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1.
Artigo em Inglês | MEDLINE | ID: mdl-32231245

RESUMO

BACKGROUND: Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date. METHODS: A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score. RESULTS: Over a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19-1.50, p < 0.001), while age, serum PSA, biopsy GG, and clinical T-stage were not (all p > 0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19-1.48, p < 0.001) and GC high-risk (vs low-risk, HR: 2.95, 95% CI: 1.79-4.87, p < 0.001) were significantly associated with metastasis. The addition of GC score to regression models based on NCCN risk group improved model AUC from 0.46 to 0.67, and CAPRA from 0.59 to 0.71. CONCLUSIONS: Among men with high-risk prostate cancer, conventional clinico-pathologic data had poor discrimination to risk stratify development of metastatic disease. GC score was a significant and independent predictor of metastasis and may help identify men best suited for treatment intensification/de-escalation.

2.
Clin Cancer Res ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341032

RESUMO

PURPOSE: A major challenge in ductal carcinoma in situ treatment is selection of the most appropriate therapeutic approach for individual patients. We conducted an external prospective-retrospective clinical validation of a DCIS biologic risk signature, DCISionRT, in a population-based observational cohort of women diagnosed with ductal carcinoma in situ and treated with breast-conserving surgery. EXPERIMENTAL DESIGN: Participants were 455 health plan members of Kaiser Permanente Northwest diagnosed with ductal carcinoma in situ and treated with breast conserving surgery with or without radiation therapy from 1990-2007. The biologic signature combined seven protein tumor markers assessed in formalin-fixed paraffin-embedded tumor tissue with four clinicopathologic factors to provide a DCISionRT test result, termed Decision Score (DS). Cox regression and Kaplan-Meier analysis were used to measure the association of the DS- continuous (linear) or categorical (DS<=3 vs DS>3)- and subsequent total ipsilateral breast events and invasive ipsilateral breast events at least 6 months after initial surgery. RESULTS: In Cox regression, the continuous and categorical DS variables were positively associated with total and invasive breast event risk after adjustment for radiation therapy. In subset analysis by treatment group, categorical Kaplan-Meier analyses showed at least 2-fold differences in 10-year risk of total breast events between the elevated-risk and low-risk DS categories. CONCLUSIONS AND RELEVANCE: In this first external validation study of the DCISionRT test, the DS was prognostic for the risk of later breast events for women diagnosed with ductal carcinoma in situ, following breast conserving surgery.

3.
Mol Carcinog ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32134153

RESUMO

A hallmark of ductal carcinoma in situ (DCIS) progression is a loss of the surrounding ductal myoepithelium. However, whether compromise in myoepithelial differentiation, rather than overt cellular loss, can be used to predict the risk of DCIS progression is unknown. Here we address this question utilizing pure and mixed DCIS cases (N = 30) as surrogates for DCIS at low and high risk for progression, respectively. We used multiplex immunohistochemical staining to evaluate the relationship between myoepithelial cell differentiation and lymphoid immune cell types associated with poor prognostic DCIS. Our results show that myoepithelial calponin-1 discriminates between pure and mixed DCIS lesions better than histological subtype, presence of necrosis, or nuclear grade. Additionally, focal loss of myoepithelial cells associated with increased PD-1+CD8+ T cells, which suggests a link between the myoepithelium and immune surveillance. To identify associations between calponin-1 expression and immune response, we performed unsupervised hierarchical clustering of myoepithelial and immune cell biomarkers on 219 DCIS lesions from 30 cases. Notably, the majority of pure (low-risk) DCIS lesions clustered in a high calponin-1, T cell low group, whereas the majority of mixed (high-risk) DCIS lesions clustered in a low calponin-1, T cell high group, specifically with CD8+ and PD-1+CD8+ T cells. However, a subset of pure DCIS lesions had a similar calponin-1 and immune signature as the majority of mixed DCIS lesions, which have low calponin-1 and T cell enrichment-raising the possibility that these pure DCIS lesions might be at a high risk for progression.

5.
Urol Oncol ; 38(2): 39.e21-39.e27, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31711836

RESUMO

OBJECTIVES: To externally validate the European Organization for the Research and Treatment of Cancer (EORTC) risk calculator and National Comprehensive Cancer Network (NCCN) guidelines in a contemporary population of U.S. non-muscle-invasive bladder cancer (NMIBC) patients treated in a community-based setting and compare our findings to those from another U.S. health system. MATERIALS AND METHODS: We identified 1,491 NMIBC patients with a median follow-up of 2.1 years (recurrence) and 4.1 years (progression). We calculated NCCN risk groupings and EORTC prognostic index for recurrence and progression. We followed Royston and Altman's guidelines for the external validation of prognostic calculators. RESULTS: For predicting recurrence using the EORTC framework, Harrell's C (a measure of discrimination) was smaller in our sample (0.66) than in the European Association of Urology sample (0.61), whereas for progression, Harrell's C was larger in our sample (0.78 vs. 0.75). The EORTC calculator overestimated progression risk in the highest stratum for our sample; calibration and discrimination were adequate for all groups except the highest risk group. For NCCN risk groupings, Harrell's C was 0.54 for recurrence and 0.62 for progression, suggesting poor to fair discrimination in our sample. The NCCN framework had slightly better performance for predicting progression vs. recurrence. CONCLUSIONS: Existing NMIBC risk-stratification frameworks have acceptable accuracy to predict outcomes. However, further innovation in NMIBC care will require predictive tools with more granularity to reflect the differential risks of subgroups of NMIBC recurrence, prior treatment histories, and other prognostic variables.

6.
Sex Transm Dis ; 47(3): 179-186, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31880738

RESUMO

BACKGROUND: Studies in countries with high human papillomavirus (HPV) vaccination coverage have demonstrated marked reductions in anogenital wart (AGW) incidence. Our goal was to assess the impact of HPV vaccination in a population with suboptimal coverage by comparing AGW incidence trends in the years before and after vaccine introduction. METHODS: We conducted a retrospective analysis of AGW incidence trends using an ecologic study design among 11- through 39-year-olds enrolled at Kaiser Permanente Northwest. We defined incidence as the proportion of persons who had a new AGW diagnosis for each calendar year in the prevaccine periods (2000 through 2006 for female individuals, 2000 through 2010 for male individuals) and the postvaccine periods (2007 through 2016 for female individuals, 2011 through 2016 for male individuals). We also described cumulative HPV vaccination coverage. RESULTS: The average annual AGW incidence rates in the prevaccine periods were 27.8 per 10,000 in female individuals and 26.9 per 10,000 in male individuals. In the postvaccine periods, AGW incidence rates decreased by 31% (P < 0.001) in female individuals and 10% (P = 0.006) in male individuals; the largest reductions were observed in 15- to 19-year-old female individuals (67%, P < 0.001) and male individuals (45%, P < 0.001). Three dose HPV coverage rates were less than 50% in all age groups and both sexes. CONCLUSIONS: In a population of young adults with moderate HPV vaccination coverage, we observed declines in AGW incidence among both female and male year after the introduction of HPV vaccination. The largest incidence reductions were observed in 15- to 19-year-olds who were most likely to have been vaccinated.

7.
Qual Life Res ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31811594

RESUMO

PURPOSE: The Bladder Cancer Quality of Life Study collected detailed and sensitive patient-reported outcomes from bladder cancer survivors in the period after bladder removal surgery, when participation in survey research may present a burden. This paper describes the study recruitment methods and examines the response rates and patterns of missing data. METHODS: Detailed surveys focusing on quality of life, healthcare decision-making, and healthcare expenses were mailed to patients 5-7 months after cystectomy. We conducted up to 10 follow-up recruitment calls. We analyzed survey completion rates following each contact in relation to demographic and clinical characteristics, and patterns of missing data across survey content areas. RESULTS: The overall response rate was 71% (n = 269/379). This was consistent across patient clinical characteristics; response rates were significantly higher among patients over age 70 and significantly lower among racial and ethnic minority patients compared to non-Hispanic white patients. Each follow-up contact resulted in marginal survey completion rates of at least 10%. Rates of missing data were low across most content areas, even for potentially sensitive questions. Rates of missing data differed significantly by sex, age, and race/ethnicity. CONCLUSIONS: Despite the effort required to participate in research, this population of cancer survivors showed willingness to share detailed information about quality of life, health care decision-making, and expenses, soon after major cancer surgery. Additional contacts were effective at increasing participation. Response patterns differed by race/ethnicity and other demographic factors. Our data collection methods show that it is feasible to gather detailed patient-reported outcomes during this challenging period.

8.
J Infect Dis ; 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31784749

RESUMO

BACKGROUND: Highly effective human papillomavirus (HPV) vaccines are used in many national programs in 3- or 2-dose schedules. We examined HPV vaccine effectiveness against HPV prevalence by number of doses. METHODS: We collected residual liquid-based cytology samples from US women aged 20-29 years who were screened for cervical cancer. Women continuously enrolled from 2006 through the specimen collection date were analyzed. Specimens were tested using the Linear Array assay. We analyzed prevalence of quadrivalent HPV vaccine (4vHPV) types (HPV 6,11,16,18) and other HPV-type categories and determined prevalence ratios (PRs) and 95% confidence intervals (CIs) for 1, 2, and 3 compared with no vaccine doses. RESULTS: Among 4269 women, 1052 (24.6%) were unvaccinated, 2610 (61.1%) received 3 doses, 304 (7.1%) received 2 doses, and 303 (7.1%) received 1 dose. The 4vHPV-type prevalence was 7.4% among unvaccinated women compared with 1.7%, 1.0%, and 1.0% among 1-, 2-, and 3-dose recipients. Among women vaccinated at ≤18 years, adjusted PRs for 1, 2, and 3 doses were 0.06 (95% CI, 0.01-0.42), 0.05 (95% CI, 0.01-0.39), and 0.06 (95% CI, 0.04-0.12). CONCLUSIONS: Among women who received their first dose at age ≤18, estimated HPV vaccine effectiveness was high regardless of number of doses.

9.
BMC Med Genomics ; 12(1): 195, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856832

RESUMO

BACKGROUND: Formalin-fixed, paraffin-embedded (FFPE) tissues for RNA-seq have advantages over fresh frozen tissue including abundance and availability, connection to rich clinical data, and association with patient outcomes. However, FFPE-derived RNA is highly degraded and chemically modified, which impacts its utility as a faithful source for biological inquiry. METHODS: True archival FFPE breast cancer cases (n = 58), stored at room temperature for 2-23 years, were utilized to identify key steps in tissue selection, RNA isolation, and library choice. Gene expression fidelity was evaluated by comparing FFPE data to public data obtained from fresh tissues, and by employing single-gene, gene set and transcription network-based regulon analyses. RESULTS: We report a single 10 µm section of breast tissue yields sufficient RNA for RNA-seq, and a relationship between RNA quality and block age that was not linear. We find single-gene analysis is limiting with FFPE tissues, while targeted gene set approaches effectively distinguish ER+ from ER- breast cancers. Novel utilization of regulon analysis identified the transcription factor KDM4B to associate with ER+ disease, with KDM4B regulon activity and gene expression having prognostic significance in an independent cohort of ER+ cases. CONCLUSION: Our results, which outline a robust FFPE-RNA-seq pipeline for broad use, support utilizing FFPE tissues to address key questions in the breast cancer field, including the delineation between indolent and life-threatening disease, biological stratification and molecular mechanisms of treatment resistance.

10.
J Clin Med ; 8(11)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31689948

RESUMO

Mammographic breast density (MD) reflects breast fibroglandular content. Its decline following adjuvant tamoxifen treated, estrogen receptor (ER)-positive breast cancer has been associated with improved outcomes. Breast cancers arise from structures termed lobules, and lower MD is associated with increased age-related lobule involution. We assessed whether pre-treatment involution influenced associations between MD decline and risk of breast cancer-specific death. ER-positive tamoxifen treated patients diagnosed at Kaiser Permanente Northwest (1990-2008) were defined as cases who died of breast cancer (n = 54) and matched controls (remained alive over similar follow-up; n = 180). Lobule involution was assessed by examining terminal duct lobular units (TDLUs) in benign tissues surrounding cancers as TDLU count/mm2, median span and acini count/TDLU. MD (%) was measured in the unaffected breast at baseline (median 6-months before) and follow-up (median 12-months after tamoxifen initiation). TDLU measures and baseline MD were positively associated among controls (p < 0.05). In multivariable regression models, MD decline (≥10%) was associated with reduced risk of breast cancer-specific death before (odds ratio (OR): 0.41, 95% CI: 0.18-0.92) and after (OR: 0.41, 95% CI: 0.18-0.94) adjustment for TDLU count/mm2, TDLU span (OR: 0.34, 95% CI: 0.14-0.84), and acini count/TDLU (OR: 0.33, 95% CI: 0.13-0.81). MD decline following adjuvant tamoxifen is associated with reduced risk of breast cancer-specific death, irrespective of pre-treatment lobule involution.

11.
Perm J ; 232019.
Artigo em Inglês | MEDLINE | ID: mdl-31496500

RESUMO

BACKGROUND: Among the approximately 53,000 patients newly diagnosed with early-stage (superficial) bladder cancer each year, there is substantial variability in the progression to muscle-invasive disease. Enhancing risk stratification and risk-stratified surveillance could minimize risks and harms to patients, as well as unnecessary costs to health systems. OBJECTIVES: As a preliminary step in developing and validating a risk assessment tool for superficial bladder cancer in a population-based clinical cohort, we interviewed urologists who might use such a tool to assess need, determine potential use cases, and identify key features to include. METHODS: Using an opportunistic and purposeful sampling design, we invited 13 urologists from a variety of practice settings and with a wide range of clinical experience to take part in qualitative interviews; 9 (5 urologic oncologists and 4 general urologists) participated. RESULTS: All urologists reported using some form of risk stratification to determine surveillance schedules for patients with bladder cancer. The following use cases were endorsed by 4 or more interviewees: 1) provide evidence to guide clinical management in specific situations, 2) generate patient-facing communication aids, 3) improve documentation about recurrence/progression risk, and 4) create scheduling and callback supports to improve the quality of follow-up care. CONCLUSION: Our findings demonstrated several potential clinical-use cases for a risk calculator and clinical decision-support tool for patients with superficial bladder cancer. Clinicians stressed the potential utility of such a tool to improve patient communication, scheduling, and tracking in general urology practice.


Assuntos
Neoplasias da Bexiga Urinária/diagnóstico , Humanos , Entrevistas como Assunto , Padrões de Prática Médica , Medição de Risco/métodos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/etiologia , Neoplasias da Bexiga Urinária/patologia , Urologistas
12.
Clin Cancer Res ; 25(22): 6721-6730, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31515456

RESUMO

PURPOSE: The heterogeneity of androgen receptor (AR)-activity (AR-A) is well-characterized in heavily treated metastatic castration-resistant prostate cancer (mCRPC). However, the diversity and clinical implications of AR-A in treatment-naïve primary prostate cancer is largely unknown. We sought to characterize AR-A in localized prostate cancer and understand its molecular and clinical implications. EXPERIMENTAL DESIGN: Genome-wide expression profiles from prostatectomy or biopsy samples from 19,470 patients were used, all with independent pathology review. This was comprised of prospective discovery (n = 5,239) and validation (n = 12,728) cohorts, six retrospective institutional cohorts with long-term clinical outcomes data (n = 1,170), and The Cancer Genome Atlas (n = 333). RESULTS: A low AR-active subclass was identified, which comprised 9%-11% of each cohort, and was characterized by increased immune signaling, neuroendocrine expression, and decreased DNA repair. These tumors were predominantly ERG and basal subtype. Low AR-active tumors had significantly more rapid development of recurrence or metastatic disease across cohorts, which was maintained on multivariable analysis [HR, 2.61; 95% confidence interval (CI), 1.22-5.60; P = 0.014]. Low AR-active tumors were predicted to be more sensitive to PARP inhibition, platinum chemotherapy, and radiotherapy, and less sensitive to docetaxel and androgen-deprivation therapy. This was validated clinically, in that low AR-active tumors were less sensitive to androgen-deprivation therapy (OR, 0.41; 95% CI, 0.21-0.80; P = 0.008). CONCLUSIONS: Leveraging large-scale transcriptomic data allowed the identification of an aggressive subtype of treatment-naïve primary prostate cancer that harbors molecular features more analogous to mCRPC. This suggests that a preexisting subgroup of patients may have tumors that are predisposed to fail multiple current standard-of-care therapies and warrant dedicated therapeutic investigation.

13.
JAMA ; 322(9): 843-856, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479136

RESUMO

Importance: Medical imaging increased rapidly from 2000 to 2006, but trends in recent years have not been analyzed. Objective: To evaluate recent trends in medical imaging. Design, Setting, and Participants: Retrospective cohort study of patterns of medical imaging between 2000 and 2016 among 16 million to 21 million patients enrolled annually in 7 US integrated and mixed-model insurance health care systems and for individuals receiving care in Ontario, Canada. Exposures: Calendar year and country (United States vs Canada). Main Outcomes and Measures: Use of computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and nuclear medicine imaging. Annual and relative imaging rates by imaging modality, country, and age (children [<18 years], adults [18-64 years], and older adults [≥65 years]). Results: Overall, 135 774 532 imaging examinations were included; 5 439 874 (4%) in children, 89 635 312 (66%) in adults, and 40 699 346 (30%) in older adults. Among adults and older adults, imaging rates were significantly higher in 2016 vs 2000 for all imaging modalities other than nuclear medicine. For example, among older adults, CT imaging rates were 428 per 1000 person-years in 2016 vs 204 per 1000 in 2000 in US health care systems and 409 per 1000 vs 161 per 1000 in Ontario; for MRI, 139 per 1000 vs 62 per 1000 in the United States and 89 per 1000 vs 13 per 1000 in Ontario; and for ultrasound, 495 per 1000 vs 324 per 1000 in the United States and 580 per 1000 vs 332 per 1000 in Ontario. Annual growth in imaging rates among US adults and older adults slowed over time for CT (from an 11.6% annual percentage increase among adults and 9.5% among older adults in 2000-2006 to 3.7% among adults in 2013-2016 and 5.2% among older adults in 2014-2016) and for MRI (from 11.4% in 2000-2004 in adults and 11.3% in 2000-2005 in older adults to 1.3% in 2007-2016 in adults and 2.2% in 2005-2016 in older adults). Patterns in Ontario were similar. Among children, annual growth for CT stabilized or declined (United States: from 10.1% in 2000-2005 to 0.8% in 2013-2016; Ontario: from 3.3% in 2000-2006 to -5.3% in 2006-2016), but patterns for MRI were similar to adults. Changes in annual growth in ultrasound were smaller among adults and children in the United States and Ontario compared with CT and MRI. Nuclear medicine imaging declined in adults and children after 2006. Conclusions and Relevance: From 2000 to 2016 in 7 US integrated and mixed-model health care systems and in Ontario, rates of CT and MRI use continued to increase among adults, but at a slower pace in more recent years. In children, imaging rates continued to increase except for CT, which stabilized or declined in more recent periods. Whether the observed imaging utilization was appropriate or was associated with improved patient outcomes is unknown.


Assuntos
Diagnóstico por Imagem/tendências , Abdome/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Diagnóstico por Imagem/estatística & dados numéricos , Cabeça/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/estatística & dados numéricos , Imagem por Ressonância Magnética/tendências , Pessoa de Meia-Idade , Ontário , Cintilografia/estatística & dados numéricos , Cintilografia/tendências , Coluna Vertebral/diagnóstico por imagem , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Tomografia Computadorizada por Raios X/tendências , Ultrassonografia/estatística & dados numéricos , Ultrassonografia/tendências , Estados Unidos , Adulto Jovem
14.
Eur Urol Oncol ; 2(5): 589-596, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31411980

RESUMO

BACKGROUND: Decipher is a genomic classifier designed to predict the development of distant metastases after surgical treatment of prostate cancer (PC). Its long-term prognostic role in a high-risk PC population has not been investigated previously. OBJECTIVE: To determine the prognostic role of the Decipher genomic classifier in two high-risk PC case-control studies. DESIGN, SETTING, AND PARTICIPANTS: Patients who developed distant metastases after surgery for high-risk, nonmetastatic PC in a European tertiary referral center from 1991 to 2011 were matched to patients not developing distant metastases (n=54). A validation study (n=298) was performed using a similar US case-control cohort. Formalin-fixed, paraffin-embedded tissue blocks from the index PC lesion were used for RNA extraction and gene expression analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome investigated was the development of distant metastasis within 10-yr follow-up. Multivariable logistic regression analysis was performed, with statistical significance considered at p<0.05. RESULTS AND LIMITATIONS: In both the European and US case-control studies, the median Decipher scores were higher in the population that developed metastases. In the multivariable analysis, each 10% increase in Decipher score translated to an increase in the risk of distant metastases within 10-yr follow-up, with an odds ratio of 1.53 (95% confidence interval [CI] 1.06-2.22; p=0.025) and 1.58 (95% CI 1.31-1.92; p<0.001) for the European and US cohorts, respectively. Median follow-up for the European cohort was 12yr (interquartile range 8-12). The study limitation is the small size of the European cohort. CONCLUSIONS: Our study validates Decipher as a predictor for metastatic recurrence even in patients with high-risk, nonmetastatic PC within 10-yr follow-up. PATIENT SUMMARY: Decipher is a test based on gene expression profiles in primary tumors in prostate cancer. It has already been proven to predict cancer recurrence after surgery, but this has not yet been shown for patients with high-risk prostate cancer. This is the first study confirming that Decipher predicts a patient's risk of developing cancer recurrence after surgery for high-risk prostate cancer.

15.
JAMA Netw Open ; 2(7): e197249, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31339541

RESUMO

Importance: The use of medical imaging has sharply increased over the last 2 decades. Imaging rates during pregnancy have not been quantified in a large, multisite study setting. Objective: To evaluate patterns of medical imaging during pregnancy. Design, Setting, and Participants: A retrospective cohort study was performed at 6 US integrated health care systems and in Ontario, Canada. Participants included pregnant women who gave birth to a live neonate of at least 24 weeks' gestation between January 1, 1996, and December 31, 2016, and who were enrolled in the health care system for the entire pregnancy. Exposures: Computed tomography (CT), magnetic resonance imaging, conventional radiography, angiography and fluoroscopy, and nuclear medicine. Main Outcomes and Measures: Imaging rates per pregnancy stratified by country and year of child's birth. Results: A total of 3 497 603 pregnancies in 2 211 789 women were included. Overall, 26% of pregnancies were from US sites. Most (92%) were in women aged 20 to 39 years, and 85% resulted in full-term births. Computed tomography imaging rates in the United States increased from 2.0 examinations/1000 pregnancies in 1996 to 11.4/1000 pregnancies in 2007, remained stable through 2010, and decreased to 9.3/1000 pregnancies by 2016, for an overall increase of 3.7-fold. Computed tomography rates in Ontario, Canada, increased more gradually by 2.0-fold, from 2.0/1000 pregnancies in 1996 to 6.2/1000 pregnancies in 2016, which was 33% lower than in the United States. Overall, 5.3% of pregnant women in US sites and 3.6% in Ontario underwent imaging with ionizing radiation, and 0.8% of women at US sites and 0.4% in Ontario underwent CT. Magnetic resonance imaging rates increased steadily from 1.0/1000 pregnancies in 1996 to 11.9/1000 pregnancies in 2016 in the United States and from 0.5/1000 pregnancies in 1996 to 9.8/1000 pregnancies in 2016 in Ontario, surpassing CT rates in 2013 in the United States and in 2007 in Ontario. In the United States, radiography rates doubled from 34.5/1000 pregnancies in 1996 to 72.6/1000 pregnancies in 1999 and then decreased to 47.6/1000 pregnancies in 2016; rates in Ontario slowly increased from 36.2/1000 pregnancies in 1996 to 44.7/1000 pregnancies in 2016. Angiography and fluoroscopy and nuclear medicine use rates were low (5.2/1000 pregnancies), but in most years, higher in Ontario than the United States. Imaging rates were highest for women who were younger than 20 years or aged 40 years or older, gave birth preterm, or were black, Native American, or Hispanic (US data only). Considering advanced imaging only, chest imaging of pregnant women was more likely to use CT in the United States and nuclear medicine imaging in Ontario. Conclusions and Relevance: The use of CT during pregnancy substantially increased in the United States and Ontario over the past 2 decades. Imaging rates during pregnancy should be monitored to avoid unnecessary exposure of women and fetuses to ionizing radiation.

16.
Vaccine ; 37(29): 3918-3924, 2019 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-31160099

RESUMO

BACKGROUND: Human papillomavirus (HPV) vaccine has been recommended in the United States since 2006 for routine vaccination of girls at age 11-12 years and through age 26 years for women not previously vaccinated. Changes in vaccine-type HPV (VT) prevalence can be used to evaluate vaccine impact, including herd effects. METHODS: We determined type-specific HPV in cytology specimens from women aged 20-29 years screened for cervical cancer at Kaiser Permanente Northwest in 2007 and in two vaccine era periods: 2012-2013 and 2015-2016. Detection and typing used L1 consensus PCR with hybridization for 37 types, including quadrivalent vaccine types (HPV 6/11/16/18). RESULTS: Among 20-24 year-olds in 2012-2013 and 2015-2016, 44% and 64% had a history of ≥1-dose vaccination. VT prevalence decreased from 13.1% in 2007 to 2.9% in 2015-2016 (prevalence ratio [PR] = 0.22; 95% confidence interval [CI] 0.17-0.29). HPV 31 prevalence was also lower in the vaccine periods compared with 2007. VT prevalence in 2015-2016 among 20-24 year-olds was lower in both vaccinated, 1.3% (PR = 0.10; 95% CI 0.06-0.16), and unvaccinated women, 5.8% (PR = 0.45; 95% CI 0.33-0.61). Among 25-29 year-olds, 21% and 32% had a history of ≥1-dose vaccination. VT prevalence decreased from 8.1% in 2007 to 5.0% in 2015-2016 (PR = 0.62; 95% CI 0.50-0.78). Non-VT high risk prevalence was higher in the vaccine periods compared with the pre-vaccine era in both age groups, however, not in 2015-2016 compared with 2012-2013. CONCLUSION: Within 9-10 years of vaccine introduction, VT prevalence decreased 78% among 20-24 year-olds and 38% in 25-29 year-olds. There were declines in both vaccinated and unvaccinated women, showing evidence of direct and herd protection.

17.
Pediatrics ; 144(1)2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31182552

RESUMO

BACKGROUND AND OBJECTIVES: After the 1996 introduction of routine varicella vaccination in the United States, most studies evaluating pediatric herpes zoster (HZ) incidence reported lower incidence over time, with varying degrees of decline. Using the combined databases of 6 integrated health care organizations, we examined HZ incidence in children over a 12-year period in the varicella vaccine era. METHODS: This study included children aged 0 through 17 years from 2003 through 2014. Using electronic medical records, we identified HZ cases through International Classification of Diseases, Ninth Revision diagnosis code 053. We calculated HZ incidence rates per 100 000 person years of health plan membership for all children and among children who were vaccinated versus unvaccinated. We calculated rates for the 12-year period and examined temporal trends. Among children who were vaccinated, we compared HZ rates by month and year of age at vaccination. RESULTS: The study included 6 372 067 children with ≥1 month of health plan membership. For the 12-year period, the crude HZ incidence rate for all subjects was 74 per 100 000 person years, and the rate among children who were vaccinated was 38 per 100 000 person years, which was 78% lower than that among children who were unvaccinated (170 per 100 000 person years; P < .0001). Overall HZ incidence declined by 72% (P < .0001) from 2003 through 2014. Annual rates in children who were vaccinated were consistently lower than in children who were unvaccinated. CONCLUSIONS: With this population-based study, we confirm the decline in pediatric HZ incidence and the significantly lower incidence among children who are vaccinated, reinforcing the benefit of routine varicella vaccination to prevent pediatric HZ.


Assuntos
Herpes Zoster/epidemiologia , Adolescente , Vacina contra Varicela , Criança , Pré-Escolar , Feminino , Herpes Zoster/prevenção & controle , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Vacinação em Massa , Estados Unidos/epidemiologia
18.
Ann Surg ; 2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-30998538

RESUMO

MINI: We examined risk of breast cancer among 17,998 women who had bariatric surgery and 53,889 women matched on body mass index with no surgery. We found bariatric surgery was associated with a reduced risk of both premenopausal [hazard ratio (HR) = 0.72, 95% confidence interval (CI), 0.54-0.94] and postmenopausal (HR = 0.55, 95% CI, 0.42-0.72) breast cancer. OBJECTIVE: This retrospective cohort study examined whether bariatric surgery is associated with reduced risk of breast cancer among pre- and postmenopausal women. BACKGROUND: Obesity is associated with increased risk of breast cancer, but the impact of weight loss on breast cancer risk has been difficult to quantify. METHODS: The cohort included obese (body mass index ≥35 kg/m) patients enrolled in an integrated health care delivery system between 2005 and 2012 (with follow-up through 2014). Female bariatric surgery patients (N = 17,998) were matched on body mass index, age, study site, and comorbidity index to 53,889 women with no bariatric surgery. Kaplan-Meier curves and Cox proportional hazards models were used to examine incident breast cancer up to 10 years after bariatric surgery. Pre- and postmenopausal women were examined separately, and further classified by estrogen receptor (ER) status. RESULTS: The analysis included 301 premenopausal and 399 postmenopausal breast cancer cases. In multivariable adjusted models, bariatric surgery was associated with a reduced risk of both premenopausal (HR = 0.72, 95% CI, 0.54-0.94) and postmenopausal (HR = 0.55, 95% CI, 0.42-0.72) breast cancer. Among premenopausal women, the effect of bariatric surgery was more pronounced among ER-negative cases (HR = 0.36, 95% CI, 0.16-0.79). Among postmenopausal women, the effect was more pronounced in ER-positive cases (HR = 0.52, 95% CI, 0.39-0.70). CONCLUSIONS: Bariatric surgery was associated with a reduced risk of breast cancer among severely obese women. These findings have significant public health relevance because the prevalence of obesity continues to rise, and few modifiable breast cancer risk factors have been identified, especially for premenopausal women.

19.
Cancer Res ; 79(7): 1705-1713, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30760517

RESUMO

Dysregulation of miRNA expression may influence breast cancer progression, and experimental evidence suggests that miRNA silencing might suppress breast cancer metastasis. However, the relationship between miRNA and metastasis must be confirmed before this approach can be applied in the clinic. To this end, we conducted a two-stage study in a cohort of 3,760 patients with breast cancer to first identify and then validate the association between miRNA expression and risk of distant metastasis. The first stage (discovery) entailed miRNA sequencing of 126 case-control pairs; qPCR was used to validate the findings in a separate set of 80 case-control pairs. The 13 miRNAs most differentially expressed between cases and controls were combined into an miRNA score that was significantly associated with risk of distant metastasis in a logistic regression model that also included clinical variables (tumor size and number of positive lymph nodes) (ORper unit increase in score = 1.30; 95% confidence interval, 1.03-1.66). The results of this study suggest that in women with invasive breast cancer, a miRNA score that incorporates both clinical variables and miRNA expression levels in breast tumor tissue is moderately predictive of risk of subsequent distant metastasis. SIGNIFICANCE: A novel predictive scoring system for patients with breast cancer includes clinical variables and the expression levels of 13 miRNAs and may help to identify those at increased risk of distant metastasis.


Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Metástase Neoplásica/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Análise de Sequência de RNA
20.
Urology ; 125: 222-229, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30471370

RESUMO

OBJECTIVE: To assess the relative contributions of patient and surgeon factors for predicting selection of ileal conduit (IC), neobladder (NB), or continent pouch (CP) urinary diversions (UD) for patients diagnosed with muscle-invasive/high-risk nonmuscle invasive bladder cancer. This information is needed to enhance research comparing cancer survivors' outcomes across different surgical treatment options. METHODS: Bladder cancer patients' age ≥21 years with cystectomy/UD performed from January 2010 to June 2015 in 3 Kaiser Permanente regions were included. All patient and surgeon data were obtained from electronic health records. A mixed effects logistic regression model was used treating surgeon as a random effect and region as a fixed effect. RESULTS: Of 991 eligible patients, 794 (80%) received IC. One hundred sixty-nine surgeons performed the surgeries and accounted for a sizeable proportion of the variability in patient receipt of UD (intraclass correlation coefficient = 0.26). The multilevel model with only patient factors showed good fit (area under the curve = 0.93, Hosmer-Lemeshow test P = .44), and older age, female sex, estimated glomerular filtration rate <45, 4+ comorbidity index score, and stage III/IV tumors were associated with higher odds of receiving an IC vs neobladder/continent pouch. However, including surgeon factors (annual cystectomy volume, specialty training, clinical tenure) had no association (P = .29). CONCLUSION: In this community setting, patient factors were major predictors of UD received. Surgeons also played a substantial role, yet clinical training and experience were not major predictors. Surgeon factors such as beliefs about UD options and outcomes should be explored.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária , Idoso , Serviços de Saúde Comunitária , Prestação Integrada de Cuidados de Saúde , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Bexiga Urinária/patologia , Derivação Urinária/métodos , Derivação Urinária/estatística & dados numéricos
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