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1.
Am J Gastroenterol ; 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39364887

RESUMEN

OBJECTIVE: Optimal management of patients with chronic hepatitis B (CHB) requires surveillance for hepatocellular carcinoma (HCC) and identification of antiviral-therapy candidates, but few dedicated CHB-surveillance models have been described. Kaiser Permanente Northern California (KPNC) developed a systematic CHB surveillance-and-management program in 2012. We report the results of the program's performance over the initial 8-year period. METHODS: We conducted a retrospective cohort study of all patients with CHB meeting guideline criteria for HCC surveillance. Eligible patients were invited into the KPNC Liver Care Program (LCP), wherein patients receive reminders to obtain semiannual laboratory and imaging surveillance, which are reviewed by nurse practitioners. Treatment-eligible patients are provided antiviral medications. RESULTS: Since its inception, 14,630 patients met study criteria and 9,373 (64.1%) enrolled in the LCP. Adherence to imaging recommendations was higher in the LCP-managed group (41.5% of patients in the LCP received ≥80% of recommended imaging compared to 10.9% among patients not enrolled (risk ratio = 3.8; p<.001)). Approximately 63% of treatment-eligible patients in both groups received medication, though full-adherence rates were higher in patients managed in the LCP (72.3% vs 63.4%, respectively, p<.001). Among the 197 patients who developed HCC, recommended surveillance imaging was performed more frequently among LCP-managed patients (71.4% vs. 53.8%, respectively, p<.05) who were also significantly more likely to be diagnosed at Barcelona Clinic Liver Cancer Stage 0/A (95.9% vs. 74.6%; p<.001). CONCLUSIONS: In this integrated healthcare system, a systematic program for surveilling and managing patients with CHB appeared beneficial for both process and clinical endpoints.

2.
Gastro Hep Adv ; 3(6): 871-879, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39280914

RESUMEN

Background and Aims: Studies show decreased rates of poor outcomes after hepatitis C virus (HCV) cure. However, there are no data comparing risk of poor outcomes to that of HCV never infected; results that could have implications for those who may not need ongoing specialty follow-up after cure. Methods: Retrospective cohort study conducted among Kaiser Permanente Northern California adults ages 18 and up between 2002 and 2019. Three cohorts were identified: 1) chronic HCV, 2) HCV cured, and 3) every chronic HCV and HCV-cured individual was matched by age, sex and race-ethnicity to 3 HCV negative controls. Outcomes of interest were cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and all-cause mortality. A low-risk group of HCV cured individuals without significant liver disease and/or concomitant liver disease cofactor(s) were identified. Results: We identified 21,184 chronic HCV, 11,950 HCV cure, and 99,402 control individuals. Five-year cumulative incidence of cirrhosis, decompensated cirrhosis, HCC and all-cause mortality was 10% vs 3.6% vs 0.8%, 12% vs 2.6% vs 0.6%, 3.9% vs 1.6% vs 0.07%, and 14% vs 2.8% vs 2.2% for chronic HCV, HCV cure, and control individuals, respectively (log-rank P < .01 for all). Compared to controls, HCV cured low-risk individuals had numerically similar 5-year cumulative incidence of cirrhosis, decompensated cirrhosis, HCC and all-cause mortality (1.2% vs 0.8%, P < .01; 0.9% vs 0.6%, P < .01; 0.5% vs 0.1%, P < .01; 1.7% vs 2.2%, P < .01). Conclusion: HCV cure provides significant health benefits but does not universally return risk of poor outcomes to that of the general population. A simple stratification at the time of HCV cure could identify low-risk individuals who can potentially be discharged from specialty clinics/HCC surveillance.

3.
JAMA Netw Open ; 7(9): e2435066, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39316399

RESUMEN

Importance: Hepatocellular carcinoma (HCC) is the leading oncologic cause of death among patients with cirrhosis, but large studies examining mortality trends are lacking. Objective: To evaluate survival among patients with HCC in one of the largest integrated health care systems in the US. Design, Setting, and Participants: This retrospective cohort study included 3441 adult patients who received a diagnosis of HCC between January 1, 2006, and December 31, 2019, with end of follow-up on December 31, 2020. The study period was further categorized as era 1, defined as 2006 to 2012, and era 2, defined as 2013 to 2019. Statistical analysis was conducted from January 2021 to June 2024. Exposures: Patient demographic characteristics and disease factors. Main Outcomes and Measures: All-cause and HCC-specific mortality were used as primary end points, and survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression analyses were adjusted for age at diagnosis, sex, race and ethnicity, cause of disease, Barcelona Clinic Liver Cancer (BCLC) stage, alpha-fetoprotein level, and treatment type. Results: Of 3441 patients with HCC, 2581 (75.0%) were men, and the median age was 65 years (IQR, 58-73 years). A total of 1195 patients (34.7%) received curative treatment, 1374 (39.9%) received noncurative treatment, and 872 (25.3%) received no treatment. During the study period, 2500 patients (72.7%) experienced all-cause mortality, and 1809 (52.6%) had HCC-specific mortality. In multivariable analysis, being 70 years of age or older (adjusted hazard ratio [AHR], 1.39; 95% CI, 1.22-1.59), male sex (AHR, 1.20; 95% CI, 1.07-1.35), BCLC stage C or D (AHR, 2.40; 95% CI, 2.15-2.67), increasing alpha-fetoprotein level (vs <20 ng/mL; 20-99 ng/mL: AHR, 1.20; 95% CI, 1.04-1.38; ≥1000 ng/mL: AHR, 2.84; 95% CI, 2.45-3.25), noncurative treatment (AHR, 2.51; 95% CI, 2.16-2.90), and no treatment (AHR, 3.15; 95% CI, 2.64-3.76) were associated with higher all-cause mortality, while Asian or Other Pacific Islander race and ethnicity (vs non-Hispanic White; AHR, 0.76; 95% CI, 0.65-0.88) was associated with lower all-cause mortality. Survival improved in diagnosis era 2 (2013-2019; n = 2007) compared with diagnosis era 1 (2006-2012; n = 1434). Conclusions and Relevance: This large, racially and ethnically diverse cohort study of patients with HCC found improving survival over time, especially among individuals with early-stage HCC receiving potentially curative treatments. This study highlights the importance of surveillance for detection of HCC at early stages, particularly among groups at risk for poorer outcomes.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Estados Unidos/epidemiología , Prestación Integrada de Atención de Salud , Modelos de Riesgos Proporcionales
4.
J Infect ; 89(5): 106258, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39216831

RESUMEN

BACKGROUND: Shorter duration therapy for hepatitis C virus (HCV) infection might reduce treatment costs and increase the number of patients treated and cured. We determined factors associated with treatment response after an 8-week sofosbuvir-based therapy and developed a simple model to predict an individual's likelihood of treatment success. METHODS: Among 2907 patients who received ledipasvir/sofosbuvir for 8 weeks, we determined failure rates by demographic and clinical characteristics, and IFNL4-∆G/TT genotype. We estimated the average IFNL4 genotype-related treatment failure rate in major ancestry groups by applying our IFNL4 genotype results to genotype distributions from reference populations. We created a treatment response model based on three personal characteristics. RESULTS: Overall, 4.4% of the patients failed treatment. We observed significantly lower failure rates for persons <50 years (1.6%), females (2.6%), those carrying the IFNL4-TT/TT genotype (1.8%), those with HCV RNA <5.8 log10 copies/mL (2.0%) or HCV genotype-1B infection (2.6%). In a model based on ancestry, age and sex, the predicted probability of treatment failure ranged from 0.5% among females of East Asian ancestry <50 years of age to 8.5% among males of African ancestry age ≥65 years. CONCLUSION: Applying this algorithm at the point-of-care might facilitate HCV elimination, especially in low- and middle-income countries.

5.
JAMA Netw Open ; 7(7): e2421019, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38990573

RESUMEN

Importance: In the US, hepatocellular carcinoma (HCC) has been the most rapidly increasing cancer since 1980, and metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to soon become the leading cause of HCC. Objective: To develop a prediction model for HCC incidence in a cohort of patients with MASLD. Design, Setting, and Participants: This prognostic study was conducted among patients aged at least 18 years with MASLD, identified using diagnosis of MASLD using International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes; natural language processing of radiology imaging report text, which identified patients who had imaging evidence of MASLD but had not been formally diagnosed; or the Dallas Steatosis Index, a risk equation that identifies individuals likely to have MASLD with good precision. Patients were enrolled from Kaiser Permanente Northern California, an integrated health delivery system with more than 4.6 million members, with study entry between January 2009 and December 2018, and follow-up until HCC development, death, or study termination on September 30, 2021. Statistical analysis was performed during February 2023 and January 2024. Exposure: Data were extracted from the electronic health record and included 18 routinely measured factors associated with MASLD. Main Outcome and Measures: The cohort was split (70:30) into derivation and internal validation sets; extreme gradient boosting was used to model HCC incidence. HCC risk was divided into 3 categories, with the cumulative estimated probability of HCC 0.05% or less classified as low risk; 0.05% to 0.09%, medium risk; and 0.1% or greater, high risk. Results: A total of 1 811 461 patients (median age [IQR] at baseline, 52 [41-63] years; 982 300 [54.2%] female) participated in the study. During a median (range) follow-up of 9.3 (5.8-12.4) years, 946 patients developed HCC, for an incidence rate of 0.065 per 1000 person-years. The model achieved an area under the curve of 0.899 (95% CI, 0.882-0.916) in the validation set. At the medium-risk threshold, the model had a sensitivity of 87.5%, specificity of 81.4%, and a number needed to screen of 406. At the high-risk threshold, the model had a sensitivity of 78.4%, a specificity of 90.1%, and a number needed to screen of 241. Conclusions and Relevance: This prognostic study of more than 1.8 million patients with MASLD used electronic health record data to develop a prediction model to discriminate between individuals with and without incident HCC with good precision. This model could serve as a starting point to identify patients with MASLD who may need intervention and/or HCC surveillance.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Femenino , Masculino , Neoplasias Hepáticas/epidemiología , Persona de Mediana Edad , Anciano , Incidencia , California/epidemiología , Adulto , Hígado Graso/epidemiología , Hígado Graso/complicaciones , Pronóstico , Factores de Riesgo , Estudios de Cohortes
6.
Network ; : 1-38, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717192

RESUMEN

Generally, financial investments are necessary for portfolio management. However, the prediction of a portfolio becomes complicated in several processing techniques which may cause certain issues while predicting the portfolio. Moreover, the error analysis needs to be validated with efficient performance measures. To solve the problems of portfolio optimization, a new portfolio prediction framework is developed. Initially, a dataset is collected from the standard database which is accumulated with various companies' portfolios. For forecasting the benefits of companies, a Multi-serial Cascaded Network (MCNet) is employed which constitutes of Autoencoder, 1D Convolutional Neural Network (1DCNN), and Recurrent Neural Network (RNN) is utilized. The prediction output for the different companies is stored using the developed MCNet model for further use. After predicting the benefits, the best company with the highest profit is selected by Integration of Artificial Rabbit and Hummingbird Algorithm (IARHA). The major contribution of our work is to increase the accuracy of prediction and to choose the optimal portfolio. The implementation is conducted in Python platform. The result analysis shows that the developed model achieves 0.89% and 0.56% regarding RMSE and MAE measures. Throughout the analysis, the experimentation of the developed model shows enriched performance.

7.
J Prim Care Community Health ; 15: 21501319241247974, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650519

RESUMEN

OBJECTIVES: Patients with pre-transplant metabolic dysfunction-associated steatohepatitis (MASH) are at high risk of metabolic syndrome (MetS) after liver transplant. While many patients are co-managed by a transplant team, most preventative screening and MetS management may occur in the primary care setting. We aimed to evaluate primary care utilization by MASH liver transplant recipients as well as MetS screening and control. METHODS: We conducted a retrospective chart review that included adults who underwent liver transplant for MASH or cryptogenic cirrhosis at a single institution from January 2010 to December 2016, had available primary care data, and at least 36-months of follow-up post-transplant. Measures included primary care utilization, adherence to screening guidelines, and control of MetS. We used Fischer's exact test to explore the association of primary care utilization with screening and control. RESULTS: A total of 37 patients met inclusion criteria with 366 visits reviewed. The median time to first visit was 68 days post-transplant and patients had a median of 9 total visits. Few patients met screening guidelines for diabetes (8.1%) or hyperlipidemia (10.8%). The percentage of patients with control of obesity, hypertension, diabetes, and hyperlipidemia decreased over the 36-month follow-up period. Primary care utilization was not associated with adherence to screening recommendations for diabetes (P = .141) or hyperlipidemia (P = .103). Higher primary care utilization was not associated with control of hypertension (P = .107), diabetes (P = .871), or hyperlipidemia (P = .999). CONCLUSION: More research is needed to investigate barriers to screening and management of MetS conditions in this high-risk patient population in the primary care setting as well as to optimize post-transplant care coordination.


Asunto(s)
Trasplante de Hígado , Síndrome Metabólico , Atención Primaria de Salud , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tamizaje Masivo/métodos , Adulto , Anciano , Receptores de Trasplantes , Aceptación de la Atención de Salud/estadística & datos numéricos , Hígado Graso , Adhesión a Directriz/estadística & datos numéricos , Hiperlipidemias
8.
Am J Gastroenterol ; 119(8): 1506-1514, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38334275

RESUMEN

INTRODUCTION: Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes. METHODS: In this retrospective cohort study, we assessed preinclusion and postinclusion HCC surveillance patterns among 597 patients with hepatitis C virus cirrhosis enrolled in a program at an integrated health system between 2013 and 2020. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre-enrollment and postenrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging examination (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan-Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality. RESULTS: The surveillance program significantly improved surveillance completion (77.6% vs 5.0%, P < 0.001) and proportion time covered (80.9% vs 15.8%, P < 0.001). Compared with prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs 44.8%, P < 0.001), early-stage (85.2% vs 44.8%, P < 0.001), with smaller maximum diameter (median 2.3 vs 3.2 cm), and more likely to undergo curative therapy (92.5% vs 72.4% P = 0.010). Survival was improved compared with prevalent cases hazard ratio (HR) 0.23 (0.11-0.51) after adjusting for age and Model for End Stage Liver Disease score. DISCUSSION: Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with hepatitis C virus cirrhosis. These findings may inform similar interventions by other healthcare systems.


Asunto(s)
Carcinoma Hepatocelular , Cirrosis Hepática , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Cirrosis Hepática/epidemiología , Anciano , Prestación Integrada de Atención de Salud , Detección Precoz del Cáncer/métodos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/epidemiología , Vigilancia de la Población , Hepatitis C/complicaciones , Hepatitis C/epidemiología
9.
ACS Omega ; 8(36): 32294-32310, 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37720748

RESUMEN

Shape memory-assisted self-healing polymers have drawn attention over the past few years owing to their interdisciplinary and wide range of applications. Self-healing and shape memory are two approaches used to improve the applicability of polymers in the biomedical field. Combining both these approaches in a polymer composite opens new possibilities for its use in biomedical applications, such as the "close then heal" concept, which uses the shape memory capabilities of polymers to bring injured sections together to promote autonomous healing. This review focuses on using shape memory-assisted self-healing approaches along with their respective affecting factors for biomedical applications such as tissue engineering, drug delivery, biomaterial-inks, and 4D printed scaffolds, soft actuators, wearable electronics, etc. In addition, quantification of self-healing and shape memory efficiency is also discussed. The challenges and prospects of these polymers for biomedical applications have been summarized.

10.
Liver Transpl ; 29(10): 1041-1049, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37159217

RESUMEN

In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Biomarcadores de Tumor , Estudios Prospectivos , alfa-Fetoproteínas/análisis , Biomarcadores , Protrombina
11.
Curr Gastroenterol Rep ; 24(1): 1-9, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35142988

RESUMEN

PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the United States (U.S.).1 The purpose of this review is to highlight published models that predict development of HCC and estimate risk of HCC recurrence after treatments. RECENT FINDINGS: There have been several models created for both de novo HCC and HCC recurrence, with the more recent models using a combination of age, sex, decompensation, and laboratory values (platelet count, albumin, bilirubin), and liver disease etiology to predict both 5 and 10-year HCC incidence. For chronic hepatitis C, sustained virologic response has been a useful component of understanding HCC risk reduction. BMI and diabetes have been utilized in non-alcoholic fatty liver disease (NAFLD) models to predict HCC risk. For HCC recurrence after treatment (for both surgical resection and liver transplant), tumor size and number, vascular invasion, alpha-fetoprotein (AFP) and neutrophil to lymphocyte ratio (NLR) are all components of HCC recurrence risk models. Although numerous HCC risk prediction models have been established over the last several years, challenges remain including how to best incorporate these models into clinical practice, improve surveillance for NAFLD-HCC development, and determine timing and duration of post-resection recurrence surveillance.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/terapia , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Respuesta Virológica Sostenida
12.
Sci Rep ; 11(1): 22304, 2021 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-34785708

RESUMEN

The article investigates electrically active ceramic composite of [Formula: see text] (HAP) and [Formula: see text] (BST) for biomedical applications. The study is a systematic blend of the materials science aspect of composites with a special focus on the dielectric and biological properties and their relationships. The article emphasized primarily extracting the dielectric constant ([Formula: see text] of the specimens (that lay in the range of 3-65) and related them to microstructural properties like the grain size and at.% of BST. A broad outlook on the importance of [Formula: see text] in determining the suitability of bioceramics for clinical applications is presented. Bioactivity analysis of the specimens led to probing the surface charges (that were negative), and it was found crucial to the growth of dense apatite layers. Furthermore, the cytocompatibility of the specimens displayed cell viability above 100% for Day 1, which increased substantially for Day 3. To reveal other biological properties of the composites, protein adsorption studies using bovine serum albumin (BSA) and fetal bovine serum (FBS) was carried out. Electrostatic interactions govern the adsorption, and the mathematical dependence on surface charges is linear. The protein adsorption is also linearly correlated with the [Formula: see text], intrinsic to the biomaterials. We delve deeper into protein-biomaterials interactions by considering the evolution of the secondary structure of BSA adsorbed into the specimens. Based on the investigations, 20 at.% HAP-80 at.% BST (20H-80B) was established as a suitable composite comprising the desired features of HAP and BST. Such explorations of electrical and biological properties are interesting for modulating the behavior of bioceramic composites. The results project the suitability of 20H-80B for designing electrically active smart scaffolds for the proposed biomedical applications and are expected to incite further clinical trials.


Asunto(s)
Materiales Biocompatibles/química , Cerámica/química , Ingeniería de Tejidos , Adsorción , Albúmina Sérica Bovina/química
13.
Cancer Epidemiol Biomarkers Prev ; 30(12): 2188-2196, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34583968

RESUMEN

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a leading cause of liver cancer. The association of HCV infection with extrahepatic cancers, and the impact of direct-acting antiviral (DAA) treatment on these cancers, is less well known. METHODS: We conducted a cohort study in a healthcare delivery system. Using electronic health record data from 2007 to 2017, we determined cancer incidence, overall and by type, in people with HCV infection and by DAA treatment status. All analyses included comparisons with a reference population of people without HCV infection. Covariate-adjusted Poisson models were used to estimate incidence rate ratios. RESULTS: 2,451 people with HCV and 173,548 people without HCV were diagnosed with at least one type of cancer. Compared with people without HCV, those with HCV were at higher risk for liver cancer [adjusted incidence rate ratio (aIRR) = 31.4, 95% confidence interval (CI) = 28.9-34.0], hematologic cancer (aIRR = 1.3, 95% CI = 1.1-1.5), lung cancer (aIRR = 1.3, 95% CI = 1.2-1.5), pancreatic cancer (aIRR = 2.0, 95% CI = 1.6-2.5), oral/oropharynx cancer (aIRR = 1.4, 95% CI = 1.1-1.8), and anal cancer (aIRR = 1.6, 95% CI = 1.1-2.4). Compared with people without HCV, the aIRR for liver cancer was 31.9 (95% CI = 27.9-36.4) among DAA-untreated and 21.2 (95% CI = 16.8-26.6) among DAA-treated, and the aIRR for hematologic cancer was 1.5 (95% CI = 1.1-2.0) among DAA-untreated and 0.6 (95% CI = 0.3-1.2) among DAA-treated. CONCLUSIONS: People with HCV infection were at increased risk of liver cancer, hematologic cancer, and some other extrahepatic cancers. DAA treatment was associated with reduced risk of liver cancers and hematologic cancers. IMPACT: DAA treatment is important for reducing cancer incidence among people with HCV infection.


Asunto(s)
Hepatitis C Crónica/epidemiología , Neoplasias/epidemiología , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/etiología , Estudios Retrospectivos , Medición de Riesgo
14.
Environ Res ; 198: 111309, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33984307

RESUMEN

SARS-CoV-2 virus and other pathogenic microbes are transmitted to the environment through contacting surfaces, which need to be sterilized for the prevention of COVID-19 and related diseases. In this study, a prototype of a cost-effective sterilization box is developed to disinfect small items. The box utilizes ultra violet (UV) radiation with heat. For performance assessment, two studies were performed. First, IgG (glycoprotein, a model protein similar to that of spike glycoprotein of SARS-COV-2) was incubated under UV and heat sterilization. An incubation with UV at 70 °C for 15 min was found to be effective in unfolding and aggregation of the protein. At optimized condition, the hydrodynamic size of the protein increased to ~171 nm from ~5 nm of the native protein. Similarly, the OD280 values also increased from 0.17 to 0.78 indicating the exposure of more aromatic moieties and unfolding of the protein. The unfolding and aggregation of the protein were further confirmed by the intrinsic fluorescence measurement and FTIR studies, showing a 70% increase in the ß-sheets and a 22% decrease in the α-helixes of the protein. The designed box was effective in damaging the protein's native structure indicating the effective inactivation of the SARS-COV-2. Furthermore, the incubation at 70 °C for 15 min inside the chamber resulted in 100% antibacterial efficacy for the clinically relevant E.coli bacteria as well as for bacteria collected from daily use items. It is the first detailed performance study on the efficacy of using UV irradiation and heat together for disinfection from virus and bacteria.


Asunto(s)
COVID-19 , Rayos Ultravioleta , Calor , Humanos , SARS-CoV-2 , Inactivación de Virus
15.
Mater Sci Eng C Mater Biol Appl ; 116: 111163, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32806279

RESUMEN

Exclusive magnetocaloric properties of orthoferrites offer advantages for their application in the magnetic hyperthermia as well as imaging applications. In the present study, the effect of yttrium concentration on the magnetic characteristics of the iron oxide based nanomaterials was analyzed to assess their potential for the hyperthermia applications. The Sol-gel method was used to synthesize the Yttrium Iron Garnet (YIG) based nanoparticles, using different molar ratios of Fe and Y precursors, followed by the calcination at 900, 1000 and 1100 °C. XRD analysis determined the formation of the pure phase of yttrium iron garnet Y3Fe5O12 (YIG) at 0.5 molar ratio of yttrium at all the calcination temperatures and pure phase of yttrium iron perovskite YFeO3 (YIP) for 1 molar ratio of yttrium at 1000 and 1100 °C. The mean particle size was observed in the range of 100 to 400 nm. The magnetic characterization studies showed the highest saturation magnetization for the sample containing 0.5 molar ratio of the yttrium calcinated at 1000 °C. The magnetization values were linearly related to the contents of YIG phases in the synthesized samples. Induction heating of YIG resulted in the hyperthermia temperature (42 to 44 °C) in 13 min with the SAR values 114.65 W/g at 1 mg/ml. The prepared samples showed no in-vitro toxic effects on the MG63 cells (>90% cell viability). In addition, in-vitro treatment at hyperthermia temperature for 15 min reduced cell viability of cancer cells (A549) to 55%, while no toxic effect was observed on MG 63 cells. The present study postulates Yttrium Iron Garnet as an effective therapeutic agent for hyperthermia cancer treatment.


Asunto(s)
Hierro , Itrio , Humanos , Hipertermia , Magnetismo , Tamaño de la Partícula
16.
Front Chem ; 8: 416, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32528930

RESUMEN

Poly(N-substituted glycine) "peptoids" are an interesting class of peptidomimics that can resist proteolysis and mimic naturally found antimicrobial peptides (AMPs), which exhibit wide spectrum activity against bacteria. This work investigates the possibility of modifying peptoid AMP mimics (AMPMs) with aliphatic lipid "tails" to generate "lipopeptoids" that can assemble into micellar nanostructures, and evaluates their antimicrobial activities. Two families of AMPMs with different distributions of hydrophobic and cationic residues were employed-one with a uniform repeating amphiphilicity, the other with a surfactant-like head-to-tail amphiphilicity. To further evaluate the interplay between self-assembly and activity, the lipopeptoids were variously modified at the AMPM chain ends with a diethylene glycol (EG2) and/or a cationic group (Nlys-Nlys dipeptoid) to adjust amphiphilicity and chain flexibility. Self-assembly was investigated by critical aggregation concentration (CAC) fluorescence assays and dynamic light scattering (DLS). The structure of a key species was also verified by small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM). To screen for antibacterial properties, we measured the minimum inhibitory concentrations (MIC) against S. aureus, E. coli, and P. aeruginosa. We found that certain combinations of lipid tail and AMPM sequences exhibit increased antibacterial activity (i.e., decreased MICs). Perhaps counter-intuitively, we were particularly interested in increased MICs in combination with low CACs. Concealing antimicrobial interactions due to packing of AMPMs in nano-assemblies could pave the way to AMPMs that may be "inert" even if unintentionally released and prevent microbes from gaining resistance to the lipopeptoids. Overall, incorporation of EG2 significantly improved lipopeptoids packing while the hydrophobic tail length was found to have a major influence over the MIC. One particular sequence, which we named C15-EG2-(kss)4, exhibited a very low CAC of 34 µM (0.0075 wt.%) and a significantly increased MIC above values for the unmodified AMPM. With the sequence design trends uncovered from this study, future work will focus on discovering more species such as C15-EG2-(kss)4 and on investigating release mechanisms and the potency of the released lipopeptoids.

17.
Open Forum Infect Dis ; 7(2): ofaa044, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32128339

RESUMEN

Among 25 291 and 4 921 830 people with and without hepatitis C, life expectancy at age 20 increased 1.8 years and 0.3 years from the interferon to interferon-free era, respectively. Increases were highest for racial and/or ethnic minority groups with hepatitis C.

19.
Clin Gastroenterol Hepatol ; 18(2): 511-513, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31009792

RESUMEN

Strategic planning for hepatitis C virus (HCV) screening and treatment requires up-to-date information on the prevalence of HCV spontaneous clearance. Published estimates of HCV spontaneous clearance range from 15% to 60%.1-3 We conducted an observational study over 20 years to evaluate trends in the prevalence of HCV spontaneous clearance. Our goals were to estimate the proportion of HCV-antibody-positive patients who were viremic, and to identify factors associated with viremia, thus facilitating prediction of the number of patients needing treatment.


Asunto(s)
Hepacivirus , Hepatitis C , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C , Humanos , Prevalencia , Viremia
20.
Int J STD AIDS ; 30(7): 689-695, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31046611

RESUMEN

U.S. guidelines recommend that patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) be prioritized for HCV treatment with direct-acting antiviral agents (DAAs), but the high cost of DAAs may contribute to disparities in treatment uptake and outcomes. We evaluated DAA initiation and effectiveness in HIV/HCV-coinfected patients in a U.S.-based healthcare system during October 2014-December 2017. Of 462 HIV/HCV-coinfected patients, 276 initiated DAAs (70% cumulative proportion treated over three years). Lower likelihood of DAA initiation was observed among patients with Medicare (government-sponsored insurance) versus commercial insurance (adjusted rate ratio [aRR] = 0.62, 95% CI = 0.46-0.84), patients with drug abuse diagnoses (aRR = 0.72, 95% CI = 0.54-0.97), patients with CD4 cell count <200 cells/µl versus ≥500 (aRR = 0.45, 95% CI = 0.23-0.91), and patients without prior HCV treatment (aRR = 0.68, 95% CI = 0.48-0.97). There were no significant differences in DAA initiation by age, gender, race/ethnicity, socioeconomic status, HIV transmission risk, alcohol use, smoking, fibrosis level, HIV RNA levels, antiretroviral therapy use, hepatitis B infection, or number of outpatient visits. Ninety-five percent of patients achieved sustained virologic response (SVR). We found little evidence of sociodemographic disparities in DAA initiation among HIV/HCV-coinfected patients, and SVR rates were high. Efforts are needed to increase DAA uptake among coinfected Medicare enrollees, patients with drug abuse diagnoses, patients with low CD4 cell count, and patients receiving first-time HCV treatment.


Asunto(s)
Antivirales/uso terapéutico , Coinfección/epidemiología , Prestación Integrada de Atención de Salud , Infecciones por VIH/tratamiento farmacológico , Hepacivirus/aislamiento & purificación , Hepatitis C/tratamiento farmacológico , Seguro de Salud/estadística & datos numéricos , Adulto , Anciano , Antivirales/economía , Coinfección/virología , Femenino , Infecciones por VIH/epidemiología , Hepacivirus/genética , Hepatitis C/epidemiología , Humanos , Masculino , Medicare , Persona de Mediana Edad , Estudios Retrospectivos , Factores Socioeconómicos , Respuesta Virológica Sostenida , Resultado del Tratamiento , Estados Unidos
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