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1.
Behav Res Methods ; 56(4): 3794-3813, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38724878

RESUMO

The use of taboo words represents one of the most common and arguably universal linguistic behaviors, fulfilling a wide range of psychological and social functions. However, in the scientific literature, taboo language is poorly characterized, and how it is realized in different languages and populations remains largely unexplored. Here we provide a database of taboo words, collected from different linguistic communities (Study 1, N = 1046), along with their speaker-centered semantic characterization (Study 2, N = 455 for each of six rating dimensions), covering 13 languages and 17 countries from all five permanently inhabited continents. Our results show that, in all languages, taboo words are mainly characterized by extremely low valence and high arousal, and very low written frequency. However, a significant amount of cross-country variability in words' tabooness and offensiveness proves the importance of community-specific sociocultural knowledge in the study of taboo language.


Assuntos
Idioma , Tabu , Humanos , Semântica , Comparação Transcultural
2.
J Med Internet Res ; 25: e39054, 2023 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-36745776

RESUMO

BACKGROUND: In 2020, at the onset of the COVID-19 pandemic, the United States experienced surges in healthcare needs, which challenged capacity throughout the healthcare system. Stay-at-home orders in many jurisdictions, cancellation of elective procedures, and closures of outpatient medical offices disrupted patient access to care. To inform symptomatic persons about when to seek care and potentially help alleviate the burden on the healthcare system, Centers for Disease Control and Prevention (CDC) and partners developed the CDC Coronavirus Self-Checker ("Self-Checker"). This interactive tool assists individuals seeking information about COVID-19 to determine the appropriate level of care by asking demographic, clinical, and nonclinical questions during an online "conversation." OBJECTIVE: This paper describes user characteristics, trends in use, and recommendations delivered by the Self-Checker between March 23, 2020, and April 19, 2021, for pursuing appropriate levels of medical care depending on the severity of user symptoms. METHODS: User characteristics and trends in completed conversations that resulted in a care message were analyzed. Care messages delivered by the Self-Checker were manually classified into three overarching conversation themes: (1) seek care immediately; (2) take no action, or stay home and self-monitor; and (3) conversation redirected. Trends in 7-day averages of conversations and COVID-19 cases were examined with development and marketing milestones that potentially impacted Self-Checker user engagement. RESULTS: Among 16,718,667 completed conversations, the Self-Checker delivered recommendations for 69.27% (n=11,580,738) of all conversations to "take no action, or stay home and self-monitor"; 28.8% (n=4,822,138) of conversations to "seek care immediately"; and 1.89% (n=315,791) of conversations were redirected to other resources without providing any care advice. Among 6.8 million conversations initiated for self-reported sick individuals without life-threatening symptoms, 59.21% resulted in a recommendation to "take no action, or stay home and self-monitor." Nearly all individuals (99.8%) who were not sick were also advised to "take no action, or stay home and self-monitor." CONCLUSIONS: The majority of Self-Checker conversations resulted in advice to take no action, or stay home and self-monitor. This guidance may have reduced patient volume on the medical system; however, future studies evaluating patients' satisfaction, intention to follow the care advice received, course of action, and care modality pursued could clarify the impact of the Self-Checker and similar tools during future public health emergencies.


Assuntos
COVID-19 , Humanos , Estados Unidos , Pandemias , Comunicação , Satisfação do Paciente , Centers for Disease Control and Prevention, U.S.
3.
Eur J Nucl Med Mol Imaging ; 48(9): 2914-2924, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33559712

RESUMO

BACKGROUND: To retrospectively assess liver tumor ablation margins using intraprocedural PET/CT images from FDG PET/CT-guided microwave or cryoablation procedures and to correlate minimum margin measurements with local progression outcomes. METHODS: Fifty-six patients (ages 36 to 85, median 62; 32 females) with 77 FDG-avid liver tumors underwent 60 FDG PET/CT guided, percutaneous microwave, or cryoablation procedures. Single breath-hold PET/CT images were used for intraprocedural assessment of the tumor ablation margin: liver tumors remained visible on PET immediately following ablation; microwave ablation zones were visible using contrast-enhanced CT; cryoablation zones (ice balls) were visible using unenhanced CT. Two readers retrospectively determined ablation margin assessability and measured the minimum ablation margin on intraprocedural PET/CT (n = 77) and postprocedural MRI (n = 56). Local tumor progression was assessed on all available follow-up imaging (1-49 months, mean 15). Local tumor progression was correlated with PET/CT minimum margin measurements using clustered survival models for 61 tumors. RESULTS: Minimum ablation margins were more often assessable using intraprocedural PET/CT (≥ 73/77 tumors, 95%) than postprocedural MRI (≤ 35/56 tumors, 63%). In 61 tumors with PET/CT-assessable margins (excluding tumors with overlapping ablations after PET/CT), there was a 6-fold increased risk of local tumor progression [hazard ratio (HR) 6.05; P = 0.004] for minimum ablation margins < 5 mm. CONCLUSION: Breath-hold PET/CT scans, during PET/CT-guided microwave or cryoablation procedures for FDG-avid liver tumors, enable reliable intraprocedural assessment of the entire tumor ablation margin; a minimum PET/CT ablation margin threshold of 5 mm correlates well with local tumor progression outcomes.


Assuntos
Neoplasias Hepáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Nature ; 513(7519): 512-6, 2014 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-25043004

RESUMO

Mutations that deregulate Notch1 and Ras/phosphoinositide 3 kinase (PI3K)/Akt signalling are prevalent in T-cell acute lymphoblastic leukaemia (T-ALL), and often coexist. Here we show that the PI3K inhibitor GDC-0941 is active against primary T-ALLs from wild-type and Kras(G12D) mice, and addition of the MEK inhibitor PD0325901 increases its efficacy. Mice invariably relapsed after treatment with drug-resistant clones, most of which unexpectedly had reduced levels of activated Notch1 protein, downregulated many Notch1 target genes, and exhibited cross-resistance to γ-secretase inhibitors. Multiple resistant primary T-ALLs that emerged in vivo did not contain somatic Notch1 mutations present in the parental leukaemia. Importantly, resistant clones upregulated PI3K signalling. Consistent with these data, inhibiting Notch1 activated the PI3K pathway, providing a likely mechanism for selection against oncogenic Notch1 signalling. These studies validate PI3K as a therapeutic target in T-ALL and raise the unexpected possibility that dual inhibition of PI3K and Notch1 signalling could promote drug resistance in T-ALL.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Indazóis/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Inibidores de Proteínas Quinases/farmacologia , Receptor Notch1/metabolismo , Sulfonamidas/farmacologia , Animais , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Células Clonais/efeitos dos fármacos , Células Clonais/metabolismo , Células Clonais/patologia , Difenilamina/análogos & derivados , Difenilamina/farmacologia , Difenilamina/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Sinergismo Farmacológico , Genes ras/genética , Indazóis/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Notch1/química , Receptor Notch1/deficiência , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/uso terapêutico
5.
AJR Am J Roentgenol ; 213(5): 1003-1007, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31216200

RESUMO

OBJECTIVE. The purpose of this study was to evaluate the technologist productivity and accuracy in assigning protocols for abdominal CT and MRI examinations compared with a standard work flow whereby protocols are assigned by physicians. MATERIALS AND METHODS. In this quality improvement project at a large academic medical center, two CT technologists and two MRI technologists assigned protocols for examinations during a 15-week study period. The primary outcome measure was mean number of protocols assigned by technologists per hour. Secondary outcome measures were proportion of examinations with protocols assigned by technologists and rate of filing of quality assurance reports for protocols completed by technologists. A two-tailed t test was used to compare mean number of protocols; a chi-square test was used to compare proportions between CT and MRI. RESULTS. The mean number of protocols assigned by technologists per hour was not different between CT and MRI (CT, 22/h; MRI, 19/h; p = 0.28). CT and MRI technologist protocols accounted for 1650 of 4867 (33.9%) CT examinations (range, 23-275 per week) and 569 of 2388 (23.8%) MRI examinations (range, 0-95 per week) (p < 0.001). Radiologist quality assurance reports on inaccurate protocols were rare: three for CT (3/1650 [0.18%]), five for MRI (5/569 [0.88%]) (p = 0.017). A retrospective review of randomly selected CT and MRI protocols revealed no errors (80/80 correct). No patients were called back for repeat imaging due to protocol error. CONCLUSION. Technologists can efficiently and accurately assign protocols for abdominal CT and MRI examinations at an academic medical center, leading to increased radiologist time spent on other value-added activities.


Assuntos
Eficiência , Imageamento por Ressonância Magnética , Radiografia Abdominal , Radiologistas/estatística & dados numéricos , Tecnologia Radiológica , Tomografia Computadorizada por Raios X , Carga de Trabalho/estatística & dados numéricos , Centros Médicos Acadêmicos , Competência Clínica , Feminino , Humanos , Masculino , Melhoria de Qualidade , Estudos Retrospectivos
6.
AJR Am J Roentgenol ; 212(2): 382-385, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30512995

RESUMO

OBJECTIVE: The purpose of this study is to determine both the frequency of repeat CT performed within 1 month after a patient visits the emergency department (ED) and undergoes CT evaluation for abdominal pain and the frequency of worsened or new CT-based diagnoses. SUBJECTS AND METHODS: Secondary analysis was performed on data collected during a prospective multicenter study. The parent study included patients who underwent CT in the ED for abdominal pain between 2012 and 2014, and these patients constituted the study group of the present analysis. The proportion of patients who underwent (in any setting) repeat abdominal CT within 1 month of the index CT examination was calculated. For each of these patients, results of the index and repeat CT scans were compared by an independent panel and categorized as follows: no change (group 1); same process, improved (group 2); same process, worse (group 3); or different process (group 4). The proportion of patients in groups 1 and 2 versus groups 3 and 4 was calculated, and patient and ED physician characteristics were compared. RESULTS: The parent study included 544 patients (246 of whom were men [45%]; mean patient age, 49.4 years). Of those 544 patients, 53 (10%; 95% CI, 7.5-13%) underwent repeat abdominal CT. Patients' CT comparisons were categorized as follows: group 1 for 43% of patients (23/53), group 2 for 26% (14/53), group 3 for 15% (8/53), and group 4 for 15% (8/53). New or worse findings were present in 30% of patients (16/53) (95% CI, 19-44%). When patients with findings in groups 1 and 2 were compared to patients with findings in groups 3 and 4, no significant difference was noted in patient age (p = 0.25) or sex (p = 0.76), the number of days between scans (p = 0.98), and the diagnostic confidence of the ED physician after the index CT scan was obtained (p = 0.33). CONCLUSION: Short-term, repeat abdominal CT was performed for 10% of patients who underwent CT in the ED for abdominal pain, and it yielded new or worse findings for 30% of those patients.


Assuntos
Dor Abdominal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Progressão da Doença , Emergências , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos
9.
Drug Metab Dispos ; 44(12): 1881-1889, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27638506

RESUMO

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Limited treatment options have only marginally impacted patient survival over the past decades. The phophatidylinositol 3-kinase (PI3K) pathway, frequently altered in GBM, represents a potential target for the treatment of this glioma. 5-(6,6-Dimethyl-4-morpholino-8,9-dihydro-6H-[1,4]oxazino[4,3-e]purin-2-yl)pyrimidin-2-amine (GDC-0084) is a PI3K inhibitor that was specifically optimized to cross the blood-brain barrier. The goals of our studies were to characterize the brain distribution, pharmacodynamic (PD) effect, and efficacy of GDC-0084 in orthotopic xenograft models of GBM. GDC-0084 was tested in vitro to assess its sensitivity to the efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) and in vivo in mice to evaluate its effects on the PI3K pathway in intact brain. Mice bearing U87 or GS2 intracranial tumors were treated with GDC-0084 to assess its brain distribution by matrix-assisted laser desorption ionization (MALDI) imaging and measure its PD effects and efficacy in GBM orthotopic models. Studies in transfected cells indicated that GDC-0084 was not a substrate of P-gp or BCRP. GDC-0084 markedly inhibited the PI3K pathway in mouse brain, causing up to 90% suppression of the pAkt signal. MALDI imaging showed GDC-0084 distributed evenly in brain and intracranial U87 and GS2 tumors. GDC-0084 achieved significant tumor growth inhibition of 70% and 40% against the U87 and GS2 orthotopic models, respectively. GDC-0084 distribution throughout the brain and intracranial tumors led to potent inhibition of the PI3K pathway. Its efficacy in orthotopic models of GBM suggests that it could be effective in the treatment of GBM. GDC-0084 is currently in phase I clinical trials.


Assuntos
Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Glioblastoma/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular , Linhagem Celular Tumoral , Cães , Feminino , Glioblastoma/tratamento farmacológico , Glioma/tratamento farmacológico , Glioma/metabolismo , Humanos , Indazóis/metabolismo , Indazóis/farmacologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Nus , Inibidores de Proteínas Quinases/farmacologia
10.
Ann Clin Psychiatry ; 27(1): 10-5, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25696776

RESUMO

BACKGROUND: To date, there has been no investigation of dissemination outcomes for cognitive-behavioral training programs for body-focused repetitive behaviors (BFRBs). METHODS: Sixty-three past participants of the Trichotillomania Learning Center (TLC) intensive professional training institutes completed an online survey assessing referral sources, skills utilization, and treatment outcomes before and after training. The intensive training focused on the treatment of trichotillomania (hair-pulling) disorder and excoriation (skin-picking) disorder using in-person or videotaped didactics, role playing, and case presentations with supervision upon request. RESULTS: Participants endorsed a greater number of referral sources and BFRB patients after attending training. Paired t tests indicated significant pre- to post-training increases in self-reported utilization of all individual cognitive-behavioral therapy (CBT) skills as well as overall mean skills usage (both P<.001). Changes after training in the reported percent of abstinent patients and mean reduction in symptom severity were also noted. CONCLUSIONS: The TLC intensive professional training institutes may be useful for disseminating CBT skills for the treatment of BFRBs, but additional research is warranted.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Disseminação de Informação , Comportamento Autodestrutivo/terapia , Pele/lesões , Tricotilomania/terapia , Humanos , Capacitação em Serviço
11.
Curr Probl Diagn Radiol ; 53(1): 68-72, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37704486

RESUMO

PURPOSE: MRI is the preferred imaging modality for primary staging of rectal cancer, used to guide treatment. Patients identified with clinical stage I disease receive upfront surgical resection; those with clinical stage II or greater undergo upfront neoadjuvant therapy. Although clinical under-/over-staging may have consequences for patients and presents opportunities for organ preservation, the correlation between clinical and pathologic staging in routine clinical practice within a single institute has not been fully established. METHODS: This retrospective, Institutional Review Board-approved study, conducted at a National Cancer Institute-Designated Comprehensive Cancer Center with a multi-disciplinary rectal cancer disease center, included patients undergoing rectal MRI for primary staging January 1, 2018-August 30, 2020. Data collection included patient demographics, initial clinical stage via MRI report, pathologic diagnosis, pathologic stage, and treatment. The primary outcome was concordance of overall clinical and pathologic staging. Secondary outcomes included reasons for mismatched staging. RESULTS: A total 105 rectal adenocarcinoma patients (64 males, mean age 57 ± 12.7 years) had staging MRI followed by surgical resection. A total of 28 patients (27%) had mismatched under-/over- staging. Ten patients (10%) were understaged with mismatched T stage group (clinical stage I, pathologic stage II), five (5%) were understaged with mismatched N stage group (clinical stage I, pathologic stage III), and 13 (12%) were overstaged (clinical stage II-III, pathologic stage 0-I). Treatment matched concordance between clinical and pathologic stages was 86%. CONCLUSION: MRI for primary rectal cancer staging has high concordance with pathology. Future studies to assess strategies for reducing clinically relevant understaging would be beneficial.


Assuntos
Neoplasias Retais , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Terapia Neoadjuvante , Estadiamento de Neoplasias , Imageamento por Ressonância Magnética/métodos
12.
Curr Probl Diagn Radiol ; 53(1): 54-61, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37716856

RESUMO

RATIONALE AND OBJECTIVES: Professional development is important to academic radiologists. We developed, implemented, and assessed an internal professional development lecture series focusing on the non-interpretative themes of Quality, Research, Education, and Wellness (QREW). MATERIALS AND METHODS: The faculty of a 29-member abdominal radiology division at an academic hospital were invited to deliver 1-hour virtual lectures on noninterpretative topics to division colleagues. Topics were curated by division leadership based on the perceived needs of faculty. Anonymous feedback was collected from attendees for quality improvement purposes and analyzed using descriptive statistics and Fisher's exact test. RESULTS: Over 17 months, 13 QREW lectures were delivered. In total, 91 feedback forms were completed by faculty (mean 7 forms, range 2-12 per session). Of these, 57 responses (63%) were by those <7 years post training ("junior faculty"), 34 responses (37%) by those ≥ 7 years from training ("senior faculty"). Most respondents reported low levels of prior instruction (80/90, 89%) and personal knowledge (49/91, 54%) on topics. Compared to senior faculty, a greater proportion of junior faculty reported less prior instruction (73% vs 98%, P < 0.001) and less personal knowledge (32% vs 65%, P < 0.01). Most respondents agreed or strongly agreed that the topics were important to their clinical practice (87/90, 97%), professional development (86/90, 96%), and personal well-being (82/91, 90%). Faculty identified the QREW program as a major contributor to their professional development. CONCLUSION: A noninterpretative professional development lecture series delivered by radiology faculty in a virtual, interactive format is feasible and effective, particularly for junior faculty.


Assuntos
Docentes , Radiologia , Humanos , Escolaridade , Radiologistas , Promoção da Saúde
15.
Bioorg Med Chem Lett ; 23(9): 2606-13, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23540645

RESUMO

A series of suitable five-membered heterocyclic alternatives to thiophenes within a thienobenzoxepin class of PI3-kinase (PI3K) inhibitors was discovered. Specific thiazolobenzoxepin 8-substitution was identified that increased selectivity over PI3Kß. PI3Kß-sparing compound 27 (PI3Kß Ki,app/PI3Kα Ki,app=57) demonstrated dose-dependent knockdown of pAKT, pPRAS40 and pS6RP in vivo as well as differential effects in an in vitro proliferation cell line screen compared to pan PI3K inhibitor GDC-0941. A new structure-based hypothesis for reducing inhibition of the PI3K ß isoform while maintaining activity against α, δ and γ isoforms is presented.


Assuntos
Benzoxepinas/química , Inibidores Enzimáticos/química , Inibidores de Fosfoinositídeo-3 Quinase , Tiazóis/química , Benzoxepinas/síntese química , Benzoxepinas/farmacologia , Sítios de Ligação , Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinase/metabolismo , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade
16.
J Am Coll Radiol ; 20(7): 687-695, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37315913

RESUMO

PURPOSE: The aim of this study was to assess MRI-targeted, systematic, or combined prostate biopsy for diagnosing prostate cancer to identify opportunities for diagnostic accuracy improvement. METHODS: This institutional review board-approved, retrospective study, performed at a large, quaternary hospital, included all men undergoing prostate multiparametric MRI (mpMRI) from January 1, 2015, to December 31, 2019, with prostate-specific antigen ≥ 4 ng/mL, biopsy target on mpMRI (Prostate Imaging Reporting and Data System [PI-RADS] 3-5 lesion), and combined targeted and systematic biopsy ≤6 months after MRI. Analysis included the highest grade lesion per patient. The primary outcome was prostate cancer diagnosis by grade group (GG; 1, 2, and ≥3). Secondary outcomes were rates of cancer upgrading by biopsy type and cancer proximity to the targeted biopsy site in patients upgraded by systematic biopsy. RESULTS: Two hundred sixty-seven biopsies (267 patients) were included; 94.4% (252 of 267) were biopsy naive. The most suspicious mpMRI lesion was PI-RADS 3 in 18.7% (50 of 267), PI-RADS 4 in 52.4% (140 of 267), and PI-RADS 5 in 28.8% (77 of 267). Prostate cancer was diagnosed in 68.5% (183 of 267): 22.1% (59 of 267) GG 1, 16.1% (43 of 267) GG 2, and 30.3% (81 of 267) GG ≥ 3. Combined biopsy (124 of 267) yielded more GG ≥ 2 prostate cancer diagnoses than systematic (87 of 267) or targeted (110 of 267) biopsy alone. More GG ≥ 2 cancers were upgraded by targeted biopsy than by systematic biopsy (P = .0062). Systematic biopsy upgrades were in close proximity to the targeted biopsy site in 42.1% (24 of 57); GG ≥ 3 cancers 62.5% (15 of 24) constituted most proximal misses. CONCLUSIONS: In men with prostate-specific antigen ≥ 4 ng/mL and PI-RADS 3, 4, or 5 lesion on mpMRI, combined biopsy led to more prostate cancer diagnoses than targeted or systematic biopsy alone. Cancers upgraded by systematic biopsy proximal and distant from the targeted biopsy site may indicate opportunities for biopsy and mpMRI improvement, respectively.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Antígeno Prostático Específico , Estudos Retrospectivos , Biópsia Guiada por Imagem/métodos , Biópsia
17.
Acad Med ; 98(10): 1185-1195, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37099328

RESUMO

PURPOSE: With the United States Medical Licensing Examination Step 1 transition to pass/fail in 2022, uncertainty exists regarding how other residency application components, including research conducted during medical school, will inform interview and ranking decisions. The authors explore program director (PD) views on medical student research, the importance of disseminating that work, and the translatable skill set of research participation. METHOD: Surveys were distributed to all U.S. residency PDs and remained open from August to November 2021 to query the importance of research participation in assessing applicants, whether certain types of research were more valued, productivity measures that reflect meaningful research participation, and traits for which research serves as a proxy. The survey also queried whether research would be more important without a numeric Step 1 score and the importance of research vs other application components. RESULTS: A total of 885 responses from 393 institutions were received. Ten PDs indicated that research is not considered when reviewing applicants, leaving 875 responses for analysis. Among 873 PDs (2 nonrespondents), 358 (41.0%) replied that meaningful research participation will be more important in offering interviews. A total of 164 of 304 most competitive specialties (53.9%) reported increased research importance compared with 99 of 282 competitive (35.1%) and 95 of 287 least competitive (33.1%) specialties. PDs reported that meaningful research participation demonstrated intellectual curiosity (545 [62.3%]), critical and analytical thinking skills (482 [55.1%]), and self-directed learning skills (455 [52.0%]). PDs from the most competitive specialties were significantly more likely to indicate that they value basic science research vs PDs from the least competitive specialties. CONCLUSIONS: This study demonstrates how PDs value research in their review of applicants, what they perceive research represents in an applicant, and how these views are shifting as the Step 1 exam transitions to pass/fail.


Assuntos
Internato e Residência , Medicina , Humanos , Estados Unidos , Faculdades de Medicina , Licenciamento , Inquéritos e Questionários
18.
Drug Metab Dispos ; 40(9): 1785-96, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22696419

RESUMO

(S)-1-{4-[2-(2-Amino-pyrimidin-5-yl)-7-methyl-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl]-piperazin-1-yl}-2-hydroxy-propan-1-one (GDC-0980) is a potent and selective inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin, two key components of the PI3K pathway, the deregulation of which is associated with the development of many cancers. The objectives of these studies were to characterize the absorption and disposition of GDC-0980 and assess its efficacy in an MCF7-neo/HER2 human breast cancer xenograft model in immunocompromised mice. Studies in parental Madin-Darby canine kidney cells indicated that GDC-0980 had high permeability (P(app) = 18 × 10⁻6 cm/s), suggesting good absorption potential. However, it was found to be a P-glycoprotein and breast cancer resistance protein substrate in transfected cells and in knockout mice studies. Plasma protein binding was low, with the fraction unbound ranging from 29 to 52% across species. GDC-0980 hepatic clearance (CL) was predicted to be low in all of the species tested from hepatocyte incubations. The plasma CL of GDC-0980 was low in mouse (6.30 ml · min⁻¹ · kg⁻¹), rat (15.4 ml · min⁻¹ · kg⁻¹), and dog (6.37 ml · min⁻¹ · kg⁻¹) and moderate in cynomolgus monkey (18.9 ml · min⁻¹ · kg⁻¹). Oral bioavailability ranged from 14.4% in monkey to 125% in dog. Predicted human plasma CL and volume of distribution using allometry were 5.1 ml · min⁻¹ · kg⁻¹ and 1.8 l/kg, respectively. Parameters estimated from the pharmacokinetic/pharmacodynamic modeling of the MCF7-neo/HER2 xenograft data indicated that the GDC-0980 plasma concentration required for tumor stasis was approximately 0.5 µM. These parameters, combined with the predicted human pharmacokinetic profile, suggested that 55 mg once daily may be a clinically efficacious dose. GDC-0980 preclinical characterization and the predictions of its human properties supported its clinical development; it is currently in Phase II clinical trials.


Assuntos
Antineoplásicos/farmacocinética , Neoplasias da Mama/tratamento farmacológico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacocinética , Absorção Intestinal , Modelos Biológicos , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/farmacocinética , Serina-Treonina Quinases TOR/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/deficiência , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/deficiência , Transportadores de Cassetes de Ligação de ATP/genética , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Área Sob a Curva , Disponibilidade Biológica , Biotransformação , Encéfalo/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/sangue , Permeabilidade da Membrana Celular , Cães , Cálculos da Dosagem de Medicamento , Feminino , Meia-Vida , Hepatócitos/metabolismo , Humanos , Injeções Intravenosas , Fígado/metabolismo , Células MCF-7 , Macaca fascicularis , Células Madin Darby de Rim Canino , Masculino , Taxa de Depuração Metabólica , Camundongos , Camundongos Knockout , Fosfatidilinositol 3-Quinase/metabolismo , Ligação Proteica , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/sangue , Pirimidinas/administração & dosagem , Pirimidinas/sangue , Ratos , Ratos Sprague-Dawley , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Especificidade da Espécie , Serina-Treonina Quinases TOR/metabolismo , Distribuição Tecidual , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Clin Neurophysiol ; 39(7): 643-646, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33675313

RESUMO

PURPOSE: Little is known about the incidence and nature of sharps injuries caused by subdermal intraoperative neurophysiologic monitoring (IONM) needle electrodes. In their institution, the authors observed a series of sharps injuries attributed to placement of needles in the orbicularis oris (OO). METHODS: One large academic institution's sharps injury monitoring database was queried for all reported events over 3 years. The de-identified list was filtered for sharps events occurring in the operating room, and the descriptions of the sharps injuries were individually evaluated. Interventions were performed to attempt to decrease the number of sharps injuries from IONM needles, particularly those placed in OO. Similar data were then collected for 3 months post-intervention. RESULTS: Pre-intervention, 327 sharps injuries were reported over the span of 3 years, of which 13 (4.0%) were attributed to IONM needles not in OO and 5 (1.5%) were attributed to IONM needles in OO. Post-intervention, 41 sharps injuries were reported in 3 months, of which 5 (12.2%) were attributed to IONM needles not in OO and 1 (2.4%) was attributed to needles in OO. CONCLUSIONS: The placement of subdermal needles in the OO presents a disproportionately high risk of sharps injury. Interventions were performed to attempt to decrease the rate of sharps injuries from needles in OO; the post-intervention increase in events was likely skewed by small sample sizes. The implementation of these changes and the ongoing surveillance of injury cases may be important data to help decrease the number of sharps injuries attributed to IONM needles.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Ferimentos Penetrantes Produzidos por Agulha , Humanos , Ferimentos Penetrantes Produzidos por Agulha/epidemiologia , Ferimentos Penetrantes Produzidos por Agulha/etiologia , Ferimentos Penetrantes Produzidos por Agulha/prevenção & controle , Agulhas , Incidência
20.
J Clin Anesth ; 82: 110956, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36029703

RESUMO

STUDY OBJECTIVE: Erector spinae plane (ESP) blocks have been recently described for postoperative pain management following spine surgery but their effects on intraoperative neuromonitoring are unknown. DESIGN: Retrospective cohort study. SETTING: Pediatric patients at a tertiary care center. PATIENTS: 26 pediatric patients who received bilateral surgically-placed ESP catheters for single-stage posterior spine fusion (PSF) from August 2020 to June 2021. INTERVENTIONS: Patients in this study did not receive any special interventions as part of this observational retrospective study. MEASUREMENTS: This retrospective study investigated the effects of local anesthesia administration through bilateral surgically-placed ESP catheters on intraoperative intercostal transcranial motor evoked potentials (tcMEPs) in the setting of a disrupted erector spinae fascial plane in pediatric patients undergoing single-stage posterior spine fusion. MAIN RESULTS: Of the 26 patients that received bilateral surgically-placed ESP catheters for pediatric posterior spine fusion surgery, none exhibited any changes in intercostal tcMEPs attributable to intraoperative lidocaine administration through the ESP catheters. CONCLUSIONS: The administration of a local anesthetic into a disrupted erector spinae fascial plane does not appear to interfere with intraoperative neuromonitoring of posterior spine fusion surgeries.


Assuntos
Bloqueio Nervoso , Criança , Potencial Evocado Motor , Humanos , Lidocaína , Dor Pós-Operatória , Estudos Retrospectivos
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