RESUMO
PURPOSE: Evaluate the behavior of lung nodules occurring in areas of pulmonary fibrosis and compare them to pulmonary nodules occurring in the non-fibrotic lung parenchyma. METHODS: This retrospective review of chest CT scans and electronic medical records received expedited IRB approval and a waiver of informed consent. 4500 consecutive patients with a chest CT scan report containing the word fibrosis or a specific type of fibrosis were identified using the system M*Model Catalyst (Maplewood, Minnesota, U.S.). The largest nodule was measured in the longest dimension and re-evaluated, in the same way, on the follow-up exam if multiple time points were available. The nodule doubling time was calculated. If the patient developed cancer, the histologic diagnosis was documented. RESULTS: Six hundred and nine patients were found to have at least one pulmonary nodule on either the first or the second CT scan. 274 of the largest pulmonary nodules were in the fibrotic tissue and 335 were in the non-fibrotic lung parenchyma. Pathology proven cancer was more common in nodules occurring in areas of pulmonary fibrosis compared to nodules occurring in areas of non-fibrotic lung (34% vs 15%, p < 0.01). Adenocarcinoma was the most common cell type in both groups but more frequent in cancers occurring in non-fibrotic tissue. In the non-fibrotic lung, 1 of 126 (0.8%) of nodules measuring 1 to 6 mm were cancer. In contrast, 5 of 49 (10.2%) of nodules in fibrosis measuring 1 to 6 mm represented biopsy-proven cancer (p < 0.01). The doubling time for squamous cell cancer was shorter in the fibrotic lung compared to non-fibrotic lung, however, the difference was not statistically significant (p = 0.24). 15 incident lung nodules on second CT obtained ≤ 18 months after first CT scan was found in fibrotic lung and eight (53%) were diagnosed as cancer. CONCLUSIONS: Nodules occurring in fibrotic lung tissue are more likely to be cancer than nodules in the nonfibrotic lung. Incident pulmonary nodules in pulmonary fibrosis have a high likelihood of being cancer.
Assuntos
Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Fibrose Pulmonar , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Nódulos Pulmonares Múltiplos/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVES: Self-sampling may increase access to cervical cancer screening in low-resource settings. Using Xpert HPV, we compared test performance of self- and clinician-collected samples in HIV-positive and HIV-negative women in South Africa. MATERIALS AND METHODS: Three hundred thirty HIV-positive and 375 HIV-negative women in the screening group and 202 HIV-negative and 200 HIV-positive women in the referral group, aged 30-65 years, participated in the study. All women self-collected a vaginal sample, and then, a cervical sample was collected by a clinician (both tested using Xpert HPV), followed by colposcopic examination and collection of histologic specimens. RESULTS: There was good agreement between self- and clinician-collected samples for detection of any high-risk human papillomavirus (HPV, κ = 0.72 [95% CI = 0.669-0.771]). Prevalence of HPV and sensitivity of the test to detect cervical intraepithelial neoplasia 2+ was similar in self- and clinician-collected samples. Specificity was lower in self-collected than in clinician-collected samples in both HIV-negative (self: 77.5% [95% CI = 72.8-81.8] vs clinician: 86.9% [95% CI = 82.9-90.2]) and HIV-positive (self: 44.0% [95% CI = 38.0-50.1] vs clinician: 59.7% [95% CI = 53.6-65.6]) women. Restricting the definition of screen-positive to 3 of 5 channels on HPV Xpert improved specificity in both HIV-negative (self: 83.2% [95% CI = 78.8-87.0] vs clinician: 89.7% [95% CI = 86.1-92.7]) and HIV-positive (self: 54.2% [95% CI = 48.1-60.2] vs clinician: 67.4% [95% CI = 61.5-72.9]) women. CONCLUSIONS: The self-collected sample had good agreement with the clinician-collected sample for the detection of HPV, and restricting the HPV types may improve the specificity in HIV-positive women.
Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Esfregaço Vaginal/métodos , Esfregaço Vaginal/estatística & dados numéricos , Adulto , Colposcopia , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Infecções por HIV , Humanos , Pessoa de Meia-Idade , África do Sul/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Adulto JovemRESUMO
OBJECTIVE: Limited evidence is available to guide treatment of depression for persons with epilepsy. We evaluated the comparative effectiveness of sertraline and cognitive behavior therapy (CBT) for depression, quality of life, seizures, and adverse treatment effects. METHODS: We randomly assigned 140 adult outpatients with epilepsy and current major depressive disorder to sertraline or weekly CBT for 16 weeks. The primary outcome was remission from depression based on the Mini International Neuropsychiatric Interview (MINI). Secondary outcomes included the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) seizure rates, the Adverse Events Profile (AEP), the Beck Depression Inventory, and MINI Suicide Risk Module. RESULTS: In the intention-to-treat analysis, 38 (52.8%; 95% confidence interval [CI] = ±12) of the 72 subjects assigned to sertraline and 41 (60.3%; 95% CI = ±11.6) of the 68 subjects in the CBT group achieved remission; the lower bound of efficacy for both groups was greater than our historical placebo control group upper bound of 33.7%. Difference in time to remission between groups was 2.8 days (95% CI = ±0.43; p = 0.79). The percent improvement of mean QOLIE-89 scores was significant for both the CBT (25.7%; p < 0.001) and sertraline (28.3%; p < 0.001) groups. The difference in occurrence of generalized tonic-clonic seizures between groups was 0.3% (95% CI = ±8.6; p = 0.95). Suicide risk at final assessment was associated with persistent depression (p < 0.0001) but not seizures or sertraline. INTERPRETATION: Depression remitted in just over one-half of subjects following sertraline or CBT. Despite the complex psychosocial disability associated with epilepsy, improving depression benefits quality of life. Serotonin reuptake inhibition does not appear to increase seizures or suicidality in persons with epilepsy. ANN NEUROL 2019;86:552-560.
Assuntos
Terapia Cognitivo-Comportamental , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/terapia , Epilepsia/tratamento farmacológico , Epilepsia/terapia , Sertralina/uso terapêutico , Adulto , Idoso , Transtorno Depressivo Maior/complicações , Epilepsia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
Background: Bisphosphonates reduce skeletal-related events (SREs) in patients with multiple myeloma (MM) and, in some studies, improved survival. Since 2011, bisphosphonate use has been recommended by NCCN for all patients with newly diagnosed MM receiving antineoplastic therapy independent of the presence of bone disease. This study investigated their use after these guidelines were established. Methods: We identified patients aged ≥65 years in the SEER-Medicare database with newly diagnosed MM between January 1, 2012, and December 31, 2013, who received antineoplastic therapy, had ≥6 months of follow-up, and did not receive prior bisphosphonates. Presence of SREs at diagnosis was identified, including pathologic fracture, spinal cord compression, radiation to bone, or surgery to bone. Use of bisphosphonates was defined as having ≥1 claim for an intravenous or oral bisphosphonate within 6 months after the start of antineoplastic therapy. We used multivariable modeling to compare users with nonusers, controlling for demographic and clinical covariates. We compared overall survival between users and nonusers using proportional hazards analysis. Results: Of 1,309 patients identified, 720 (55%) used a bisphosphonate. Factors associated with use included SRE at diagnosis (adjusted odds ratio [AOR], 2.60; 95% CI, 1.98-3.40), hypercalcemia (AOR, 1.74; 95% CI, 1.26-2.41), and use of proteasome inhibitor + immunomodulatory imide therapy (AOR, 1.70; 95% CI, 1.21-2.39). Chronic kidney disease (AOR, 0.48; 95% CI, 0.35-0.66) was associated with decreased use. Bisphosphonate use was associated with reduced mortality (hazard ratio, 0.70; 95% CI, 0.56-0.88). Conclusions: Although bisphosphonate use is recommended for all patients with newly diagnosed MM receiving antineoplastic therapy, 45% of patients in the United States did not receive this guideline-recommended care.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas/prevenção & controle , Mieloma Múltiplo/complicações , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/normas , Doenças Ósseas/epidemiologia , Doenças Ósseas/etiologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Medicare/estatística & dados numéricos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Pamidronato/uso terapêutico , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Programa de SEER/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia , Ácido Zoledrônico/uso terapêuticoRESUMO
BACKGROUND: BRCA1 and BRCA2 mutations confer a substantial breast risk of developing breast cancer to those who carry them. For this reason, the United States Preventative Services Task Force (USPSTF) has recommended that all women be screened in the primary care setting for a family history indicative of a mutation, and women with strong family histories of breast or ovarian cancer be referred to genetic counseling. However, few high-risk women are being routinely screened and fewer are referred to genetic counseling. To address this need we have developed two decision support tools that are integrated into clinical care. METHOD: This study is a cluster randomized controlled trial of high-risk patients and their health care providers. Patient-provider dyads will be randomized to receive either standard education that is supplemented with the patient-facing decision aid, RealRisks, and the provider-facing Breast Cancer Risk Navigation Toolbox (BNAV) or standard education alone. We will assess these tools' effectiveness in promoting genetic counseling uptake and informed and shared decision making about genetic testing. DISCUSSION: If found to be effective, these tools can help integrate genomic risk assessment into primary care and, ultimately, help expand access to risk-appropriate breast cancer prevention options to a broader population of high-risk women. TRIAL REGISTRATION: This trial is retrospectively registered with ClinicalTrials.gov Identifier: NCT03470402 : 20 March 2018.
Assuntos
Técnicas de Apoio para a Decisão , Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Internet , Atenção Primária à Saúde , Encaminhamento e Consulta , Neoplasias da Mama/genética , Protocolos Clínicos , Tomada de Decisões , Feminino , Testes Genéticos , Humanos , Mutação , Neoplasias Ovarianas/genética , Projetos de Pesquisa , Medição de RiscoRESUMO
Non-adherence to adjuvant endocrine therapy (ET) for breast cancer (BC) is common. Our goal was to determine the associations between psychosocial factors and ET non-persistence. We recruited women with BC receiving care in an integrated healthcare system between 2006 and 2010. Using a subset of patients treated with ET, we investigated factors related to ET non-persistence (discontinuation) based on pharmacy records (≥90 days gap). Serial interviews were conducted at baseline and every 6 months. The Functional Assessment of Cancer Therapy (FACT), Medical Outcomes Survey, Treatment Satisfaction Questionnaire (TSQM), Impact of Events Scale (IES), Interpersonal Processes of Care measure, and Decision-making beliefs and concerns were measured. Multivariate models assessed factors associated with non-persistence. Of the 523 women in our final cohort who initiated ET and had a subsequent evaluation, 94 (18 %) were non-persistent over a 2-year follow-up. The cohort was primarily white (74.4 %), stage 1 (60.6 %), and on an aromatase inhibitor (68.1 %). Women in the highest income category had a lower odds of being non-persistent (OR 0.43, 95 % CI 0.23-0.81). Quality of life and attitudes toward ET at baseline were associated with non-persistence. At follow-up, the FACT, TSQM, and IES were associated with non-persistence (p < 0.001). Most women continued ET. Women who reported a better attitude toward ET, better quality of life, and more treatment satisfaction, were less likely to be non-persistent and those who reported intrusive/avoidant thoughts were more likely to be non-persistent. Interventions to enhance the psychosocial well-being of patients should be evaluated to increase adherence.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Adesão à Medicação/psicologia , Qualidade de Vida/psicologia , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Quimioterapia Adjuvante , Feminino , Humanos , Adesão à Medicação/etnologia , Fatores de RiscoRESUMO
For many women with non-metastatic breast cancer, adjuvant chemotherapy prevents recurrence and extends survival. Women who discontinue chemotherapy early may reduce those benefits, but little is known about what predicts early discontinuation. We sought to determine prospectively the rate and reasons for early discontinuation of adjuvant chemotherapy in women with breast cancer. We conducted a prospective cohort study among three U.S. health care organizations. Of 1158 women with newly diagnosed non-metastatic breast cancer, 2006-2010, we analyzed 445 (38.4 %) patients who initiated standard adjuvant chemotherapy as defined by accepted guidelines. We interviewed patients at baseline and twice during treatment regarding sociodemographic/psychosocial factors and treatment decision-making and collected clinical data. They were categorized according to the number of cycles required by the chemotherapy regimen they had initiated. The outcome was early discontinuation (<80 % of planned cycles). Of patients analyzed, 392 (88.1 %) completed the prescribed therapy. The strongest predictor was receipt of a regimen entailing >4 cycles of therapy (18.1 % for longer regimens, 7.4 % for 4 cycles) (odds ratio [OR] 2.59, 95 % CI 1.32-5.08), controlling for race, age, stage, hormone receptor status, social support, optimism, spirituality, stress, and physical symptoms. Higher levels of psychological symptoms on the Memorial symptom assessment scale also increased the odds of early discontinuation (OR 1.92, 95 % CI 0.998-3.68). The large majority of patients who initiated adjuvant chemotherapy for breast cancer completed their prescribed regimens, but early discontinuation was associated with lengthier regimens and, with borderline statistical significance, for those with psychological side effects.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Cooperação do Paciente/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Autorrelato , Resultado do TratamentoRESUMO
The confidence intervals for the ratio of two median residual lifetimes are developed for left-truncated and right-censored data. The approach of Su and Wei (1993) is first extended by replacing the Kaplan-Meier survival estimator with the estimator of the conditional survival function (Lynden-Bell, 1971). This procedure does not involve a nonparametric estimation of the probability density function of the failure time. However, the Su and Wei type confidence intervals are very conservative even for larger sample size. Therefore, this article proposes an alternative confidence interval for the ratio of two median residual lifetimes, which is not only without nonparametric estimation of the density function of failure times but is also computationally simpler than the Su and Wei type confidence interval. A simulation study is conducted to examine the accuracy of these confidence intervals and the implementation of these confidence intervals to two real data sets is illustrated.
Assuntos
Intervalos de Confiança , Expectativa de Vida , Modelos Estatísticos , Razão de Chances , Modelos de Riscos Proporcionais , Análise de Sobrevida , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Tamanho da Amostra , Sensibilidade e Especificidade , Taiwan/epidemiologiaRESUMO
BACKGROUND: Lower levels of global DNA methylation in tissue and blood have been associated with increased cancer risk. Conversely, cross-sectional analyses of healthier lifestyle patterns have been associated with higher levels of global DNA methylation. OBJECTIVE: In this trial, we explored the associations between changes in lifestyle modifications (diet, weight loss), metabolic markers, and global epigenetic biomarkers in white blood cells. METHODS: Study participants were Hispanic, African American, and Afro-Caribbean overweight and sedentary female breast cancer survivors (n = 24) who participated in a larger randomized, crossover, pilot study of a 6-mo weight loss intervention and who had available blood specimens. Anthropometric measures, a food-frequency questionnaire, and peripheral blood were collected at baseline, 6 mo, and 12 mo. Plasma samples were analyzed for metabolic markers (insulin, glucose). We measured DNA methylation of long interspersed nucleotide element 1 (LINE-1) and satellite 2 by pyrosequencing and MethyLight, respectively, and global DNA methylation by the luminometric methylation assay (LUMA). RESULTS: DNA methylation of LINE-1 was statistically significantly elevated at 6 mo [75.5% vs. 78.5% (P < 0.0001)] and 12 mo [75.5% vs. 77.7% (P < 0.0001)], compared to baseline. Over a 12-mo period, changes in percentage body fat and plasma glucose concentrations were positively associated with LINE-1 DNA methylation (ß = 0.19, P = 0.001) and LUMA DNA methylation levels (ß = 0.24, P = 0.02), respectively. Similarly, 12-mo changes in dietary measures such as vegetable (ß = 0.009, P = 0.048), protein (ß = 0.04, P = 0.001), and total caloric (ß = 0.05, P = 0.01) intake were positively associated with changes in LUMA DNA methylation, as was intake of fruit positively associated with changes in LINE-1 DNA methylation (ß = 0.004, P = 0.02). CONCLUSIONS: Our hypothesis-generating results suggest that lifestyle modifications may be associated with changes in global DNA methylation detectable at 6 and 12 mo. These biomarkers may be useful intermediate biomarkers to use in future intervention trials. This trial was registered at clinicaltrials.gov as NCT00811824.
Assuntos
Neoplasias da Mama/terapia , Metilação de DNA/genética , Comportamento Alimentar , Marcadores Genéticos , Sobreviventes , Redução de Peso , Adulto , Negro ou Afro-Americano/genética , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Estudos Cross-Over , Ingestão de Energia , Feminino , Seguimentos , Hispânico ou Latino/genética , Humanos , Estilo de Vida , Elementos Nucleotídeos Longos e Dispersos/genética , Pessoa de Meia-Idade , Atividade Motora , Avaliação Nutricional , Projetos Piloto , Adulto JovemRESUMO
Pocock et al. (2012, European Heart Journal 33, 176-182) proposed a win ratio approach to analyzing composite endpoints comprised of outcomes with different clinical priorities. In this article, we establish a statistical framework for this approach. We derive the null hypothesis and propose a closed-form variance estimator for the win ratio statistic in all pairwise matching situation. Our simulation study shows that the proposed variance estimator performs well regardless of the magnitude of treatment effect size and the type of the joint distribution of the outcomes.
Assuntos
Algoritmos , Interpretação Estatística de Dados , Avaliação de Resultados em Cuidados de Saúde/métodos , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Intervalos de Confiança , Inibidores do Fator Xa/uso terapêutico , Humanos , Razão de Chances , Reprodutibilidade dos Testes , Medição de Risco/métodos , Sensibilidade e Especificidade , Distribuições Estatísticas , Análise de Sobrevida , Resultado do TratamentoRESUMO
IMPORTANCE: Advantages of using efavirenz as part of treatment for children infected with human immunodeficiency virus (HIV) include once-daily dosing, simplification of co-treatment for tuberculosis, preservation of ritonavir-boosted lopinavir for second-line treatment, and harmonization of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz in children exposed to nevirapine for prevention of mother-to-child transmission. OBJECTIVE: To evaluate whether nevirapine-exposed children achieving initial viral suppression with ritonavir-boosted lopinavir-based therapy can transition to efavirenz-based therapy without risk of viral failure. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label noninferiority trial conducted at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa, from June 2010 to December 2013, enrolling 300 HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission who were aged 3 years or older and had plasma HIV RNA of less than 50 copies/mL during ritonavir-boosted lopinavir-based therapy; 298 were randomized and 292 (98%) were followed up to 48 weeks after randomization. INTERVENTIONS: Participants were randomly assigned to switch to efavirenz-based therapy (n = 150) or continue ritonavir-boosted lopinavir-based therapy (n = 148). MAIN OUTCOMES AND MEASURES: Risk difference between groups in (1) viral rebound (ie, ≥1 HIV RNA measurement of >50 copies/mL) and (2) viral failure (ie, confirmed HIV RNA >1000 copies/mL) with a noninferiority bound of -0.10. Immunologic and clinical responses were secondary end points. RESULTS: The Kaplan-Meier probability of viral rebound by 48 weeks was 0.176 (n = 26) in the efavirenz group and 0.284 (n = 42) in the ritonavir-boosted lopinavir group. Probabilities of viral failure were 0.027 (n = 4) in the efavirenz group and 0.020 (n = 3) in the ritonavir-boosted lopinavir group. The risk difference for viral rebound was 0.107 (1-sided 95% CI, 0.028 to ∞) and for viral failure was -0.007 (1-sided 95% CI, -0.036 to ∞). We rejected the null hypothesis that efavirenz is inferior to ritonavir-boosted lopinavir (P < .001) for both end points. By 48 weeks, CD4 cell percentage was 2.88% (95% CI, 1.26%-4.49%) higher in the efavirenz group than in the ritonavir-boosted lopinavir group. CONCLUSIONS AND RELEVANCE: Among HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission and with initial viral suppression with ritonavir-boosted lopinavir-based therapy, switching to efavirenz-based therapy compared with continuing ritonavir-boosted lopinavir-based therapy did not result in significantly higher rates of viral rebound or viral failure. This therapeutic approach may offer advantages in children such as these. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01146873.
Assuntos
Antirretrovirais/administração & dosagem , Benzoxazinas/administração & dosagem , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Lopinavir/administração & dosagem , Nevirapina/administração & dosagem , Alcinos , Criança , Pré-Escolar , Ciclopropanos , Quimioterapia Combinada , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Masculino , África do Sul , Carga ViralRESUMO
In 2006, the IOM released a report citing the importance of "survivorship plans" to improve quality of life and care coordination for cancer survivors, but little has been done to evaluate their efficacy. Women with early-stage breast cancer were randomized within 6 weeks of completing adjuvant therapy to a survivorship intervention group (SI) or control group (CG). All subjects were given the NCI publication, "Facing Forward: Life after Cancer Treatment." The SI also met with a nurse/nutritionist to receive a treatment summary, surveillance, and lifestyle recommendations. Both groups completed questionnaires on the impact of cancer (IOC), patient satisfaction (FACIT-TS-PS), and assessment of survivor concerns (ASC) at baseline, 3 and 6 months. Within and between group t tests and linear regression analyses were performed. Among 126 women (60 CG, 66 SI), mean age was 54 years, 48 % were Hispanic, and the groups were well-balanced by baseline characteristics. No significant differences between the CG and SI on the FACIT-TS-PS or IOC at 3 and 6 months were seen. The ASC health worry subscale was lower (less worry) in the SI compared to CG (p = 0.02). At all time-points, Hispanic women had higher (worse) health worry (p = 0.0008), social-life interference (p = 0.009), and meaning of cancer scales (p = 0.0004), and more trust in medical professionals (p = 0.03) compared to non-Hispanic women. While the SI did not lead to significant improvements in most patient-reported outcomes, it was associated with decreased health worry. Future interventions should determine the most efficient and effective method for delivering survivorship care plans.
Assuntos
Neoplasias da Mama/psicologia , Neoplasias da Mama/terapia , Qualidade de Vida , Sobreviventes , Neoplasias da Mama/etnologia , Quimioterapia Adjuvante , Feminino , Hispânico ou Latino , Humanos , Pessoa de Meia-Idade , Satisfação do Paciente , Análise de Regressão , Inquéritos e Questionários , Sobreviventes/psicologiaRESUMO
PURPOSE: Many women with hormone receptor-positive breast cancer discontinue effective aromatase inhibitor (AI) treatment due to joint symptoms. METHODS: We conducted a single-arm, open-label, phase II study evaluating glucosamine-sulfate (1,500 mg/day) + chondroitin-sulfate (1,200 mg/day) for 24 weeks to treat joint pain/stiffness in postmenopausal women with early stage breast cancer who developed moderate-to-severe joint pain after initiating AIs. The primary endpoint was improvement in pain/stiffness at week 24 assessed by the Outcome Measure in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Secondary endpoints assessed changes in pain, stiffness, and function using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index for hips/knees and the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) for hands/wrists. The Brief Pain Inventory (BPI) assessed pain interference, severity, and worst pain. RESULTS: Of 53 patients enrolled, 39 were evaluable at week 24. From baseline to week 24, 46 % of patients improved according to OMERACT-OARSI criteria. At week 24, there were improvements (all P < 0.05) in pain and function as assessed by WOMAC and M-SACRAH, and in pain interference, severity, and worst pain as assessed by BPI. Estradiol levels did not change from baseline. The most commonly reported side effects were headache (28 %), dyspepsia (15 %), and nausea (17 %). CONCLUSIONS: In this single-arm study, 24 weeks of glucosamine/chondroitin resulted in moderate improvements in AI-induced arthralgias, with minimal side effects, and no changes in estradiol levels. These results suggest a need to evaluate efficacy in a placebo-controlled trial.
Assuntos
Inibidores da Aromatase/efeitos adversos , Artralgia/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Condroitina/uso terapêutico , Glucosamina/uso terapêutico , Adulto , Idoso , Artralgia/induzido quimicamente , Quimioterapia Combinada , Feminino , Articulação do Quadril , Humanos , Articulação do Joelho , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Global DNA hypomethylation is associated with genomic instability and human cancer and blood DNAs collected at the time of cancer diagnosis have been used to examine the relationship between global methylation and cancer risk. To test the hypothesis that global hypomethylation is associated with increased risk of hepatocellular carcinoma (HCC), we conducted a prospective case-control study nested within a community-based cohort with 16 years of follow-up. We measured methylation levels in Satellite 2 (Sat2) by MethyLight and LINE-1 by pyrosequencing using baseline white blood cell DNA from 305 HCC cases and 1254 matched controls. We found that Sat2 hypomethylation was associated with HCC risk [odds ratio (OR) per unit decrease in natural log Sat2 methylation = 1.77, 95% confidence interval (CI) = 1.06-2.95]. The association was significant among individuals diagnosed with HCC before age 62 (OR per unit decrease in natural log Sat2 methylation = 2.47, 95% CI = 1.06-5.73) but not after (OR = 1.67, 95% CI = 0.84-3.32). We did not observe an association of LINE-1 with HCC overall risk by age at diagnosis. Among carriers of hepatitis B virus surface antigen (HBsAg), with each 1U decrease in natural log Sat2 methylation level, the OR for HCC increased by 2.19 (95% CI = 1.00-4.89). LINE-1 hypomethylation was associated with about a 2-fold increased risk of HCC, with ORs (95% CI) of 2.39 (1.06-5.39), 2.09 (0.91-4.77) and 2.28 (0.95-5.51, P(trend) = 0.14) for HBsAg carriers in the third, second and lowest quartile of LINE-1 methylation, respectively compared with carriers in the fourth. These results suggest that global hypomethylation may be a useful biomarker of HCC susceptibility.
Assuntos
Carcinoma Hepatocelular/sangue , Metilação de DNA , Neoplasias Hepáticas/sangue , Linfócitos/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , TaiwanRESUMO
Adjuvant hormonal therapy for non-metastatic hormone receptor (HR)-positive breast cancer decreases risk of breast cancer recurrence and increases survival. However, some women do not initiate this life-saving treatment. We used a prospective cohort design to investigate factors related to non-initiation of hormonal therapy among women with newly diagnosed, non-metastatic HR-positive breast cancer recruited from three U.S. sites. Serial interviews were conducted at baseline and during treatment to examine sociodemographic factors, tumor characteristics, and treatment decision-making factors. Multivariate modeling assessed associations between variables of interest and hormonal therapy initiation. Of 1,050 breast cancer patients recruited, 725 (69%) had HR-positive breast cancer, of whom 87 (12.0%) based on self-report and 122 (16.8%) based on medical record/pharmacy fill rates did not initiate hormonal therapy. In a multivariable analysis, non-initiation of hormonal therapy, defined by medical record/pharmacy, was associated with having greater negative beliefs about efficacy of treatment (OR 1.42, 95% CI 1.18-1.70). Non-initiation was less likely in those who found the quality of patient/physician communication to be higher (OR 0.96, 95% CI 0.93-0.99), the hormonal therapy treatment decision an easy one to make (OR 0.45, 95% CI 0.23-0.90) or neither easy nor difficult (OR 0.34, 95% CI 0.20-0.58); and had more positive beliefs about hormonal therapy efficacy (OR 0.40, 95% CI 0.34-0.62). Factors influencing non-initiation of adjuvant hormonal therapy are complex and influenced by patient beliefs regarding treatment efficacy and side effects. Educational interventions to women about the benefits of hormonal therapy may decrease negative beliefs and increase hormone therapy initiation.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/terapia , Neoplasias Hormônio-Dependentes/terapia , Qualidade da Assistência à Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante/estatística & dados numéricos , Tomada de Decisões , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Hormônio-Dependentes/metabolismo , Estudos Prospectivos , Receptores de Superfície Celular/metabolismo , Análise de RegressãoRESUMO
In oncology, quality of care is a major issue for patients and providers. Significant variations in care, including nonreceipt of adjuvant systemic therapy, nonadherence to therapy, and/or early discontinuation of therapy, occur frequently and may impact survival. Reasons for these variations are not well understood, but may play a role in the prominent disparity in breast cancer survival between blacks and whites. Since May 2006, the Breast Cancer Quality of Care Study (BQUAL) has recruited 1158 women with nonmetastatic breast cancer from several centers across the country, with completed data on 1057 participants to date. Detailed information on demographic, behavioral, biomedical, and emotional factors related to chemotherapy use was collected on each participant at baseline and at two follow-up interviews during the first 6 months. In addition, for women with ER+ tumors, further questionnaires were completed every 6 months regarding hormonal therapy use. Each participant was also asked to provide a DNA sample, and to allow medical record review. We surveyed physicians providing care to the study participants regarding attitudes toward adjuvant treatment. The mean age of participants was 58 years (SD 11.6), and 15% (n = 160) were black. The majority had an annual household income <$90,000 (n = 683), had college education or higher (n = 802), 55.9% were married, and 57.9% were not currently employed. Seventy-six percent had hormone-receptor-positive tumors, 49.9% initiated chemotherapy and 82.7% started hormonal therapy. Blacks were more likely to have lower annual household income (p < 0001), less education (p = 0.0005), ER negative tumor status (p = 0.02), and poorly differentiated cancer (p = 0.0002). The main endpoints of the study are noninitiation of chemotherapy or hormonal therapy, nonadherence to therapy and early discontinuation of therapy. Treatment and outcomes will be compared on the 15% of participants who are black versus other participants. The BQUAL Study will be a rich ongoing source of information regarding reasons for differences in receipt of both adjuvant chemotherapy and hormonal therapy. This information may be useful in planning interventions to improve quality of care.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Idoso , Antineoplásicos Hormonais/uso terapêutico , População Negra , Neoplasias da Mama/etnologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/psicologia , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Garantia da Qualidade dos Cuidados de Saúde , Receptores de Estrogênio , Classe Social , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND: Human papillomavirus (HPV) testing is the cornerstone of cervical cancer screening, with outstanding sensitivity but only moderate specificity. We evaluated whether reflex testing for cancer biomarkers improves the sensitivity/specificity balance of screening. METHODS: Cervical samples from women in Cape Town, South Africa, ages 30-65 years, were collected and tested with Xpert HPV and with real-time PCR to detect mRNA for cyclin-dependent kinase inhibitor 2A (CDKN2A), topoisomerase 2 alpha (TOP2A), and Ki67 (MKi67). Women with histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+; 85 women without and 166 with HIV) and women with no cervical disease (331 without and 257 with HIV) were included. RESULTS: When used as reflex tests after a positive HPV result, biomarkers discriminated well between women with and without CIN2+. The inclusion of both CDKN2A and MKi67 had the best performance, with area under the curve (AUC) of 0.9171 and 0.8734 in women without and with HIV, respectively. Although excellent, these performance parameters did not improve on an approach utilizing only HPV testing with more stringent cycle threshold cutoffs and HPV genotype selection, which achieved AUC of 0.9059 and 0.8705 in women without and with HIV, respectively. CONCLUSIONS: Biomarkers can be used as triage after positive HPV results but do not outperform an approach utilizing higher viral load cutoffs on selected high-risk genotypes. IMPACT: A screening approach using HPV testing alone can be more easily implemented at the point of care.
Assuntos
Alphapapillomavirus , Infecções por HIV , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Idoso , Biomarcadores Tumorais , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Reflexo , Sensibilidade e Especificidade , África do SulRESUMO
BACKGROUND: Among Latinos, greater acculturation to the United States (US) is associated with risk of obesity and obesity-related comorbidities. Less is known about the associations between acculturation and obesity-related modifiable risk factors, such as diet quality and physical activity (PA) among Latina breast cancer survivors. OBJECTIVE: The aim of this study was to explore associations between acculturation and weight status, diet quality, and PA among Latina breast cancer survivors. DESIGN: This is a cross-sectional secondary analysis of baseline data on demographic and clinical characteristics, acculturation, anthropometric measures, diet quality, and PA collected from Latina breast cancer survivors enrolled in the ¡Mi Vida Saludable! (My Healthy Life) behavioral diet and PA intervention trial. PARTICIPANTS/SETTING: Participants were Latina women (n = 167) residing in New York City, with a medical history of stage 0 to III breast cancer, no evidence of recurrent or metastatic disease, and at least 90 days post cancer treatment who participated in the ¡Mi Vida Saludable! randomized controlled trial between July 2016 and October 2018. MAIN OUTCOME MEASURES: Acculturation status was measured by the Short Acculturation Scale for Hispanics score, language preference, place of birth, and duration of US residence. Weight, height, and waist and hip circumferences were measured at an in-person clinic visit. Diet information was collected via 3 telephone-based 24-hour dietary recalls and PA information was collected via staff administered 7-day recalls. STATISTICAL ANALYSES PERFORMED: Linear regression models examined associations between acculturation and weight status, diet quality, and PA. RESULTS: Based on the Short Acculturation Scale for Hispanics acculturation score, more acculturated compared with less acculturated Latinas were younger in age, more educated, and had higher annual household incomes (all, P < .05). Compared with Spanish-speaking Latinas, English-speaking Latinas had larger waist circumference (103 vs 96.1 cm; P = .01) and poorer-quality diets (Healthy Eating Index 2015 scores, 57.3 vs 71.5; P < .001). Greater levels of acculturation were also associated with higher levels of leisure walking at a moderate-to-vigorous intensity (265.8 vs 179.0 min/wk; P =.04). CONCLUSIONS: Greater levels of acculturation were associated with higher central obesity and poorer-quality diets. Future lifestyle modification trials tailored to the unique role of acculturation on adopting behavior change recommendations is a promising next step in this line of research.
Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Aculturação , Estudos Transversais , Dieta , Exercício Físico , Feminino , Hispânico ou Latino , Humanos , Obesidade/terapia , Estados UnidosRESUMO
Significant underutilization of breast cancer chemoprevention remains, despite guidelines stating that physicians should recommend chemoprevention with antiestrogen therapy to high-risk women. We randomized women, ages 35 to 75 years, who met high-risk criteria for breast cancer, without a personal history of breast cancer or prior chemoprevention use, to standard educational materials alone or combined with a web-based decision aid. All healthcare providers, including primary care providers and breast specialists, were given access to a web-based decision support tool. The primary endpoint was chemoprevention uptake at 6 months. Secondary outcomes included decision antecedents (perceived breast cancer risk/worry, chemoprevention knowledge, self-efficacy) and decision quality (decision conflict, chemoprevention informed choice) based upon patient surveys administered at baseline, 1 and 6 months after randomization. Among 282 evaluable high-risk women enrolled from November 2016 to March 2020, mean age was 57 years (SD, 9.9) and mean 5-year invasive breast cancer risk was 2.98% (SD, 1.42). There was no significant difference in chemoprevention uptake at 6 months between the intervention and control groups (2.1% vs. 3.5%). Comparing the intervention and control arms at 1 month, there were significant differences among high-risk women in accurate breast cancer risk perceptions (56% vs. 39%, P = 0.017), adequate chemoprevention knowledge (49% vs. 27%, P < 0.001), mean decision conflict (34.0 vs. 47.0, P < 0.001), and informed choice (41% vs. 23%, P = 0.003). These differences were no longer significant at 6 months. Although our decision support tools did not result in a significant increase in chemoprevention uptake, we did observe improvements in decision antecedents and decision quality measures. PREVENTION RELEVANCE: In this randomized controlled trial of decision support for 300 high-risk women and 50 healthcare providers, we did not observe a significant increase in chemoprevention uptake, which remained low at under 5%. However, these decision support tools may increase knowledge and informed choice about breast cancer chemoprevention.