RESUMEN
BACKGROUND AND AIMS: Pancreatic cancer is a lethal cancer of increasing incidence, presenting with several clinically detectable signals allowing for earlier diagnosis. However, there are limited data related to diagnostic process, including prevalence of diagnostic delays and their contributing factors. We aimed to develop a standardized definition of diagnostic delay, evaluate its prevalence, and identify its contributing factors among pancreatic cancer patients. METHODS: We convened an expert panel who defined diagnostic delay among pancreatic cancer patients. We then conducted a retrospective cohort study among pancreatic adenocarcinoma patients consecutively diagnosed from 2007 to 2019 at a tertiary care Veterans Affairs medical center. We manually reviewed diagnostic delay instances for contributing factors. Secondary analyses, using multivariate logistic regression and Cox proportional hazards models, explored associations between diagnostic delays and cancer outcomes. RESULTS: Diagnostic delay was defined as cancer diagnosis made ≥60 days after first clinical presence of predefined red flag(s). Among 197 pancreatic adenocarcinoma patients, 38.6% experienced a diagnostic delay. Among delay cases, the most common primary contributing factor was related to the patient-provider encounter (44.7% with lack of recognition of objective weight loss). Patients with delays were more likely to be diagnosed at advanced stage disease (adjusted odds ratio, 1.62; 95% confidence interval, 0.79-3.30) and less likely to receive potentially curative treatment (adjusted odds ratio, 0.72; 95% confidence interval, 0.28-1.84), although these trends did not reach statistical significance. CONCLUSIONS: Over one-third of pancreatic cancer patients experienced a diagnostic delay, mostly due to inadequate recognition of red flag findings. Results can inform targeted interventions to reduce preventable diagnostic delays among pancreatic cancer patients.
RESUMEN
OBJECTIVE: The objective is to determine cervical cancer screening rates and factors associated with decreased cervical cancer screening in women with systemic lupus erythematosus (SLE). METHODS: We conducted a cross-sectional study that enrolled consecutive women (age 21-64 years) with SLE. We collected demographics, clinical characteristics, constructs of the Health Beliefs Model (HBM) (ie, susceptibility, severity, barriers, benefits, cues to action, and self-efficacy), and self-reported cervical cancer screening (confirmed with the electronic medical record). The primary outcome was adherence to cervical cancer screening according to current guidelines. Multivariable logistic regression models were used to examine the association between SLE disease activity and cervical cancer screening and explore mediation effects from HBM constructs. RESULTS: We enrolled 130 women with SLE. The median age was 42 years (interquartile range 32-52 years). The cervical cancer screening adherence rate was 61.5%. Women with high SLE disease activity were less likely to have cervical cancer screening versus those with low disease activity (odds ratio 0.59, 95% confidence interval [CI] 0.39-0.89; P = 0.01), which remained statistically significant after adjusting for baseline demographics and drug therapy in a multivariable model (odds ratio 0.25, 95% CI 0.08-0.79; P = 0.02). Regarding the HBM constructs, increased perceived barriers to cervical cancer screening (r = -0.30, P < 0.01) and decreased self-efficacy (r = -0.21, P = 0.02) correlated with decreased cervical cancer screening. CONCLUSION: Patients with SLE with high disease activity undergo cervical cancer screening less frequently than those with low disease activity. Perceived barriers to cervical cancer screening are moderately correlated with decreased screening. These data highlight the need to develop strategies to increase cervical cancer screening in this high-risk patient population.
Asunto(s)
Detección Precoz del Cáncer , Lupus Eritematoso Sistémico , Cooperación del Paciente , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Persona de Mediana Edad , Adulto , Estudios Transversales , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/psicología , Detección Precoz del Cáncer/psicología , Adulto Joven , Conocimientos, Actitudes y Práctica en Salud , Modelo de Creencias sobre la SaludRESUMEN
OBJECTIVES: People with HIV (PWH) may have an increased burden of penile cancer. We aimed to evaluate the risk of penile cancer in PWH compared with that of the general population. DESIGN: We conducted a nationwide retrospective matched cohort study of penile cancer incidence among veterans with HIV (VWH) compared with veterans without HIV. METHODS: We compared penile cancer incidence rates in 44â173 VWH to those of veterans without HIV ( N â=â159â443; 4â:â1 matched in age). We used Cox regression models to estimate hazard ratios and 95% confidence intervals (CIs) for associations with HIV infection and for penile cancer risk factors. RESULTS: HIV positivity was associated with an increased risk of penile cancer, with adjusted hazard ratios of 2.63 (95% CI 1.64-4.23) when adjusting for age, race/ethnicity, baseline BMI, smoking and alcohol use, economic means test, and history of condyloma. The risk increased to hazard ratioâ=â4.25 (95% CI 2.75-6.57) when adjusting for all factors except history of condyloma. Risk factors for penile cancer in VWH included lower nadir CD4 + count, less than 50% of follow-up time with undetectable HIV viral load, and history of condyloma. CONCLUSION: VWH - particularly those with low CD4 + counts, detectable HIV viral loads, or history of condyloma - are at increased risk of penile cancer, suggesting the penile cancer prevention activities are needed in this population.
Asunto(s)
Infecciones por VIH , Neoplasias del Pene , Veteranos , Humanos , Masculino , Neoplasias del Pene/epidemiología , Neoplasias del Pene/virología , Veteranos/estadística & datos numéricos , Estudios Retrospectivos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Persona de Mediana Edad , Estados Unidos/epidemiología , Incidencia , Adulto , Factores de Riesgo , Medición de Riesgo , AncianoRESUMEN
BACKGROUND AND AIMS: The value of HCC surveillance is determined by the balance between benefits and harms; however, no studies have enumerated psychological harms. APPROACH AND RESULTS: We fielded surveys measuring psychological harms to patients with cirrhosis in a multicenter randomized trial of HCC surveillance outreach. All patients with positive or indeterminate surveillance results and matched patients with negative results were invited to complete surveys measuring (1) depression through the Patient Health Questionnaire-ninth version, (2) anxiety through State-Trait Anxiety Inventory, (3) HCC-specific worry through Psychological Consequences Questionnaire, and (4) decisional regret. Patients were classified into 4 groups: true positive (TP), false positive (FP), indeterminate, and true negative (TN). Multivariable longitudinal regression analysis using the generalized estimating equation method was performed to compare the means of measures across groups. We conducted 89 semistructured interviews in a subset of patients stratified by health system and test results. Of 2872 patients in the trial, 311 completed 1+ follow-up survey (63 FP, 77 indeterminate, 38 TP, and 133 TN). Moderate depression decreased in TN patients, increased in TP, and had intermittent but mild increases in those with FP and indeterminate results. High anxiety temporarily increased in patients with TP results but resolved over time and was stable in those with FP and indeterminate results. Decisional regret was low and did not differ across groups. In semistructured interviews, patients reported apprehension, anxiety, emotional distress, and coping related to HCC surveillance. CONCLUSIONS: Psychological harms of HCC surveillance appear mild but differ by test result. Future research should determine the impact of psychological harms on the value of HCC surveillance programs.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Neoplasias Hepáticas/epidemiología , Cirrosis Hepática/complicaciones , Ansiedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: The overall value of hepatocellular carcinoma screening is defined by the balance of benefits and harms. Studies have only reported physical harms with none describing financial harms. METHODS: We conducted a multicenter pragmatic randomized clinical trial of hepatocellular carcinoma screening outreach among 2872 patients with cirrhosis from March 2018 to April 2021. Patients with positive or indeterminate results and matched patients with negative results completed surveys at baseline and at follow-up measuring financial harms via Cancer Self-Administered Questionnaire and financial burden via Comprehensive Score for Financial Toxicity Functional Assessment of Chronic Illness Therapy. Univariable and multivariable longitudinal regression analyses were performed to compare changes in financial harms across groups: true positive, true negative, false positive, and indeterminate. Semistructured interviews were conducted in a subset of patients, sampled by center and test result. RESULTS: Of 311 patients who completed at least 1 follow-up survey (75% response rate), 37 had true positive, 133 true negative, 64 false positive, and 77 indeterminate results. Financial harms increased in true positive and false positive patients with no significant changes noted among those with true negative or indeterminate results. At follow-up, 21.8% of patients reported moderate-severe financial burden, which was not significantly associated with test results. Semistructured interviews revealed variation in the frequency and severity of financial harms based on test results, with increased harm in those with false positive results. CONCLUSIONS: Financial harms of hepatocellular carcinoma screening vary by test result and can pose a barrier that must be considered when determining the optimal screening program.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Estrés Financiero , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnósticoRESUMEN
OBJECTIVES: Among patients with pancreatic cancer, studies show racial disparities at multiple steps of the cancer care pathway. Access to healthcare is a frequently cited cause of these disparities. It remains unclear if racial disparities exist in an integrated, equal access public system such as the Veterans Affairs healthcare system. METHODS: We identified all patients diagnosed with pancreatic adenocarcinoma in the national Veterans Affairs Central Cancer Registry from January 2010 to December 2018. We examined the independent association between race and 3 endpoints: stage at diagnosis, receipt of treatment, and survival while adjusting for sociodemographic factors and medical comorbidities. RESULTS: We identified 8529 patients with pancreatic adenocarcinoma, of whom 79.5% were White and 20.5% were Black. Black patients were 19% more likely to have late-stage disease and 25% less likely to undergo surgical resection. Black patients had 13% higher mortality risk compared with White patients after adjusting for sociodemographic characteristics and medical comorbidities. This difference in mortality was no longer statistically significant after additionally adjusting for cancer stage and receipt of potentially curative treatment. CONCLUSIONS: Equal access to healthcare might have reduced but failed to eliminate disparities. Dedicated efforts are needed to understand reasons underlying these disparities in an attempt to close these persistent gaps.
Asunto(s)
Adenocarcinoma , Disparidades en Atención de Salud , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/epidemiología , Adenocarcinoma/etnología , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Negro o Afroamericano/estadística & datos numéricos , Disparidades en Atención de Salud/etnología , Disparidades en Atención de Salud/estadística & datos numéricos , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/etnología , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/terapia , Estados Unidos/epidemiología , Veteranos/estadística & datos numéricos , Blanco/estadística & datos numéricos , Servicios de Salud para Veteranos/estadística & datos numéricosRESUMEN
Importance: US surgical quality improvement (QI) programs use data from a systematic sample of surgical cases, rather than universal review of all cases, to assess and compare risk-adjusted hospital postoperative complication rates. Given decreasing postoperative complication rates over time and the types of cases eligible for abstraction, it is unclear whether case sampling is robust for identifying hospitals with higher than expected complications. Objective: To compare the assessment of hospital 30-day complication rates derived from sampling strategy used by some US surgical QI programs relative to universal review of all cases. Design, Setting, and Participants: This US hospital-level analysis took place from January 1, 2016, through September 30, 2020. Data analysis was performed from July 1, 2022, through December 21, 2022. Quarterly, risk-adjusted, 30-day complication observed to expected (O-E) ratios were calculated for each hospital using the sample (n = 502â¯730) and universal review (n = 1â¯725â¯364). Outlier hospitals (ie, those with higher than expected mortality) were identified using an O-E ratio significantly greater than 1.0. Patients 18 years and older who underwent a noncardiac operation at US Department of Veterans Affairs (VA) hospitals with a record in the VA Surgical Quality Improvement Program (systematic sample) and the VA Corporate Data Warehouse surgical domain (100% of surgical cases) were included. Main Outcome Measure: Thirty-day complications. Results: Most patients in both the representative sample and the universal sample were men (90.2% vs 91.2%) and White (74.7% vs 74.5%). Overall, 30-day complication rates were 7.6% and 5.3% for the sample and universal review cohorts, respectively (P < .001). Over 2145 hospital quarters of data, hospitals were identified as an outlier in 15.0% of quarters using the sample and 18.2% with universal review. Average hospital quarterly complication rates were 4.7%, 7.2%, and 7.4% for outliers identified using the sample only, universal review only, and concurrent identification in both data sources, respectively. For nonsampled cases, average hospital quarterly complication rates were 7.0% at outliers and 4.4% at nonoutliers. Among outlier hospital quarters in the sample, 54.2% were concurrently identified with universal review. For those identified with universal review, 44.6% were concurrently identified using the sample. Conclusion: In this observational study, case sampling identified less than half of hospitals with excess risk-adjusted postoperative complication rates. Future work is needed to ascertain how to best use currently collected data and whether alternative data collection strategies may be needed to better inform local QI efforts.
Asunto(s)
Mejoramiento de la Calidad , Indicadores de Calidad de la Atención de Salud , Masculino , Humanos , Femenino , Complicaciones Posoperatorias/mortalidad , Hospitales , MorbilidadRESUMEN
BACKGROUND: Emergency presentation (EP) of cancer, a new cancer diagnosis made following an emergency department (ED) visit, is associated with worse patient outcomes and greater organizational stress on healthcare systems. Pancreatic cancer has the highest rate of EPs among European studies but remains understudied in the U.S. AIMS: To evaluate the association between pancreatic cancer EPs and cancer stage, treatment, and survival. METHODS: We conducted a retrospective cohort study among patients with pancreatic adenocarcinoma diagnosed from 2007 to 2019 at a tertiary-care Veterans Affairs medical center. Electronic health records were reviewed to identify EP cases, defined as a new pancreatic cancer diagnosis made within 30 days of an ED visit where cancer was suspected. We used multivariate logistic regression models and Cox proportional hazards models to examine the associations between EPs and cancer stage, treatment, and survival. RESULTS: Of 243 pancreatic cancer patients, 66.7% had EPs. There was no difference in stage by EP status. However, patients diagnosed through EPs were 72% less likely to receive cancer treatment compared to non-emergency presenters (adjusted OR 0.28; 95% CI 0.13-0.57). Patients with EPs also had a 73% higher mortality risk (adjusted HR 1.73; 95% CI 1.29-2.34). This difference in mortality remained statistically significant after adjusting for cancer stage and receipt of cancer treatment (adjusted HR 1.47; 95% CI 1.09-1.99). CONCLUSIONS: Pancreatic cancer EPs are common and independently associated with lower treatment rates and survival. Enhanced understanding of process breakdowns that lead to EPs can help identify care gaps and inform future quality improvement efforts.
Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Adenocarcinoma/epidemiología , Adenocarcinoma/terapia , Servicio de Urgencia en Hospital , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Modelos LogísticosRESUMEN
INTRODUCTION: There are limited longitudinal data on the cost of treating patients with cirrhosis, which hampers value-based improvement initiatives. METHODS: We conducted a retrospective cohort study of patients with cirrhosis seen in the Veterans Affairs health care system from 2011 to 2015. Patients were followed up through 2019. We identified a sex-matched and age-matched control cohort without cirrhosis. We estimated incremental annual health care costs attributable to cirrhosis for 4 years overall and in subgroups based on severity (compensated, decompensated), cirrhosis complications (ascites, encephalopathy, varices, hepatocellular cancer, acute kidney injury), and comorbidity (Deyo index). RESULTS: We compared 39,361 patients with cirrhosis with 138,964 controls. The incremental adjusted costs for caring of patients with cirrhosis were $35,029 (95% confidence interval $32,473-$37,585) during the first year and ranged from $14,216 to $17,629 in the subsequent 3 years. Cirrhosis complications accounted for most of these costs. Costs of managing patients with hepatic encephalopathy (year 1 cost, $50,080) or ascites ($50,364) were higher than the costs of managing patients with varices ($20,488) or hepatocellular cancer ($37,639) in the first year. Patients with acute kidney injury or those who had multimorbidity were the most costly at $64,413 and $66,653 in the first year, respectively. DISCUSSION: Patients with cirrhosis had substantially higher health care costs than matched controls and multimorbid patients had even higher costs. Cirrhosis complications accounted for most of the excess cost, so preventing complications has the largest potential for cost saving and could serve as targets for improvement.
RESUMEN
Objective: The intensity of an antibiotic stewardship intervention to achieve clinical impact is not known. We conducted a multisite dissemination project of an intervention to reduce treatment of asymptomatic bacteriuria (ASB) and studied: (1) the association between implementation metrics and clinical outcomes and (2) the cost of implementation. Design/Setting/Participants: A central site facilitated a multimodality intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB at 4 Veterans Affairs medical centers. Methods: The intervention consisted of a decision support aid algorithm and interactive teaching cases that provided in the moment audit and feedback on how to manage ASB. Implementation outcomes included minutes spent in intervention delivery, number of healthcare professionals reached, and number of sessions delivered. Clinical outcomes included days of antibiotic therapy (DOT), length of antibiotic therapy (LOT), and number of urine cultures ordered per 1000 bed days. Personnel reported weekly time logs. Results: Minutes spent in intervention delivery were inversely correlated with two clinical outcomes, DOT (R -0.3, P = .04) and LOT (R -0.3, P = .02). Number of healthcare professionals reached and number of sessions delivered were not correlated with clinical outcomes of DOT (R -0.003, P = .98, R = -0.059, P = .69) or LOT (R +0.073, P = .62, R -0.102, P = .49). Physician champions spent an average of 3.8% of effort on the intervention. The implementation cost was USD 22,299/year per site on average. Conclusions: The amount of time local teams spent in delivery of an antibiotic stewardship intervention was correlated with the desired decrease in antibiotic use. Implementing this successful antibiotic stewardship intervention required minimal time.
RESUMEN
BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis. METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating characteristic curve (AUROC). External validation was performed in a cohort of 21,550 patients with cirrhosis seen in the U.S Veterans Affairs system between 2018 and 2019 with follow-up through 2021. RESULTS: We developed the model in 2431 patients (mean age 60 years, 31% women, 24% cured hepatitis C, 16% alcoholic liver disease, and 29% nonalcoholic fatty liver disease). The selected model had a C-index of 0.77 (95% confidence interval [CI], 0.73-0.81), and the predictors were age, sex, smoking, alcohol use, body mass index, etiology, α-fetoprotein, albumin, alanine aminotransferase, and platelet levels. The AUROCs were 0.75 (95% CI, 0.65-0.85) at 1 year and 0.77 (95% CI, 0.71-0.83) at 2 years, and the model was well calibrated. In the external validation cohort, the AUROC at 2 years was 0.70 with excellent calibration. CONCLUSION: The risk index, including objective and routinely available risk factors, can differentiate patients with cirrhosis who will develop HCC and help guide discussions regarding HCC surveillance and prevention. Future studies are needed for additional external validation and refinement of risk stratification.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Femenino , Persona de Mediana Edad , Masculino , Neoplasias Hepáticas/complicaciones , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Estudios Prospectivos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/epidemiología , Factores de Riesgo , Medición de RiesgoRESUMEN
BACKGROUND: HIV infection has been associated with survival disparities among persons with hepatocellular carcinoma (HCC). However, most studies examining survival do not control for provider (e.g. type of HCC treatment given) or individual-level factors (e.g. homelessness, substance use) that could impact survival. In this study, we evaluate the effect of HIV status on survival among persons with HCC, in a comprehensive model that accounts for key individual, provider, and systems-level factors. METHODS: We conducted a retrospective cohort study of persons with HIV (PWH) matched 1â:â1 to HIV-negative controls based on age and year of HCC diagnosis in the national Veterans Administration (VA) health system. The primary outcome was survival. We used Cox regression models to evaluate the effect of HIV status on risk of death. RESULTS: This cohort included 200 matched pairs diagnosed with HCC between 2009 and 2016. A total of 114 PWH (57.0%) and 115 HIV-negative patients (57.5%) received guideline-concordant therapy ( P â=â0.92). Median survival was 13.4âmonths [95% confidence interval (CI) 8.7-18.1] among PWH and 19.1âmonths (95% CI 14.6-24.9) for HIV-negative patients. In adjusted models, older age, homelessness, advanced Barcelona Clinic Liver Cancer (BCLC) stage, and not receiving any HCC treatment predicted risk of death. HIV status was not associated with risk of death [adjusted hazard ratio (aHR) 0.95; 95% CI 0.75-1.20; P â=â0.65]. CONCLUSION: HIV status was not associated with worse survival among HCC patients, in a single-payer, equal access healthcare system. These results suggest that HIV infection alone should not exclude PWH from receiving standard therapy.
Asunto(s)
Carcinoma Hepatocelular , Infecciones por VIH , Neoplasias Hepáticas , Veteranos , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Background: Preventing HIV infection remains a critically important tool in the continuing fight against HIV/AIDS. The primary aim is to evaluate the effect and interactions between a composite area-level social determinants of health measure and an area-level measure of residential segregation on the risk of HIV/AIDS in U.S. Veterans. Methods: Using the individual-level patient data from the U.S. Department of Veterans Affairs, we constructed a case-control study of veterans living with HIV/AIDS (VLWH) and age-, sex assigned at birth- and index date-matched controls. We geocoded patient's residential address to ascertain their neighborhood and linked their information to two measures of neighborhood-level disadvantage: area deprivation index (ADI) and isolation index (ISOL). We used logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for comparing VLWH with matched controls. We performed analyses for the entire U.S. and separately for each U.S. Census division. Findings: Overall, living in minority-segregated neighborhoods was associated with a higher risk of HIV (OR: 1.88 (95% CI: 1.79-1.97) while living in higher ADI neighborhoods was associated with a lower risk of HIV (OR: 0.88; 95% CI: 0.84-0.92). The association between living in a higher ADI neighborhood and HIV was inconsistent across divisions, while living in minority-segregated neighborhoods was consistently associated with increased risk across all divisions. In the interaction model, individuals from low ADI and high ISOL neighborhoods had a higher risk of HIV in three divisions: East South Central; West South Central, and Pacific. Interpretation: Our results suggest that residential segregation may prevent people in disadvantaged neighborhoods from protecting themselves from HIV independent from access to health care. There is the need to advance knowledge about the neighborhood-level social-structural factors that influence HIV vulnerability toward developing interventions needed to achieve the goal of ending the HIV epidemic. Funding: US National Cancer Institute.
RESUMEN
INTRODUCTION AND OBJECTIVES: In clinical trials, patients with hepatitis C virus (HCV) genotype (GT)1a infection and baseline resistance-associated substitutions (RASs) at amino acid positions 28, 30, 31, or 93 receiving elbasvir/grazoprevir for 12 weeks achieved lower rates of sustained virologic response (SVR) than those without baseline RASs. SVR rates in patients with RASs were improved when elbasvir/grazoprevir treatment duration was extended from 12 to 16 weeks and administered concomitantly with ribavirin. MATERIALS AND METHODS: This was a retrospective, observational analysis using electronic health record abstraction. Patients with HCV GT1a infection and RASs at positions 28, 30, 31, or 93 who were prescribed 16 weeks of elbasvir/grazoprevir and ≥ 1 prescription for ribavirin were included. SVR was defined as HCV RNA below the lower limit of quantification ≥ 70 days after end of treatment. RESULTS: The primary analysis included patients with baseline RASs at positions 30, 31, or 93 (n = 76); a secondary analysis included patients with RASs at positions 28, 30, 31, or 93 (n = 93). SVR was achieved by 77.6% (59/76) of patients in the primary analysis and 80.6% (75/93) of those in the secondary analysis. Of the 18 (19.4%) patients in the secondary cohort who failed to achieve SVR, 8 relapsed (4 with treatment-emergent NS5A substitutions) and 10 did not have viral sequencing to distinguish relapse from reinfection. CONCLUSIONS: This analysis highlights the opportunities in leveraging real-world data to further understand treatment outcomes in smaller, discrete subgroups of patients with HCV infection who cannot be thoroughly evaluated in clinical trials.
Asunto(s)
Hepatitis C Crónica , Hepatitis C , Humanos , Ribavirina/uso terapéutico , Hepacivirus/genética , Antivirales/efectos adversos , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Quimioterapia Combinada , Recurrencia Local de Neoplasia/inducido químicamente , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Respuesta Virológica Sostenida , ARN Viral/genética , Genotipo , Farmacorresistencia Viral/genéticaRESUMEN
The comparative effectiveness of tenofovir (TDF) vs entecavir (ETV) in reducing the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) remains unclear. Data from a retrospective Korean cohort study published by Choi et al1 initially suggested a lower-than-expected incidence of HCC in patients on long-term TDF. However, additional studies from Korea did not show a statistically significant difference in HCC incidence rate between TDF and ETV groups,2,3 and subsequent studies reported mixed results ranging from no association or a slight advantage for TDF.4 Most of these studies examined Asian patients from Korea, Taiwan, and China.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B Crónica , Neoplasias Hepáticas , Humanos , Tenofovir/uso terapéutico , Carcinoma Hepatocelular/etiología , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Virus de la Hepatitis B , Antivirales/uso terapéutico , Estudios de Cohortes , Estudios Retrospectivos , Neoplasias Hepáticas/etiología , Resultado del TratamientoRESUMEN
OBJECTIVE: People living with HIV have high rates of obesity and obesity-related comorbidities. Our study sought to evaluate weight trajectory in a retrospective cohort of people living with HIV and matched HIV-negative veterans (controls) and to evaluate risk factors for weight gain. METHODS: This was a retrospective database analysis of data extracted from the VA Corporate Data Warehouse that included people living with HIV (n = 22 421) and age-matched HIV-negative controls (n = 63 072). The main outcomes were baseline body weight and weight change from baseline at 1, 2, and 5 years after diagnosis (baseline visit for controls). RESULTS: Body weight at baseline was lower in people living with HIV than in controls. People living with HIV on antiretroviral therapy (ART) gained more weight than did controls. In a sub-analysis of ART-exposed people living with HIV, age >50 years, African American race, body mass index (BMI) <25, CD4 ≤200, and HIV diagnosis year after 2000 were associated with more weight gain at year 1. Nucleoside reverse transcriptase inhibitors (NRTI) plus non-NRTIs (NNRTIs) were associated with less weight gain than NRTIs plus protease inhibitors, NRTIs plus integrase inhibitors, or NRTIs plus other agents at year 1. CONCLUSIONS: Among US veterans, those living with HIV had lower rates of obesity than age-matched HIV-negative controls; however, primarily in the first 2 years after starting ART, people living with HIV gained more weight than did controls.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Veteranos , Humanos , Persona de Mediana Edad , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Fármacos Anti-VIH/uso terapéutico , Peso Corporal , Obesidad/complicaciones , Obesidad/epidemiología , Aumento de Peso , Inhibidores de la Transcriptasa Inversa/uso terapéuticoRESUMEN
Increasing rates of human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) have largely offset declines in tobacco-associated head and neck squamous cell carcinoma (HNSCC) at non-OPC sites. Host immunity is an important modulator of HPV infection, persistence, and clearance, and also of immune evasion in both virally- and nonvirally-driven cancers. However, the association between collective known cancer-related immune gene variants and HNSCC susceptibility has not been fully characterized. Here, we conducted a genetic association study in the multiethnic Veterans Affairs Million Veteran Program cohort, evaluating 16,050 variants in 1,576 immune genes in 4,012 HNSCC cases (OPC = 1,823; non-OPC = 2,189) and 16,048 matched controls. Significant polymorphisms were further examined in a non-Hispanic white (NHW) validation cohort (OPC = 1,206; non-OPC = 955; controls = 4,507). For overall HNSCC susceptibility in NHWs, we discovered and validated a novel 9q31.1 SMC2 association and replicated the known 6p21.32 HLA-DQ-DR association. Six loci/genes for overall HNSCC susceptibility were selectively enriched in African-Americans (6p21.32 HLA-G, 9q21.33 GAS1, 11q12.2 CD6, 11q23.2 NCAM1/CD56, 17p13.1 CD68, 18q22.2 SOCS6); all 6 genes function in antigen-presenting regulation and T-cell activation. Two additional loci (10q26 DMBT1, 15q22.2 TPM1) were uncovered for non-OPC susceptibility, and three loci (11q24 CRTAM, 16q21 CDH5, 18q12.1 CDH2) were identified for HPV-positive OPC susceptibility. This study underscores the role of immune gene variants in modulating susceptibility for both HPV-driven and non-HPV-driven HNSCC. Additional large studies, particularly in racially diverse populations, are needed to further validate the associations and to help elucidate other potential immune factors and mechanisms that may underlie HNSCC risk. SIGNIFICANCE: Several inherited variations in immune system genes are significantly associated with susceptibility to head and neck cancer, which could help improve personalized cancer risk estimates.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Veteranos , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Inmunogenética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias Orofaríngeas/complicaciones , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Virus del Papiloma Humano , Proteínas de Unión al Calcio , Proteínas de Unión al ADN , Proteínas Supresoras de Tumor , Proteínas Supresoras de la Señalización de CitocinasRESUMEN
BACKGROUND & AIMS: Currently, there is no consistent information on the course of fibrosis-4 (FIB-4) score changes in non-alcoholic fatty liver disease (NAFLD) or their association with subsequent risk of cirrhosis and/or hepatocellular carcinoma (HCC). Thus, we aimed to evaluate the association between longitudinal changes in FIB-4 and subsequent risk of HCC and a composite endpoint of cirrhosis and HCC in patients with NAFLD. METHODS: We conducted a retrospective cohort study of patients with NAFLD seen in 130 Veterans Administration hospitals between 1/1/2004-12/31/2008, with follow-up through to 12/31/2018. We calculated FIB-4 longitudinally and categorized patients based on risk of advanced fibrosis (low-risk FIB-4 <1.45, indeterminate-risk FIB-4 1.45-2.67, and high-risk FIB-4 >2.67). We used landmark Fine-Gray competing risks models to determine the effects of change in FIB-4 between NAFLD diagnosis date and 3-year landmark time on the subsequent risk of HCC and a composite endpoint. RESULTS: Among the 202,319 patients with NAFLD in the 3-year landmark analysis, 473 progressed to HCC at an incidence rate of 0.28 per 1,000 person years (PY) (95% CI 0.26-0.30). The incidence rate of the composite endpoint was 1.31 per 1,000 PY (95% CI 1.25-1.37). At baseline, 74.7%, 21.4%, and 3.8% of patients had a low, indeterminate, and high FIB-4, respectively. Compared to patients who were at stable low FIB-4 at both time points, the risk of HCC and that of the composite endpoint was higher for all other subgroups with the highest risk in patients with persistently high FIB-4 (HCC adjusted sub-distribution hazard ratio 57.7, 95% CI 40.5-82.2 and composite endpoint hazard ratio 28.6, 95% CI 24.6-33.2). CONCLUSION: Longitudinal changes in FIB-4 were strongly associated with progression to cirrhosis and HCC. IMPACT AND IMPLICATIONS: Tools to stratify the risk of HCC development in patients with NAFLD are currently lacking. The fibrosis-4 (FIB-4) score is a widely available non-invasive test for liver fibrosis, a primary determinant of the development of cirrhosis and HCC. In a large retrospective cohort of patients with NAFLD, we found that serial changes in FIB-4 over time were strongly associated with progression to cirrhosis and HCC. Integrating serial measurements of non-invasive tests for fibrosis into the care pathway for patients with NAFLD could help tailor HCC risk prevention.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Carcinoma Hepatocelular/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estudios Retrospectivos , Neoplasias Hepáticas/patología , Factores de Riesgo , Cirrosis Hepática/diagnósticoRESUMEN
INTRODUCTION: There are limited data on the effect and evolution of risk factors for hepatocellular carcinoma (HCC) in patients with virologically cured hepatitis C virus (HCV) infection. METHODS: We conducted a retrospective cohort study of patients with HCV who achieved sustained virological response with direct-acting antivirals from 130 Veterans Administration hospitals during 2014-2018, followed through 2021. Cox proportional hazards models were constructed at 3 landmark times (baseline and 12 and 24 months after sustained virological response) to examine associations between demographic, clinical, and behavioral factors and HCC risk, stratified by cirrhosis status. RESULTS: Among 92,567 patients (32% cirrhosis), 3,247 cases of HCC were diagnosed during a mean follow-up of 2.5 years. In patients with cirrhosis, male sex (hazard ratios [HR]: 1.89, 1.93, and 1.99), cirrhosis duration ≥5 years (HR: 1.71, 1.79, and 1.34), varices (HR: 1.73, 1.60, and 1.56), baseline albumin (HR: 0.48, 0.47, and 0.49), and change in albumin (HR: 0.82 and 0.90) predicted HCC risk at each landmark time. HCV genotype 3, previous treatment, bilirubin, smoking, and race influenced HCC risk at baseline, but their effects attenuated over time. In patients without cirrhosis, diabetes (HR: 1.54, 1.42, and 1.47) and hypertension (HR: 1.59, 1.65, and 1.74) were associated with HCC risk at all landmark times. Changes in fibrosis-4 scores over time were associated with HCC risk both in patients with and without cirrhosis. DISCUSSION: Risk factors for HCC were different in patients with and without cirrhosis and some also evolved during follow-up. These factors can help with risk stratification and HCC surveillance decisions in patients with cured HCV.