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4.
Curr Opin Pharmacol ; 63: 102183, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35176546

RESUMO

Eosinophilic esophagitis (EoE) is an antigen-mediated chronic T helper type 2 (Th2)-associated inflammatory disorder that has emerged in the last three decades as an increasingly common cause of esophageal symptoms. Despite rising incidence and prevalence, there are currently no approved therapies for EoE in the United States and only one oral topical corticosteroid approved in Europe and Canada. Current management relies on labor- and endoscopy-intensive dietary elimination, proton-pump inhibitors (PPIs) with only moderate efficacy, and use of inhaled or nebulized topical corticosteroids designed for asthma and limited by accessibility. Fortunately, progress in elucidating the underlying pathophysiology of EoE has led to the development of new therapies derived from molecular targets necessary for disease pathogenesis. We summarize established and emerging medical therapies for EoE, with a focus on new treatments with specific molecular targets that are likely to change EoE management paradigms in the next decade.


Assuntos
Esofagite Eosinofílica , Dieta , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/tratamento farmacológico , Glucocorticoides , Humanos , Inibidores da Bomba de Prótons/uso terapêutico
5.
J Natl Cancer Inst ; 114(4): 528-539, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35026030

RESUMO

BACKGROUND: The incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants. METHODS: Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS: Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores. CONCLUSIONS: Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
8.
Am J Prev Med ; 62(3): 387-394, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34763959

RESUMO

INTRODUCTION: The Patient Protection and Affordable Care Act eliminated cost sharing for preventive services, including colorectal cancer screening for individuals aged 50-75 years with private health insurance. This study examines the impact of the Affordable Care Act's removal of cost sharing for colorectal cancer screening on colorectal cancer incidence and mortality. METHODS: Trends in colorectal cancer incidence and colorectal cancer‒related mortality were modeled among 2,113,283 Kaiser Permanente Northern California members aged ≥50 years between 2003 and 2016 using an interrupted time-series design. As a sensitivity analysis, a controlled analysis utilized a comparison group of members covered with pre‒Affordable Care Act zero cost sharing for colorectal cancer screening. Analyses were performed in 2019 and 2020. RESULTS: The colorectal cancer incidence dropped by 17% around the time the Affordable Care Act was enacted (change in level incidence rate ratio; 95% CI=0.77, 0.90, 2-sided p-value <0.0001), followed by a 3% further decrease per year (95% CI=0.93, 1.00, p=0.05). A similar pattern was observed for colorectal cancer‒related mortality. The controlled results indicated that the elimination of cost sharing for screening due to the Affordable Care Act was associated with greater improvements in colorectal cancer outcomes among members previously covered by health plans with out-of-pocket costs for screening than among those with health plans with zero cost sharing for screening before the Affordable Care Act. CONCLUSIONS: The elimination of cost sharing for colorectal cancer screening due to the Affordable Care Act was associated with a decrease in age-, race/ethnicity-, and sex-adjusted colorectal cancer incidence and colorectal cancer‒related mortality, implying that policies that remove barriers to screening, particularly financial burden from cost sharing, can result in improved colorectal cancer outcomes.


Assuntos
Neoplasias Colorretais , Patient Protection and Affordable Care Act , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Custo Compartilhado de Seguro , Detecção Precoce de Câncer , Humanos , Incidência , Cobertura do Seguro , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
9.
Clin Gastroenterol Hepatol ; 20(1): 145-152, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33010408

RESUMO

BACKGROUND AND AIMS: Programmatic colorectal cancer (CRC) screening increases uptake, but the design and resources utilized for such models are not well known. We characterized program components and participation at each step in a large program that used mailed fecal immunochemical testing (FIT) with opportunistic colonoscopy. METHODS: Mixed-methods with site visits and retrospective cohort analysis of 51-75-year-old adults during 2017 in the Kaiser Permanente Northern California integrated health system. RESULTS: Among 1,023,415 screening-eligible individuals, 405,963 (40%) were up to date with screening at baseline, and 507,401 of the 617,452 not up-to-date were mailed a FIT kit. Of the entire cohort (n = 1,023,415), 206,481 (20%) completed FIT within 28 days of mailing, another 61,644 (6%) after a robocall at week 4, and 40,438 others (4%) after a mailed reminder letter at week 6. There were over 800,000 medical record screening alerts generated and about 295,000 FIT kits distributed during patient office visits. About 100,000 FIT kits were ordered during direct-to-patient calls by medical assistants and 111,377 people (11%) completed FIT outside of the automated outreach period. Another 13,560 (1.3%) completed a colonoscopy, sigmoidoscopy, or fecal occult blood test unrelated to FIT. Cumulatively, 839,463 (82%) of those eligible were up to date with screening at the end of the year and 12,091 of 14,450 patients (83.7%) with positive FIT had diagnostic colonoscopy. CONCLUSIONS: The >82% screening participation achieved in this program resulted from a combination of prior endoscopy (40%), large initial response to mailed FIT kits (20%), followed by smaller responses to automated reminders (10%) and personal contact (12%).


Assuntos
Neoplasias Colorretais , Sangue Oculto , Adulto , Idoso , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos
10.
Cancer Epidemiol Biomarkers Prev ; 31(4): 775-782, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-34906968

RESUMO

BACKGROUND: Models can help guide colorectal cancer screening policy. Although models are carefully calibrated and validated, there is less scrutiny of assumptions about test performance. METHODS: We examined the validity of the CRC-SPIN model and colonoscopy sensitivity assumptions. Standard sensitivity assumptions, consistent with published decision analyses, assume sensitivity equal to 0.75 for diminutive adenomas (<6 mm), 0.85 for small adenomas (6-10 mm), 0.95 for large adenomas (≥10 mm), and 0.95 for preclinical cancer. We also selected adenoma sensitivity that resulted in more accurate predictions. Targets were drawn from the Wheat Bran Fiber study. We examined how well the model predicted outcomes measured over a three-year follow-up period, including the number of adenomas detected, the size of the largest adenoma detected, and incident colorectal cancer. RESULTS: Using standard sensitivity assumptions, the model predicted adenoma prevalence that was too low (42.5% versus 48.9% observed, with 95% confidence interval 45.3%-50.7%) and detection of too few large adenomas (5.1% versus 14.% observed, with 95% confidence interval 11.8%-17.4%). Predictions were close to targets when we set sensitivities to 0.20 for diminutive adenomas, 0.60 for small adenomas, 0.80 for 10- to 20-mm adenomas, and 0.98 for adenomas 20 mm and larger. CONCLUSIONS: Colonoscopy may be less accurate than currently assumed, especially for diminutive adenomas. Alternatively, the CRC-SPIN model may not accurately simulate onset and progression of adenomas in higher-risk populations. IMPACT: Misspecification of either colonoscopy sensitivity or disease progression in high-risk populations may affect the predicted effectiveness of colorectal cancer screening. When possible, decision analyses used to inform policy should address these uncertainties.See related commentary by Etzioni and Lange, p. 702.


Assuntos
Adenoma , Neoplasias Colorretais , Adenoma/diagnóstico , Adenoma/epidemiologia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Humanos , Políticas
11.
Gastroenterology ; 162(4): 1098-1110.e2, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34922947

RESUMO

BACKGROUND & AIMS: The management of gastrointestinal (GI) cancers is associated with high health care spending. We estimated trends in United States (US) health care spending for patients with GI cancers between 1996 and 2016 and developed projections to 2030. METHODS: We used economic data, adjusted for inflation, developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. Corresponding US age-adjusted prevalence of GI cancers was estimated from the Global Burden of Diseases Study. Prevalence-adjusted temporal trends in the US health care spending in patients with GI cancers, stratified by cancer site, age, and setting of care, were estimated using joinpoint regression, expressed as annual percentage change (APC) with 95% confidence intervals (CIs). Autoregressive integrated moving average models were used to project spending to 2030. RESULTS: In 2016, total spending for GI cancers was primarily attributable to colorectal ($10.50 billion; 95% CI, $9.35-$11.70 billion) and pancreatic cancer ($2.55 billion; 95% CI, $2.23-$2.82 billion), and primarily for inpatient care (64.5%). Despite increased total spending, more recent per-patient spending for pancreatic (APC 2008-2016, -1.4%; 95% CI, -2.2% to -0.7%), gallbladder/biliary tract (APC 2010-2016, -4.3%; 95% CI, -4.8% to -3.8%), and gastric cancer (APC 2011-2016, -4.4%; 95% CI, -5.8% to -2.9%) decreased. Increasing price and intensity of care provision was the largest driver of higher expenditures. By 2030, it is projected more than $21 billion annually will be spent on GI cancer management. CONCLUSIONS: Total spending for GI cancers in the US is substantial and projected to increase. Expenditures are primarily driven by inpatient care for colorectal cancer, although per-capita spending trends differ by GI cancer type.


Assuntos
Neoplasias Gastrointestinais , Gastos em Saúde , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/terapia , Hospitalização , Humanos , Prevalência , Estados Unidos/epidemiologia
12.
Aliment Pharmacol Ther ; 54(10): 1232-1242, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34587323

RESUMO

INTRODUCTION: Post-colonoscopy colorectal cancers (PCCRCs) have been proposed as a performance metric for colonoscopy quality assurance programs. Previously, there was no standardised terminology or reporting methods. In 2018, the World Endoscopy Organization (WEO) advised standardised definitions and prevalence calculation methodology. AIMS: To assess PCCRC burden using WEO standardised methods, to explore causes of heterogeneity, and to review changes in prevalence over time METHODS: We updated a prior systematic review by searching Ovid MEDLINE and EMBASE databases from 1 January 2013 to 31 January 2021 to identify population-based studies (or multicentre studies representative of the local population) reporting PCCRC prevalence (PROSPERO [CRD42020183796]). Two authors independently determined study eligibility, assessed quality, and extracted data. We estimated the PCCRC 3-year prevalence using WEO-recommended methodologies and investigated between-study sources of heterogeneity. We examined changes in prevalence over time. RESULTS: Fifteen studies reporting on 25 872 PCCRC cases met eligibility criteria. Pooled PCCRC 3 year prevalence was 8.2% (95% CI = 6.9%-9.4%, I2  = 98.2%) across four European studies using WEO precise methodology. Proximal PCCRC prevalence was greater than distal (9.7% [95% CI = 7.0%-12.4%] vs 5.4% [95% CI = 2.9%-7.8%], I2  = 99.2%). Seven studies reporting PCCRC rates over time showed no consistent trend: four showed a decrease, one an increase and two were unchanged. Between-study heterogeneity was high. CONCLUSIONS: Pooled 3-year PCCRC prevalence was 8.2% (95% CI = 6.9%-9.4%). Despite WEO standardised methodology to define and calculate PCCRC rates, there was significant heterogeneity among studies. Comparing rates between populations remains challenging and additional studies are needed to better understand the global PCCRC burden to inform quality assurance programs.


Assuntos
Neoplasias Colorretais , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Humanos , Prevalência , Fatores de Risco
13.
Gut ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380653

RESUMO

OBJECTIVE: The longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood. DESIGN: This community-based, case-control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006-2016. Nested within this population, we identified 695 cases of CRC and 3475 CRC-free controls (matched 5:1 to cases for age, sex and year of colonoscopy). Two expert pathologists reviewed the tissue slides of all SPs identified on the first colonoscopy and reclassified them to sessile serrated lesions (SSLs), hyperplastic polyps (HPs) and traditional serrated adenomas. SPs with borderline characteristics of SSLs but insufficient to make a definitive diagnosis were categorised as unspecified SPs. The association with development of CRC was assessed using multivariable logistic regression. RESULTS: Compared with individuals with no polyp, the adjusted ORs (aORs) for SSL alone or with synchronous adenoma were 2.9 (95% CI: 1.8 to 4.8) and 4.4 (95% CI: 2.7 to 7.2), respectively. The aORs for SSL with dysplasia, large proximal SSL,and small proximal SSL were 10.3 (95% CI: 2.1 to 50.3), 12.8 (95% CI: 3.5 to 46.9) and 1.9 (95% CI: 0.8 to 4.7), respectively. Proximal unspecified SP also conferred an increased risk (aOR: 5.8, 95% CI: 2.2 to 15.2). Women with SSL were associated with higher risk (aOR: 4.4; 95% CI: 2.3 to 8.2) than men (aOR: 1.7; 95% CI: 0.8 to 3.8). CONCLUSION: Increased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs.

14.
Gastrointest Endosc ; 94(2): 207-221.e14, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34023065

RESUMO

Cholangitis is a GI emergency requiring prompt recognition and treatment. The purpose of this document from the American Society for Gastrointestinal Endoscopy's (ASGE) Standards of Practice Committee is to provide an evidence-based approach for management of cholangitis. This document addresses the modality of drainage (endoscopic vs percutaneous), timing of intervention (<48 hours vs >48 hours), and extent of initial intervention (comprehensive therapy vs decompression alone). Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to formulate recommendations on these topics. The ASGE suggests endoscopic rather than percutaneous drainage and biliary decompression within 48 hours. Additionally, the panel suggests that sphincterotomy and stone removal be combined with drainage rather than decompression alone, unless patients are too unstable to tolerate more extensive endoscopic treatment.


Assuntos
Colangite , Doença Aguda , Colangite/terapia , Drenagem , Emergências , Humanos , Estados Unidos
15.
Gastrointest Endosc ; 94(2): 222-234.e22, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34023067

RESUMO

This clinical guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the management of patients with malignant hilar obstruction (MHO). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework and addresses primary drainage modality (percutaneous transhepatic biliary drainage [PTBD] vs endoscopic biliary drainage [EBD]), drainage strategy (unilateral vs bilateral), and stent selection (plastic stent [PS] vs self-expandable metal stent [SEMS]). Regarding drainage modality, in patients with MHO undergoing drainage before potential resection or transplantation, the panel suggests against routine use of PTBD as first-line therapy compared with EBD. In patients with unresectable MHO undergoing palliative drainage, the panel suggests PTBD or EBD. The final decision should be based on patient preferences, disease characteristics, and local expertise. Regarding drainage strategy, in patients with unresectable MHO undergoing palliative stent placement, the panel suggests placement of bilateral stents compared with a unilateral stent in the absence of liver atrophy. Finally, regarding type of stent, in patients with unresectable MHO undergoing palliative stent placement, the panel suggests placing SEMSs or PSs. However, in patients who have a short life expectancy and who place high value on avoiding repeated interventions, the panel suggests using SEMSs compared with PSs. If optimal drainage strategy has not been established, the panel suggests placing PSs. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.


Assuntos
Neoplasias dos Ductos Biliares , Colestase , Stents Metálicos Autoexpansíveis , Colestase/etiologia , Colestase/cirurgia , Drenagem , Endoscopia Gastrointestinal , Humanos , Cuidados Paliativos , Stents , Resultado do Tratamento , Estados Unidos
19.
Gastroenterology ; 160(4): 1041-1049, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33417940

RESUMO

Rising trends in the incidence and mortality of early-onset colorectal cancer (CRC) in those who are younger than 50 years have been well established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC, as well as on identifying strategies for early detection and prevention. In this review, we provide a contemporary update on early-onset CRC with a particular focus on epidemiology, molecular characterization, red flag signs and symptoms, and screening for early-onset CRC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/normas , Programas de Rastreamento/normas , Idade de Início , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Humanos , Programas de Rastreamento/métodos , Instabilidade de Microssatélites , Guias de Prática Clínica como Assunto , Medicina de Precisão/métodos , Medicina de Precisão/normas , Fatores de Risco , Triagem/normas
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