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BACKGROUND: Most patients with metastatic gastroesophageal adenocarcinoma (mGEA) progress on immune checkpoint inhibitors (ICIs). Novel approaches to overcome resistance to ICI in mGEA are needed. Cabozantinib is a multi-tyrosine kinase inhibitor thought to enhance the immunomodulatory effects of ICI. This study evaluated the combination of cabozantinib and pembrolizumab in ICI refractory or resistant mGEA. METHODS: Investigator-initiated, single-arm, single institution, and phase II study in patients with mGEA. Patients had progressed on ICI and/or had PD-L1 CPS score ≤10%. Cabozantinib dose was 40 mg p.o. daily on days 1-21 of a 21-day cycle, with pembrolizumab 200 mg i.v. on day 1. The primary endpoint was progression-free survival at 6 months (PFS-6). RESULTS: Twenty-seven patients were enrolled. Median age 58 years (24-87), female (nâ =â 14), ECOG 0/1â =â 13/14, GC/GEJâ =â 16/11, and non-Hispanic White/Hispanic/Asianâ =â 12/8/7. The primary endpoint was met. After a median follow-up of 31.4 months (range 3.3-42.5), PFS-6 was 22.2% (95% CI 9.0-39.0). The median PFS and OS are 2.3 months (95% CI 1.7-4.1) and 5.5 months (3.1-14.0), respectively. The most common mutations were TP53 (78.3%) and CDH1/PIK3CA/CTNNB1 (17.4% each). The most common grade (G) treatment-related adverse events (TRAE) were diarrhea (25.9%), fatigue (18.5%), hypertension, and muscle cramps (14.8% each). G3-4 TRAE were seen in nâ =â 3 patients (hypertension, thromboembolic event, esophageal perforation; each nâ =â 1). No G5 was observed. CONCLUSIONS: The addition of cabozantinib to pembrolizumab shows clinical benefit in ICI-resistant or refractory mGEA with a tolerable safety profile. (ClinicalTrials.gov Identifier: NCT04164979. IRB Approved: UCI 18-124, University of California Irvine IRB#20195426.).
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Adenocarcinoma , Anilidas , Anticorpos Monoclonais Humanizados , Neoplasias Esofágicas , Inibidores de Checkpoint Imunológico , Piridinas , Neoplasias Gástricas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Piridinas/farmacologia , Piridinas/administração & dosagem , Idoso , Anilidas/uso terapêutico , Anilidas/administração & dosagem , Anilidas/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Adulto , Idoso de 80 Anos ou mais , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Resistencia a Medicamentos Antineoplásicos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto Jovem , Junção Esofagogástrica/patologiaRESUMO
Current guidelines recommend neoadjuvant (NAC) and/or adjuvant chemotherapy for locally advanced gastric cancers (LAGCs). However, the choice and duration of NAC regimen is standardized, rather than personalized to biologic response, despite the availability of several different classes of agents for the treatment of gastric cancer (GC). The current trial will use a tumor-informed ctDNA assay (Signatera™) and monitor response to NAC. Based on ctDNA kinetics, the treatment regimen is modified. This is a prospective single center, single-arm, open-label study in clinical stage IB-III GC. ctDNA is measured at baseline and repeated every 8 weeks. Imaging is performed at the same intervals. The primary end point is the feasibility of this approach, defined as percentage of patients completing gastrectomy.
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Terapia Neoadjuvante , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Ensaios Clínicos Fase I como Assunto , Estudos de Viabilidade , Gastrectomia/métodos , Humanos , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológicoRESUMO
Background: The epidemiology of Mycoplasma pneumoniae (Mp) among US children (<18 years) hospitalized with community-acquired pneumonia (CAP) is poorly understood. Methods: In the Etiology of Pneumonia in the Community study, we prospectively enrolled 2254 children hospitalized with radiographically confirmed pneumonia from January 2010-June 2012 and tested nasopharyngeal/oropharyngeal swabs for Mp using real-time polymerase chain reaction (PCR). Clinical and epidemiological features of Mp PCR-positive and -negative children were compared using logistic regression. Macrolide susceptibility was assessed by genotyping isolates. Results: One hundred and eighty two (8%) children were Mp PCR-positive (median age, 7 years); 12% required intensive care and 26% had pleural effusion. No in-hospital deaths occurred. Macrolide resistance was found in 4% (6/169) isolates. Of 178 (98%) Mp PCR-positive children tested for copathogens, 50 (28%) had ≥1 copathogen detected. Variables significantly associated with higher odds of Mp detection included age (10-17 years: adjusted odds ratio [aOR], 10.7 [95% confidence interval {CI}, 5.4-21.1] and 5-9 years: aOR, 6.4 [95% CI, 3.4-12.1] vs 2-4 years), outpatient antibiotics ≤5 days preadmission (aOR, 2.3 [95% CI, 1.5-3.5]), and copathogen detection (aOR, 2.1 [95% CI, 1.3-3.3]). Clinical characteristics were non-specific. Conclusions: Usually considered as a mild respiratory infection, Mp was the most commonly detected bacteria among children aged ≥5 years hospitalized with CAP, one-quarter of whom had codetections. Although associated with clinically nonspecific symptoms, there was a need for intensive care in some cases. Mycoplasma pneumoniae should be included in the differential diagnosis for school-aged children hospitalized with CAP.
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Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/patologia , Hospitalização , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/patologia , Adolescente , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mycoplasma pneumoniae/efeitos dos fármacos , Pneumonia por Mycoplasma/microbiologia , Estudos Prospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Discrimination is a major driver of health disparities among minority groups and can impede the reach of public health programs. In the Dominican Republic, residents of bateyes, or agricultural 'company towns,' often face barriers to health care. This study examined the extent of perceived discrimination among batey populations and places the findings within the context of disease elimination efforts. METHODS: In March-April 2016, a stratified, multi-stage cluster survey that included the 9-item Everyday Discrimination Scale (EDS) was conducted among residents (n = 768) of bateyes across the Dominican Republic. Exploratory factor analysis, differential item functioning, and linear and logistic regression were used to assess associations between EDS scores, ethnic group status, reasons for discrimination, and healthcare-seeking behavior. RESULTS: Three ethnic groups were identified in the population: Haitian-born persons (42.5%), Dominican-born persons with Haitian descent (25.5%), and Dominican-born persons without Haitian descent (32.0%). Mean EDS scores (range 0-45) were highest among persons born in Haiti (18.2, 95% confidence interval [CI] = 16.4-20.1), followed by persons with Haitian descent (16.5, 95% CI = 14.9-18.0), and those without Haitian descent (13.3, 95% CI = 12.1-14.5). Higher EDS scores were significantly associated with Haitian birth (ß = 6.8, 95% CI = 4.2-9.4; p < 0.001) and Haitian descent (ß = 6.1, 95% CI = 3.2-9.0; p < 0.001). Most respondents (71.5%) had scores high enough to elicit reasons for their discrimination. Regardless of ethnic group, poverty was a common reason for discrimination, but Haitian-born and Haitian-descended people also attributed discrimination to their origin, documentation status, or skin color. EDS scores were not significantly associated with differences in reported care-seeking for recent fever (ß = 1.7, 95% CI = - 1.4-4.9; p = 0.278). CONCLUSION: Perceived discrimination is common among batey residents of all backgrounds but highest among Haitian-born people. Discrimination did not appear to be a primary barrier to care-seeking, suggesting other explanations for reduced care-seeking among Haitian populations. Public health community engagement strategies should avoid exacerbating stigma, build active participation in programs, and work towards community ownership of disease control and elimination goals.
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Agricultura , Etnicidade , Acessibilidade aos Serviços de Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Pobreza , Discriminação Social , Migrantes , Adolescente , Adulto , Idoso , Erradicação de Doenças , República Dominicana , Feminino , Haiti , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Minoritários , Saúde Pública , Características de Residência , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: African Americans and Hispanics are reported to have higher mortality from esophageal cancer (EC) than Caucasians. In this study, we analyzed the independent effects of race, gender, treatment, and socioeconomic status (SES) on overall survival (OS). METHODS: Data for all EC cases between 2004 and 2010 with follow-up through 2012 were obtained from the California Cancer Registry. We conducted descriptive analyses of clinical variables and survival analyses by Kaplan-Meier and Cox proportional hazards methods. RESULTS: African Americans and Hispanics were more likely to be in the lower SES strata and less likely to receive surgery than Caucasians in this cohort. The proportion of patients receiving chemotherapy and radiotherapy was similar across different racial/ethnic groups. After adjustment for stage, grade, histology, treatments, and SES in multivariate analyses, the mortality risk in African Americans (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.85-1.07) and Hispanics (HR 0.96, 95% CI 0.89-1.07) did not differ from Caucasians (HR = 1.00, referent), with histology, SES, and surgery largely accounting for unadjusted OS differences. We also observed that African American men had higher adjusted risk of death relative to Caucasian men (HR 1.24, 95% CI 1.07-1.42), but this effect was not observed for African American women compared to Caucasian women (HR 1.12, 95% CI 0.94-1.35). CONCLUSIONS: Race is not an independent risk factor for OS in our population-based analysis of EC cases. Rather, observed differences in OS by race/ethnicity result from differences in cancer histology, SES, surgery, and gender. Our findings support further health disparities research for this disease.
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BACKGROUND: Few blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate--a common scenario in the management of rheumatoid arthritis. METHODS: We conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48. RESULTS: Both groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (-2.1 with triple therapy and -2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications. CONCLUSIONS: With respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275.)
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Imunoglobulina G/uso terapêutico , Metotrexato/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Sulfassalazina/uso terapêutico , Idoso , Antirreumáticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Etanercepte , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Imunoglobulina G/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Sulfassalazina/efeitos adversos , Falha de TratamentoRESUMO
OBJECTIVES: Although antibiotic prescriptions are decreasing in the United States, broad-spectrum prescribing is increasing. It is unknown if decreases observed in national antibiotic prescribing differ by provider group. Understanding prescribing trends over time by provider group can be helpful for customizing antimicrobial stewardship efforts. Therefore, the purposes of this study were to describe outpatient antibiotic prescribing by provider group overall and adjusted for population and number of providers. In addition, trends in prescribing by class and seasonal variation are described by provider group over 6 years. DESIGN: Cross-sectional observation of outpatient antibiotic prescriptions. SETTING AND PARTICIPANTS: A population-level analysis of U.S. prescribing from 2005 to 2010 with the use of the IMS Health Xponent dataset. MAIN OUTCOME MEASURES: Number and rates of prescriptions dispensed overall and by provider group. RESULTS: The majority (81.0%) of antibiotics were prescribed by physicians, followed by dentists (10.4%), nurse practitioners (NPs; 4.5%), and physician assistants (PAs; 4.2%). The percentage of antibiotic prescriptions decreased for physicians, but increased significantly for NPs and PAs. Provider-based and population-based prescribing rates decreased for physicians and dentists and increased for NPs and PAs. Penicillins were prescribed most frequently by all provider groups, decreasing for physicians and dentists. Increased prescribing of broad-spectrum agents was observed for NPs and PAs. With the exception of dentists, antibiotic prescriptions were higher in winter than in summer, with the largest seasonal increase by NPs. CONCLUSION: Over 6 years, antibiotic prescriptions overall and for broad-spectrum agents decreased for physicians and increased for NPs and PAs. Thus, increasing trends in the US of broad-spectrum antibiotic prescriptions can be attributed to midlevel providers. Interventions should be designed to reverse increasing prescribing trends, especially of broad-spectrum agents prescribed by NPs and PAs. Stewardship efforts should also be targeted towards dentists, since this group prescribes a higher proportion of antibiotics compared with midlevel providers.
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Antibacterianos/uso terapêutico , Padrões de Prática Odontológica/estatística & dados numéricos , Padrões de Prática em Enfermagem/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Assistência Ambulatorial/estatística & dados numéricos , Estudos Transversais , Humanos , Assistentes Médicos/estatística & dados numéricos , Estações do Ano , Estados UnidosRESUMO
OBJECTIVE: This study was conducted to evaluate the responses of 3,265 health professionals who took a continuing education (CE) activity during June 2009 - April 2012 for a comprehensive set of good laboratory practice recommendations for molecular genetic testing. DESIGN: Participants completed an evaluation questionnaire as part of the CE activity. Responses were summarized to assess the participants' learning outcomes and commitment to applying the knowledge gained. PARTICIPANTS: Participants included nurses (47%), laboratory professionals (18%), physicians (14%), health educators (4%), public health professionals (2%), office staff (1%), and other health professionals (10%). RESULTS: Only 32% of all participants correctly answered all 12 open-book knowledge-check questions, ranging from 4 to 42% among the different professional groups (P<0.0001). However, over 80% of all participants expressed confidence in describing the practice recommendations, and 75% indicated the recommendations would improve the quality of their practice. Developing health education materials and local practice guidelines represented the common areas in which participants planned to use the knowledge gained (49% and 18% of all participants, respectively). CONCLUSION: Despite perceived self-efficacy in most participants, as high as 68% did not fully use the learning materials provided to answer the knowledge-check questions. These findings suggest the need for improved CE activities that motivate effective learning and address the specific needs of different health professions.
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BACKGROUND: Appropriate antibiotic prescribing is an essential strategy to reduce the spread of antibiotic resistance. US prescribing practices have not been thoroughly characterized. We analyzed outpatient antibiotic prescribing data to identify where appropriate antibiotic prescribing interventions could have the most impact. METHODS: Oral antibiotic prescriptions dispensed during 2011 were extracted from the IMS Health Xponent database. The number of prescriptions and census denominators were used to calculate prescribing rates. Prescription totals were calculated for each provider specialty. Regression modeling was used to examine the association between socioeconomic and population health factors and prescribing rates. RESULTS: Healthcare providers prescribed 262.5 million courses of antibiotics in 2011(842 prescriptions per 1000 persons). Penicillins and macrolides were the most common antibiotic categories prescribed. The most commonly prescribed individual antibiotic agent was azithromycin. Family practitioners prescribed the most antibiotic courses (24%). The prescribing rate was higher in the South census region (931 prescriptions per 1000 persons) than in the West (647 prescriptions per 1000 persons; P < .001); this pattern was observed among all age groups, including children ≤ 2 and persons ≥ 65 years of age. Counties with a high proportion of obese persons, infants and children ≤ 2 years of age, prescribers per capita, and females were more likely to be high prescribing by multivariable analysis (adjusted odds ratio, >1.0). CONCLUSIONS: Efforts to characterize antibiotic prescribing practices should focus on the South census region and family practitioners. Further understanding of the factors leading to high prescribing among key target populations will inform appropriate prescribing interventions.
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Antibacterianos/uso terapêutico , Prescrições de Medicamentos , Padrões de Prática Médica , Administração Oral , Adolescente , Adulto , Idoso , Azitromicina/uso terapêutico , Criança , Pré-Escolar , Prescrições de Medicamentos/normas , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Geografia , Humanos , Lactente , Recém-Nascido , Macrolídeos/uso terapêutico , Masculino , Medicina , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Penicilinas/uso terapêutico , Fatores de Tempo , Estados Unidos , Adulto JovemRESUMO
Real-time PCR (rt-PCR) is an important diagnostic tool for the identification of Bordetella pertussis, Bordetella holmesii, and Bordetella parapertussis. Most U.S. public health laboratories (USPHLs) target IS481, present in 218 to 238 copies in the B. pertussis genome and 32 to 65 copies in B. holmesii. The CDC developed a multitarget PCR assay to differentiate B. pertussis, B. holmesii, and B. parapertussis and provided protocols and training to 19 USPHLs. The 2012 performance exercise (PE) assessed the capability of USPHLs to detect these three Bordetella species in clinical samples. Laboratories were recruited by the Wisconsin State Proficiency Testing program through the Association of Public Health Laboratories, in partnership with the CDC. Spring and fall PE panels contained 12 samples each of viable Bordetella and non-Bordetella species in saline. Fifty and 53 USPHLs participated in the spring and fall PEs, respectively, using a variety of nucleic acid extraction methods, PCR platforms, and assays. Ninety-six percent and 94% of laboratories targeted IS481 in spring and fall, respectively, in either singleplex or multiplex assays. In spring and fall, respectively, 72% and 79% of USPHLs differentiated B. pertussis and B. holmesii and 68% and 72% identified B. parapertussis. IS481 cycle threshold (CT) values for B. pertussis samples had coefficients of variation (CV) ranging from 10% to 28%. Of the USPHLs that differentiated B. pertussis and B. holmesii, sensitivity was 96% and specificity was 95% for the combined panels. The 2012 PE demonstrated increased harmonization of rt-PCR Bordetella diagnostic protocols in USPHLs compared to that of the previous survey.
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Bordetella pertussis/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Coqueluche/diagnóstico , Coqueluche/microbiologia , Bordetella pertussis/classificação , História do Século XXI , Humanos , Ensaio de Proficiência Laboratorial , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estados Unidos/epidemiologia , Coqueluche/epidemiologia , Coqueluche/históriaRESUMO
OBJECTIVES: To identify household-level factors associated with influenza among young children in a crowded community in Dhaka, Bangladesh. METHODS: We conducted a case-control study using existing active surveillance for respiratory illness. Cases were children aged 12-59 months with laboratory-confirmed influenza. Controls were children frequency-matched by age group with no respiratory illness in the prior 6 months. We interviewed caregivers and observed household handwashing behaviour. Soap consumption was estimated by summing weight differences of three bars of soap sequentially left in each household. We measured concentrations of airborne particulate matter <2.5 µg in diameter (PM2.5) in a subset of households. We used logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI). RESULTS: We enrolled 145 cases and 341 controls between March 2009 and April 2010. Case and control household members were observed to wash hands with similar frequency during a 5-h period (mean, 0.64 events vs. 0.63, P = 0.87), and similar daily soap consumption per capita (mean 2.92 grams vs. 2.93, P = 0.92). Case households were more likely than controls to have crowded (≥4 persons) sleeping areas (aOR = 1.67, CI: 1.06-2.63) and cross-ventilated cooking spaces (aOR = 1.75, CI: 1.16-2.63). Case and control households had similar median 24-h geometric mean PM2.5 concentrations in the cooking (69.2 vs. 69.6 µg/m(3), P = 0.45) and sleeping (65.4 vs. 67.4 µg/m(3), P = 0.19) spaces. CONCLUSIONS: Handwashing with soap was practiced infrequently and was not associated with paediatric influenza in this community. Interventions aimed at crowded households may reduce influenza incidence in young children.
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Poluição do Ar em Ambientes Fechados/análise , Desinfecção das Mãos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Material Particulado/análise , Sabões/provisão & distribuição , Bangladesh/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Aglomeração , Feminino , Humanos , Lactente , Influenza Humana/transmissão , Masculino , Vigilância da População , Pobreza , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Antibiotic-resistant bacteria are an increasing threat to the effectiveness of antibiotics. The majority of antibiotics are prescribed in primary care settings for upper respiratory tract infections. The purpose of this study was to describe seasonal trends in outpatient antibiotic prescriptions (Rx) in the United States over a 5-year period. This study was a retrospective, cross-sectional observation of systemic antibiotic prescriptions in the outpatient setting from 2006 to 2010. Winter months were defined as the first and fourth quarters of the calendar year. Antibiotic prescribing rates were calculated (prescriptions/1,000 population) using annual U.S. Census Bureau population data. Over 1.34 billion antibiotic prescriptions were dispensed over the 5-year period. The antibiotic prescription (Rx) rate decreased from 892 Rx/1,000 population in 2006 to 867 Rx/1,000 population in 2010. Penicillins and macrolides were the primary antibiotic classes prescribed, but penicillin prescribing decreased while macrolide prescribing increased over the study period. Overall, antibiotic prescriptions were 24.5% higher in winter months than in the summer, with the largest difference (28.8%) in 2008 and the smallest (20.4%) in 2010. This seasonality was consistently drug class dependent, driven by 75% and 100% increases in penicillin and macrolide prescriptions, respectively, in the winter months. The mean outpatient antibiotic prescription rate decreased in the United States from 2006 to 2010. More antibiotic prescribing, predominately driven by the macrolide and penicillin classes, in the outpatient setting was observed in the winter months. Understanding annual variability in antibiotic use can assist with designing interventions to improve the judicious use of antibiotics.
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Antibacterianos , Prescrições/estatística & dados numéricos , Estudos Transversais , Humanos , Macrolídeos , Pacientes Ambulatoriais , Penicilinas , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/tendências , Estudos Retrospectivos , Estações do AnoRESUMO
We studied whether the Etest can be used as an alternative to agar dilution to determine antimicrobial susceptibilities of ceftriaxone, cefixime, and cefpodoxime in Neisseria gonorrhoeae surveillance. One hundred fifteen clinical and laboratory isolates of N. gonorrhoeae were tested following the Clinical Laboratory Improvement Amendments (CLIA)-approved CLSI standard agar dilution method and, separately, by the Etest according to the manufacturer's recommendations. The MICs were determined and compared. Ten laboratory-generated mutants were used to simulate substantially nonsusceptible specimens. The Etest and agar dilution methods were well correlated. Statistical tests produced regression R2 values of 88%, 82%, and 85% and Pearson correlation coefficients of 92%, 91%, and 92% for ceftriaxone, cefixime, and cefpodoxime, respectively. When paired comparisons were made, the two tests were 88.7%, 80%, and 87% within 1 log2 dilution from each other for ceftriaxone, cefixime, and cefpodoxime, respectively. The within-2-log2 agreements were 99.1%, 98.3%, and 94.8% for ceftriaxone, cefixime, and cefpodoxime, respectively. Notwithstanding the good correlations and the within-2-log2 general agreement, the Etest results produced slightly lower MICs than the agar dilution results. In conclusion, we found that the Etest can be effectively used as an alternative to agar dilution testing to determine the susceptibility of N. gonorrhoeae to ceftriaxone, cefixime, and cefpodoxime, although we recommend further research into extremely resistant isolates. For isolates within the typical range of clinical MICs, reexamination of the Etest interpretation of susceptible and nonsusceptible categories would likely allow for successful transition from agar dilution to the Etest.
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Testes de Sensibilidade a Antimicrobianos por Disco-Difusão/métodos , Gonorreia/diagnóstico , Neisseria gonorrhoeae/isolamento & purificação , Ágar , Antibacterianos/farmacologia , Gonorreia/microbiologia , Humanos , Neisseria gonorrhoeae/efeitos dos fármacosRESUMO
Since the establishment of sequence-based typing as the gold standard for DNA-based typing of Legionella pneumophila, the Legionella laboratory at the Centers for Disease Control and Prevention (CDC) has conducted routine sequence-based typing (SBT) analysis of all incoming L. pneumophila serogroup 1 (Lp1) isolates to identify potential links between cases and to better understand genetic diversity and clonal expansion among L. pneumophila bacteria. Retrospective genotyping of Lp1 isolates from sporadic cases and Legionnaires' disease (LD) outbreaks deposited into the CDC reference collection since 1982 has been completed. For this study, we compared the distribution of sequence types (STs) among Lp1 isolates implicated in 26 outbreaks in the United States, 571 clinical isolates from sporadic cases of LD in the United States, and 149 environmental isolates with no known association with LD. The Lp1 isolates under study had been deposited into our collection between 1982 and 2012. We identified 17 outbreak-associated STs, 153 sporadic STs, and 49 environmental STs. We observed that Lp1 STs from outbreaks and sporadic cases are more similar to each other than either group is to environmental STs. The most frequent ST for both sporadic and environmental isolates was ST1, accounting for 25% and 49% of the total number of isolates, respectively. The STs shared by both outbreak-associated and sporadic Lp1 included ST1, ST35, ST36, ST37, and ST222. The STs most commonly found in sporadic and outbreak-associated Lp1 populations may have an increased ability to cause disease and thus may require special attention when detected.
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Microbiologia Ambiental , Legionella pneumophila/classificação , Legionella pneumophila/genética , Doença dos Legionários/epidemiologia , Doença dos Legionários/microbiologia , Tipagem Molecular , Surtos de Doenças , Feminino , Genótipo , Humanos , Legionella pneumophila/isolamento & purificação , Masculino , Epidemiologia Molecular , Prevalência , Estados Unidos/epidemiologiaAssuntos
Abscesso , Linfo-Histiocitose Hemofagocítica/diagnóstico , Metotrexato/administração & dosagem , Pescoço/diagnóstico por imagem , Policondrite Recidivante , Prednisona/administração & dosagem , Abscesso/diagnóstico por imagem , Abscesso/microbiologia , Abscesso/fisiopatologia , Abscesso/terapia , Idoso , Antibacterianos , Antirreumáticos/administração & dosagem , Diagnóstico Diferencial , Pavilhão Auricular/patologia , Humanos , Masculino , Nariz/patologia , Policondrite Recidivante/diagnóstico , Policondrite Recidivante/imunologia , Policondrite Recidivante/fisiopatologia , Policondrite Recidivante/terapia , Propionibacterium acnes/isolamento & purificação , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
CONTEXT.: Two major categories of laboratories performing nonwaived testing under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) are the Certificate of Accreditation (CoA) and Certificate of Compliance (CoC) laboratories. Accreditation organizations collect more detailed laboratory personnel information than the Centers for Medicare & Medicaid Services (CMS) Quality Improvement and Evaluation System (QIES). OBJECTIVE.: To estimate total numbers of testing personnel and testing volumes in CoA and CoC laboratories, by laboratory type and state. DESIGN.: We developed a statistical inference method by using the respective correlations between testing personnel counts and test volume by laboratory type. RESULTS.: QIES reported 33 033 active CoA and CoC laboratories in July 2021. We estimated testing personnel to be 328 000 (95% CI, 309 000-348 000), which is supported by the count of 318 780 reported by the US Bureau of Labor Statistics. There were twice as many testing personnel in hospital laboratories as in independent laboratories (158 778 versus 74 904, P < .001). Independent laboratories had the highest test volume per person, which was twice as high as physician office laboratories (62 228 versus 30 102, P < .001). Hospital and independent laboratories comprised 34% of all CoA and CoC laboratories but performed the largest portion of testing (81%). Physician office laboratories, accounting for 44% of all CoA and CoC laboratories, performed a comparatively low proportion of total tests (9%). CONCLUSIONS.: Numbers of testing personnel vary considerably by laboratory type and across states. These data can provide valuable insight when assessing laboratory workforce training needs and planning for public health emergencies.
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Serviços de Laboratório Clínico , Laboratórios Hospitalares , Idoso , Humanos , Estados Unidos , Laboratórios , Laboratórios Clínicos , Medicare , Acreditação , Técnicas de Laboratório ClínicoRESUMO
INTRODUCTION: This study determined the safety and recommended phase 2 dose (RP2D) of the multikinase inhibitor cabozantinib in combination with trifluridine/tipiracil (FTD/TPI) in refractory metastatic colorectal carcinoma (mCRC). PATIENTS AND METHODS: Single institution investigator-initiated phase 1 study using 3+3 design. Eligible mCRC patients had received prior standard regimens. Cabozantinib was given orally (p.o.) at 20 mg (dose level [DL] 0) or 40 mg (DL 1) daily on days 1-28, and FTD/TPI p.o. at 35 mg/m2 on days 1-5 and 8-12 every 28 days. Prophylactic growth-factor support was allowed. RESULTS: Fifteen patients were enrolled. Median age 56 years (31-80), male (12/15), ECOG 0/1 = 9/6. Three patients were treated at DL 0 and another nine were treated at DL 1, none exhibiting a DLT. Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%), and rash (25%). G3-4 TRAE were neutropenia (25%) and thrombocytopenia, hypokalemia, and weight loss (each 8%). No serious TRAE or G5 were reported. The RP2D was determined to be DL 1. Median PFS was 3.8 months (95% CI 1.9-6.8) and disease control rate was 86.7%. CONCLUSION: The combination of cabozantinib and FTD/TPI is feasible and tolerable at standard doses with the use of growth factors and showed encouraging clinical activity in refractory mCRC. CLINICALTRIALS: GOV: NCT04868773.
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Adenocarcinoma , Anilidas , Neoplasias Colorretais , Demência Frontotemporal , Neutropenia , Piridinas , Pirrolidinas , Timina , Humanos , Masculino , Pessoa de Meia-Idade , Uracila/efeitos adversos , Trifluridina , Demência Frontotemporal/induzido quimicamente , Demência Frontotemporal/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Neutropenia/induzido quimicamenteRESUMO
After potentially curative treatment, colorectal cancer (CRC) patients remain at high risk for recurrence, second primary CRC, and high-risk adenomas. In combination with existing data, our previous findings provide a rationale for reducing tissue polyamines as tertiary prevention in non-metastatic CRC patients. The goal of this study was to demonstrate rectal tissue polyamine reduction in optimally treated stage I-III CRC patients after intervention with daily oral aspirin + dietary arginine restriction. A single-institution phase IIa clinical trial was conducted. Patients were treated with aspirin 325 mg/day and an individualized dietary regimen designed to reduce arginine intake by ≥30% over a 12-week study period. Dietary intake, endoscopy with rectal biopsies, and phlebotomy were performed pre- and post-intervention. The primary endpoint was to demonstrate ≥50% decrease in rectal tissue putrescine levels from baseline as a measure of polyamine reduction in the target tissue. Twenty eligible patients completed the study. After study intervention, mean dietary arginine intake decreased from 3.7 g/day ± 1.3 SD to 2.6 g/day ± 1.2 SD (29.7% decrease, p < 0.02 by Sign test). Mean plasma arginine levels decreased from 46.0 ng/mL ± 31.5 SD at baseline to 35 ng/mL ± 21.7 SD (p < 0.001). Rectal tissue putrescine levels were 0.90 nMol/mg-protein pre-intervention and 0.99 nMol/mg-protein post-intervention (p < 0.64, NS). No significant differences were observed for the other tissue polyamines investigated: spermidine (p < 0.13), spermine (p < 0.21), spermidine:spermine ratio (p < 0.71). Among CRC survivors, treatment with daily oral aspirin and an individualized dietary arginine restriction intervention resulted in lower calculated dietary arginine intake and plasma arginine levels but did not affect rectal tissue polyamine levels.
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In estimates of illness severity from the spring wave of the 2009 influenza A (H1N1) pandemic, reported case fatality proportions were less than 0.05%. In prior pandemics, subsequent waves of illness were associated with higher mortality. The authors evaluated the burden of the pandemic H1N1 (pH1N1) outbreak in metropolitan Atlanta, Georgia, in the fall of 2009, when increased influenza activity heralded the second wave of the pandemic in the United States. Using data from a community survey, existing surveillance systems, public health laboratories, and local hospitals, they estimated numbers of pH1N1-associated illnesses, emergency department (ED) visits, hospitalizations, intensive care unit (ICU) admissions, and deaths occurring in metropolitan Atlanta during the period August 16, 2009-September 26, 2009. The authors estimated 132,140 pediatric and 132,110 adult symptomatic cases of pH1N1 in metropolitan Atlanta during the investigation time frame. Among children, these cases were associated with 4,560 ED visits, 190 hospitalizations, 51 ICU admissions, and 4 deaths. Among adults, they were associated with 1,130 ED visits, 590 hospitalizations, 140 ICU admissions, and 63 deaths. The combined symptomatic case hospitalization proportion, case ICU admission proportion, and case fatality proportion were 0.281%, 0.069%, and 0.024%, respectively. Influenza burden can be estimated using existing data and local surveys. The increased severity reported for subsequent waves in past pandemics was not evident in this investigation. Nevertheless, the second pH1N1 pandemic wave led to substantial numbers of ED visits, hospitalizations, and deaths in metropolitan Atlanta.
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Efeitos Psicossociais da Doença , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/epidemiologia , Pandemias , Índice de Gravidade de Doença , Saúde da População Urbana/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Serviço Hospitalar de Emergência/estatística & dados numéricos , Georgia/epidemiologia , Inquéritos Epidemiológicos , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Influenza Humana/mortalidade , Influenza Humana/terapia , Unidades de Terapia Intensiva/estatística & dados numéricos , Pessoa de Meia-Idade , Vigilância da População , Estações do Ano , Adulto JovemRESUMO
We present a statistical summary of results from the Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis Drug Susceptibility Testing, 1994 to 2008, implemented by the U.S. Centers for Disease Control and Prevention (CDC). During that period, a total of 57,733 test results for culture isolates were reported by 216 participating laboratories for the first-line antituberculosis drugs used in the United States-isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Using Clinical Laboratory and Standards Institute (CLSI)-recommended concentrations for one or more of three methods, agar proportion (AP), BACTEC460 (Bactec), and MGIT-960 (MGIT), yielded overall agreement of 97.0% for first-line drugs. For susceptible strains, agreement was 98.4%; for resistant strains, agreement was 91.0%, with significantly lower accuracy (chi-square test, P < 0.0001). For resistant strains, overall agreement by methods was 91.3% for AP, 93.0% for Bactec, and 82.6% for MGIT and by drugs was 92.2% for INH, 91.5% for RMP, 79.0% for EMB, and 97.5% for PZA. For some strains, performance by method varied significantly. Use of duplicate strains in the same shipment and repeat strains over time revealed consistent performance even for strains with higher levels of interlaboratory discordance. No overall differences in performance between laboratories were observed based on volume of testing or type of facility (e.g., health department, hospital, independent). By all methods, decreased performance was observed for strains with low-level INH resistance, RMP resistance, and EMB-resistant strains. These results demonstrate a high level of performance in detection of drug-resistant M. tuberculosis in U.S. laboratories.