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1.
Lupus ; 30(3): 403-411, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33307984

RESUMO

SummaryPatients with systemic lupus erythematosus (SLE) have an increased risk of developing osteoporosis and fractures due to systemic inflammation and glucocorticoids (GCs). Professional organizations recommend bone mineral density (BMD) testing in SLE patients on GCs, especially within 6 months of initiation. Using a validated algorithm, we identified SLE patients in an electronic health record cohort with long-term GC exposure (≥90 days). Our primary outcome was ever BMD testing. We assessed the impact of patient and provider factors on testing. We identified 693 SLE cases with long-term GC exposure, 41% of whom had BMD testing performed. Only 18% of patients had BMD testing within 6 months of GC initiation. In a logistic regression model for BMD testing, male sex (OR = 0.49, 95% CI 0.27 - 0.87, p = 0.01) was associated with being less likely to have BMD testing after adjusting for race and ethnicity. In contrast, older age (OR = 1.04, p < 0.001) and nephritis (OR = 1.83, p = 0.003) were associated with being more likely to have BMD testing after adjusting for race and ethnicity. Bone health in SLE patients remains an area in need of improvement with attention to patients who are younger and male.


Assuntos
Absorciometria de Fóton/estatística & dados numéricos , Densidade Óssea , Glucocorticoides/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Idoso , Bases de Dados Factuais , Feminino , Glucocorticoides/administração & dosagem , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Estudos Retrospectivos , Reumatologia/normas
2.
Lupus ; 28(8): 977-985, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31189414

RESUMO

Antimalarials (AMs) reduce disease activity and improve survival in patients with systemic lupus erythematosus (SLE), but studies have reported low AM prescribing frequencies. Using a real-world electronic health record cohort, we examined if patient or provider characteristics impacted AM prescribing. We identified 977 SLE cases, 94% of whom were ever prescribed an AM. Older patients and patients with SLE nephritis were less likely to be on AMs. Current age (odds ratio = 0.97, p < 0.01) and nephritis (odds ratio = 0.16, p < 0.01) were both significantly associated with ever AM use after adjustment for sex and race. Of the 244 SLE nephritis cases, only 63% were currently on AMs. SLE nephritis subjects who were currently prescribed AMs were more likely to be followed by a rheumatologist than a nephrologist and less likely to have undergone dialysis or renal transplant (both p < 0.001). Non-current versus current SLE nephritis AM users had higher serum creatinine (p < 0.001), higher urine protein (p = 0.05), and lower hemoglobin levels (p < 0.01). As AMs reduce disease damage and improve survival in patients with SLE, our results demonstrate an opportunity to target future efforts to improve prescribing rates among multi-specialty providers.


Assuntos
Antimaláricos/uso terapêutico , Registros Eletrônicos de Saúde/estatística & dados numéricos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Nefrite Lúpica/tratamento farmacológico , Adulto , Idoso , Estudos de Coortes , Creatinina/sangue , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/epidemiologia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Estados Unidos/epidemiologia
3.
Epidemiol Infect ; 147: e247, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364582

RESUMO

Dogs harbor numerous zoonotic pathogens, many of which are controlled through vaccination programs. The delivery of these programs can be difficult where resources are limited. We developed a dynamic model to estimate vaccination coverage and cost-per-dog vaccinated. The model considers the main factors that affect vaccination programs: dog demographics, effectiveness of strategies, efficacy of interventions and cost. The model was evaluated on data from 18 vaccination programs representing eight countries. Sensitivity analysis was performed for dog confinement and vaccination strategies. The average difference between modelled vaccination coverage and field data was 3.8% (2.3%-5.3%). Central point vaccination was the most cost-effective vaccination strategy when >88% of the dog population was confined. More active methods of vaccination, such as door-to-door or capture-vaccinate-release, achieved higher vaccination coverage in free-roaming dog populations but were more costly. This open-access tool can aid in planning more efficient vaccination campaigns in countries with limited resources.


Assuntos
Vacinação em Massa/veterinária , Vacina Antirrábica/administração & dosagem , Raiva/prevenção & controle , Cobertura Vacinal/economia , Vacinação/estatística & dados numéricos , África Oriental , África do Norte , Animais , Ásia , América Central , Análise Custo-Benefício , Cães , Humanos , Vacinação em Massa/economia , América do Norte , Raiva/epidemiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Vacinação/economia
4.
Anaerobe ; 52: 16-21, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29864681

RESUMO

The excess from fecal samples submitted to a centralized laboratory in Roanoke, Virginia for routine C. difficile testing was used for this research study. We tested all samples, including any formed samples usually not assayed in diagnostic laboratories. Our first aim was to rank ribotypes by their frequency. Between 2007 and 2013, fluoroquinolone resistant 027 (027FQR), a multi-drug resistant ribotype, was 32% of 3118 Clostridium difficile isolates and the most common of 128 ribotypes. 027FQR was in 45% of cytotoxin positive but only 17% of cytotoxin negative fecal samples (p = 0.001) and 34% of unformed but only 21% of formed stool samples (p = 0.001), strong associations with features of symptomatic infection. Conversely, 014/020 (10% of isolates, third most common ribotype) was more often in unformed than formed stools (14% versus 9%; p = 0.002) and in cytotoxin negative than cytotoxin positive samples (11% versus 8%, p = 0.01). Fecal lactoferrin levels, an indication of intestinal inflammation, were significantly higher with 027FQR than with 014/020 infections (median 308 versus 26 ng/mL, p = 0.02). 027FQR fecal bioburdens and toxin levels were significantly higher than their 014/020 equivalents (median 104.1 versus 103.2/g feces, p = 0.01; median TcdA 58.7 versus 1.3 ng/g feces, p = 0.04; median TcdB 43.4 versus 0.3 ng/g feces, p = 0.001). Binary toxin was present in 40% of 027FQR positive samples but none of the 014/020 or non-toxigenic C. difficile positive samples. 027FQR made no more TcdA/cell than did 014/020 (p = 0.7) but did make close to significantly more TcdB/cell (p = 0.08).


Assuntos
Antibacterianos/farmacologia , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/isolamento & purificação , Farmacorresistência Bacteriana Múltipla , Toxinas Bacterianas/análise , Toxinas Bacterianas/metabolismo , Clostridioides difficile/classificação , Clostridioides difficile/genética , Fezes/microbiologia , Humanos , Ribotipagem , Virginia
5.
J Am Water Works Assoc ; 110(4): E2-E18, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36999079

RESUMO

De facto reuse is the percentage of drinking water treatment plant (DWTP) intake potentially composed of effluent discharged from upstream wastewater treatment plants (WWTPs). Results from grab samples and a De Facto Reuse in our Nation's Consumable Supply (DRINCS) geospatial watershed model were used to quantify contaminants of emerging concern (CECs) concentrations at DWTP intakes to qualitatively compare exposure risks obtained by the two approaches. Between nine and 71 CECs were detected in grab samples. The number of upstream WWTP discharges ranged from 0 to >1,000; comparative de facto reuse results from DRINCS ranged from <0.1 to 13% during average flow and >80% during lower streamflows. Correlation between chemicals detected and DRINCS modeling results were observed, particularly DWTPs withdrawing from midsize water bodies. This comparison advances the utility of DRINCS to identify locations of DWTPs for future CEC sampling and treatment technology testing.

6.
Dis Esophagus ; 30(1): 1-7, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27001442

RESUMO

The aim of this study was to evaluate the worldwide trends in surgical techniques for esophageal cancer surgery by comparing it to our survey from 2007. In addition, new questions were added for gastroesophageal junction (GEJ) cancer. An international survey on surgery of esophageal and GEJ cancer was performed among surgical members of the International Society for Diseases of the Esophagus, the World Organization for Specialized Studies on Disease of the Esophagus, the International Gastric Cancer Association. Also, surgeons from personal networks were contacted. The participants filled out a web based questionnaire about surgical strategies for esophageal and gastroesophageal cancer. The overall response rate was 478/1147 (42%). The respondents represented 49 different countries and 6 different continents. The annual cumulative number of esophageal and gastric resections per surgeon was low (≤11) in 11%, medium (11-21) in 17%, and high (≥21) in 72% of respondents. In a subgroup analysis of esophageal surgeons the number of high volume surgeons increased from 45 to 54% over the past 7 years. The preferred lymph node dissection was two-field in 86%. A gastric conduit was the preferred method of reconstruction in 95%. In 2014, the preferred approach to esophagectomy was minimally invasive transthoracic in 43%, compared with 14% in 2007. In minimally invasive transthoracic esophagectomy the cervical anastomosis was favored in 54% of respondents in 2014 compared with 87% in 2007. The preferred technique of construction of the cervical anastomosis was hand-sewn in 64% and stapled in 36%, whereas the thoracic anastomosis was stapled in 77% and hand-sewn in 23%. The preferred surgical approach for Siewert type 1 tumors (5-1 cm proximal of the GEJ) was esophagectomy in 93% of respondents, whereas 6% favored gastrectomy and 3% combined a distal esophagectomy with a proximal gastrectomy. For Siewert type 2 tumors (1-2 cm from the GEJ) an extended gastrectomy was favored by 66% of respondents, followed by esophagectomy in 27% and total gastrectomy in 7%. Siewert type 3 tumors (2-5 cm distal of the GEJ) were preferably treated with gastrectomy in 90% of respondents, esophagectomy in 6%, and extended gastrectomy in 4%. The preferred curative surgical treatment of esophageal cancer is minimally invasive transthoracic esophagectomy with a two-field lymph node dissection and gastric conduit reconstruction. A strong worldwide trend toward minimally invasive surgery is observed. The preferred surgical treatment of GEJ tumors is esophagectomy for Siewert type 1 tumors and gastrectomy for Siewert type 3 tumors. The majority of surgeons favor an extended gastrectomy for Siewert type 2 tumors.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/tendências , Junção Esofagogástrica/cirurgia , Gastrectomia/tendências , Excisão de Linfonodo/tendências , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Anastomose Cirúrgica/tendências , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica/patologia , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Padrões de Prática Médica/tendências , Neoplasias Gástricas/patologia , Inquéritos e Questionários
7.
Biol Lett ; 11(7)2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26156129

RESUMO

Top predators are disappearing worldwide, significantly changing ecosystems that depend on top-down regulation. Conflict with humans remains the primary roadblock for large carnivore conservation, but for the eastern wolf (Canis lycaon), disagreement over its evolutionary origins presents a significant barrier to conservation in Canada and has impeded protection for grey wolves (Canis lupus) in the USA. Here, we use 127,235 single-nucleotide polymorphisms (SNPs) identified from restriction-site associated DNA sequencing (RAD-seq) of wolves and coyotes, in combination with genomic simulations, to test hypotheses of hybrid origins of Canis types in eastern North America. A principal components analysis revealed no evidence to support eastern wolves, or any other Canis type, as the product of grey wolf × western coyote hybridization. In contrast, simulations that included eastern wolves as a distinct taxon clarified the hybrid origins of Great Lakes-boreal wolves and eastern coyotes. Our results support the eastern wolf as a distinct genomic cluster in North America and help resolve hybrid origins of Great Lakes wolves and eastern coyotes. The data provide timely information that will shed new light on the debate over wolf conservation in eastern North America.


Assuntos
Coiotes/genética , Análise de Sequência de DNA , Lobos/genética , Animais , Coiotes/classificação , Genética Populacional , Hibridização Genética , América do Norte , Análise de Componente Principal , Lobos/classificação
8.
Eur J Clin Microbiol Infect Dis ; 33(6): 1045-51, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24449345

RESUMO

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n = 191) were positive by toxigenic culture and 61% (n = 129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 µg/g versus 106 µg/g stool; p < 0.0001). Forty percent of patients (n = 85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79% vs. 50%; p < 0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 µg/g; p = 0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18%; p = 0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR = 1.1), intensive care unit treatment (OR = 2.7), CI (OR = 1.2), 027 CDI (OR = 2.1), white blood cell count (OR = 1.0), albumin level (OR = 0.1), and stool toxin-positive 027 CDI (OR = 2.5) were significantly associated with 100-day mortality (p < 0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.


Assuntos
Toxinas Bacterianas/análise , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/mortalidade , Infecções por Clostridium/patologia , Fezes/química , Lactoferrina/análise , Ribotipagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Clostridioides difficile/classificação , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
9.
Br J Anaesth ; 112(5): 920-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24523436

RESUMO

BACKGROUND: Transthoracic oesophagectomy requires prolonged one-lung ventilation causing systemic and local inflammatory responses. Application of continuous positive airway pressure (CPAP) to the collapsed lung potentially reduces pulmonary damage, hypoxia, and consequent inflammation. This randomized controlled trial studied the influence of CPAP applied to the collapsed right lung during thoracoscopic oesophagectomy on local and systemic inflammatory response. METHODS: Broncho-alveolar lavage fluid (BALF) from the right collapsed and left ventilated lung and serum samples were obtained during surgery from 30 patients undergoing thoracolaparoscopic oesophagectomy for cancer who were randomized for one-lung ventilation with or without CPAP applied to the collapsed right lung. Concentrations of cytokines and chemokines, in BALF and serum, were determined with Luminex. RESULTS: Patients from the control (no CPAP) group had significantly increased concentrations of interleukin (IL)-1α, IL-1ß, IL-10, tumour necrosis factor-alpha, macrophage inflammatory protein (MIP)-1α, pulmonary and activation-regulated chemokine (PARC), and IL-8 in the collapsed (right) lung when compared with patients from the CPAP group (P<0.05). The ventilated (left) lung of the control group showed increased concentrations of monocyte chemoattractant protein (MCP)-1 and MIP-1α (P<0.05). Serum concentrations of cytokines and chemokines increased during surgery, but did not differ between the control and CPAP groups. CONCLUSIONS: A significantly lower local immune response was observed during one-lung ventilation when CPAP was applied to the collapsed lung. The findings suggest a beneficial effect of CPAP on the collapsed lung during oesophagectomy with one-lung ventilation.


Assuntos
Quimiocinas/imunologia , Pressão Positiva Contínua nas Vias Aéreas/métodos , Citocinas/imunologia , Esofagectomia/métodos , Inflamação/imunologia , Ventilação Monopulmonar/métodos , Idoso , Quimiocina CCL3/imunologia , Quimiocinas CC/imunologia , Feminino , Humanos , Imunidade , Interleucina-1/imunologia , Interleucina-10/imunologia , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/imunologia
10.
Eur J Clin Microbiol Infect Dis ; 32(12): 1517-23, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23771554

RESUMO

We evaluated blood and fecal biomarkers as indicators of severity in symptomatic patients with confirmed Clostridium difficile infection (CDI). Recruitment included patients with CDI based on clinical symptoms and supporting laboratory findings. Disease severity was defined by physician's assessment and blood and fecal biomarkers were measured. Toxigenic culture done using spore enrichment and toxin B detected by tissue culture were done as confirmatory tests. Polymerase chain reaction (PCR) ribotyping was performed on each isolate. There were 98 patients recruited, with 85 (87%) confirmed cases of toxigenic CDI (21 severe, 57 moderate, and seven mild), of which 68 (80%) were also stool toxin-positive. Elevated lactoferrin (p = 0.01), increased white blood cell (WBC) count (p = 0.08), and low serum albumin (p = 0.03) were all associated with the more severe cases of CDI. Ribotype 027 infection accounted for 71% of severe cases (p < 0.01) and patients with stool toxin had significantly higher lactoferrin levels and WBC counts (p < 0.05). Our findings show that elevated fecal lactoferrin, along with increased WBC count and low serum albumin, were associated with more severe CDI. In addition, patients infected with ribotype 027 and those with stool toxin had significantly higher fecal lactoferrin and WBC counts.


Assuntos
Toxinas Bacterianas/metabolismo , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/metabolismo , Lactoferrina/metabolismo , Idoso , Análise de Variância , Toxinas Bacterianas/sangue , Biomarcadores/sangue , Biomarcadores/metabolismo , Infecções por Clostridium/sangue , Infecções por Clostridium/enzimologia , Infecções por Clostridium/microbiologia , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Lactoferrina/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Ribotipagem , Albumina Sérica/metabolismo
11.
Int J Sports Med ; 34(1): 14-20, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22893325

RESUMO

This study aimed to explore muscle oxygen extraction and muscle activation pattern during bilateral intermittent submaximal isometric knee-extensions by combining Near-infrared Spectroscopy (NIRS) and Electromyography (EMG) measurements from the M. Vastus Lateralis. A group of highly specifically trained boys (youth sailors) (n=10) and untrained matched controls (n=10) performed 12 bouts of 90 s bilateral submaximal (30-40% MVC) isometric knee-extension interspersed with 6 s recovery-periods. Patterns of deoxygenated haemoglobin and myoglobin concentration (Deoxy[Hb+Mb]) were observed during each bout and the entire protocol. Reoxygenation Index (RI) was assessed for each recovery period as the amplitude of Deoxy[Hb+Mb]-decrease relative to amplitude of Deoxy[Hb+Mb]-increase during each bout. Root Mean Square (RMS) and Mean Power Frequency (MPF) were calculated for each bout as an average of the final 60 s. Deoxy[Hb+Mb], RI, RMS and MPF were analyzed by repeated-measures ANOVA. Results indicated significantly higher Deoxy[Hb+Mb]-increase and lower RI in specifically trained boys compared to untrained controls. These differences are presumably related to the differences in EMG-measurements which demonstrated lower RMS-increase and MPF-decrease for trained compared to untrained boys. In conclusion, specifically trained boys indicate delayed onset of muscle fatigue in comparison to untrained controls, which might be associated with the different pattern of muscle O2-extraction or muscle activation pattern (i. e., a more accurate recruitment of slow-twitch fibres).


Assuntos
Articulação do Joelho/fisiologia , Fadiga Muscular/fisiologia , Oxigênio/metabolismo , Músculo Quadríceps/fisiologia , Adolescente , Análise de Variância , Criança , Eletromiografia , Hemoglobinas/metabolismo , Humanos , Contração Isométrica/fisiologia , Masculino , Fibras Musculares de Contração Lenta/fisiologia , Mioglobina/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho
12.
J Clin Microbiol ; 50(4): 1425-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22301027

RESUMO

gluD was highly conserved and glutamate dehydrogenase (GDH) was readily expressed in vitro by all 77 Clostridium difficile ribotypes assayed. All ribotypes, including ARL 002, ARL 027, and ARL 106, were reactive in assays that detect C. difficile GDH.


Assuntos
Proteínas de Bactérias/genética , Clostridioides difficile/enzimologia , Sequência Conservada , Glutamato Desidrogenase/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Proteínas de Bactérias/química , Clostridioides difficile/genética , Glutamato Desidrogenase/química , Ribotipagem , Análise de Sequência de DNA , Análise de Sequência de Proteína
13.
Med Phys ; 39(2): 866-73, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22320796

RESUMO

PURPOSE: To develop an automated method to detect breast masses on dedicated breast CT (BCT) volumes and to conduct a preliminary evaluation of its performance. This method can be used in a computer-aided detection (CADe) system for noncontrast enhanced BCT. METHODS: The database included patient images, which were acquired under an IRB-approved protocol. The database in this study consisted of 132 cases. 50 cases contained 58 malignant masses, and 23 cases contained 24 benign masses. 59 cases did not contain any biopsy-proven lesions. Each case consisted of an unenhanced CT volume of a single breast. First, each breast was segmented into adipose and glandular tissues using a fuzzy c-means clustering algorithm. The glandular breast regions were then sampled at a resolution of 2 mm. At each sampling step, a 3.5-cm(3) volume-of-interest was subjected to constrained region segmentation and 17 characteristic features were extracted, yielding 17 corresponding feature volumes. Four features were selected using step-wise feature selection and merged with linear discriminant analysis trained in the task of distinguishing between normal breast glandular regions and masses. Detection performance was measured using free-response receiver operating characteristic analysis (FROC) with leave-one-case-out evaluation. RESULTS: The feature selection stage selected features that characterized the shape and margin strength of the segmented region. CADe sensitivity per case was 84% (std = 4.2%) at 2.6 (std = 0.06) false positives per volume, or 6 × 10(-3) per slice (at an average of 424 slices per volume in this data set). CONCLUSIONS: This preliminary study demonstrates the feasibility of our approach for CADe for BCT.


Assuntos
Algoritmos , Imageamento Tridimensional/métodos , Mamografia/métodos , Reconhecimento Automatizado de Padrão/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Feminino , Humanos , Projetos Piloto , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
Eur J Clin Microbiol Infect Dis ; 31(7): 1551-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22167256

RESUMO

We evaluated Clostridium difficile prevalence rates in 2,807 clinically indicated stool specimens stratified by inpatient (IP), nursing home patient (NH), outpatient (OP), age, gender, and specimen consistency using bacterial culture, toxin detection, and polymerase chain reaction (PCR) ribotyping. Rates were determined based on the detection of toxigenic C. difficile isolates. We identified significant differences in the rates between patient populations and with age. Specimens from NH had a higher rate (46%) for toxigenic C. difficile than specimens from IP (18%) and OP (17%). There were no gender-related differences in the rates. Liquid specimens had a lower rate (15%) than partially formed and soft specimens (25%) and formed specimens (18%) for the isolation of toxigenic C. difficile. The nontoxigenic rate was lowest for NH (4%) and highest for patients<20 years of age (23%). We identified 31 different toxigenic ribotypes from a sampling of 190 isolates that showed the lowest diversity in NH. Fluoroquinolone resistance was observed in 93% of the 027 isolates, all of the 053 isolates, and in four other ribotypes. We observed different rates for toxigenic C. difficile in stratified patient populations, with the highest rate for NH, a low overall nontoxigenic rate, and fluoroquinolone resistance.


Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Clostridioides difficile/classificação , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Farmacorresistência Bacteriana , Fezes/microbiologia , Feminino , Fluoroquinolonas/farmacologia , Instalações de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Ribotipagem , Fatores de Risco , Fatores Sexuais , Adulto Jovem
16.
Transgenic Res ; 20(3): 643-53, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20872247

RESUMO

Inactivation of the endogenous pig immunoglobulin (Ig) loci, and replacement with their human counterparts, would produce animals that could alleviate both the supply and specificity issues of therapeutic human polyclonal antibodies (PAbs). Platform genetics are being developed in pigs that have all endogenous Ig loci inactivated and replaced by human counterparts, in order to address this unmet clinical need. This report describes the deletion of the porcine kappa (κ) light chain constant (Cκ) region in pig primary fetal fibroblasts (PPFFs) using gene targeting technology, and the generation of live animals from these cells via somatic cell nuclear transfer (SCNT) cloning. There are only two other targeted loci previously published in swine, and this is the first report of a targeted disruption of an Ig light chain locus in a livestock species. Pigs with one targeted Cκ allele (heterozygous knockout or ±) were bred together to generate Cκ homozygous knockout (-/-) animals. Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph nodes (MLNs) from Cκ -/- pigs were devoid of κ-containing Igs. Furthermore, there was an increase in lambda (λ) light chain expression when compared to that of wild-type littermates (Cκ +/+). Targeted inactivation of the Ig heavy chain locus has also been achieved and work is underway to inactivate the pig lambda light chain locus.


Assuntos
Clonagem de Organismos , Marcação de Genes , Cadeias kappa de Imunoglobulina/genética , Técnicas de Transferência Nuclear , Deleção de Sequência , Suínos , Animais , Feminino , Fibroblastos , Genes de Imunoglobulinas/genética , Humanos , Cadeias kappa de Imunoglobulina/metabolismo , Masculino
17.
Transgenic Res ; 20(3): 625-41, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20872248

RESUMO

A poly(A)-trap gene targeting strategy was used to disrupt the single functional heavy chain (HC) joining region (J(H)) of swine in primary fibroblasts. Genetically modified piglets were then generated via somatic cell nuclear transfer (SCNT) and bred to yield litters comprising J(H) wild-type littermate (+/+), J(H) heterozygous knockout (±) and J(H) homozygous knockout (-/-) piglets in the expected Mendelian ratio of 1:2:1. There are only two other targeted loci previously published in swine, and this is the first successful poly(A)-trap strategy ever published in a livestock species. In either blood or secondary lymphoid tissues, flow cytometry, RT-PCR and ELISA detected no circulating IgM(+) B cells, and no transcription or secretion of immunoglobulin (Ig) isotypes, respectively in J(H) -/- pigs. Histochemical and immunohistochemical (IHC) studies failed to detect lymph node (LN) follicles or CD79α(+) B cells, respectively in J(H) -/- pigs. T cell receptor (TCR)(ß) transcription and T cells were detected in J(H) -/- pigs. When reared conventionally, J(H) -/- pigs succumbed to bacterial infections after weaning. These antibody (Ab)- and B cell-deficient pigs have significant value as models for both veterinary and human research to discriminate cellular and humoral protective immunity to infectious agents. Thus, these pigs may aid in vaccine development for infectious agents such as the pandemic porcine reproductive and respiratory syndrome virus (PRRSV) and H1N1 swine flu. These pigs are also a first significant step towards generating a pig that expresses fully human, antigen-specific polyclonal Ab to target numerous incurable infectious diseases with high unmet clinical need.


Assuntos
Anticorpos/metabolismo , Linfócitos B/metabolismo , Modelos Animais de Doenças , Marcação de Genes , Cadeias Pesadas de Imunoglobulinas/genética , Isotipos de Imunoglobulinas/genética , Poli A/genética , Animais , Animais Recém-Nascidos , Anticorpos/genética , Anticorpos/imunologia , Linfócitos B/imunologia , Infecções Bacterianas/imunologia , Células Cultivadas , Fibroblastos , Engenharia Genética/métodos , Humanos , Cadeias Pesadas de Imunoglobulinas/metabolismo , Isotipos de Imunoglobulinas/metabolismo , Imuno-Histoquímica , Suínos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transfecção
18.
Med Phys ; 47(2): 467-479, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31808950

RESUMO

PURPOSE: A modular phantom for dosimetry and imaging performance evaluation in cone-beam computed tomography (CBCT) is reported, providing a tool for quantitative technical assessment that can be adapted to a broad variety of CBCT imaging configurations and clinical applications. METHODS: The phantom presents a set of modules that can be ordered in various configurations suitable to a particular CBCT system. Modules include slabs containing a uniform medium, low-contrast inserts, line-spread features, and disk features suitable to measurement of image uniformity, noise, noise-power spectrum (NPS), contrast, contrast-to-noise ratio (CNR), Hounsfield (HU) accuracy, linearity, spatial resolution modulation transfer function (MTF), and magnitude of cone-beam artifact. Automated software recognizes the phantom configuration in DICOM images and provides structured reporting of such test measures. In any modular configuration, the phantom permits measurement of air kerma in central and peripheral locations with an air ionization chamber (e.g., Farmer chamber). The utility and adaptability of the phantom were demonstrated across a spectrum of CBCT systems, including scanners for orthopaedic imaging (Carestream OnSight 3D, Rochester NY), breast imaging (Doheny prototype, UC Davis), image-guided surgery (IGS, Medtronic O-arm, Littleton MA), angiography (Siemens Artis Zeego, Forcheim Germany), and image-guided radiation therapy (IGRT, Elekta Synergy XVI, Stockholm Sweden). RESULTS: The phantom provided a consistent platform for quantitative assessment of dose and imaging performance compatible with a broad spectrum of CBCT systems. The purpose of the survey was not to obtain head-to-head performance comparison of systems designed for such distinct clinical applications. Rather, the survey demonstrated the suitability of the phantom to a broad spectrum of systems in a manner that provides characterization pertinent to disparate applications and imaging tasks. For example: the orthopaedic CBCT system (pertinent clinical tasks relating to high-resolution bone imaging) was shown to achieve MTF consistent with imaging of high-contrast trabecular bone structures (i.e., the MTF reduced to 10% at spatial frequency, f 10  = 1.2 mm-1 ); the breast system (even higher-resolution imaging of microcalcifications) exhibited f 10  = 2.2 mm-1 ; the IGS system (tasks including both bone and soft-tissue contrast resolution) provided f 10  = 0.9 mm-1 and soft-tissue CNR  = 1.64; the angiography system (soft-tissue body interventions) demonstrated CNR  = 1.2 in soft tissues approximating liver lesions; and the IGRT system (pertinent tasks emphasizing HU linearity and image uniformity) showed linear response with HU values ( R 2  = 1), with a cupping artifact ( t cup  = 5.8%) due to x-ray scatter. CONCLUSIONS: The phantom provides an adaptable, quantitative basis for CBCT dosimetry and imaging performance evaluation suitable to a broad variety of CBCT systems. The dosimetry and image quality metrics are consistent with up-to-date methods for rigorous, quantitative, physics testing and should be suitable to emerging standards for CBCT quality assurance.


Assuntos
Tomografia Computadorizada de Feixe Cônico/instrumentação , Imagens de Fantasmas , Doses de Radiação , Artefatos , Controle de Qualidade , Razão Sinal-Ruído
19.
Phys Med ; 74: 133-142, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32470909

RESUMO

Virtual clinical trials (VCT) are in-silico reproductions of medical examinations, which adopt digital models of patients and simulated devices. They are intended to produce clinically equivalent outcome data avoiding long execution times, ethical issues related to radiation induced risks and huge costs related to real clinical trials with a patient population. In this work, we present a platform for VCT in 2D and 3D X-ray breast imaging. The VCT platform uses Monte Carlo simulations based on the Geant4 toolkit and patient breast models derived from a cohort of high resolution dedicated breast CT (BCT) volume data sets. Projection images of the breast and three-dimensional glandular dose maps are generated for a given breast model, by simulating both 2D full-field digital mammography (DM) and 3D BCT examinations. Uncompressed voxelized breast models were derived from segmented patient images. Compressed versions of the digital breast phantoms for DM were generated using a previously published digital compression algorithm. The Monte Carlo simulation framework has the capability of generating and tracking ~105 photons/s using a server equipped with 16-cores and 3.0 GHz clock speed. The VCT platform will provide a framework for scanner design optimization, comparison between different scanner designs and between different modalities or protocols on computational breast models, without the need for scanning actual patients as in conventional clinical trials.


Assuntos
Mama/diagnóstico por imagem , Ensaios Clínicos como Assunto , Mamografia , Método de Monte Carlo , Humanos , Imageamento Tridimensional
20.
Br J Surg ; 96(8): 878-86, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19591168

RESUMO

BACKGROUND: Thoracoscopic oesophagectomy was introduced to reduce the morbidity of transthoracic oesophagectomy. The aim was to assess the short- and mid-term results of robot-assisted thoracoscopic oesophagectomy for oesophageal cancer. METHODS: Between October 2003 and May 2007, 47 patients with resectable oesophageal cancer underwent robot-assisted thoracoscopic oesophagectomy. Clinical data were collected prospectively. RESULTS: Conversion to thoracotomy was necessary in seven patients. Median operating time was 450 min and median blood loss 625 ml. Median postoperative ventilation time was 1 day, intensive care stay 3 days and hospital stay 18 days. Twenty-one of 47 patients had pulmonary complications. Three patients died in hospital. A median of 29 (range 8-68) lymph nodes was dissected and R0 resection was achieved in 36 patients. Twenty-three patients had stage IVa disease. After a median follow-up of 35 months, median disease-free survival was 15 (95 per cent confidence interval 12 to 18) months. CONCLUSION: Robot-assisted thoracoscopic oesophagectomy was oncologically acceptable. Operating time, blood loss and pulmonary complications might decrease with further experience.


Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Robótica , Toracoscopia/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Neoplasias Esofágicas/patologia , Feminino , Humanos , Tempo de Internação , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Resultado do Tratamento
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