetes Mellitus/terapia , Procedimentos Cirúrgicos Eletivos , Hipoglicemia/epidemiologia , Tempo de Internação/estatística & dados numéricos , Enfermeiros Especialistas , Readmissão do Paciente/estatística & dados numéricos , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus/metabolismo , Feminino , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico , Humanos , Hipoglicemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/enfermagem , Enfermagem Perioperatória , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
The UK National Diabetes Inpatient COVID Response Group was formed at the end of March 2020 to support the provision of diabetes inpatient care during the COVID pandemic. It was formed in response to two emerging needs. First to ensure that basic diabetes services are secured and maintained at a time when there was a call for re-deployment to support the need for general medical expertise across secondary care services. The second was to provide simple safe diabetes guidelines for use by specialists and non-specialists treating inpatients with or suspected of COVID-19 infection. To date the group, comprising UK-based specialists in diabetes, pharmacy and psychology, have produced two sets of guidelines which will be continually revised as new evidence emerges. It is supported by Diabetes UK, the Association of British Clinical Diabetologists and NHS England.
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Infecções por Coronavirus/terapia , Atenção à Saúde/métodos , Diabetes Mellitus/terapia , Hospitalização , Pneumonia Viral/terapia , Betacoronavirus , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Diabetes Mellitus/epidemiologia , Gerenciamento Clínico , Humanos , Pandemias , Readmissão do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , SARS-CoV-2 , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Gonorrhea is the second most commonly reported notifiable condition in the United States. Infrequently, Neisseria gonorrhoeae can cause disseminated gonococcal infection (DGI). Eculizumab, a monoclonal antibody, inhibits terminal complement activation, which impairs the ability of the immune system to respond effectively to Neisseria infections. This series describes cases of N. gonorrhoeae infection among patients receiving eculizumab. METHODS: Pre- and postmarketing safety reports of N. gonorrhoeae infection in patients receiving eculizumab worldwide were obtained from US Food and Drug Administration safety databases and the medical literature, including reports from the start of pivotal clinical trials in 2004 through 31 December 2017. Included patients had at least 1 eculizumab dose within the 3 months prior to N. gonorrhoeae infection. RESULTS: Nine cases of N. gonorrhoeae infection were identified; 8 were classified as disseminated (89%). Of the disseminated cases, 8 patients required hospitalization, 7 had positive blood cultures, and 2 required vasopressor support. One patient required mechanical ventilation. Neisseria gonorrhoeae may have contributed to complications prior to death in 1 patient; however, the fatality was attributed to underlying disease per the reporter. CONCLUSIONS: Patients receiving eculizumab may be at higher risk for DGI than the general population. Prescribers are encouraged to educate patients receiving eculizumab on their risk for serious gonococcal infections and perform screening for sexually transmitted diseases (STDs) per the Centers for Disease Control and Prevention STD treatment guidelines or in suspected cases. If antimicrobial prophylaxis is used during eculizumab therapy, prescribers should consider trends in gonococcal antimicrobial susceptibility due to emerging resistance concerns.
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Anticorpos Monoclonais Humanizados/efeitos adversos , Infecções por Neisseriaceae , Adolescente , Adulto , Inativadores do Complemento/efeitos adversos , Feminino , Gonorreia/diagnóstico , Gonorreia/etiologia , Humanos , Hospedeiro Imunocomprometido , Infecções por Neisseriaceae/diagnóstico , Infecções por Neisseriaceae/etiologia , Adulto JovemAssuntos
Anticorpos Antivirais , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Esclerose Múltipla , Natalizumab , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/etiologia , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/imunologia , Natalizumab/efeitos adversos , Natalizumab/uso terapêutico , Vírus JC/imunologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/complicações , Evolução Fatal , Anticorpos Antivirais/sangue , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Feminino , Adulto , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
Previous work suggests that key factors for replicability, a necessary feature for theory building, include statistical power and appropriate research planning. These factors are examined by analyzing a collection of 12 standardized meta-analyses on language development between birth and 5 years. With a median effect size of Cohen's d = .45 and typical sample size of 18 participants, most research is underpowered (range = 6%-99%; median = 44%); and calculating power based on seminal publications is not a suitable strategy. Method choice can be improved, as shown in analyses on exclusion rates and effect size as a function of method. The article ends with a discussion on how to increase replicability in both language acquisition studies specifically and developmental research more generally.
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Desenvolvimento da Linguagem , Linguagem Infantil , Pré-Escolar , Fixação Ocular/fisiologia , Humanos , Lactente , Metanálise como Assunto , Projetos de Pesquisa , Tamanho da AmostraRESUMO
The concept of induction followed by a long-term maintenance treatment has attracted much attention for the treatment of multiple sclerosis over the 30 past years. It was first demonstrated by the combination of induction therapy with mitoxantrone (six-monthly courses) followed by maintenance therapy with an immunomodulatory treatment such as an interferon-ß or glatiramer acetate. Long-term observational studies confirmed that this therapeutic regimen provides a rapid reduction in disease activity and sustained disease control up to at least five years in 60% of patients. A better treatment response was observed in patients with early signs of aggressive disease, as shown in randomised studies (using six-monthly 12mg/m2 of mitoxantrone intravenously at a cumulative dose of 72mg/m2, followed by an interferon-ß) as well as in long-term observational studies. But the safety profile of mitoxantrone make it more particularly suitable for young patients with frequent early relapses with incomplete recovery and multiple gadolinium-enhancing T1 lesions or spinal cord lesions on magnetic resonance imaging. More recently approved, the second candidate for an induction strategy is alemtuzumab: phases II and III randomised studies showed the superiority of alemtuzumab 12mg per day given intravenously for only five days and repeated for 3 days one year later, compared with interferon-ß three times a week. Like with mitoxantrone, results supported the concept of long-term benefit after a short induction rather than escalation, in a subset of patients with early very active MS, with a sustained control of the disease for up to 7 years in 60% of patients in the phase III extension studies and in a long-term observational study. On the contrary, when alemtuzumab was first studied later in the disease course, results were disappointing. However, the risk of developing manageable but potentially severe systemic autoimmune diseases within the years following the last course of alemtuzumab make it, like mitoxantrone, more suitable for patients with early aggressive MS. More recently, cladribine an oral immunosuppressant, showed interesting results in a phase III study extension suggesting its potential induction effect, since after two cycles of treatment (5 days repeated 1 month later) at one year of interval, the remained low up to 4 years of follow-up, in the absence of any new treatment. However, today other immunosuppressive drugs have proved to be strongly and rapidly efficacious in treating highly active MS patients but through a mechanism of continuous immunosuppression (i.e., natalizumab and ocrelizumab). Indeed, disease activity can reappear rapidly after stopping these drugs, sometimes associated with a rebound of the inflammatory process, which is the contrary of a mechanism of induction that is associated with a remnant effect. Taking into account advantages and disadvantages of the different DMDs, which enriched the today therapeutic arsenal for MS, we propose in this paper some algorithms summarizing our reflexion about using an escalation strategy or an induction strategy according to disease course and activity.
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Imunossupressores/administração & dosagem , Esclerose Múltipla/tratamento farmacológico , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Imunossupressores/efeitos adversos , Esclerose Múltipla/patologiaRESUMO
BACKGROUND: Launched in the US in 2012, Choosing Wisely® is a campaign promoted by the American Board of Internal Medicine (ABIM) Foundation with the goal of improving healthcare effectiveness by avoiding wasteful or unnecessary medical tests, treatments and procedures. It uses concise recommendations produced by national medical societies to start discussions between physicians and patients on the relevance of these services as part of a shared decision-making process. The Multiple Sclerosis Focus Group (Groupe de Reflexion Autour de la Sclérose en Plaques; GRESEP) undertook a pilot study to assess the relevance and feasibility of this approach in the management of multiple sclerosis (MS) in France. METHODS: Recommendations were developed using the formal consensus method from the guidelines of the French National Health Authority (HAS). A steering committee selected the themes and drafted concise evidence reviews. An independent rating group then assessed these recommendations for clarity, relevance and feasibility. RESULTS: Seven recommendations were accepted: (1) avoid systematic ordering of multimodal evoked potential studies for diagnosing MS; (2) do not treat MS relapses with low-dose oral corticosteroids; (3) when treating MS relapse with high-dose corticosteroids, the systematic use of the intravenous route is unnecessary if the oral route can be used; (4) systematic hospitalization is not necessary for treating MS relapse with high-dose corticosteroid therapy, particularly if the oral route is used, except for the first treated relapse and the presence of exclusion or non-eligibility criteria; (5) in the absence of clinical signs or symptoms of urinary infection, avoid systematic screening with urine microscopy and culture before the administration of corticosteroid therapy for MS relapse in patients using intermittent self-catheterization; (6) avoid antibiotic treatment of clinically asymptomatic MS patients using intermittent self-catheterization, even if urine microscopy and culture reveal the presence of microorganisms; and (7) avoid introducing symptomatic drug treatment for MS-related fatigue. CONCLUSION: This pilot study, the first of its kind in France, has demonstrated the relevance and feasibility of adapting the Choosing Wisely® model to MS by practitioners specializing in the disorder. However, the acceptability of these recommendations by other practitioners in other specialist fields as well as their impact on everyday clinical practices now need to be studied.
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Gerenciamento Clínico , Esclerose Múltipla/terapia , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Tomada de Decisões , Estudos de Viabilidade , França , Guias como Assunto , Humanos , Esclerose Múltipla/diagnóstico , Participação do Paciente , Pacientes , Médicos , Projetos Piloto , Recidiva , Procedimentos Desnecessários , UrináliseRESUMO
AIM: To determine whether a handheld 'perioperative passport' could improve the experience of perioperative care for people with diabetes and overcome some of the communication issues commonly identified in inpatient extracts. METHODS: Individuals with diabetes undergoing elective surgery requiring at least an overnight stay were identified via a customized information technology system. Those allocated to the passport group were given the perioperative passport before their hospital admission. A 26-item questionnaire was completed after surgery by 50 participants in the passport group (mean age 69 years) and by 35 participants with diabetes who followed the usual surgical pathway (mean age 70 years). In addition, the former group had a structured interview about their experience of the passport. RESULTS: The prevalence of those who reported having received prior information about their expected diabetes care was 35% in the control group vs 92% in the passport group (P<0.001). The passport group found the information given significantly more helpful (P<0.001), including the advice on medication adjustment (P=0.008). Furthermore, those with the passport were more involved in planning their diabetes care (P <0.001), less anxious whilst in hospital (P<0.044) and better prepared to manage their diabetes on discharge (P≤0.001). The mean length of hospital stay was shorter in the passport group, although the difference did not reach significance (4.4 vs 6.5 days; P<0.058). Content analysis indicated that the passport was well liked and innovative. CONCLUSION: Our data indicate that the perioperative passport is effective in both informing and involving people in their diabetes care throughout the perioperative period.
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Procedimentos Clínicos/organização & administração , Diabetes Mellitus/terapia , Prontuários Médicos/normas , Participação do Paciente/métodos , Assistência Perioperatória/normas , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Comunicação , Procedimentos Clínicos/normas , Procedimentos Cirúrgicos Eletivos/métodos , Procedimentos Cirúrgicos Eletivos/psicologia , Procedimentos Cirúrgicos Eletivos/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente/organização & administração , Planejamento de Assistência ao Paciente/normas , Assistência Perioperatória/métodos , Relações Médico-Paciente , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Increased risk of prostate cancer (PCa) is observed in men with BRCA1/BRCA2 mutations. Sex and gender are key determinants of health and disease although unequal care exists between the sexes. Stereotypical male attitudes are shown to lead to poor health outcomes. METHODS: Men with BRCA1/2 mutations and diagnosed with PCa were identified and invited to participate in a qualitative interview study. Data were analysed using a framework approach. "Masculinity theory" was used to report the impact of having both a BRCA1/2 mutation and PCa. RESULTS: Eleven of 15 eligible men were interviewed. The umbrella concept of "Ambiguity in a Masculine World" was evident. Men's responses often matched those of women in a genetic context. Men's BRCA experience was described, as "on the back burner" but "a bonus" enabling familial detection and early diagnosis of PCa. Embodiment of PCa took precedence as men revealed stereotypical "ideal" masculine responses such as stoicism and control while creating new "masculinities" when faced with the vicissitudes of having 2 gendered conditions. CONCLUSION: Health workers are urged to take a reflexive approach, void of masculine ideals, a belief in which obfuscates men's experience. Research is required regarding men's support needs in the name of equality of care.