Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
1.
Harm Reduct J ; 21(1): 71, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549074

RESUMO

BACKGROUND: This study compares emergency department (ED) revisits for patients receiving hospital-based substance-use support compared to those who did not receive specialized addiction services at Health Sciences North in Sudbury, Ontario, Canada. METHODS: The study is a retrospective observational study using administrative data from all patients presenting with substance use disorder (SUD) at Health Sciences North from January 1, 2018, and August 31, 2022 with ICD-10 codes from the Discharge Abstract Database (DAD) and the National Ambulatory Care Database (NACRS). There were two interventions under study: addiction medicine consult services (AMCS group), and specialized addiction medicine unit (AMU group). The AMCS is a consult service offered for patients in the ED and those who are admitted to the hospital. The AMU is a specialized inpatient medical unit designed to offer addiction support to stabilize patients that operates under a harm-reduction philosophy. The primary outcome was all cause ED revisit within 30 days of the index ED or hospital visit. The secondary outcome was all observed ED revisits in the study period. Kaplan-Meier curves were used to measure the proportion of 30-day revisits by exposure group. Odds ratios and Hazard Ratios were calculated using logistic regression models with random effects and Cox-proportional hazard model respectively. RESULTS: A total of 5,367 patients with 10,871 ED index visits, and 2,127 revisits between 2018 and 2022 are included in the study. 45% (2,340/5,367) of patient were not admitted to hospital. 30-day revisits were less likely among the intervention group: Addiction Medicine Consult Services (AMCS) in the ED significantly reduced the odds of revisits (OR 0.53, 95% CI 0.39-0.71, p < 0.01) and first revisits (OR 0.42, 95% CI 0.33-0.53, p < 0.01). The AMU group was associated with lower revisits odds (OR 0.80, 95% CI 0.66-0.98, p = 0.03). For every additional year of age, the odds of revisits slightly decreased (OR 0.99, 95% CI 0.98-1.00, p = 0.01) and males were found to have an increased risk compared to females (OR 1.50, 95% CI 1.35-1.67, p < 0.01). INTERPRETATION: We observe statistically significant differences in ED revisits for patients receiving hospital-based substance-use support at Health Sciences North. Hospital-based substance-use supports could be applied to other hospitals to reduce 30-day revisits.


Assuntos
Readmissão do Paciente , Transtornos Relacionados ao Uso de Substâncias , Masculino , Feminino , Humanos , Estudos Retrospectivos , Serviço Hospitalar de Emergência , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Hospitais , Ontário/epidemiologia
2.
Curr Treat Options Oncol ; 25(1): 20-26, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38170388

RESUMO

OPINION STATEMENT: Sentinel lymph node mapping (SLNM) and dissection (SLND) should be used as an alternative to full inguinofemoral lymph node dissection (IFLND) in select patients with early-stage vulvar cancer. IFLND is associated with high postoperative complications such as wound breakdown, lymphedema, lymphocyst formation, and infection. SLND in select patients offers a safe, effective, and less morbid alternative. Candidates for SLND include patients with a unifocal vulvar tumor less than four centimeters, clinically negative lymph nodes, and no prior inguinofemoral surgeries. SLND should ideally be performed by a high-volume SLN surgeon. Most commonly, SLND is performed using both radiocolloid lymphoscintigraphy (e.g., Technetium-99) and a visual tracer such as blue dye; however, near infrared imaging with indocyanine green injection is becoming more widely adopted. Further prospective studies are needed to examine the safety and efficacy of various techniques for SLND. SLND has been demonstrated to be cost-effective, especially when including perioperative complications. Further studies are needed to demonstrate quality of life differences between IFLND and SLND.


Assuntos
Linfadenopatia , Linfonodo Sentinela , Neoplasias Vulvares , Feminino , Humanos , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/patologia , Qualidade de Vida , Excisão de Linfonodo/métodos , Linfadenopatia/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia
3.
New Phytol ; 240(5): 2020-2034, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37700504

RESUMO

Agriculture is a major source of nutrient pollution, posing a threat to the earth system functioning. Factors determining the nutrient use efficiency of plant-soil systems need to be identified to develop strategies to reduce nutrient losses while ensuring crop productivity. The potential of soil biota to tighten nutrient cycles by improving plant nutrition and reducing soil nutrient losses is still poorly understood. We manipulated soil biota communities in outdoor lysimeters, planted maize, continuously collected leachates, and measured N2 O- and N2 -gas emissions after a fertilization pulse to test whether differences in soil biota communities affected nutrient recycling and N losses. Lysimeters with strongly simplified soil biota communities showed reduced crop N (-20%) and P (-58%) uptake, strongly increased N leaching losses (+65%), and gaseous emissions (+97%) of N2 O and N2 . Soil metagenomic analyses revealed differences in the abundance of genes responsible for nutrient uptake, nitrate reduction, and denitrification that helped explain the observed nutrient losses. Soil biota are major drivers of nutrient cycling and reductions in the diversity or abundance of certain groups (e.g. through land-use intensification) can disrupt nutrient cycling, reduce agricultural productivity and nutrient use efficiency, and exacerbate environmental pollution and global warming.


Assuntos
Nitrogênio , Solo , Nitrogênio/análise , Agricultura , Gases , Biota , Nutrientes , Óxido Nitroso , Fertilizantes
4.
J Voice ; 2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37308368

RESUMO

OBJECTIVE: The purpose of this study is to analyze the voice used in kapa haka, a contemporary indigenous vocal performance from New Zealand, which includes the well-known haka. This is the first study of its kind and is a preliminary investigation into the vocal and acoustic description of kapa haka. A significant goal of this study is to contribute ideas and potential definitions of vocal qualities to the community of kapa haka trainers that were specific to the genre. This strengths-based project raises up these vocal practices as legitimate and authentic colors within a vocal tradition that has seen generational learning disrupted by colonial interventions and is now flourishing within the community. METHODS: Eight kapa haka performers (three females, five males) were involved in the study, they were all experienced performers; furthermore, two had formal classical voice training. They were individually recorded speaking and performing three different genres of kapa haka (moteatea, waiata, and haka); all recordings were in te reo Maori (the Maori language). In addition, electroglottograph (EGG) signals were collected. An auditory-perceptual evaluation of the kapa haka voice was completed by three singer-researcher-pedagogues familiar with Western and non-western genres of singing. They all have experience appropriately collecting and analyzing data from indigenous communities, and they all understand the sociopolitical context of the vocal genre within the local colonial history. A specific evaluation instrument was created, and the results were validated. The acoustic and time-aligned EGG data was annotated at the phoneme level, and the signal analysis was performed in MATLAB. Averaged EGG pulses from /a/ segments were investigated, along with long-term average spectrums of the performances obtained from both the audio signal and the EGG signals. RESULTS: The perceptual analysis suggests the biggest difference in vocal styles was between the haka and the other two genres (and speech). The acoustic and EGG results support these findings. CONCLUSIONS: Common characteristics, perceptually and acoustically, were identified in the kapa haka performance styles across the eight performers.

5.
Gynecol Oncol ; 174: 114-120, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37182431

RESUMO

OBJECTIVE: Malignancy-associated bowel obstruction (MBO) is a potential sequela of advanced gynecologic cancers, adversely impacting both quality of life and prognosis. The Henry score (HS) was developed in a gastrointestinal cancer-predominant population to predict 30-day mortality. We aim to characterize MBO in gynecologic cancers and assess the utility of the HS in this population. METHODS: This is a retrospective review of patients with gynecologic cancer and MBO admitted to a single academic institution from 2016 to 2021. The primary outcome is to characterize malignant small and large bowel obstructions in primary and recurrent gynecologic cancer using readmission and mortality rates. Secondary outcomes are to assess the Henry score and inpatient MBO management. RESULTS: 179 patients totaling 269 were admissions identified, most commonly affecting patients with ovarian cancer. The majority (89.4%) were managed non-operatively while 10.6% were managed surgically. No significant differences were observed in survival for medical versus surgical management. Thirty-day mortality increased with increasing HS (0%, 0-1; 14.3%, 2-3; 40.9%, 4-5). Over 1/3 (34.1%) of patients were readmitted for recurrent or persistent MBO. Goals of care conversations were documented for 56.8% of patients with HS 4-5. Mortality rates across the entire cohort were high-20.1% and 60.9% had died by 1 and 6 months, respectively. CONCLUSIONS: Survival rates following an initial MBO admission are poor. The HS has utility in gynecologic cancers for assessing 30-day mortality and may be a useful tool to aid in the management and counseling of patients with gynecologic cancer and MBO.


Assuntos
Neoplasias dos Genitais Femininos , Obstrução Intestinal , Neoplasias Ovarianas , Humanos , Feminino , Qualidade de Vida , Cuidados Paliativos , Recidiva Local de Neoplasia/complicações , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/terapia , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Obstrução Intestinal/etiologia , Obstrução Intestinal/terapia
6.
Sensors (Basel) ; 23(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36991710

RESUMO

A low-resource emotional speech synthesis system for empathetic speech synthesis based on modelling prosody features is presented here. Secondary emotions, identified to be needed for empathetic speech, are modelled and synthesised in this investigation. As secondary emotions are subtle in nature, they are difficult to model compared to primary emotions. This study is one of the few to model secondary emotions in speech as they have not been extensively studied so far. Current speech synthesis research uses large databases and deep learning techniques to develop emotion models. There are many secondary emotions, and hence, developing large databases for each of the secondary emotions is expensive. Hence, this research presents a proof of concept using handcrafted feature extraction and modelling of these features using a low-resource-intensive machine learning approach, thus creating synthetic speech with secondary emotions. Here, a quantitative-model-based transformation is used to shape the emotional speech's fundamental frequency contour. Speech rate and mean intensity are modelled via rule-based approaches. Using these models, an emotional text-to-speech synthesis system to synthesise five secondary emotions-anxious, apologetic, confident, enthusiastic and worried-is developed. A perception test to evaluate the synthesised emotional speech is also conducted. The participants could identify the correct emotion in a forced response test with a hit rate greater than 65%.


Assuntos
Percepção da Fala , Fala , Humanos , Percepção da Fala/fisiologia , Emoções/fisiologia , Ansiedade
7.
J Low Genit Tract Dis ; 27(2): 120-124, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745862

RESUMO

OBJECTIVE: Human papillomavirus (HPV)-related squamous intraepithelial lesion (SIL) or malignancy is associated with a significantly increased risk of second-site SIL or malignancy. The primary objective of this study was to determine the feasibility and acceptability of concurrent anal, cervical, and vulvovaginal screening in patients with a history of HPV-related gynecologic high-grade SIL or malignancy. The secondary objective was to assess subjects' knowledge regarding HPV screening and risks. METHODS: Women with high-grade cervical, vulvar, or vaginal SIL or malignancy were enrolled during a 1-year pilot period. Subjects with cervical SIL or malignancy underwent vulvar examination and anoscopy. Subjects with vulvovaginal SIL or malignancy underwent Pap test if indicated and anoscopy. Appropriate referrals were made for abnormal findings. Feasibility was assessed by compliance using study acceptance rate, screening procedure adherence, and referral adherence. Acceptability was assessed using a Likert-scaled question after completion of screening procedures. RESULTS: One hundred three women with a diagnosis of high-grade vulvovaginal or cervical SIL or carcinoma were approached regarding study enrollment; of these, 74 (71.8%) enrolled. The median score on the HPV knowledge assessment was 8.1 ± 1.6 (max score 10). Seventy-three (98.6%) of 74 patients rated the screening procedures as acceptable (score of 5/5). On examination, 14 (18.9%) subjects had abnormalities noted; 7 (9.5%) were referred for colorectal surgical evaluation, and 6/7 (85.7%) were compliant with their referral appointments. CONCLUSIONS: Screening examinations for other HPV-related SILs and malignancies, including Pap tests, vulvovaginal inspection, and anoscopy, are acceptable to patients, with abnormal findings in almost 1 in 5 women.


Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias dos Genitais Femininos , Infecções por Papillomavirus , Lesões Intraepiteliais Escamosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Papillomavirus Humano , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Projetos Piloto , Esfregaço Vaginal/métodos , Papillomaviridae , Displasia do Colo do Útero/patologia , Carcinoma de Células Escamosas/complicações , Lesões Intraepiteliais Escamosas/complicações
8.
Oncologist ; 28(1): 33-39, 2023 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35962742

RESUMO

OBJECTIVE: The majority of tumor sequencing currently performed on cancer patients does not include a matched normal control, and in cases where germline testing is performed, it is usually run independently of tumor testing. The rates of concordance between variants identified via germline and tumor testing in this context are poorly understood. We compared tumor and germline sequencing results in patients with breast, ovarian, pancreatic, and prostate cancer who were found to harbor alterations in genes associated with homologous recombination deficiency (HRD) and increased hereditary cancer risk. We then evaluated the potential for a computational somatic-germline-zygosity (SGZ) modeling algorithm to predict germline status based on tumor-only comprehensive genomic profiling (CGP) results. METHODS: A retrospective chart review was performed using an academic cancer center's databases of somatic and germline sequencing tests, and concordance between tumor and germline results was assessed. SGZ modeling from tumor-only CGP was compared to germline results to assess this method's accuracy in determining germline mutation status. RESULTS: A total of 115 patients with 146 total alterations were identified. Concordance rates between somatic and germline alterations ranged from 0% to 85.7% depending on the gene and variant classification. After correcting for differences in variant classification and filtering practices, SGZ modeling was found to have 97.2% sensitivity and 90.3% specificity for the prediction of somatic versus germline origin. CONCLUSIONS: Mutations in HRD genes identified by tumor-only sequencing are frequently germline. Providers should be aware that technical differences related to assay design, variant filtering, and variant classification can contribute to discordance between tumor-only and germline sequencing test results. In addition, SGZ modeling had high predictive power to distinguish between mutations of somatic and germline origin without the need for a matched normal control, and could potentially be considered to inform clinical decision-making.


Assuntos
Neoplasias , Masculino , Humanos , Estudos Retrospectivos , Atenção Terciária à Saúde , Neoplasias/patologia , Genômica , Mutação , Mutação em Linhagem Germinativa
9.
Gynecol Oncol ; 165(1): 4-10, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35078649

RESUMO

OBJECTIVE: To assess the effects of a quality improvement (QI) initiative designed to reduce non-surgical readmissions on a gynecologic oncology service. METHODS: A two-phase QI initiative was implemented on an inpatient gynecologic oncology service to reduce non-surgical 30-day readmissions. Phase 1, from July 2018 to June 2020, included trainee education, frequent physical therapy consultation, pharmacy discharge medication review, 72-h post-discharge telephone call, and standardized 10-day clinic follow-up after discharge. Phase 2, from July 2020 to December 2020, incorporated a nurse practitioner to perform discharge navigation and arrange outpatient follow-up. The incidence of non-surgical readmissions during these phases was compared to that of a baseline period (July 2017-June 2018). We also assessed readmissions to identify common indications and evaluate potential demographic and clinical risk factors. RESULTS: Of 390 total non-surgical gynecologic oncology admissions, 100 were readmitted within 30 days (25.6%). Gastrointestinal tract (GI) obstruction, malignancy-associated pain and infection were the most common symptomatic diagnoses at the index admission, and 30% of readmitted patients had an identical indication for readmission. Compared to the baseline period, we observed a reduction in non-surgical readmissions from 34.1% to 22.6% in Phase 1 and to 18.9% in Phase 2 (p < 0.03) based on internal review, and a reduction from 13.9% to 11.9% in Phase 1 and to 4.7% in Phase 2 (p = 0.04) based on healthcare performance tracking data. CONCLUSIONS: 30-day hospital readmission among non-surgical gynecologic oncology patients is common. Implementation of a multifaceted readmissions reduction QI initiative significantly improved readmission rates.


Assuntos
Neoplasias dos Genitais Femininos , Readmissão do Paciente , Assistência ao Convalescente , Feminino , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Alta do Paciente , Estudos Retrospectivos , Fatores de Risco
10.
Gynecol Oncol ; 164(2): 288-294, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34922770

RESUMO

OBJECTIVE: We designed a multi-faceted intervention to increase the rate of outpatient goals of care (GOC) conversations in women with gynecologic cancers who are at high-risk of death. METHODS AND MATERIALS: A multidisciplinary team developed an educational program around GOC conversations at end-of-life and chose criteria to prospectively identify patients at high-risk of death who might benefit from timely GOC conversations: recurrent or metastatic endometrial, cervical or vulvar cancer or platinum-resistant ovarian cancer. Gynecologic oncology provider consensus was built regarding the need to improve the quality and timing of GOC conversations. Eligible outpatients were prospectively identified and providers alerted pre-encounter; timely GOC documentation within 3 visits of high-risk identification was tracked. Our institution concurrently and subsequently tracked GOC documentation during the last 6 months of life among all established oncology patients. RESULTS: Of 220 pilot period high-risk patients (96 pre- and 124 during pilot period 2017-2018), timely GOC discussion documentation increased from 30.2% to 88.7% (p < 0.001) and this increase was sustained over time. In the post-pilot period (2019-2020), among patients seen by oncologists during last 6 months of life, compared to other cancer types, gynecologic cancer patients had a higher rate of GOC documentation (81% versus 9%; p < 0.001), a lower rate of receiving chemotherapy during the last 14 days of life (2% vs 5%; p = 0.051), and no difference in end-of-life admissions (29% vs 31%; p = NS). CONCLUSIONS: Implementation of systematic outpatient identification of high-risk gynecologic oncology patients is feasible, sustainable, and increases the timely conduct of GOC conversations.


Assuntos
Planejamento Antecipado de Cuidados , Neoplasias dos Genitais Femininos/terapia , Planejamento de Assistência ao Paciente , Medição de Risco , Idoso , Assistência Ambulatorial , Comunicação , Feminino , Humanos , Pessoa de Meia-Idade , Relações Médico-Paciente , Projetos Piloto , Assistência Terminal , Fatores de Tempo , Fluxo de Trabalho
11.
Gynecol Oncol Rep ; 36: 100755, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33855146

RESUMO

Authorship confers credit to those responsible for a publication. In 1985, the International Committee of Medical Journal Editors criteria were founded to standardize authorship assignment. We sought to investigate practices and values in authorship assignment in Society of Gynecologic Oncology (SGO) members. An anonymous online survey was distributed to SGO members from 09/2018-10/2018. Three multivariable logistic regression models were fit to predict ICJME authorship acceptance, assignment and denial. Of 1111 members surveyed, 266 responses were received (23.9%); 30.6% reported prior authorship assignment that did not meet ICMJE criteria, and 18.8% (n = 50) reported a history of accepting authorship not meeting ICJME criteria. Reasons for non-adherence included: inclusion of the author's patients in the study (59.3%), resumé building (45.7%), and networking for career advancement (22.2%). The majority responded that ICJME criteria were generalizable (91.3%), helpful (83.8%), and considered non-adherence as scientific misconduct (66.0%). On multivariable analysis, practice duration of 5-20 years (HR 0.40, 95% CI 0.16, 0.99, p < 0.05) or > 20 years (HR 0.22, 95% CI 0.08, 0.59, p < 0.05) were significant predictors for adherence with ICMJE authorship assignment compared to fellows and those in practice < 5 years. Similarly, practice duration of 5-20 years (HR 10.0, 95% CI 2.0, 49.2, p < 0.05) or > 20 years (HR 25.9, 95% CI 1.06, 3.9, p < 0.05) were significant predictors for denial of authorship assignment compared to fellows and those in practice < 5 years. While the majority of respondents report that ICJME criteria are helpful, adherence to these criteria is a concern, especially in fellows and early-career faculty.

12.
Gynecol Oncol ; 161(2): 508-511, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33771398

RESUMO

OBJECTIVE: We sought to categorize the processes by which gynecologic oncology patients stop chemotherapy and to evaluate associations between these processes and end-of-life outcome metrics. METHODS: A cohort of patients with metastatic or recurrent gynecologic cancer in an outpatient setting from January 2016 to May 2018 was identified. All deceased patients in this cohort were included for analysis. Processes of discontinuing chemotherapy were categorized as: 1) definitive decision inpatient; 2) definitive decision outpatient; 3) delayed decision (eg: treatment break and never resumed chemotherapy); 4) no decision. Associations between patient characteristics and clinical outcomes of those who made a definitive outpatient decision versus those who made any other type of decision were assessed. RESULTS: 220 patients were identified; 205 patients were deceased at time of analysis. Of these, 36.6% made a definitive decision to stop chemotherapy as an outpatient, while 41.5% never made a decision to discontinue chemotherapy. Making a definitive decision as an outpatient, when compared to all other decision types, was associated with significantly lower incidence of death in the hospital (5.6% vs 21.1%, p < 0.004) and hospitalization within 30 days of death (20.8% vs 56.6%, p < 0.001), and significantly increased median time from last chemotherapy to death (135.5 vs 62 days, p < 0.001). CONCLUSION: Only one in three women in this cohort of patients deceased from gynecologic cancer made a definitive decision to discontinue chemotherapy in an outpatient setting, and this process was associated with improved end-of-life outcomes. Future efforts should examine the impact of interventions designed to increase the proportion of patients who transition away from chemotherapy via shared decision making in the outpatient setting.


Assuntos
Antineoplásicos/administração & dosagem , Tomada de Decisões , Neoplasias dos Genitais Femininos/tratamento farmacológico , Idoso , Estudos de Coortes , Feminino , Neoplasias dos Genitais Femininos/psicologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/psicologia , Pacientes Ambulatoriais , Suspensão de Tratamento
13.
Int J Gynecol Cancer ; 31(5): 779-783, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443030

RESUMO

BACKGROUND: Identifying mutation-carrying relatives of patients with hereditary cancer syndromes via cascade testing is an underused first step in primary cancer prevention. A feasibility study of facilitated genetic testing of at-risk relatives of patients with a known pathogenic mutation demonstrated encouraging uptake of cascade testing. PRIMARY OBJECTIVE: Our primary objective is to compare the proportion of genetic testing of identified first-degree relatives of probands with a confirmed BRCA1/2 mutation randomized to a facilitated cascade testing strategy versus standard of care, proband-mediated, information sharing. STUDY HYPOTHESIS: We hypothesize that facilitated cascade testing will drive significantly higher uptake of genetic testing than the standard of care. TRIAL DESIGN: The FaCT (Facilitated Cascade Testing) trial is a prospective multi-institutional randomized study comparing the efficacy of a multicomponent facilitated cascade testing intervention with the standard of care. Patients with a known BRCA1/2 mutation (probands) cared for at participating sites will be randomized. Probands randomized to the standard of care group will be instructed to share a family letter with their first-degree relatives and encourage them to complete genetic testing. First-degree relatives of probands randomized to the intervention arm will receive engagement strategies with a patient navigator, an educational video, and accessible genetic testing services. MAJOR INCLUSION/EXCLUSION CRITERIA: Adult participants who are first-degree relatives of a patient with a BRCA1/2 mutation and have not had prior genetic testing will be included. PRIMARY ENDPOINT: Analyses will assess the proportion of first-degree relatives identified by the proband who complete genetic testing by 6 months in the intervention arm versus the control arm. SAMPLE SIZE: One hundred and fifty probands with a BRCA1/2 mutation will be randomized. Each proband is expected to provide an average of 3 relatives, for an expected 450 participants. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: January 2024. TRIAL REGISTRATION: NCT04613440.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Neoplasias Ovarianas/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/diagnóstico , Família , Feminino , Humanos , Masculino , Mutação , Neoplasias Ovarianas/diagnóstico , Estudos Prospectivos , Medição de Risco
14.
Target Oncol ; 16(1): 109-118, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33400095

RESUMO

BACKGROUND: Recent advances in next-generation sequencing have allowed for an increase in molecular tumor profiling. OBJECTIVE: We sought to assess the actionability and clinical utilization of molecular tumor profiling results obtained via Foundation Medicine tumor sequencing tests in uterine and ovarian cancers. PATIENTS AND METHODS: We performed a single-institution retrospective chart review to obtain demographic and clinical information in patients with uterine and ovarian cancer whose tumors were submitted to Foundation Medicine for molecular tumor profiling over a 7-year period. Alterations identified on testing were stratified according to the OncoKB database actionability algorithm. Descriptive statistics were primarily used to analyze the data. RESULTS: Tumors from 185 women with gynecologic cancer were submitted for molecular tumor profiling between 2013 and 2019. The majority of tests (144/185; 78%) were ordered after a diagnosis of recurrence. In 60 (32%), no actionable molecular alteration was identified. Thirteen (7%) identified an alteration that directed to a US Food and Drug Administration-approved therapy in that tumor type, while 112 (61%) had alterations with investigational or hypothetical treatment implications. In patients with any actionable finding, treatment was initiated in 27 (15%) based on these results. CONCLUSIONS: The majority of uterine and ovarian cancers (93%) did not have molecular alterations with corresponding Food and Drug Administration-approved treatments. Even in patients with a potentially actionable alteration, gynecologic oncologists were more likely to choose an alternative therapy. Further investigation is warranted to determine which patients with uterine and ovarian cancer are most likely to benefit from molecular tumor profiling and the ideal timing of testing. The potential to identify effective therapeutic options in a minority of patients needs to be balanced with the current limited clinical applicability of these results in most cases.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Ovarianas/genética , Neoplasias Uterinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
15.
Clin Infect Dis ; 73(11): e4531-e4538, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-32772111

RESUMO

BACKGROUND: Diphtheria is a potentially fatal respiratory disease caused by toxigenic Corynebacterium diphtheriae. Although resistance to erythromycin has been recognized, ß-lactam resistance in toxigenic diphtheria has not been described. Here, we report a case of fatal respiratory diphtheria caused by toxigenic C. diphtheriae resistant to penicillin and all other ß-lactam antibiotics, and describe a novel mechanism of inducible carbapenem resistance associated with the acquisition of a mobile resistance element. METHODS: Long-read whole-genome sequencing was performed using Pacific Biosciences Single Molecule Real-Time sequencing to determine the genome sequence of C. diphtheriae BQ11 and the mechanism of ß-lactam resistance. To investigate the phenotypic inducibility of meropenem resistance, short-read sequencing was performed using an Illumina NextSeq500 sequencer on the strain both with and without exposure to meropenem. RESULTS: BQ11 demonstrated high-level resistance to penicillin (benzylpenicillin minimum inhibitory concentration [MIC] ≥ 256 µg/ml), ß-lactam/ß-lactamase inhibitors and cephalosporins (amoxicillin/clavulanic acid MIC ≥ 256 µg/mL; ceftriaxone MIC ≥ 8 µg/L). Genomic analysis of BQ11 identified acquisition of a novel transposon carrying the penicillin-binding protein (PBP) Pbp2c, responsible for resistance to penicillin and cephalosporins. When strain BQ11 was exposed to meropenem, selective pressure drove amplification of the transposon in a tandem array and led to a corresponding change from a low-level to a high-level meropenem-resistant phenotype. CONCLUSIONS: We have identified a novel mechanism of inducible antibiotic resistance whereby isolates that appear to be carbapenem susceptible on initial testing can develop in vivo resistance to carbapenems with repeated exposure. This phenomenon could have significant implications for the treatment of C. diphtheriae infection, and may lead to clinical failure.


Assuntos
Corynebacterium diphtheriae , Difteria , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Corynebacterium diphtheriae/genética , Difteria/tratamento farmacológico , Humanos , Lactamas/uso terapêutico , Testes de Sensibilidade Microbiana , Penicilinas/uso terapêutico
16.
Sleep ; 44(5)2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33378539

RESUMO

STUDY OBJECTIVES: Consumer sleep-tracking devices are widely used and becoming more technologically advanced, creating strong interest from researchers and clinicians for their possible use as alternatives to standard actigraphy. We, therefore, tested the performance of many of the latest consumer sleep-tracking devices, alongside actigraphy, versus the gold-standard sleep assessment technique, polysomnography (PSG). METHODS: In total, 34 healthy young adults (22 women; 28.1 ± 3.9 years, mean ± SD) were tested on three consecutive nights (including a disrupted sleep condition) in a sleep laboratory with PSG, along with actigraphy (Philips Respironics Actiwatch 2) and a subset of consumer sleep-tracking devices. Altogether, four wearable (Fatigue Science Readiband, Fitbit Alta HR, Garmin Fenix 5S, Garmin Vivosmart 3) and three nonwearable (EarlySense Live, ResMed S+, SleepScore Max) devices were tested. Sleep/wake summary and epoch-by-epoch agreement measures were compared with PSG. RESULTS: Most devices (Fatigue Science Readiband, Fitbit Alta HR, EarlySense Live, ResMed S+, SleepScore Max) performed as well as or better than actigraphy on sleep/wake performance measures, while the Garmin devices performed worse. Overall, epoch-by-epoch sensitivity was high (all ≥0.93), specificity was low-to-medium (0.18-0.54), sleep stage comparisons were mixed, and devices tended to perform worse on nights with poorer/disrupted sleep. CONCLUSIONS: Consumer sleep-tracking devices exhibited high performance in detecting sleep, and most performed equivalent to (or better than) actigraphy in detecting wake. Device sleep stage assessments were inconsistent. Findings indicate that many newer sleep-tracking devices demonstrate promising performance for tracking sleep and wake. Devices should be tested in different populations and settings to further examine their wider validity and utility.


Assuntos
Actigrafia , Sono , Adulto , Feminino , Humanos , Polissonografia , Reprodutibilidade dos Testes , Fases do Sono , Adulto Jovem
17.
Obstet Gynecol ; 136(6): 1145-1153, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33156183

RESUMO

INTRODUCTION: To gain a better understanding of gynecologic oncology patient adherence to oral anticancer agents through both a cross-sectional survey of adherence and qualitative interviews with patients and clinicians regarding their experience with these medications. METHODS: Eligible participants completed a survey for this cross-sectional study that included an assessment of adherence, distress, quality of life, and health literacy. Any woman taking an oral anticancer agent for a gynecologic malignancy at a tertiary academic medical center for 30 days or more was eligible. Semi-structured qualitative interviews (n=14) were then conducted to explore experiences with oral anticancer agents. We also conducted a qualitative group interview with physicians and nurse practitioners. RESULTS: One hundred women taking oral anticancer agents were enrolled. Fifty-four percent reported perfect adherence to their medication, 21% reported equivocal adherence (demonstrating at least one nonadherent behavior in the previous 7 days), and 25% reported nonadherence (demonstrating more than one nonadherent behavior in the previous 7 days). Qualitative analysis identified five major themes: ease of use compared with traditional therapy; the mental burden of self-administrated medication; perceived importance of the medication; management of side effects; and the desire for consistent physician communication. Common misperceptions expressed in the health care professional interviews included high adherence to oral medications and a belief that cost was the biggest barrier to adherence. CONCLUSION: Almost half of the patients surveyed reported equivocal or nonadherence to their oral anticancer agent. The qualitative interviews identified several important themes, many of which were not recognized by physicians and nurse practitioners. These findings highlight the need for patient and health care professional interventions to improve patient adherence.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias dos Genitais Femininos/tratamento farmacológico , Letramento em Saúde/estatística & dados numéricos , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Administração Oral , Idoso , Antineoplásicos/efeitos adversos , Estudos Transversais , Feminino , Neoplasias dos Genitais Femininos/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Qualidade de Vida , Autoadministração/psicologia , Autoadministração/estatística & dados numéricos , Estresse Psicológico , Inquéritos e Questionários
18.
Int J Gynecol Cancer ; 30(10): 1583-1588, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32839226

RESUMO

OBJECTIVE: Limited information exists regarding risk reduction strategies for women with moderate and low penetrance ovarian cancer susceptibility mutations. We sought to assess current risk reduction practice patterns for carriers of these mutations through a survey of members of the Society of Gynecologic Oncology. METHODS: Society of Gynecologic Oncology members were emailed a survey consisting of two vignettes: (1) a 35-year-old premenopausal woman; (2) a 55-year-old postmenopausal woman with comorbidities. Each vignette contained sub-scenarios in which the patient had either a BRCA1 (relative risk (RR)=30-60), RAD51C (RR=5.0), or ATM (RR=1.5-2.0) mutation. Respondents were queried about their preferred management approach. Summary statistics were performed to describe results of the survey. We used χ2 testing for statistical analyses, comparing results according to mutation type and demographic information. RESULTS: A total of 193 (15%) of 1284 Society of Gynecologic Oncology members responded. For the premenopausal woman, 99%, 80%, and 40% would perform a risk reducing salpingo-oophorectomy prior to menopause in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. For the postmenopausal woman, 98%, 85%, and 42% would proceed with risk reducing salpingo-oophorectomy in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. Response distribution for carriers of RAD51C and ATM mutations were different from BRCA1 in both vignettes (p<0.001). CONCLUSIONS: Respondents were more likely to perform risk reducing salpingo-oophorectomy, in the setting of a BRCA1, RAD51C, and ATM mutation, earlier and more frequently in the setting of a BRCA1 mutation. However, there was a lack of consensus about management of the moderate and low penetrance mutations, suggesting that more data regarding age specific risks and appropriate risk reduction strategies for these alterations are needed.


Assuntos
Carcinoma Epitelial do Ovário/prevenção & controle , Ginecologia/métodos , Neoplasias Ovarianas/prevenção & controle , Adulto , Fatores Etários , Proteínas Mutadas de Ataxia Telangiectasia , Carcinoma Epitelial do Ovário/genética , Proteínas de Ligação a DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Padrões de Prática Médica/estatística & dados numéricos , Fatores de Risco , Salpingo-Ooforectomia/estatística & dados numéricos , Inquéritos e Questionários , Ubiquitina-Proteína Ligases
19.
Int J Gynecol Cancer ; 30(11): 1738-1747, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32771986

RESUMO

BACKGROUND: Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial. OBJECTIVE: To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes. METHODS: A multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis. RESULTS: 405 patients were included with the median age of 67 years (range 27-92, IQR 59-73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively). CONCLUSION: Adjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.


Assuntos
Carcinoma Endometrioide/terapia , Quimiorradioterapia Adjuvante/métodos , Neoplasias do Endométrio/terapia , Idoso , Braquiterapia , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Metástase Linfática/prevenção & controle , Metástase Linfática/radioterapia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco
20.
Value Health ; 23(8): 994-1002, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32828227

RESUMO

OBJECTIVES: To evaluate the outbreak size and hospital cost effects of bacterial whole-genome sequencing availability in managing a large-scale hospital outbreak. METHODS: We built a hybrid discrete event/agent-based simulation model to replicate a serious bacterial outbreak of resistant Escherichia coli in a large metropolitan public hospital during 2017. We tested the 3 strategies of using whole-genome sequencing early, late (actual outbreak), or not using it and assessed their associated outbreak size and hospital cost. The model included ward dynamics, pathogen transmission, and associated hospital costs during a 5-month outbreak. Model parameters were determined using data from the Queensland Hospital Admitted Patient Data Collection (N = 4809 patient admissions) and local clinical knowledge. Sensitivity analyses were performed to address model and parameter uncertainty. RESULTS: An estimated 197 patients were colonized during the outbreak, with 75 patients detected. The total outbreak cost was A$460 137 (US$317 117), with 6.1% spent on sequencing. Without sequencing, the outbreak was estimated to result in 352 colonized patients, costing A$766 921 (US$528 547). With earlier detection from use of routine sequencing, the estimated outbreak size was 3 patients and cost A$65 374 (US$45 054). CONCLUSIONS: Using whole-genome sequencing in hospital outbreak management was associated with smaller outbreaks and cost savings, with sequencing costs as a small fraction of total hospital costs, supporting the further investigation of the use of routine whole-genome sequencing in hospitals.


Assuntos
Escherichia coli/genética , Administração Hospitalar/economia , Sequenciamento Completo do Genoma/economia , Redução de Custos , Infecção Hospitalar/microbiologia , Infecção Hospitalar/prevenção & controle , Surtos de Doenças , Hospitais com mais de 500 Leitos , Custos Hospitalares , Humanos , Queensland , Centros de Atenção Terciária
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA