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2.
J Clin Microbiol ; 58(11)2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-32817233

RESUMO

We prospectively compared health care worker-collected nasopharyngeal swabs (NPS) to self-collected anterior nasal swabs (ANS) and straight saliva for the diagnosis of coronavirus disease 2019 (COVID-19) in 354 patients. The percent positive agreement between NPS and ANS or saliva was 86.3% (95% confidence interval [CI], 76.7 to 92.9%) and 93.8% (95% CI, 86.0 to 97.9%), respectively. The percent negative agreement was 99.6% (95% CI, 98.0 to 100.0%) for NPS versus ANS and 97.8% (95% CI, 95.3 to 99.2%) for NPS versus saliva. More cases were detected by the use of NPS (n = 80) and saliva (n = 81) than by the use of ANS (n = 70), but no single specimen type detected all severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Técnicas de Diagnóstico Molecular , Pneumonia Viral/diagnóstico , Manejo de Espécimes/métodos , Adolescente , Adulto , Idoso , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Nariz/virologia , Pandemias , SARS-CoV-2 , Saliva/virologia , Autocuidado , Adulto Jovem
3.
Mol Autism ; 11(1): 12, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024554

RESUMO

BACKGROUND: Williams syndrome (WS) and autism spectrum disorder (ASD) are neurodevelopmental disorders that demonstrate overlapping genetic associations, dichotomous sociobehavioral phenotypes, and dichotomous pathological differences in neuronal distribution in key social brain areas, including the prefrontal cortex and the amygdala. The serotonergic system is critical to many processes underlying neurodevelopment and is additionally an important neuromodulator associated with behavioral variation. The amygdala is heavily innervated by serotonergic projections, suggesting that the serotonergic system is a significant mediator of neuronal activity. Disruptions to the serotonergic system, and atypical structure and function of the amygdala, are implicated in both WS and ASD. METHODS: We quantified the serotonergic axon density in the four major subdivisions of the amygdala in the postmortem brains of individuals diagnosed with ASD and WS and neurotypical (NT) brains. RESULTS: We found opposing directions of change in serotonergic innervation in the two disorders, with ASD displaying an increase in serotonergic axons compared to NT and WS displaying a decrease. Significant differences (p < 0.05) were observed between WS and ASD data sets across multiple amygdala nuclei. LIMITATIONS: This study is limited by the availability of human postmortem tissue. Small sample size is an unavoidable limitation of most postmortem human brain research and particularly postmortem research in rare disorders. CONCLUSIONS: Differential alterations to serotonergic innervation of the amygdala may contribute to differences in sociobehavioral phenotype in WS and ASD. These findings will inform future work identifying targets for future therapeutics in these and other disorders characterized by atypical social behavior.


Assuntos
Tonsila do Cerebelo/patologia , Transtorno do Espectro Autista/patologia , Axônios/patologia , Serotonina , Síndrome de Williams/patologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
BMJ Glob Health ; 5(2): 1-13, Feb., 2020. graf., tab.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1052967

RESUMO

BACKGROUND: Non-communicable diseases (NCDs) are the leading cause of death globally. In 2014, the United Nations committed to reducing premature mortality from NCDs, including by reducing the burden of healthcare costs. Since 2014, the Prospective Urban and Rural Epidemiology (PURE) Study has been collecting health expenditure data from households with NCDs in 18 countries. METHODS: Using data from the PURE Study, we estimated risk of catastrophic health spending and impoverishment among households with at least one person with NCDs (cardiovascular disease, diabetes, kidney disease, cancer and respiratory diseases; n=17 435), with hypertension only (a leading risk factor for NCDs; n=11 831) or with neither (n=22 654) by country income group: high-income countries (Canada and Sweden), upper middle income countries (UMICs: Brazil, Chile, Malaysia, Poland, South Africa and Turkey), lower middle income countries (LMICs: the Philippines, Colombia, India, Iran and the Occupied Palestinian Territory) and low-income countries (LICs: Bangladesh, Pakistan, Zimbabwe and Tanzania) and China. RESULTS: The prevalence of catastrophic spending and impoverishment is highest among households with NCDs in LMICs and China. After adjusting for covariates that might drive health expenditure, the absolute risk of catastrophic spending is higher in households with NCDs compared with no NCDs in LMICs (risk difference=1.71%; 95% CI 0.75 to 2.67), UMICs (0.82%; 95% CI 0.37 to 1.27) and China (7.52%; 95% CI 5.88 to 9.16). A similar pattern is observed in UMICs and China for impoverishment. A high proportion of those with NCDs in LICs, especially women (38.7% compared with 12.6% in men), reported not taking medication due to costs. CONCLUSIONS: Our findings show that financial protection from healthcare costs for people with NCDs is inadequate, particularly in LMICs and China. While the burden of NCD care may appear greatest in LMICs and China, the burden in LICs may be masked by care foregone due to costs. The high proportion of women reporting foregone care due to cost may in part explain gender inequality in treatment of NCDs. (AU)


Assuntos
Sistemas de Saúde , Doenças Cardiovasculares , Seguro Saúde , Diabetes Mellitus
5.
Neuroimage Clin ; 22: 101800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30991618

RESUMO

The threshold for amyloid positivity by visual assessment on PET has been validated by comparison to amyloid load measured histopathologically and biochemically at post mortem. As such, it is now feasible to use qualitative visual assessment of amyloid positivity as an in-vivo gold standard to determine those factors which can modify the quantitative threshold for amyloid positivity. We calculated quantitative amyloid load, measured as Standardized Uptake Value Ratios (SUVRs) using [18-F]florbetaben PET scans, for 159 Hispanic and non-Hispanic participants, who had been classified clinically as Cognitively Normal (CN), Mild Cognitive Impairment (MCI) or Dementia (DEM). PET scans were visually rated as amyloid positive (A+) or negative (A-), and these judgments were used as the gold standard with which to determine (using ROC analyses) the SUVR threshold for amyloid positivity considering factors such as age, ethnicity (Hispanic versus non-Hispanic), gender, cognitive status, and apolipoprotein E ε4 carrier status. Visually rated scans were A+ for 11% of CN, 39.0% of MCI and 70% of DEM participants. The optimal SUVR threshold for A+ among all participants was 1.42 (sensitivity = 94%; specificity = 92.5%), but this quantitative threshold was higher among E4 carriers (SUVR = 1.52) than non-carriers (SUVR = 1.31). While mean SUVRs did not differ between Hispanic and non-Hispanic participants;, a statistically significant interaction term indicated that the effect of E4 carrier status on amyloid load was greater among non-Hispanics than Hispanics. Visual assessment, as the gold standard for A+, facilitates determination of the effects of various factors on quantitative thresholds for amyloid positivity. A continuous relationship was found between amyloid load and global cognitive scores, suggesting that any calculated threshold for the whole group, or a subgroup, is artefactual and that the lowest calculated threshold may be optimal for the purposes of early diagnosis and intervention.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Disfunção Cognitiva , Demência , Hispânico ou Latino , Neuroimagem/normas , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina , Disfunção Cognitiva/etnologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Demência/etnologia , Demência/genética , Demência/metabolismo , Demência/fisiopatologia , Feminino , Hispânico ou Latino/genética , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/normas , Sensibilidade e Especificidade , Fatores Sexuais , Estilbenos
6.
J Clin Microbiol ; 54(3): 785-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26719436

RESUMO

We evaluated a multiplexed PCR panel for the detection of 16 bacterial, viral, and fungal pathogens in cerebrospinal fluid. Panel results were compared to routine testing, and discrepancies were resolved by additional nucleic acid amplification tests or sequencing. Overall, the positive and negative agreements across methods were 92.9% and 91.9%, respectively.


Assuntos
Automação , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/etiologia , Reação em Cadeia da Polimerase Multiplex , Humanos , Reação em Cadeia da Polimerase Multiplex/métodos , Kit de Reagentes para Diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
7.
Lab Chip ; 16(4): 668-78, 2016 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-26725379

RESUMO

The miniaturization of integrated fluidic processors affords extensive benefits for chemical and biological fields, yet traditional, monolithic methods of microfabrication present numerous obstacles for the scaling of fluidic operators. Recently, researchers have investigated the use of additive manufacturing or "three-dimensional (3D) printing" technologies - predominantly stereolithography - as a promising alternative for the construction of submillimeter-scale fluidic components. One challenge, however, is that current stereolithography methods lack the ability to simultaneously print sacrificial support materials, which limits the geometric versatility of such approaches. In this work, we investigate the use of multijet modelling (alternatively, polyjet printing) - a layer-by-layer, multi-material inkjetting process - for 3D printing geometrically complex, yet functionally advantageous fluidic components comprised of both static and dynamic physical elements. We examine a fundamental class of 3D printed microfluidic operators, including fluidic capacitors, fluidic diodes, and fluidic transistors. In addition, we evaluate the potential to advance on-chip automation of integrated fluidic systems via geometric modification of component parameters. Theoretical and experimental results for 3D fluidic capacitors demonstrated that transitioning from planar to non-planar diaphragm architectures improved component performance. Flow rectification experiments for 3D printed fluidic diodes revealed a diodicity of 80.6 ± 1.8. Geometry-based gain enhancement for 3D printed fluidic transistors yielded pressure gain of 3.01 ± 0.78. Consistent with additional additive manufacturing methodologies, the use of digitally-transferrable 3D models of fluidic components combined with commercially-available 3D printers could extend the fluidic routing capabilities presented here to researchers in fields beyond the core engineering community.

8.
Antimicrob Agents Chemother ; 59(11): 6725-32, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26282428

RESUMO

Neither breakpoints (BPs) nor epidemiological cutoff values (ECVs) have been established for Candida spp. with anidulafungin, caspofungin, and micafungin when using the Sensititre YeastOne (SYO) broth dilution colorimetric method. In addition, reference caspofungin MICs have so far proven to be unreliable. Candida species wild-type (WT) MIC distributions (for microorganisms in a species/drug combination with no detectable phenotypic resistance) were established for 6,007 Candida albicans, 186 C. dubliniensis, 3,188 C. glabrata complex, 119 C. guilliermondii, 493 C. krusei, 205 C. lusitaniae, 3,136 C. parapsilosis complex, and 1,016 C. tropicalis isolates. SYO MIC data gathered from 38 laboratories in Australia, Canada, Europe, Mexico, New Zealand, South Africa, and the United States were pooled to statistically define SYO ECVs. ECVs for anidulafungin, caspofungin, and micafungin encompassing ≥97.5% of the statistically modeled population were, respectively, 0.12, 0.25, and 0.06 µg/ml for C. albicans, 0.12, 0.25, and 0.03 µg/ml for C. glabrata complex, 4, 2, and 4 µg/ml for C. parapsilosis complex, 0.5, 0.25, and 0.06 µg/ml for C. tropicalis, 0.25, 1, and 0.25 µg/ml for C. krusei, 0.25, 1, and 0.12 µg/ml for C. lusitaniae, 4, 2, and 2 µg/ml for C. guilliermondii, and 0.25, 0.25, and 0.12 µg/ml for C. dubliniensis. Species-specific SYO ECVs for anidulafungin, caspofungin, and micafungin correctly classified 72 (88.9%), 74 (91.4%), 76 (93.8%), respectively, of 81 Candida isolates with identified fks mutations. SYO ECVs may aid in detecting non-WT isolates with reduced susceptibility to anidulafungin, micafungin, and especially caspofungin, since testing the susceptibilities of Candida spp. to caspofungin by reference methodologies is not recommended.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Equinocandinas/farmacologia , Lipopeptídeos/farmacologia , Anidulafungina , Candida/genética , Caspofungina , Micafungina , Testes de Sensibilidade Microbiana , Mutação/genética
9.
Aliment Pharmacol Ther ; 42(4): 428-40, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26081839

RESUMO

BACKGROUND: Certolizumab pegol (CZP) is Food and Drug Administration (FDA)-approved to treat Crohn's disease (CD). However, the efficacy and safety of CZP outside clinical trials are not well established. AIM: To report the efficacy, safety and predictors of response to CZP in CD patients treated during a 6-year period since FDA-approval at a tertiary care centre. METHODS: All CD patients who received CZP at our institution between 2008 and 2013 were evaluated through retrospective medical record-based review of steroid-free complete response (SCR), loss of response and safety. RESULTS: A total of 358 patients were included. One hundred twelve patients (31.3%) and 189 (52.8%) received CZP as their second and third biological agent, respectively. The probability of SCR at 26 week was 19.9% (95% CI, 15.9-24.5). The probability of survival free of loss of response at 2 year was 45.7% (95% CI, 32.5-59.5). A predictor of SCR was age at CD diagnosis of >40 years old (hazard ratio, HR relative to those <17, 4.69; 95% CI, 1.75-12.61). Negative predictors included present perianal fistula (HR, 0.39; 95% CI, 0.16-0.98) and prior primary nonresponse to adalimumab (ADA; HR relative to secondary loss of response, 0.18; 95% CI, 0.04-0.76). Twenty-three patients (6.4%) experienced serious adverse events and 19 patients (5.3%) discontinued CZP due to adverse events. CONCLUSIONS: Certolizumab pegol was both effective and well tolerated for the treatment of Crohn's disease in this large tertiary care centre enriched with biologics-exposed patients. It may be more effective in patients without early-aged Crohn's disease diagnosis, prior primary nonresponse to adalimumab and present perianal fistula.


Assuntos
Certolizumab Pegol/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fístula Retal/patologia , Adalimumab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Produtos Biológicos/uso terapêutico , Certolizumab Pegol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration , Adulto Jovem
10.
IEEE Trans Nanobioscience ; 14(3): 313-22, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25622324

RESUMO

Protein molecular motors, which convert, directly and efficiently, chemical energy into motion, are excellent candidates for integration in hybrid dynamic nanodevices. To integrate and use the full potential of molecular motors in these devices, their design requires a quantitative and precise prediction of the fundamental mechanical and physicochemical features of cytoskeletal proteins operating in artificial environments. In that regard, the behavior of protein molecular motors constructs in/on nano-confined spaces or nanostructured surfaces that aim to control their motility is of critical interest. Here, we used a standard gliding motility assay to study the actin filaments sliding on a surface comprising heavy mero myosin (HMM) micro- and nano-patterns. To print HMM, we used negative tone, micro contact printing of a blocking protein (bovine serum albumin, BSA) on a nitrocellulose surface, followed by specific adsorption of HMM on BSA-free surfaces. While the large BSA-free patterns allowed for selective confinement of actin filaments motility, the BSA-stamped areas displayed intricate nano-sized HMM patterns, which enabled a deeper analysis of the nano-mechanics of actomyosin motility in confined spaces.


Assuntos
Citoesqueleto de Actina/metabolismo , Bioimpressão/métodos , Miosinas/metabolismo , Nanotecnologia/métodos , Citoesqueleto de Actina/química , Animais , Músculo Esquelético/química , Miosinas/química , Coelhos , Propriedades de Superfície
11.
New Dir Youth Dev ; 2014(143): 103-31, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25530243

RESUMO

Little is known about how the adoption of evidence-based physical activity (PA) curricula by out-of-school time (OST) programs affects children's physical fitness, and there are no clear guidelines of what constitutes reasonable gains given the types of PA instruction currently offered in these programs. Using a three-wave, quasi-experimental, naturalistic observation design, this study evaluated the implementation of an evidence-based PA instruction curriculum (Sports, Play, and Active Recreation for Kids [SPARK]) and examined whether the potential health benefits of evidence-based PA instruction can be replicated in this context when compared to OST programs that do not use evidence-based PA curricula. Quality of PA instruction and SPARK implementation fidelity were also assessed. Results indicated that children in the non-evidence-based/standard PA instruction programs engaged in higher levels of moderate-to-vigorous PA (MVPA) and showed greater improvements in fitness levels over time. The findings from this chapter suggest that while it is generally accepted that evidence-based approaches yield higher levels of PA when implemented by researchers under controlled conditions, findings are inconsistent when evidence-based PA instruction is implemented in the field, under presumably less controlled conditions. It appears that when it comes to PA instruction in afterschool, either less structured activities or well-implemented evidence-based practices could be the key to promoting higher PA levels and greater health and fitness for school-aged children.


Assuntos
Currículo , Prática Clínica Baseada em Evidências/métodos , Exercício Físico , Promoção da Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde , Aptidão Física , Adolescente , Criança , Feminino , Humanos , Masculino , Instituições Acadêmicas
12.
J Vet Intern Med ; 28(5): 1442-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25274438

RESUMO

BACKGROUND: Endoscopy is performed for direct inspection of the mucosa and acquisition of biopsies in dogs with inflammatory bowel disease (IBD). AIM: To evaluate the interobserver agreement in the endoscopic assessment of duodenal mucosa in dogs with IBD. METHODS: Thirty-five archived endoscopic images of grossly normal (n = 6) and inflamed (n = 29) duodenal mucosa were displayed to 3 expert and 5 trainee endoscopists. Each image was assessed independently by endoscopists for mucosal abnormalities using established indices (of hyperemia, granularity, friability, lymphatic dilatation, and erosions) or interpreted as normal mucosa (trial 1). A repeated trial (trial 2) was performed with the same images presented in random order 1 month later, and accompanied by a visual template. RESULTS: There was slight interobserver agreement in initial mucosal assessment for expert and trainee endoscopists in trial 1 (kappa ≤ 0.02, P > .05). Interobserver agreement improved in trial 2 for both expert and trainee endoscopists (kappa = 0.2, P > .05) for experts and (P < .05) for trainees. There was a significant (P < .01) improvement in trainee endoscopy scores of lesions from trial 1 to trial 2. Regression analysis showed a significant (P < .01) difference between expert versus trainee endoscopy scores in trial 1. Repeat lesion assessment aided by use of a visual template (trial 2) improved the overall scores of trainee endoscopists to near that of expert endoscopists (P = .06). CONCLUSIONS AND CLINICAL IMPORTANCE: Interobserver agreement of IBD mucosal appearance from endoscopic findings benefitted from operator experience.


Assuntos
Doenças do Cão/diagnóstico , Duodenoscopia/veterinária , Duodeno/patologia , Doenças Inflamatórias Intestinais/veterinária , Animais , Doenças do Cão/patologia , Cães , Feminino , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/patologia , Masculino , Variações Dependentes do Observador
13.
Transpl Infect Dis ; 16(3): 421-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24797543

RESUMO

BACKGROUND: Levofloxacin is routinely used for the prevention of invasive bacterial infections during autologous peripheral blood stem cell transplantation (APBSCT). However, increasing rates of bacterial sepsis were noted at our institution among multiple myeloma (MM) patients undergoing outpatient APBSCT with melphalan-based chemotherapy and levofloxacin prophylaxis. We assessed the impact of a change in antibacterial prophylaxis from oral levofloxacin (Period 1) to sequential oral levofloxacin followed by ertapenem (Period 2). METHODS: Electronic medical records were reviewed to identify MM patients who underwent APBSCT in the outpatient clinic between October 2007 and April 2012. RESULTS: Over a 4.5-year period, 165 outpatient APBSCTs were eligible for the analysis. Fewer overall bacteremias occurred during Period 2 as compared with Period 1 (0.5 cases per 100 person-days vs. 2.4 cases per 100 person-days, P<0.001). In addition, fewer patients were hospitalized for neutropenic fever while receiving sequential prophylaxis (45.7% vs. 75.7% of outpatient APBSCT recipients during Periods 2 and 1, respectively; P<0.001). In Kaplan-Meier analysis, receipt of sequential prophylaxis (Period 2) was significantly associated with overall bacteremia-free survival within 30 days after the APBSCT (P<0.001). No significant differences were seen in the number of patients developing Clostridium difficile infection or ertapenem-resistant gram-negative bacteremia between study periods. CONCLUSION: In conclusion, sequential prophylaxis may effectively prevent episodes of bacteremia and hospitalizations in neutropenic MM outpatient APBSCT recipients. Prospective studies that involve larger numbers of MM patients with extended periods of follow-up are ultimately required to define the safety and efficacy of sequential antibacterial prophylaxis.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/prevenção & controle , Levofloxacino/uso terapêutico , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , beta-Lactamas/uso terapêutico , Idoso , Antibacterianos/administração & dosagem , Antineoplásicos , Ertapenem , Feminino , Hospitalização , Humanos , Levofloxacino/administração & dosagem , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Retrospectivos , beta-Lactamas/administração & dosagem
15.
Inflamm Bowel Dis ; 18(12): 2203-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22419661

RESUMO

BACKGROUND: Not all patients with Crohn's disease (CD) respond or maintain response to anti-tumor necrosis factor (TNF) agents and alternative treatment is necessary. Natalizumab, a monoclonal antibody to alpha-4 integrin approved for CD, has demonstrated efficacy in randomized clinical trials. We describe our experience with natalizumab in clinical practice at Mayo Clinic Rochester. METHODS: Consecutive patients prescribed natalizumab for active CD were invited to participate and were followed prospectively. Incidence of infection, hospitalization, neoplasm, or other adverse events were recorded. Clinical activity was assessed using the Harvey-Bradshaw Index at each 30-day infusion visit. RESULTS: Between April 2008 and September 2010, 36 patients were prescribed natalizumab and 30 (83.3%) agreed to participate. Median disease duration was 9 years (range, 3-43). Twenty-three patients had prior exposure to two anti-TNF agents, seven to one agent. All patients experienced at least one adverse event; none of the 13 patients in whom natalizumab was stopped (43%) discontinued due to adverse events. Five patients had infusions held for infection. No patient developed progressive multifocal leukoencephalopathy (PML). Fourteen patients (46%) had clinical response. The cumulative probability of achieving complete response within 1 year was 56% (28%-73%). Four of seven patients were weaned off corticosteroids. CONCLUSIONS: In our experience with natalizumab in clinical practice, adverse events were manageable and did not result in treatment cessation. No PML cases were seen and clinical response was similar to that in clinical trials. Natalizumab results in clinical benefit in patients who have active disease and have failed anti-TNF therapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Natalizumab , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
16.
Clin Genet ; 81(5): 403-12, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22097934

RESUMO

The evidence-based review (EBR) process has been widely used to develop standards for medical decision-making and to explore complex clinical questions. This approach can be applied to genetic tests, such as chromosomal microarrays, in order to assist in the clinical interpretation of certain copy number variants (CNVs), particularly those that are rare, and guide array design for optimal clinical utility. To address these issues, the International Standards for Cytogenomic Arrays Consortium has established an EBR Work Group charged with building a framework to systematically assess the potential clinical relevance of CNVs throughout the genome. This group has developed a rating system enumerating the evidence supporting or refuting dosage sensitivity for individual genes and regions that considers the following criteria: number of causative mutations reported; patterns of inheritance; consistency of phenotype; evidence from large-scale case-control studies; mutational mechanisms; data from public genome variation databases; and expert consensus opinion. The system is designed to be dynamic in nature, with regions being reevaluated periodically to incorporate emerging evidence. The evidence collected will be displayed within a publically available database, and can be used in part to inform clinical laboratory CNV interpretations as well as to guide array design.


Assuntos
Variações do Número de Cópias de DNA/genética , Medicina Baseada em Evidências , Dosagem de Genes , Genoma Humano , Humanos , Fenótipo
17.
J Fish Dis ; 34(10): 783-91, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21916903

RESUMO

Yersinia ruckeri is the causative agent of enteric redmouth disease (ERM), a common pathogen affecting aquaculture facilities and implicated in large losses of cultured fish. Fisheries scientists continue to gain a greater understanding of the disease and the pathogen by investigating methods of identification and pre- and post-infection treatment. In this study, a real-time PCR probe set for Y. ruckeri was developed to detect daily changes in the bacterial load during pathogen challenges. Two species of fish, Chinook salmon, Oncorhynchus tshawytscha, and steelhead trout, Oncorhynchus mykiss, were exposed to two strains of Y. ruckeri (Hag and SC) during bath challenges. A subset of fish was killed daily for 14 days, and the kidney tissue was biopsied to enumerate copies of pathogen DNA per gram of tissue. While Chinook exposed to either the Hag or SC strains exhibited similar pathogen loads, those exposed to the Hag strain displayed higher mortality (∼66%) than fish exposed to the SC strain (∼24% mortality). Steelhead exposed to the Hag strain exhibited a greater pathogen load and higher mortality (∼42%) than those exposed to the SC strain (<1% mortality). Steelhead challenged with either strain showed lower pathogen loads than Chinook. The study illustrates the efficacy of the probe set to enumerate Y. ruckeri bacterial growth in the kidneys of fish. Also, strains of Y. ruckeri display species-specific growth patterns that result in differential mortality and pathogen load.


Assuntos
Primers do DNA , Doenças dos Peixes/microbiologia , Oncorhynchus mykiss , Reação em Cadeia da Polimerase em Tempo Real , Salmão , Yersiniose/veterinária , Yersinia ruckeri , Animais , Carga Bacteriana , Doenças dos Peixes/mortalidade , RNA Ribossômico 16S/genética , Yersiniose/microbiologia , Yersiniose/mortalidade , Yersinia ruckeri/genética , Yersinia ruckeri/patogenicidade
18.
Int J Qual Health Care ; 23(4): 445-55, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21672923

RESUMO

OBJECTIVE: To assess the quality of medical treatment by disaggregating quality into components that distinguish between insufficient and unnecessary care. DESIGN: Randomly selected doctors were asked how they would treat a sick child. Their responses were disaggregated into how much of an evidence-based essential treatment plan was completed and the number of additional non-essential treatments that were given. Key variables included the expected cost, the health consequences of insufficient and unnecessary care and comparisons between public and private physicians. Responses to 160 clinical performance vignettes (CPVs) were analysed. SETTING: Philippines. PARTICIPANTS: One hundred and forty-three public and private physicians in the Philippines, collected in November 2003-December 2004 and September 2006-June 2007. INTERVENTIONS: CPVs administered to physicians. MAIN OUTCOME MEASURES: Process quality measures (accounting for the possibility of both over-treatment and under-treatment). RESULTS: Based on CPVs, doctors gave both insufficient and unnecessary treatment to under-five children in 69% of cases. Doctors who provided the least sufficient care were also the most likely to give costly or harmful unnecessary care. Insufficient care typically had potentially worse health consequences for the patient than unnecessary care, though unnecessary care remains a concern because of overuse of antibiotics (47%) and unnecessary hospitalization (34%). CONCLUSIONS: Quality of care is complex, but over- and under-treatment coexist and, in our analysis physicians that were more likely to under-treat a sick child were also those more likely to over-treat.


Assuntos
Pesquisa sobre Serviços de Saúde/métodos , Padrões de Prática Médica/normas , Indicadores de Qualidade em Assistência à Saúde , Adulto , Feminino , Humanos , Masculino , Filipinas , Padrões de Prática Médica/estatística & dados numéricos , Procedimentos Desnecessários/estatística & dados numéricos
19.
J Clin Densitom ; 13(3): 277-82, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20605499

RESUMO

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determined the contribution of inflammatory markers to 1-yr changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss project who were randomly assigned to 1 of 3 treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy X-ray absorptiometry and the 4% distal tibia by peripheral quantitative computed tomography. Serum inflammatory markers (C-reactive protein, interleukin [IL]-1 beta, IL-6, tumor necrosis factor-alpha [TNF-alpha], and white blood cell count [WBC]) were measured at baseline, 6, and 12 mo. Because of attrition or missing values, data analysis at 12 mo includes only 235 women. Significant associations among IL-6, TNF-alpha, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1-6.1% of the variance to the observed 12-mo changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.


Assuntos
Densidade Óssea/fisiologia , Mediadores da Inflamação/fisiologia , Pós-Menopausa/fisiologia , Proteína C-Reativa/análise , Proteína C-Reativa/fisiologia , Feminino , Fêmur/fisiologia , Humanos , Mediadores da Inflamação/sangue , Interleucina-1beta/sangue , Interleucina-1beta/fisiologia , Interleucina-6/sangue , Interleucina-6/fisiologia , Contagem de Leucócitos , Vértebras Lombares/fisiologia , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/fisiologia
20.
Physiol Biochem Zool ; 83(3): 446-58, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20367319

RESUMO

Recently, a segment of the Adams-Shuswap sockeye salmon (Oncorhynchus nerka) population initiated freshwater migration several weeks earlier than historically recorded, resulting in high mortality rates. The comigrating Chilko population maintained their historic river entry timing and did not experience elevated mortality. To test the hypothesis that population-specific differences in physiological condition would differentially influence behavior and survival when exposed to fisheries capture stress, we physiologically sampled individuals from both populations at the onset of the freshwater phase of their reproductive migration and tracked the remainder of their migrations using radio telemetry. Adams-Shuswap individuals had slower migration rates and were less likely to reach natal subwatersheds relative to Chilko individuals. Metabolic and osmoregulatory impairment was related to mortality for Adams-Shuswap individuals but not for Chilko individuals. Similarly, physiological condition correlated with migration rate for Adams-Shuswap but not Chilko fish. Survival to natal subwatersheds was 1.9 times higher for Chilko relative to Adams-Shuswap, a result that did not emerge until individuals approached natal subwatersheds several days after the stressor was applied. We conclude that physiological condition differentially affects the behavior and survival of these two populations, which may be a consequence of the early-entry phenomenon by a segment of the Adams-Shuswap population.


Assuntos
Migração Animal/fisiologia , Reprodução/fisiologia , Rios , Salmão/fisiologia , Animais , Colúmbia Britânica , Metabolismo Energético/fisiologia , Natação/fisiologia
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