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1.
Cell Mol Life Sci ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31560077

RESUMO

In cancer, many genes are mutated by genome rearrangement, but our understanding of the functional consequences of this remains rudimentary. Here we report the F-box protein encoded by FBXL17 is disrupted in the region of the gene that encodes its substrate-binding leucine rich repeat (LRR) domain. Truncating Fbxl17 LRRs impaired its association with the other SCF holoenzyme subunits Skp1, Cul1 and Rbx1, and decreased ubiquitination activity. Loss of the LRRs also differentially affected Fbxl17 binding to its targets. Thus, genomic rearrangements in FBXL17 are likely to disrupt SCFFbxl17-regulated networks in cancer cells. To investigate the functional effect of these rearrangements, we performed a yeast two-hybrid screen to identify Fbxl17-interacting proteins. Among the 37 binding partners Uap1, an enzyme involved in O-GlcNAcylation of proteins was identified most frequently. We demonstrate that Fbxl17 binds to UAP1 directly and inhibits its phosphorylation, which we propose regulates UAP1 activity. Knockdown of Fbxl17 expression elevated O-GlcNAcylation in breast cancer cells, arguing for a functional role for Fbxl17 in this metabolic pathway.

2.
Health Serv Res ; 54(4): 730-738, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31218670

RESUMO

OBJECTIVE: To investigate how changes in insurer participation and composition as well as state policies affect health plan affordability for individual market enrollees. DATA SOURCES: 2014-2019 Qualified Health Plan Landscape Files augmented with supplementary insurer-level information. STUDY DESIGN: We measured plan affordability for subsidized enrollees using premium spreads, the difference between the benchmark plan and the lowest cost plan, and premium levels for unsubsidized enrollees. We estimated how premium spreads and levels varied with insurer participation, insurer composition, and state policies using log-linear models for 15 222 county-years. PRINCIPAL FINDINGS: Increased insurer participation reduces premium levels, which is beneficial for unsubsidized enrollees. However, it also reduces premium spreads, leading to lower plan affordability for subsidized enrollees. States responding to cost-sharing reduction subsidy payment cuts by increasing only silver plans' premiums increase premium spreads, particularly when premium increases are restricted to on-Marketplace silver plans. The latter approach also protects unsubsidized, off-Marketplace enrollees from experiencing premium shocks. CONCLUSIONS: Insurer participation and insurer composition affect subsidized and unsubsidized enrollees' health plan affordability in different ways. Decisions by state regulators regarding health plan pricing can significantly affect health plan affordability for each enrollee segment.

3.
Lancet ; 393(10191): 2599-2612, 2019 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-31178152

RESUMO

BACKGROUND: Adjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is non-inferior to the standard 12-month treatment regarding disease-free survival. METHODS: This study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006-007018-39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140). FINDINGS: Between Oct 4, 2007, and July 31, 2015, 2045 patients were assigned to 12-month trastuzumab treatment and 2044 to 6-month treatment (one patient was excluded because they were double randomised). Median follow-up was 5·4 years (IQR 3·6-6·7) for both treatment groups, during which a disease-free survival event occurred in 265 (13%) of 2043 patients in the 6-month group and 247 (12%) of 2045 patients in the 12-month group. 4-year disease-free survival was 89·4% (95% CI 87·9-90·7) in the 6-month group and 89·8% (88·3-91·1) in the 12-month group (hazard ratio 1·07 [90% CI 0·93-1·24], non-inferiority p=0·011), showing non-inferiority of the 6-month treatment. 6-month trastuzumab treatment resulted in fewer patients reporting severe adverse events (373 [19%] of 1939 patients vs 459 [24%] of 1894 patients, p=0·0002) or stopping early because of cardiotoxicity (61 [3%] of 1939 patients vs 146 [8%] of 1894 patients, p<0·0001). INTERPRETATION: We have shown that 6-month trastuzumab treatment is non-inferior to 12-month treatment in patients with HER2-positive early breast cancer, with less cardiotoxicity and fewer severe adverse events. These results support consideration of reduced duration trastuzumab for women at similar risk of recurrence as to those included in the trial. FUNDING: UK National Institute for Health Research, Health Technology Assessment Programme.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Trastuzumab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Pessoa de Meia-Idade , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Trastuzumab/efeitos adversos , Resultado do Tratamento , Reino Unido , Adulto Jovem
4.
Health Aff (Millwood) ; 38(4): 675-683, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30933593

RESUMO

The individual and small-group health insurance markets have experienced considerable changes since the passage of the Affordable Care Act in 2010, affecting access, choice, and affordability for enrollees in these markets. We examined how health plan access, choice, and affordability varied between the individual on-Marketplace, individual off-Marketplace, and small-group markets in 2018. We found relatively similar outcomes across the three markets with respect to deductibles and out-of-pocket spending maximums. However, the small-group market maintained greater plan choice and lower premiums-outcomes that appear to be associated with higher insurer participation. States may consider a variety of policy proposals such as reinsurance or the introduction of a public option to increase insurer participation and improve the plan choices offered in the individual market.

6.
BMC Public Health ; 19(1): 291, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30866884

RESUMO

BACKGROUND: State and Territorial Health Departments (SHDs) have a unique role in protecting and promoting workers' health. This mixed-methods study presents the first systematic investigation of SHDs' activities and capacity in both Occupational Safety and Health (OSH) and Workplace Health Promotion (WHP) in the United States (US). METHODS: National survey of OSH and WHP practitioners from each of 56 SHDs, followed by in-depth interviews with a subset of survey respondents. We calculated descriptive statistics for survey variables and conducted conventional content analysis of interviews. RESULTS: Seventy percent (n = 39) of OSH and 71% (n = 40) of WHP contacts responded to the survey. Twenty-seven (n = 14 OSH, n = 13 WHP) participated in follow-up interviews. Despite limited funding, staffing, or organizational support, SHDs reported a wide array of activities. We assessed OSH and WHP surveillance activities, support that SHDs provided to employers to implement OSH and WHP interventions (implementation support), OSH and WHP services provided directly to workers, OSH follow-back investigations, and OSH standard and policy development. Each of the categories we asked about (excluding OSH standard and policy development) were performed by more than half of responding SHDs. Surveillance was the area of greatest OSH activity, while implementation support was the area of greatest WHP activity. Respondents characterized their overall capacity as low. Thirty percent (n = 9) of WHP and 19% (n = 6) of OSH respondents reported no funds at all for OSH/WHP work, and both groups reported a median 1.0 FTEs working on OSH/WHP at the SHD. Organizational support for OSH and WHP was characterized as "low" to "moderate". To increase SHDs' capacity for OSH and WHP, interview respondents recommended that OSH and WHP approaches be better integrated into other public health initiatives (e.g., infectious disease prevention), and that federal funding for OSH and WHP increase. They also discussed specific recommendations for improving the accessibility and utility of existing funding mechanisms, and the educational resources they desired from the CDC. CONCLUSIONS: Results revealed current activities and specific strategies for increasing capacity of SHDs to promote the safety and health of workers and workplaces - an important public health setting for reducing acute injury and chronic disease.


Assuntos
Saúde do Trabalhador , Administração em Saúde Pública , United States Occupational Safety and Health Administration , Humanos , Pesquisa Qualitativa , Inquéritos e Questionários , Estados Unidos
7.
Br J Cancer ; 120(6): 647-657, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30787463

RESUMO

BACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). RESULTS: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10-8. For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10-7, hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84-0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10-7, HR = 1.27, 95% CI = 1.16-1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. CONCLUSIONS: We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30554298

RESUMO

Using the 2010-2015 Medical Expenditure Panel Survey-Insurance Component, this study investigates the effect of the Affordable Care Act's Medicaid eligibility expansion on four employer-sponsored insurance (ESI) outcomes: offers of health insurance, eligibility, take-up, and the out-of-pocket premium paid by employees for single coverage. Using a difference-in-differences identification strategy, we cannot reject the hypothesis of a zero effect of the Medicaid eligibility expansion on an establishment's probability of offering ESI, the percentage of an establishment's workforce that takes up coverage, or the out-of-pocket premium for single coverage. We find some evidence suggestive of an inverse relationship between the expansion of Medicaid and the percentage of an establishment's workers eligible for ESI. In line with other employer- and individual-level studies of the effect of the ACA on employment-related outcomes, we find that employer provision of health insurance was largely unaffected by the Medicaid expansions.

9.
Public Health Nutr ; 21(15): 2875-2883, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29976263

RESUMO

OBJECTIVE: To examine level of participation and satisfaction with the Healthy Savings Program (HSP), a programme that provides price discounts on healthier foods. DESIGN: For Study 1, a survey was distributed to a random sample of adults who were invited to participate in a version of the HSP that provided a discount for the purchase of fresh produce and discounts on other healthier foods. In Study 2, interviews were conducted with a convenience sample of adults invited to participate in a version of the HSP that provided price discounts on specific products only (no fresh produce discount). SETTING: The HSP is provided to all employer-based insurance plan members of a large health plan. Employers can choose to enhance the version of the HSP that their employees receive by paying for a weekly discount on fresh produce. SUBJECTS: Employees in employer groups that received the enhanced HSP (Study 1) and employees in an employer group (Study 2) that received the standard HSP. RESULTS: Among survey respondents in Study 1, 69·3 % reported using the HSP card. Most were satisfied with the fresh produce discount and ease of use of the HSP card. Satisfaction was lower for selection of participating stores, amounts of discounts and selection of discounted products. In Study 2, barriers to the use of the HSP card cited included the limited number of participating stores and the limited selection of discounted products. CONCLUSIONS: Satisfaction with some elements of the HSP was high while other elements may need improvement to increase programme use.

10.
Popul Health Manag ; 21(5): 415-421, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29393807

RESUMO

Elderly seasonal migrators share time between homes in different states, presenting challenges for care coordination and patient attribution methods. Medicare has prioritized alternative payment models, putting health care providers at risk for quality and value of services delivered to their attributed patients, regardless of the location of care. Little research is available to guide providers and payers on the service use of seasonal migrators. The authors use claims data on fee-for-service (FFS) Medicare beneficiaries' locations throughout the year to (1) identify seasonal migrators and (2) describe the care they receive in each seasonal home, focusing on primary care and emergency department (ED) visits and the relationships between the two. In all, 5.5% of the Medicare aged FFS population were identified as seasonal migrators, with 4.1% following the traditional snowbird pattern of migration, spending warm months in the north and cold months in the south. Migrators had higher rates of ED visits and primary care treatable (PCT) ED visits than the nonmigratory groups, controlling for location, age, race, sex, Medicaid status, season, and comorbidities. They also had more visits with specialist physicians, more days with outpatient services, and more days seeing a physician in any setting. Having local primary care strongly reduced rates of both PCT ED visits and total ED visits for all migration categories, with the greatest reduction seen in PCT ED visits by migrators (local primary care was associated with a 58% reduction in PCT ED visits by snowbirds and a 65% reduction in PCT ED visits by other migrators).

11.
Matern Child Health J ; 22(2): 216-225, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29098488

RESUMO

Objectives The United States is one of only three countries worldwide with no national policy guaranteeing paid leave to employed women who give birth. While maternity leave has been linked to improved maternal and child outcomes in international contexts, up-to-date research evidence in the U.S. context is needed to inform current policy debates on paid family leave. Methods Using data from Listening to Mothers III, a national survey of women ages 18-45 who gave birth in 2011-2012, we conducted multivariate logistic regression to predict the likelihood of outcomes related to infant health, maternal physical and mental health, and maternal health behaviors by the use and duration of paid maternity leave. Results Use of paid and unpaid leave varied significantly by race/ethnicity and household income. Women who took paid maternity leave experienced a 47% decrease in the odds of re-hospitalizing their infants (95% CI 0.3, 1.0) and a 51% decrease in the odds of being re-hospitalized themselves (95% CI 0.3, 0.9) at 21 months postpartum, compared to women taking unpaid or no leave. They also had 1.8 times the odds of doing well with exercise (95% CI 1.1, 3.0) and stress management (95% CI 1.1, 2.8), compared to women taking only unpaid leave. Conclusions for Practice Paid maternity leave significantly predicts lower odds of maternal and infant re-hospitalization and higher odds of doing well with exercise and stress management. Policies aimed at expanding access to paid maternity and family leave may contribute toward reducing socio-demographic disparities in paid leave use and its associated health benefits.

12.
Health Aff (Millwood) ; 37(12): 1931-1939, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30633676

RESUMO

In recent years state and federal policies have encouraged the use of telemedicine by formalizing payments for it. Telemedicine has the potential to expand access to timely care and reduce costs, relative to in-person care. Using information from the Minnesota All Payer Claims Database, we conducted a population-level analysis of telemedicine service provision in the period 2010-15, documenting variation in provision by coverage type, provider type, and rurality of patient residence. During this period the number of telemedicine visits increased from 11,113 to 86,238, and rates of use varied extensively by coverage type and rurality. In metropolitan areas telemedicine visits were primarily direct-to-consumer services provided by nurse practitioners or physician assistants and covered by commercial insurance. In nonmetropolitan areas telemedicine use was chiefly real-time provider-initiated services delivered by physicians to publicly insured populations. Recent federal and state legislation that expanded coverage and increased provider reimbursement for telemedicine services could lead to expanded use of telemedicine, including novel approaches in new patient populations.


Assuntos
Revisão da Utilização de Seguros/estatística & dados numéricos , Reembolso de Seguro de Saúde/estatística & dados numéricos , Saúde da População/estatística & dados numéricos , Telemedicina/economia , Telemedicina/estatística & dados numéricos , Setor de Assistência à Saúde/estatística & dados numéricos , Humanos , Reembolso de Seguro de Saúde/economia , Medicaid/economia , Medicaid/estatística & dados numéricos , Medicare/economia , Medicare/estatística & dados numéricos , Minnesota , Médicos/estatística & dados numéricos , População Rural , Telemedicina/tendências , Estados Unidos
13.
Int J Epidemiol ; 46(6): 1814-1822, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29232439

RESUMO

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95). Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Receptores Estrogênicos/genética , Causalidade , Europa (Continente)/epidemiologia , Feminino , Variação Genética , Humanos , Análise da Randomização Mendeliana , Metanálise como Assunto , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Análise de Sobrevida
14.
Prev Med ; 105: 135-141, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28890355

RESUMO

Wellness programs are a popular strategy utilized by large U.S. employers. As mobile health applications and wearable tracking devices increase in prevalence, many employers now offer physical activity tracking applications. This longitudinal study evaluates the impact of engagement with a web-based, physical activity tracking program on changes in individuals' biometric outcomes in an employer population. The study population includes active employees and adult dependents continuously enrolled in an eligible health plan and who have completed at least two biometric screenings (n=36,882 person-years with 11,436 unique persons) between 2011 and 2014. Using difference-in-differences (DID) regression, we estimate the effect of participation in the physical activity tracking application on BMI, total cholesterol, and blood pressure. Participation was significantly associated with a reduction of 0.275 in BMI in the post-period, relative to the comparison group, representing a 1% change from baseline BMI. The program did not have a statistically significant impact on cholesterol or blood pressure. Sensitivity checks revealed slightly larger BMI reductions among participants with higher intensity of tracking activity and in the period following the employer's shift to an outcomes-based incentive design. Results are broadly consistent with the existing literature on changes in biometric outcomes from workplace initiatives promoting increased physical activity. Employers should have modest expectations about the potential health benefits of such programs, given current designs and implementation in real-world settings.


Assuntos
Exercício , Promoção da Saúde/métodos , Avaliação de Resultados (Cuidados de Saúde)/estatística & dados numéricos , Local de Trabalho/psicologia , Adulto , Índice de Massa Corporal , Feminino , Humanos , Estudos Longitudinais , Masculino , Motivação
15.
Mod Pathol ; 30(8): 1069-1077, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28548129

RESUMO

The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists' reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57-0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation of residual cancer burden was a simple and reproducible method of quantifying response to neoadjuvant chemotherapy as demonstrated by performance comparison of the two pathologists.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasia Residual/epidemiologia , Patologia Clínica/normas , Garantia da Qualidade dos Cuidados de Saúde , Adulto , Idoso , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Lancet Oncol ; 18(6): 755-769, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28479233

RESUMO

BACKGROUND: The tAnGo trial was designed to investigate the potential role of gemcitabine when added to anthracycline and taxane-containing adjuvant chemotherapy for early breast cancer. When this study was developed, gemcitabine had shown significant activity in metastatic breast cancer, and there was evidence of a favourable interaction with paclitaxel. METHODS: tAnGo was an international, open-label, randomised, phase 3 superiority trial that enrolled women aged 18 years or older with newly diagnosed, early-stage breast cancer who had a definite indication for chemotherapy, any nodal status, any hormone receptor status, Eastern Cooperative Oncology Group performance status of 0-1, and adequate bone marrow, hepatic, and renal function. Women were recruited from 127 clinical centres and hospitals in the UK and Ireland, and randomly assigned (1:1) to one of two treatment regimens: epirubicin, cyclophosphamide, and paclitaxel (four cycles of 90 mg/m2 intravenously administered epirubicin and 600 mg/m2 intravenously administered cyclophosphamide on day 1 every 3 weeks, followed by four cycles of 175 mg/m2 paclitaxel as a 3 h infusion on day 1 every 3 weeks) or epirubicin, cyclophosphamide, and paclitaxel plus gemcitabine (the same chemotherapy regimen as the other group, with the addition of 1250 mg/m2 gemcitabine to the paclitaxel cycles, administered intravenously as a 0·5 h infusion on days 1 and 8 every 3 weeks). Patients were randomly assigned by a central computerised deterministic minimisation procedure, with stratification by country, age, radiotherapy intent, nodal status, and oestrogen receptor and HER-2 status. The primary endpoint was disease-free survival and the trial aimed to detect 5% differences in 5-year disease-free survival between the treatment groups. Recruitment completed in 2004 and this is the final, intention-to-treat analysis. This trial is registered with EudraCT (2004-002927-41), ISRCTN (51146252), and ClinicalTrials.gov (NCT00039546). FINDINGS: Between Aug 22, 2001, and Nov 26, 2004, 3152 patients were enrolled and randomly assigned to epirubicin, cyclophosphamide, paclitaxel, and gemcitabine (gemcitabine group; n=1576) or to epirubicin, cyclophosphamide, and paclitaxel (control group; n=1576). 11 patients (six in the gemcitabine group and five in the control group) were ineligible because of pre-existing metastases and were therefore excluded from the analysis. At this protocol-specified final analysis (median follow-up 10 years [IQR 10-10]), 1087 disease-free survival events and 914 deaths had occurred. Disease-free survival did not differ significantly between the treatment groups at 10 years (65% [63-68] in the gemcitabine group vs 65% [62-67] in the control group), and median disease-free survival was not reached (adjusted hazard ratio 0·97 [95% CI 0·86-1·10], p=0·64). Toxicity, dose intensity, and a detailed safety substudy showed both regimens to be safe, deliverable, and tolerable. Grade 3 and 4 toxicities were reported at expected levels in both groups. The most common were neutropenia (527 [34%] of 1565 patients in the gemcitabine group vs 412 [26%] of 1567 in the control group), myalgia and arthralgia (207 [13%] vs 186 [12%]), fatigue (207 [13%] vs 152 [10%]), infection (202 [13%] vs 141 [9%]), vomiting (143 [9%] vs 108 [7%]), and nausea (132 [8%] vs 102 [7%]). INTERPRETATION: The addition of gemcitabine to anthracycline and taxane-based adjuvant chemotherapy at this dose and schedule confers no therapeutic advantage in terms of disease-free survival in early breast cancer, although it can cause increased toxicity. Therefore, gemcitabine has not been added to standard adjuvant chemotherapy in breast cancer for any subgroup. FUNDING: Cancer Research UK core funding for Clinical Trials Unit at the University of Birmingham, Eli Lilly, Bristol-Myers Squibb, and Pfizer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Metástase Linfática , Mastectomia Segmentar , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Radioterapia , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Taxa de Sobrevida
17.
Int J Health Econ Manag ; 17(4): 395-412, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28447230

RESUMO

We investigate determinants of market entry and premiums within the context of the Affordable Care Act's Marketplaces for individual insurance. Using Bresnahan and Reiss (1991) as the conceptual framework, we study how competition and firm heterogeneity relate to premiums in 36 states using Federally Facilitated or Supported Marketplaces in 2016. Our primary data source is the Qualified Health Plan Landscape File, augmented with market characteristics from the American Community Survey and Area Health Resource File as well as insurer-level information from federal Medical Loss Ratio annual reports. We first estimate a model of insurer entry and then investigate the relationship between a market's predicted number of entrants and insurer-level premiums. Our entry model results suggest that competition is increasing with the number of insurers, most notably as the market size increases from 3 to 4 entrants. Results from the premium regression suggest that each additional entrant is associated with approximately 4% lower premiums, controlling for other factors. An alternative explanation for the relationship between entrants and premiums is that more efficient insurers (who can price lower) are the ones that enter markets with many entrants, and this is reflected in lower premiums. An exploratory analysis of insurers' non-claims costs (a proxy for insurer efficiency) reveals that average costs among entrants are rising slightly with the number of insurers in the market. This pattern does not support the hypothesis that premiums decrease with more entrants because those entrants are more efficient, suggesting instead that the results are being driven mostly by price competition.

18.
Health Aff (Millwood) ; 36(2): 222-228, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28167709

RESUMO

The corporate wellness industry is diversifying and now includes legacy wellness companies, divisions of health plans or delivery systems, and new technology-focused solution enterprises. We conducted in-depth interviews with leaders in the industry to understand the changes in its supply side, the drivers of these changes, future trends, and their implications for employers and policy makers. Three key trends emerged from the interviews: The industry is expanding and becoming increasingly diverse and competitive; wellness companies are redefining their business models to promote a culture of health; and the value proposition of employee wellness programs is shifting from a return on investment to a new idea: value on investment. Our findings clarify wellness companies' innovations, their contributions to population health improvement efforts, and the need for additional evidence to demonstrate the value of the new generation of wellness products and services.


Assuntos
Planos de Assistência de Saúde para Empregados/tendências , Promoção da Saúde/organização & administração , Promoção da Saúde/tendências , Modelos Organizacionais , Humanos , Entrevistas como Assunto , Formulação de Políticas
19.
LDI Issue Brief ; 21(3): 1-5, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28106361

RESUMO

In a review of the evidence, the authors find that the ACA had minimal effect on employment, hours of work, and compensation. This brief provides critical perspective on the effects of reforms on labor markets for federal and state policymakers as they consider changing or repealing the law.


Assuntos
Emprego/legislação & jurisprudência , Patient Protection and Affordable Care Act/economia , Salários e Benefícios/legislação & jurisprudência , Trocas de Seguro de Saúde , Humanos , Renda , Cobertura do Seguro , Estados Unidos
20.
Br J Cancer ; 115(12): 1462-1470, 2016 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-27875516

RESUMO

BACKGROUND: We report cardiac events in the Persephone trial which compares 6-12 months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage breast cancer. METHODS: Clinical cardiac events were defined as any of the following: symptoms and/or signs of congestive heart failure (CHF) and new or altered CHF medication. In addition, left ventricular ejection fraction (LVEF) was measured at baseline and then 3 monthly for 12 months. RESULTS: A total of 2500 patients, aged 22-82, were included: 1251 randomised to 12 months and 1249 to 6 months of trastuzumab treatment. A total of 93% (2335/2500) received anthracyclines, 49% of these (1136/2335) with taxanes. Cardiotoxicity delayed treatment in 6% of 12-month and 4% of 6-month patients (P=0.01), and stopped treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients (P<0.0001). Between 7 and 12 months, more 12-month than 6-month patients had LVEFs<50% (8% vs 5%; P=0.004). LVEFs showed quadratic change over time, and 6-month patients had a more rapid recovery (P=0.02). In a landmark analysis twice as many 12-month patients, free of cardiac events at 6 months, had cardiac problems in months 7-12 (6% (66/1046) vs 3% (29/1035) of 6-month patients (P=0.0002)). Lower baseline LVEF predicted more cardiac dysfunction in both arms (reference ⩾65%: 55 to <65% OR 1.61 (95% CI 1.26-2.04); <55% OR 5.22 (3.42-7.95)) as did increasing age (reference <50: 50-59 OR 1.58 (1.17-2.12), 60-69 OR 1.91 (1.42-2.57)) 70+ OR 2.72 (1.82-4.08)) and prior use of cardiac medication (OR 8.46 (4.69-15.25)). >3 cycles of anthracycline was associated with higher risk of cardiac events only for 12-month patients (OR 1.41 (1.04-1.90)), and not for 6-month patients (OR 1.28 (0.91-1.79)). CONCLUSIONS: We demonstrate significantly fewer cardiac events from 6 months of adjuvant trastuzumab compared with that from 12 months. This cardiac signal adds importance to the question of the optimum duration of adjuvant trastuzumab treatment. If 6 months is proven to have non-inferior outcomes to 12 months treatment, these data would support 6 months as the standard of care.


Assuntos
Antineoplásicos/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Trastuzumab/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Adulto Jovem
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