192 results on '"Nunes, David"'
Search Results
152. Molecular characterization of a major high molecular weight mucin from human sublingual gland
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Troxler, Robert F., primary, Iontcheva, Iveta, additional, Oppenheim, Frank G., additional, Nunes, David P., additional, and Offner, Gwynneth D., additional
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- 1997
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153. Interaction of bovine gallbladder mucin and calcium-binding protein: Effects on calcium phosphate precipitation
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Afdhal, Nezam H., primary, Ostrow, J.Donald, additional, Koehler, Ronald, additional, Niu, Niu, additional, Groen, Albert K., additional, Veis, Arthur, additional, Nunes, David P., additional, and Offner, Gwynneth D., additional
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- 1995
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154. Mucin-vesicle interactions in model bile: Evidence for vesicle aggregation and fusion before cholesterol crystal formation
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Afdhal, Nezam H., primary, Niu, Niu, additional, Nunes, David P., additional, Bansil, Rama, additional, Cao, Xing Xiang, additional, Gantz, Donald, additional, Small, Donald M., additional, and Offner, Gwynneth D., additional
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- 1995
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155. Pathogenesis of cholesterol gallstones
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Offner, Gwynneth D., primary and Nunes, David P., additional
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- 1994
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156. lnterleukin-6 Is Associated with Noninvasive Markers of Liver Fibrosis in HIV-infected Patients with Alcohol Problems.
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Fuster, Daniel, Tsui, Judith I., Cheng, Debbie M., Quinn, Emily K., Armah, Kaku A., Nunes, David, Freiberg, Matthew S., and Samet, Jeffrey H.
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Both HIV and hepatitis C virus (HCV) cause chronic inflammation and alterations in serum inflammatory cytokines. The impact of inflammatory cytokines on liver fibrosis is not well understood. We studied the association between interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-a and liver fibrosis in HIV-infected patients with current or past alcohol problems (CAGE >2 or physician investigator diagnosis). Liver fibrosis was estimated with FIB-4 (FIB-4 <1.45 defined the absence of liver fibrosis and FIB-4 >3.25 defined advanced fibrosis). Logistic regression was used to assess the association between cytokines and fibrosis, adjusting for age, sex, CD4, HIV RNA, current antiretroviral therapy, body mass index, and HCV. Secondary analyses explored whether the association between HCV and liver fibrosis was mediated by these cytokines. Participants (n = 308) were all HIV-infected; 73% were male with a mean age of 42 years; half had detectable HCV-RNA, 60.7% had an absence of liver fibrosis, and 10.1% had advanced fibrosis. In models that adjusted for each cytokine separately, higher levels of IL-6 were significantly associated with an absence of fibrosis [adjusted OR (95% CI): 0.43 (0.19, 0.98), p = 0.05] and were borderline significant for advanced fibrosis [ad-justed OR (95% CI): 8.16 (0.96, 69.54), p = 0.055]. In the final model, only higher levels of IL-6 remained significantly associated with advanced liver fibrosis [adjusted OR (95% CI): 11.78 (1.17, 118.19), p = 0.036], Adjustment for inflammatory cytokines attenuated the adjusted OR for the association between HCV and fibrosis in the case of IL-6 [for the absence of fibrosis from 0.32 (0.17, 0.57) p< 0.01 to 0.47 (0.23, 0.96) p = 0.04; and for advanced fibrosis from 7.22 (2.01, 25.96) p< 0.01 to 6.62 (1.20, 36.62) p = 0.03], suggesting IL-6 may be a partial mediator of the association between HCV and liver fibrosis. IL-6 was strongly and significantly as-sociated with liver fibrosis in a cohort of HIV-infected patients with alcohol problems. IL-6 may be a useful predictive marker for liver fibrosis for HIV-infected patients. [ABSTRACT FROM AUTHOR]
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- 2013
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157. Noninvasive Markers of Liver Fibrosis Are Highly Predictive of Liver-Related Death in a Cohort of HCV-Infected Individuals With and Without HIV Infection.
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Nunes, David, Fleming, Catherine, Offner, Gwynneth, Craven, Donald, Fix, Oren, Heeren, Timothy, Koziel, Margaret J., Graham, Camilla, Tumilty, Sheila, Skolnik, Paul, Stuver, Sherri, Horsburgh, C. Robert, and Cotton, Deborah
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LIVER , *FIBROSIS , *AMINOTRANSFERASES , *HIV infections , *RESEARCH - Abstract
OBJECTIVES:Noninvasive markers of liver fibrosis correlate with the stage of liver fibrosis, but have not been widely applied to predict liver-related mortality.METHODS:We assessed the ability of two indices of liver fibrosis, aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fib-4, and two markers of extracellular matrix metabolism, hyaluronic acid (HA) and YKL40, to predict liver mortality in a prospective cohort of hepatitis C virus (HCV)-infected individuals with and without HIV coinfection. These were compared with two established prognostic scores, the Child–Pugh–Turcotte (CPT) and model of end-stage liver disease (MELD) scores.RESULTS:A total of 303 subjects, of whom 207 were HIV positive at study entry, were followed up for a mean period of 3.1 years. There were 33 deaths due to liver disease. The ability of each test and score to predict 3-year liver mortality was expressed as the area under the receiver operator curve. The area under the receiver operator curve 95% confidence intervals were: HA 0.92 (0.86–0.96), CPT 0.91 (0.79–0.96), APRI 0.88 (0.80–0.93), Fib-4 0.87 (0.77–0.92), MELD 0.84 (71–0.91). In multivariate analyses HA, APRI, and fib-4 were independent predictors of mortality when included in models with MELD or CPT.CONCLUSION:Noninvasive markers of liver fibrosis are highly predictive of liver outcome in HCV-infected individuals with and without HIV coinfection. These markers seem to have a prognostic value independent of CPT and MELD. [ABSTRACT FROM AUTHOR]
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- 2010
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158. Pharmacist-Managed Helicobacter pyloriTreatment Service Within a Gastroenterology Clinic: Workflow and Real-World Experiences
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Bhat, Shubha and Nunes, David
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Background Treatment eradication rates of Helicobacter pylori, a gastrointestinal infection, are 70% to 90% in clinical studies but lower in real-world settings. Potential barriers include multidrug regimen complexity or prescribing/administration errors. A pharmacist-managed H pyloritreatment service was implemented to address these barriers and optimize treatment outcomes. The clinical pharmacist provided 2 services: (1) treatment education and monitoring for treatment-naïve patients and (2) treatment initiation, education, and monitoring for treatment-experienced patients.Objective We aimed to evaluate the impact of a pharmacist-managed H pyloritreatment service within a gastroenterology clinic.Methods We conducted a retrospective observational cohort study of all patients referred to and seen in the pharmacist-managed H pyloritreatment service from July 10, 2019, to December 31, 2020. Patient demographics, prior treatment history, course(s) of treatment prescribed, frequency of follow-ups, and outcomes posttreatment were collected.Results The clinical pharmacist managed 60 referrals for 55 unique patients over a mean of 5 ± 2 visits. Five patients failed H pyloritreatment and were re-referred. Identified barriers included prescribing/dispensing and administration errors. Posttreatment, 38 referrals tested for H pylorieradication, of which 100% of treatment-naïve patients and 69% of treatment-experienced patients were cured, and 13 (22%) referrals were lost to follow-up.Conclusion and Relevance This study described and assessed the impact of a pharmacist-managed H pyloritreatment service in a gastroenterology clinic, in which various barriers were effectively addressed to optimize treatment outcomes. Future studies should focus on long-term outcome, impact on health care costs, and patient satisfaction with this service.
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- 2021
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159. Human-in-the-Loop Cyber-Physical-Systems based on Smartphones
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Nunes, David Sousa and Silva, Jorge Sá
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Smartphones ,Cyber-Physical Systems ,Humanos na malha de controlo ,Human-in-the-Loop ,Sistemas Ciber-Físicos ,Engenharia e Tecnologia [Domínio/Área Científica] - Abstract
Tese de doutoramento em Ciências e Tecnologias da Informação, apresentada ao Departamento de Engenharia Informática da Faculdade de Ciências e Tecnologia da Universidade de Coimbra Technological devices increasingly become smaller, more mobile, powerful and efficient. However, each time we have to hurdle through unintuitive menus, errors and incompatibilities we become stressed by our technology. As first put forward by the renowned computer scientist Mark Weiser, the ultimate form of computers may be an extension of our subconscious. The ideal computer would be capable of truly understanding people's unconscious actions and desires. Instead of humans adapting to technology and learning how to use it, it would be technology that would adapt to the disposition and uniqueness of each human being. This thesis focuses on the realm of Human-in-the-loop Cyber-Physical Systems (HiTLCPSs). HiTLCPSs infer the users’ intents, psychological states, emotions and actions, using this information to determine the system's behavior. This involves using a large variety of sensors and mobile devices to monitor and evaluate human nature. Therefore, this technology has strong ties with wireless sensor networks, robotics, machine-learning and the Internet of Things. In particular, our work focuses on the usage of smartphones within these systems. It begins by describing a framework to understand the principles and theory of HiTLCPSs. It provides some insights into current research being done on this topic, its challenges, and requirements. Another of the thesis' objectives is to present our innovative taxonomy of human roles, where we attempt to understand how a human may interact with HiTLCPSs and how to best explore this resource. This thesis also describes concrete examples of the practical usage of HiTL paradigms. As such, we included a comprehensive description of our research work and associated prototypes, where the major theoretical concepts behind HiTLCPS were applied and evaluated to specific scenarios. Finally, we discuss our personal view on the future and evolution of these systems. A tecnologia tem vindo a tornar-se cada vez mais pequena, móvel, poderosa e eficiente. No entanto, lidar com menus pouco intuitivos, erros, e incompatibilidades, causa frustração aos seus utilizadores. Segundo o reconhecido cientista Mark Weiser, os computadores do futuro poderão vir a existir como se fossem uma extensão do nosso subconsciente. O computador ideal seria capaz de entender, em toda a sua plenitude, as ações e os desejos inconscientes dos seres humanos. Em vez de serem os humanos a adaptarem-se à tecnologia e a aprender a usá-la, seria a tecnologia a aprender a adaptar-se à disposição e individualidade de cada ser humano. Esta tese foca-se na área dos Human-in-the-loop Cyber-Physical Systems (HiTLCPSs). Os HiTLCPSs inferem as intenções, estados psicológicos, emoções e ações dos seus utilizadores, usando esta informação para determinar o comportamento do sistema ciber-físico. Isto envolve a utilização de uma grande variedade de sensores e dispositivos móveis que monitorizam e avaliam a natureza humana. Assim sendo, esta tecnologia tem fortes ligações com redes de sensores sem fios, robótica, algoritmos de aprendizagem de máquina e a Internet das Coisas. Em particular, o nosso trabalho focou-se na utilização de smartphones dentro destes sistemas. Começamos por descrever uma estrutura para compreender os princípios e teoria associados aos HiTLCPSs. Esta análise permitiu-nos adquirir alguma clareza sobre a investigação a ser feita sobre este tópico, e sobre os seus desafios e requisitos. Outro dos objetivos desta tese é o de apresentar a nossa inovadora taxonomia sobre os papeis do ser humano nos HiTLCPSs, onde tentamos perceber as possíveis interações do ser humano com estes sistemas e as melhores formas de explorar este recurso. Esta tese também descreve exemplos concretos da utilização prática dos paradigmas HiTL. Desta forma, incluímos uma descrição do nosso trabalho experimental e dos protótipos que lhe estão associados, onde os conceitos teóricos dos HiTLCPSs foram aplicados e avaliados em diversos casos de estudo. Por fim, apresentamos a nossa perspetiva pessoal sobre o futuro e evolução destes sistemas. Fundação Luso-Americana para o Desenvolvimento FP7-ICT-2007-2 GINSENG project iCIS project (CENTRO-07-ST24-FEDER-002003) SOCIALITE project (PTDC/EEI-SCR/2072/2014)
160. 602 Liver related morbidity and mortality in patients with hepatitis C virus (HCV) infection: an interim analysis of the impact of HIV coinfection
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Nunes, David, Fleming, Catherine, Christiansen, Demian, Heeren, Timothy, Zamor, Philippe, Graham, Cammy, Koziel, Margaret, Craven, Donald, and Horsburgh, Robert
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- 2003
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161. 203 - Improved Antibody Response to three Additional Hepatitis B Vaccine doses Following Initial Vaccination Failure in Inflammatory Bowel Disease Patients.
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Pratt, Perry, Nunes, David, and Farraye, Francis
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- 2017
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162. Antituberculosis Drugs and Hepatotoxicity.
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Yew, Wing W., Leung, Chi C., Saukkonen, Jussi J., Cohn, David L., Jasmer, Robert M., Sghenker, Steven, Jereb, John A., Nolan, Charles M., Peloquin, Charles A., Gordin, Fred M., Nunes, David, Bernardo, John, Venkataramanan, Raman, and Sterling, Timothy R.
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- 2007
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163. Pope Resources Ltd. Partnership (POPEZ).
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Nunes, David L.
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CORPORATE divestiture ,TIMBER ,REAL property ,INVESTMENTS - Abstract
The article presents an interview with David L. Nunes, president and CEO of Pope Resources Ltd. Partnership. The company was an outcome of a spinoff from Pope & Talbot in 1985. The company operates in three business segments: fee timber, third-party timberland management and consulting, and real estate segment. Nunes further disclosed that the company has acquired two properties thus increasing their harvest in the 2004 to 2006 time frame. Also, the company is considering undertaking infrastructure investments in a YMCA facility.
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- 2005
164. More Intestinal Worms on Colonoscopy.
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Dunzendorfer, Thomas, Nunes, David P., and Kasznica, John
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LETTERS to the editor ,COLONOSCOPY - Abstract
Presents a letter to the editor in response to the article "A Case of Trichuris Trichiura Infection Diagnosed by Colonoscopy," by M. Yoshida, H. Kutsumi, M. Ogawa et al, in the 1996 issue.
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- 1996
165. Differential regulation of MUC5ACand MUC5Bgenes in HT29 colonic carcinoma cells
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Keaveny, Andrew P., Nunes, David P., Troxler, Robert F., and Offner, Gwynneth D.
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- 2000
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166. SERUM FIBROSIS MARKERS ACCURATELY PREDICT RAPID FIBROSIS PROGRESSION AFTER LIVER TRANSPLANTATION FOR HEPATITIS C.
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Pungpapong, Surakit, Nunes, David P, Krishna, Murli, Nakhleh, Raouf, Chambers, Kyle, Ghabril, Marwan, Steers, Jeffrey L, Dickson, Rolland C, and Keaveny, Andrew P
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- 2006
167. Relationship of Objectively Measured Physical Activity, Sedentary Behavior and Sleep Time with Cardiovascular and Mtabolic Outcomes in Adolescents (A Pilot Study): ABCD Growth Study.
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Wigna, Andrea, Urban, Jacqueline B, Torres, Wésley, Moraes-Chagas, Lucas G, Dias, Jefferson S, Nunes, David S, de-Menezes, Veronica A, and Fernandes, Rômulo A
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BLOOD sugar analysis , *SEDENTARY lifestyles , *CARDIOVASCULAR diseases risk factors , *TRIGLYCERIDES , *KRUSKAL-Wallis Test , *PILOT projects , *CAROTID intima-media thickness , *CONFIDENCE intervals , *CROSS-sectional method , *LOW density lipoproteins , *PHYSICAL activity , *SLEEP , *RISK assessment , *INSULIN , *T-test (Statistics) , *COMPARATIVE studies , *SEX distribution , *ACCELEROMETRY , *HEALTH behavior , *TEENAGERS' conduct of life , *RESEARCH funding , *DESCRIPTIVE statistics , *ANALYSIS of covariance , *HIGH density lipoproteins , *BLOOD pressure measurement , *DATA analysis software , *ADOLESCENCE - Abstract
Study objective: Different behaviors are considered important factors that may influence a healthy lifestyle. Given this fact, we aim to analyze the relationship between moderate-vigorous physical activity (MVPA), sleep time, and sedentary time, with cardiometabolic outcomes in adolescents. Methods: Cross-sectional study, with 152 eutrophic and healthy adolescents. The behavioral variables were collected objectively and the arterial thickness was measured through ultrasound. Blood variables (LDL, TG, HDL, glucose, and insulin) were collected in a private laboratory. To analyze the data, the Student t test and Kruskal-Wallis test were used to compare the groups. All analyses adopted p < 0.05. Results: Girls who demonstrated better combined behaviors, presented significant results for TG (p = 0.045), BP (p = 0.016), and cardiovascular score (p = 0.049) when compared to their peers. Furthermore, the practice of physical activity combined with sufficient sleep time was associated with lower values of arterial thickening (p = 0.017). Conclusions: In view of the results presented, it is possible to state that the aggregation of behaviors was more consistent in females and that the practice of physical activity and adequate sleep time can reflect on cardiovascular health. [ABSTRACT FROM AUTHOR]
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- 2022
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168. Estimating the causal effect of treatment with direct-acting antivirals on kidney function among individuals with hepatitis C virus infection.
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O'Donnell, Adrienne, Pham, Nathan, Battisti, Leandra, Epstein, Rachel, Nunes, David, Sawinski, Deirdre, and Lodi, Sara
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KIDNEY physiology , *ANTIVIRAL agents , *HEPATITIS C virus , *ELECTRONIC health records , *CHRONIC kidney failure - Abstract
Background: Direct-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated. Methods: We analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018. We compared the following hypothetical interventions using causal inference methods: 1) initiation of DAA and 2) no DAA initiation. For patients with normal kidney function at baseline (eGFR>90 ml/min/1.73m2), we estimated and compared the risk for reaching Stage 3 chronic kidney disease (CKD) (eGFR≤60 ml/min/1.73m2) under each intervention. For patients with baseline CKD Stages 2–4 (15
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- 2022
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169. Health-Related Quality of Life of Patients with HIV Disease: Impact of Hepatitis C Coinfection.
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Fleming, Catherine A., Christiansen, Demian, Nunes, David, Heeren, Timothy, Thornton, David, Horsburgh, C. Robert, Jr., Koziel, Margaret James, Graham, Camilla, and Craven, Donald E.
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HIV-positive persons , *HEPATITIS C virus , *VIRUS diseases , *QUALITY of life , *MULTIVARIATE analysis - Abstract
Health-related quality of life (HRQOL) is diminished in patients infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but the effect of HIV/HCV coinfection on HRQOL is unknown. We compared the HRQOL of urban HIV/HCV coinfected patients with that of patients infected with either HCV or HIV alone. We then compared the 3 groups with a US population sample, adjusting for demographic characteristics. HRQOL for the group of HIV/HCV coinfected patients was statistically similar to that of HRQOL in patients with either HCV or HIV alone, but the 3 groups had a significantly decreased HRQOL than did the adjusted US population. Using multivariate techniques, we determined that age, unemployment, injection drug use, and depression were associated with impaired HRQOL. These findings underscore the importance of a multidisciplinary approach to the treatment of these patient populations. [ABSTRACT FROM AUTHOR]
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- 2004
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170. Intensive Pharmacy Care Improves Outcomes of Hepatitis C Treatment in a Vulnerable Patient Population at a Safety-Net Hospital.
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Tran, Ashley N., Sachdev, Rishabh, Fricker, Zachary P., Leber, Michael, Zahorian, Toni, Shah, Bhavesh, Nunes, David P., and Long, Michelle T.
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CRITICAL care medicine , *HEPATITIS C treatment , *MEDICAL virology , *ANTIVIRAL agents , *FIBROSIS , *HEPATITIS C diagnosis , *COMPARATIVE studies , *HEPATITIS C , *HEPATITIS viruses , *HOSPITAL pharmacies , *RESEARCH methodology , *MEDICAL cooperation , *QUALITY assurance , *RESEARCH , *EVALUATION research , *AT-risk people , *HUMAN research subjects , *RETROSPECTIVE studies - Abstract
Background: Treatment of hepatitis C virus (HCV) with direct-acting antiviral (DAA) regimens has resulted in high rates of sustained virologic response (SVR). Treatment of vulnerable populations may be improved by incorporating an on-site intensive specialty pharmacy (ON-ISP).Aims: To describe outcomes of HCV treatment at a safety-net hospital and proportion of subjects achieving SVR for those using the ON-ISP compared to an off-site pharmacy (OFF-SP).Methods: A retrospective cohort study of 219 subjects treated for HCV with DAA at Boston Medical Center was conducted. Subject characteristics, virologic response, and pharmacy services used were recorded. We used multivariable logistic regression to test the association between ON-ISP and SVR after adjusting for covariates.Results: SVR occurred in 71% of subjects by intention-to-treat (73% among ON-ISP users vs 57% among OFF-SP users) and 95% completing treatment per-protocol (96% among ON-ISP users vs 87% among OFF-SP users). Adjustment for age, sex, ethnicity, insurance, fibrosis, prior treatment, and MELD revealed an increased likelihood of SVR among users of ON-ISP: OR 6.0 (95% CI 1.18-31.0). No significant difference in treatment delay or adverse events was seen among users of either pharmacy type.Conclusions: HCV treatment with DAA was well tolerated, but the rate of SVR was low (71%) compared to trials. This was due to loss to follow-up, as the per-protocol rate of SVR was much higher (95%). Use of ON-ISP was associated with an increase in SVR and may be valuable for improving care for vulnerable populations. [ABSTRACT FROM AUTHOR]- Published
- 2018
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171. Chronic hepatitis C virus infection is associated with all-cause and liver-related mortality in a cohort of HIV-infected patients with alcohol problems.
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Fuster, Daniel, Cheng, Debbie M., Quinn, Emily K., Nunes, David, Saitz, Richard, Samet, Jeffrey H., and Tsui, Judith I.
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ALCOHOLISM , *ANALYSIS of variance , *CHI-squared test , *CONFIDENCE intervals , *ENZYME-linked immunosorbent assay , *FISHER exact test , *HIV-positive persons , *LIVER failure , *QUESTIONNAIRES , *RESEARCH funding , *SURVIVAL analysis (Biometry) , *SURVIVAL , *PROPORTIONAL hazards models , *DATA analysis software , *DESCRIPTIVE statistics , *KAPLAN-Meier estimator , *CHRONIC hepatitis C - Abstract
Aims To assess the association between hepatitis C virus ( HCV) infection and overall and liver-related death in human immunodeficiency virus ( HIV)-infected patients with alcohol problems. Design We analyzed data from a cohort of HIV-infected adults with current or past alcohol problems enrolled between 2001 and 2003, searching for causes of death until 2010 using the National Death Index. Setting and participants Participants were HIV-infected adults with current or past alcohol problems, recruited in Boston, MA from HIV clinics at two hospitals, homeless shelters, drug treatment programs, subject referrals, flyers and another cohort study with comparable recruitment sites. Measurements The primary and secondary outcomes were all-cause and liver-related mortality, respectively. The main independent variable was hepatitis C virus ( HCV) RNA status (positive versus negative). Mortality rates and Kaplan- Meier survival curves were calculated by HCV status for both overall and liver-related mortality. Cox proportional hazards models were used to assess the association between HCV infection and overall and liver-related death, adjusting for alcohol and drug use over time. Findings A total of 397 adults (50% HCV-infected) were included. As of 31 December 2009, 83 cohort participants had died (60 HCV-infected, 23 HCV-uninfected; log-rank test P < 0.001), and 26 of those deaths were liver-related (21 HCV-infected, five HCV-uninfected; log-rank test P < 0.001). All-cause and liver-related mortality rates were 4.68 and 1.64 deaths per 100 person-years for HCV-infected patients and 1.65 and 0.36 per 100 person-years for those without HCV, respectively. In the fully adjusted Cox model, HCV infection was associated with both overall [hazard ratio ( HR) = 2.55, 95% confidence interval ( CI) = 1.50-4.33, P < 0.01], and liver-related mortality ( HR = 3.24, 95% CI = 1.18-8.94, P = 0.02]. Conclusion Hepatitis C virus infection is associated independently with all-cause and liver-related mortality in human immunodeficiency virus-infected patients with alcohol problems, even when accounting for alcohol and other drug use. [ABSTRACT FROM AUTHOR]
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- 2014
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172. Impact of Lifetime Alcohol Use on Liver Fibrosis in a Population of HIV-Infected Patients With and Without Hepatitis C Coinfection.
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Fuster, Daniel, Tsui, Judith I., Cheng, Debbie M., Quinn, Emily K., Bridden, Carly, Nunes, David, Libman, Howard, Saitz, Richard, and Samet, Jeffrey H.
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COMPLICATIONS of alcoholism , *CONFIDENCE intervals , *EPIDEMIOLOGY , *HEPATITIS C , *HIV-positive persons , *LIVER diseases , *LONGITUDINAL method , *SCIENTIFIC observation , *QUESTIONNAIRES , *RESEARCH funding , *LOGISTIC regression analysis , *DATA analysis , *FIBROSIS , *PREDICTIVE tests , *CROSS-sectional method , *RECEIVER operating characteristic curves , *DATA analysis software , *DESCRIPTIVE statistics - Abstract
Background The effect of alcohol on liver disease in HIV infection has not been well characterized. Methods We performed a cross-sectional multivariable analysis of the association between lifetime alcohol use and liver fibrosis in a longitudinal cohort of HIV-infected patients with alcohol problems. Liver fibrosis was estimated with 2 noninvasive indices, ' FIB-4,' which includes platelets, liver enzymes, and age; and aspartate aminotransferase/platelet ratio index (' APRI'), which includes platelets and liver enzymes. FIB-4 <1.45 and APRI <0.5 defined the absence of liver fibrosis. FIB-4 >3.25 and APRI >1.5 defined advanced liver fibrosis. The main independent variable was lifetime alcohol consumption (<150 kg, 150 to 600 kg, >600 kg). Results Subjects ( n = 308) were 73% men, mean age 43 years, 49% with hepatitis C virus ( HCV) infection, 60% on antiretroviral therapy, 49% with an HIV RNA load <1,000 copies/ml, and 18.7% with a CD4 count <200 cells/mm3. Forty-five percent had lifetime alcohol consumption >600 kg, 32.7% 150 to 600 kg, and 22.3% <150 kg; 33% had current heavy alcohol use, and 69% had >9 years of heavy episodic drinking. Sixty-one percent had absence of liver fibrosis and 10% had advanced liver fibrosis based on FIB-4. In logistic regression analyses, controlling for age, gender, HCV infection, and CD4 count, no association was detected between lifetime alcohol consumption and the absence of liver fibrosis ( FIB-4 <1.45) (adjusted odds ratio [ AOR] = 1.12 [95% CI: 0.25 to 2.52] for 150 to 600 kg vs. <150 kg; AOR = 1.11 [95% CI: 0.52 to 2.36] for >600 kg vs. <150 kg; global p = 0.95). Additionally, no association was detected between lifetime alcohol use and advanced liver fibrosis ( FIB-4 >3.25). Results were similar using APRI, and among those with and without HCV infection. Conclusions In this cohort of HIV-infected patients with alcohol problems, we found no significant association between lifetime alcohol consumption and the absence of liver fibrosis or the presence of advanced liver fibrosis, suggesting that alcohol may be less important than other known factors that promote liver fibrosis in this population. [ABSTRACT FROM AUTHOR]
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- 2013
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173. Awareness of hepatitis C diagnosis is associated with less alcohol use among persons co-infected with HIV.
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Tsui, Judith I., Saitz, Richard, Cheng, Debbie M., Nunes, David, Libman, Howard, Alperen, Julie K., and Samet, Jeffrey H.
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HEPATITIS C diagnosis , *ALCOHOLISM , *HIV-positive persons , *REGRESSION analysis , *MENTAL depression , *COMPLICATIONS of alcoholism , *PSYCHOLOGY of alcoholism , *HIV infection complications , *COGNITION , *ALCOHOL drinking , *HEALTH behavior , *HEPATITIS C , *LONGITUDINAL method , *RESEARCH funding , *DISEASE complications , *PSYCHOLOGY ,HIV infections & psychology - Abstract
Background and Objective: It is unknown whether testing HIV-infected individuals for hepatitis C virus (HCV) and informing them of their HCV status impacts subsequent alcohol use. We hypothesized that HIV-infected individuals with current or past alcohol problems who reported being told they had HCV were more likely to 1) abstain from alcohol and 2) not drink unhealthy amounts compared to individuals who had not been told.Design, Participants, and Measurements: Data from a prospective, observational cohort study (HIV-Longitudinal Interrelationships of Viruses and Ethanol) were used to assess the association between awareness of having HCV at baseline and subsequent abstinence and not drinking unhealthy amounts as reported at 6-month follow-up intervals. General estimating equations logistic regression was used to account for the correlation from using repeated observations from the same subject over time. We adjusted for age, sex, race, homelessness, injection drug use, depressive symptoms, and having abnormal liver tests.Results: Participants who reported being told they had HCV were more likely to report abstaining from alcohol (AOR = 1.60; 95% CI: 1.13 to 2.27) and not drinking unhealthy amounts (AOR = 1.46; 95% CI: 1.01 to 2.11).Conclusions: Among patients infected with HIV who had a history of alcohol problems, reporting being told one had HCV was associated with greater abstinence from alcohol and less unhealthy amounts of drinking. [ABSTRACT FROM AUTHOR]- Published
- 2007
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174. Effect of Exposure to Injection Drugs or Alcohol on Antigen-Specific Immune Responses in HIV and Hepatitis C Virus Coinfection.
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Graham, Camilla S., Wells, Annalee, Edwards, Erika M., Herren, Timothy, Tumilty, Sheila, Stuver, Sherri O., Samet, Jeffrey H., Nunes, David, Horsburgh Jr., C. Robert, and Koziel, Margaret James
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HIV , *HEPATITIS C virus , *GLYCOPROTEINS , *ANTIVIRAL agents , *CYTOKINES , *TUMOR necrosis factors - Abstract
Background. Ongoing substance use is a potential confounder for immunological studies on hepatitis C virus (HCV), but there is little in the literature regarding the effects of injection drug use (IDU) or alcohol on HCV-specific immune responses. We wanted to determine whether IDU or alcohol affected immune responses in HCV-infected and human immunodeficiency virus (HIV)/HCV coinfected subjects. Methods. Eight-four subjects with HIV/HCV and 57 with HCV were classified as either injection drug users, drinkers, or nonusers based on questionnaire results. Immune responses were studied with enzyme-linked immunosorbent spot assay for interferon (IFN)-γ, interleukin (IL)-10, and tumor necrosis factor (TNF)-α against HCV proteins Core, NS3, and NS5 and recall antigens. Results. Subjects with HIV/HCV, in aggregate, had significantly lower HCV-specific IFN-g and TNF-aresponses than subjects with HCV. However, HIV/HCV injection drug users had HCV specific IFN-γ and IL-10 responses that were similar to those of HCV injection drug users and were significantly higher than in nonusers with HIV/HCV. Conversely, subjects who drank alcohol had similar immune responses to those who were abstinent, among both subjects with HIV/HCV and subjects with HCV. Conclusions. Studies that examine IFN-γ or IL-10 immune responses in HIV/HCV-coinfected or HCV-infected persons need to consider current IDU. Alcohol, at levels consumed in this cohort, does not appear to have as much of an effect on antigen-specific immune responses. [ABSTRACT FROM AUTHOR]
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- 2007
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175. Substance abuse treatment and receipt of liver specialty care among persons coinfected with HIV/HCV who have alcohol problems
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Palepu, Anita, Cheng, Debbie M., Kim, Theresa, Nunes, David, Vidaver, John, Alperen, Julie, Saitz, Richard, and Samet, Jeffrey H.
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SUBSTANCE abuse treatment , *LIVER diseases , *HEPATITIS C virus , *MEDICAL care - Abstract
Abstract: We examined the association of substance abuse treatment with access to liver specialty care among 231 persons coinfected with HIV and hepatitis C virus (HCV) with a history of alcohol problems who were recruited and followed up in the HIV-Longitudinal Interrelationships of Viruses and Ethanol cohort study from 2001 to 2004. Variables regarding demographics, substance use, health service use, clinical variables, and substance abuse treatment were from a standardized research questionnaire administered biannually. We defined substance abuse treatment services as any of the following in the previous 6 months: 12 weeks in a halfway house or residential facility, 12 visits to a substance abuse counselor or mental health professional, day treatment for at least 30 days, or any participation in a methadone maintenance program. Liver specialty care was defined as a visit to a liver doctor, a hepatologist, or a specialist in treating hepatitis C in the past 6 months. At study entry, most of the 231 subjects (89%, n = 205) had seen a primary care physician, 50% had been exposed to substance abuse treatment, and 50 subjects (22%) had received liver specialty care. An additional 33 subjects (14%) reported receiving liver specialty care during the follow-up period. In the multivariable model, we observed a clinically important although not statistically significant association between having been in substance abuse treatment and receiving liver specialty care (adjusted odds ratio = 1.38; 95% confidence interval = 0.9–2.11). Substance abuse treatment systems should give attention to the need of patients to receive care for prevalent treatable diseases such as HIV/HCV coinfection and facilitate its medical care to improve the quality of care for individuals with substance use disorders. The data illustrate the need for clinical care models that give explicit attention to the coordination of primary health care with addiction and hepatitis C specialty care while providing ongoing support to engage and retain these patients with complex health needs. [Copyright &y& Elsevier]
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- 2006
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176. Challenges in the Treatment of Patients Coinfected with HIV and Hepatitis C Virus: Need for Team Care.
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Fleming, Catherine A., Tumilty, Sheila, Murray, Jessica E., and Nunes, David
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HIV , *HEPATITIS C virus , *PATIENTS , *MEDICAL care , *NUCLEOSIDES , *TRIAZOLES , *ANTINEOPLASTIC agents - Abstract
We estimate that only one-third of patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are eligible for therapy for HCV with interferon (IFN) and ribavirin, and, of those who are eligible, two-thirds decline treatment. To date we have initiated treatment with IFN and ribavirin for 8% of coinfected patients evaluated, and <1% of patients have had a sustained virological response. During this process, we have identified many problems that significantly limit our ability to initiate and complete treatment with IFN in this population and have categorized these difficulties into 4 main challenges. They include access to care, contraindications or barriers to treatment, patients' reluctance to start treatment with IFN, and the low tolerability of treatment. If patients coinfected with HCV and HIV are to be treated for hepatitis C in greater numbers, these issues will need to be addressed. [ABSTRACT FROM AUTHOR]
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- 2005
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177. Suporte para refatorização automática de lógica de negócio baseada em modelos
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Fernandes, Tiago Fernando Santos Braga, Ribeiro, António Nestor, Nunes, David Varela, and Universidade do Minho
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Graph theory ,Métricas de complexidade ,OutSystems ,Refactoring ,Teoria de Grafos ,Low-code ,Code complexity metrics ,Program slicing ,Refatorização ,Engenharia e Tecnologia::Engenharia Eletrotécnica, Eletrónica e Informática - Abstract
Dissertação de mestrado em Engenharia Informática, Software’s structure profoundly affects its development and maintenance costs. Poor software’s structure may lead to well-known design flaws, such as large modules or long methods. A possible approach to reduce a module’s complexity is the Extract Method refactoring technique. This technique allows the decomposition of a large and complex method into smaller and simpler ones, while reducing the original method’s size and improving its readability and comprehension. Nowadays, it’s almost mandatory that Integrated Development Environments (IDEs) support this and other refactoring techniques. Despite the wide availability of the extract method operation on IDEs, the identification of portions of code that are worthwhile to refactor still relies mostly on developer knowledge and expertise. Thus, the purpose of this dissertation is to empower the OutSystems platform with a system that is able to analyse modules complexity and automatically suggest Extract Method refactoring opportunities., A estrutura das aplicações de software afeta significativamente os seus custos de desenvolvimento e de manutenção. Uma fraca estruturação do código pode levar a problemas de design, como é o exemplo de módulos de grande dimensão, ou Long Methods. Uma das abordagens para reduzir a complexidade de módulos é a aplicação da técnica de refatorização Extract Method. Esta técnica permite extrair comportamento de um método complexo em métodos mais simples, reduzindo o tamanho do método original e aprimorando a sua leitura e compreensão. Hoje em dia, é quase imperativo que os IDEs suportem esta e outras técnicas de refatorização. Apesar dos IDEs disponibilizarem a operação de extração de métodos, a identificação de secções do código potencialmente úteis para refatorizar continua a ser uma operação que depende do conhecimento e experiência do programador. Assim, o objetivo desta dissertação é prover a plataforma OutSystems de um sistema capaz de analisar a complexidade de módulos e automaticamente sugerir oportunidades de refatorização Extract Method.
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- 2017
178. The Happy System - A system that inferences human emotions and improves behavior: two study cases
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Figueira, Ashley Vicente Luis, Silva, Jorge Miguel Sá, and Nunes, David
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Informática ,Sistemas ciber-físicos ,Internet das coisas ,Engenharia biomédica ,Bem-estar ,Ser humano - Abstract
Os aparelhos e dispositivos de uso diário estão cada vez mais inteligentes e interligados. De facto, a internet das coisas (IoT) é usada cada vez mais para apoiar novos tipos de sistemas ciber-físicos (CPS). A IoT e os CPSs são conceitos que estão intimamente relacionados e que incorporam objetos físicos e funcionais com a inteligência, permitindo assim que eles detetem e controlem estes objetos dentro da sua rede, possibilitando a recolha e troca de informação. Disto, surgem oportunidades para uma integração mais direta entre o mundo físico e os sistemas baseados em computadores, resultando numa maior eficiência, precisão e benefícios sociais. Os CPSs, normalmente, são aplicações não centradas no ser humano. Em vez disso, os CPSs consideram o ser humano como um elemento externo do sistema. Para melhor servir as necessidades do ser humano, os CPS no futuro terão de reforçar a sua ligação com o elemento humano. Estes dispositivos interligados e inteligentes usam vários sensores que podem ser usados para monitorizar e avaliar vários parâmetros humanos, estados emocionais, como emoções, e a sua atividade física, melhorando, assim, a qualidade de vida dos seres humanos. Os seres humanos tornam-se, assim, parte integrante dos CPSs e entramos agora no reino do Human-in-the-loop Cyber- Physical Systems (HiLCPS), ou seja, sistemas físicos cibernéticos que têm em consideração a interação humana. Neste estudo, destacamos os telemóveis, uma vez que a deteção de emoções nos sistemas ciber-físicos foi amadurecendo com estes dispositivos. Na verdade, os telemóveis são cada vez mais usados como assistentes pessoais, ajudado o ser humano a ser mais eficaz nas tarefas do dia-a-dia. Usados em todo o mundo, eles são capazes de processar grandes quantidades de dados fazendo com que o telemóvel seja um dispositivo com as características-chave necessárias para a criação de uma plataforma poderosa, sensível ao contexto de sistemas pessoais. Como tal, os telemóveis podem ser usados para desenvolver sistemas ou aplicações capazes de detetar emoções humanas, podendo ter assim um tremendo impacto social positivo. Estes dispositivos representam um recurso computacional versátil, com uma grande capacidade de deteção e inferência. Estão amplamente presentes em países em desenvolvimento onde a pobreza é mais elevada e, para alem disto, mesmo o telemóvel mais barato tem vários sensores importantes, tais como o microfone e o acelerômetro. O objetivo desta tese foi implementar e estudar sistemas inovadores de HiLCPSs. Esta é uma área muito recente e há várias questões e investigações importantes a serem avaliadas. Tanto quanto sabemos, esta é uma das primeiras tentativas de implementar dois sistemas human-in-the-loop com base na Internet das Coisas, usando algoritmos de machine learning, processamento de sinal, bem como um sistema inovador de beacons. Consequentemente, este trabalho resultou em quatro publicações em conferências internacionais - um deles, onde o Ashley Figueira é o primeiro autor, a submissão ao Foro Cyted, três propostas de projetos internacionais e uma participação na Euorpean Social Innovation Competition 2016, atualmente um dos 30 semifinalistas em 1095 participantes. As aplicações desenvolvidas durante este projeto foram o WeDoCare e o HappySpeak. Ambas as implementações, centradas no conceito de Human-in-the-Loop, tentam ajudar a resolver problemas em cenários do mundo real e ajudar os seres humanos a melhorar o seu estado de espírito e bem-estar. Estas duas aplicações são baseadas numa arquitetura desenvolvida pelo Eng. David Nunes. Este sistema foi utilizado para desenvolver outras aplicações, nomeadamente, o HappyHour e o HappyWalk. Escolhemos dar o nome de The Happy System a este sistema. Este sistema tenta produzir uma mudança no comportamento do utilizador, a fim de melhorar o seu estado emocional. Isto é feito através da recolha de dados de vários sensores, processamento e inferência de emoções através de algoritmos de machine-learning, em seguida, dependendo da emoção inferida, o sistema dá sugestões ao seu utilizador. O HappySpeak e o WeDoCare são ambos dois casos de teste do The Happy System. O HappySPEAK é uma aplicação que visa detetar se o utilizador se sente isolado e dar sugestões que podem ajudá-lo a superar esse problema. Embora a aplicação possa ser usada por qualquer utilizador, os imigrantes são os candidatos perfeitos. Isto porque, em geral, os imigrantes viajam sozinhos para um país que não conhecem e geralmente sem ninguém - tornando-os mais suscetíveis ao isolamento social. O WeDoCare, por outro lado, visa detetar, de uma forma automática, ataques violentos contra os seus utilizadores através de um detetor de gritos, utilizando os sensores do telemóvel, mais em concreto o microfone. A aplicação tira proveito desse mecanismo para ajudar as pessoas, alertando os cidadãos que estão nas redondezas de que alguém está em perigo, dando aos usuários a oportunidade de colaborar e ajudar. Ambas as soluções estão integradas nos conceitos de computação afetiva e internet das coisas.
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- 2016
179. HappyHour Emotion: Sistema de Caraterização de Pontos de Interesse
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Carmona, Pedro Gonçalo Sousa de Figueiredo, Silva, Jorge Miguel Sá, and Nunes, David
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Estado emocional ,Aplicações Web ,Caracterização de pontos de interesse - Abstract
Dissertação de Mestrado em Engenharia Informática apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra Ao longo desta dissertação é exposto o estudo realizado para o desenvolvimento do projeto HappyHour, que engloba três componentes fisicas: um servidor Web, um servidor REST e uma aplicação móvel. Hoje em dia, existe uma pluralidade de sensores que tornam os smartphones propícios ao desenvolvimento de aplicações que interpretam o contexto do utilizador. O HappyHour era um sistema que caracterizava pontos de interesse. Com o trabalho realizado nesta tese foi possível estender as funcionalidades para caracterizar o utilizador com base na sua emoção. É documentado um estudo comparativo com aplicações concorrentes onde se destaca o HappyHour por enveredar por um caminho próprio. Esta aplicação procura ligar o contexto da localização do utilizador ao seu contexto emocional. O modelo utilizado para desenvolver a aplicação assenta na contextualização emocional do utilizador. Em particular, procura-se identificar a euforia, o aborrecimento, a ansiedade e o estado de calma. Desenvolveu-se uma prova de conceito para identicar as emoções através de um mecanismo de machine learning supervisionado. Após ser identificada a emoção, o utilizador é notificado para corrigir a informação. De seguida, utiliza-se o contexto emocional para implementar um determinado mecanismo que possa influenciar positivamente o seu estado emocional. Pretende-se que o utilizador se distancie de estados negativos. Para além disto, são utilizadas tecnologias inovadoras como o MultipathTCP. A aplicação Web é direcionada para os gestores de pontos de interesse e permite notificar pessoas com base na sua localização e emoção. A utilização do contexto emocional aliado à sua localização poderá impulsionar as aplicações do contexto móvel a entregar informações mais relevantes para o utilizador, e adaptarem-se para melhorarem o seu estado emocional, como se pretende com este projeto.
- Published
- 2014
180. Sports participation plays a relevant role in the relationship between birth weight and bone mineral content in adolescents.
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Urban JB, Torres W, Nunes DS, Pelegrini A, Kemper HCG, and Fernandes RA
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The Developmental Origins of Health and Disease hypothesis (DOHaD) proposes that growth during the prenatal period might play a critical role in health, affecting the development of diseases, such as osteoporosis. Bone health is particularly affected by human behaviors when sports participation constitutes the main manifestation of physical exercise. The aim of this study is to analyze the relationship between birth weight (BW) and bone mineral content (BMC) among adolescents, as well as to identify if sports participation and maturity can affect this relationship. The sample was composed of adolescents with ages ranging from 11 to 18 years, stratified according to normal birth weight (n = 331), low birth weight (n = 36), and macrosomia (n = 47), extracted from a wider cross-sectional study (ABCD Growth Study). BW was self-reported by the adolescent's parent. Sports participation was assessed by face-to-face interview. BMC was assessed using dual-energy X-ray absorptiometry. In the multivariate models, the relationships between BW and BMC remained non-significant, while sports participation was significantly related to BMC on lower limbs among boys (r = 0.154; p value = .001) and BMC of upper limbs among girls (r = 0.124; p value = .044). APHV was related to BMC of upper limbs among boys (r = 0.137; p value = .001). In conclusion, BMC was not affected by BW, while this phenomenon seems to be significantly affected by the positive impact of sports participation and maturation on it., (© 2024 Wiley Periodicals LLC.)
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- 2024
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181. Pursuit or discontinuation of anti-PD1 after 2 years of treatment in long-term responder patients with non-small cell lung cancer.
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Ardin C, Humez S, Leroy V, Ampere A, Bordier S, Escande F, Turlotte A, Stoven L, Nunes D, Cortot A, and Gauvain C
- Abstract
Background: The optimal duration of immune checkpoint inhibitor (ICI) treatment for patients with advanced non-small cell lung cancer (NSCLC) remains to be determined. Treatment durations in cornerstone phase 3 clinical trials vary between a fixed 2-year duration and pursuit until disease progression. Clinical practices may thus differ according to the attending physician., Objectives: Here we provide real-world data about treatment decisions at 2 years, with subsequent clinical outcomes., Design and Methods: This multicentric observational study included patients with advanced NSCLC whose disease was controlled after 2 years of pembrolizumab or nivolumab. The primary outcome was the decision to discontinue ICI treatment or not, along with factors motivating this decision. Secondary outcomes included progression-free survival (PFS) (according to treatment continuation or not) and adverse events., Results: A total of 91 patients were included, of which 60 (66%) had been pre-treated. The programmed death-ligand 1 expression level was ⩾50% in 43 patients (47%). In 61 patients (67%), ICI was continued after 2 years of treatment. This decision was significantly associated with the care center ( p < 0.001) but neither with the tumor response at 2 years, as evaluated by CT scan or PET scan, nor with clinical status, immune-related adverse events, or previous locally treated oligo-progressive disease under ICI. Two years after the 2-year decision, PFS was 68.5%, [95% confidence interval (CI) (53.3-88.0)] in the 'ICI discontinuation' group and 64.1% [95% CI (51.9-79.2)] in the 'ICI pursuit' group; hazard ratio for relapse was 1.14 [95% CI (0.54-2.30), p = 0.77]. The overall survival rate at 24 months after discontinuation was 89.2% [95% CI (78.4-100)] for the 'discontinuation' group and 93.1% [95% CI (85.8-100)] for the 'pursuit' group. Given insufficient power, overall survival could not be compared., Conclusion: The decision to continue ICI or not after 2 years of treatment depends mainly on the care center and does not seem to impact survival. Larger, randomized data sets are required to confirm this result., Competing Interests: AC reports grants to institution from Meck and Roche; consulting fees from Novartis; honoraria from Sanofi, Pfizer, Novartis, Takeda, Amgen; payment for expert testimony from Pfizer, Takeda, Novartis, Janssen, Roche, Abbvie; support for attending meetings and/or travel from Novartis and Takeda; consulting or advisory role with Novartis and InhaTarget. CG declares receiving support for attending meetings and/or travel from Pfizer and Novartis. The other authors declare that there is no conflict of interest., (© The Author(s), 2023.)
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- 2023
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182. A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.
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Kanagaratnam P, Francis DP, Chamie D, Coyle C, Marynina A, Katritsis G, Paiva P, Szigeti M, Cole G, de Andrade Nunes D, Howard J, Esper R, Khan M, More R, Barreto G, Meneguz-Moreno R, Arnold A, Nowbar A, Kaura A, Mariveles M, March K, Shah J, Nijjer S, Lip GYH, Mills N, Camm AJ, Cooke GS, Corbett SJ, Llewelyn MJ, Ghanima W, Toshner M, Peters N, Petraco R, Al-Lamee R, Boshoff ASM, Durkina M, Malik I, Ruparelia N, Cornelius V, and Shun-Shin M
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- Humans, SARS-CoV-2, Bayes Theorem, Aspirin therapeutic use, Hemorrhage chemically induced, Hemorrhage drug therapy, Treatment Outcome, COVID-19, Acute Coronary Syndrome diagnosis, Acute Coronary Syndrome drug therapy
- Abstract
Background: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease., Objectives: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors., Methods: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death)., Results: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse)., Conclusion: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality., Competing Interests: Declaration of competing interests P.K. receives research grants and consulting fees from Biosense-Webster, Abbott-Medical, Medtronic, and Boston Scientific. A patent for Ripple Mapping is licensed to Biosense-Webster, and royalties are paid to Imperial College. C.C. is the recipient of a British Heart Foundation Clinical Research Training Fellowship (number FS/20/14/34917). A.A. has had support to attend conferences from Bayer. A.N. received a research grant from the NIHR Academy. S.N. received payment or honoraria for speaker events/presentations from Bayer, Pfizer, and Philips and participates on an Advisory Board for Astra Zeneca. G.Y.H.L. is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. No fees are received personally. N.M. is supported by a Chair Award, Program Grant, and Research Excellence Award (CH/F/21/90010, RG/20/10/34966, and RE/18/5/34216, respectively) from the British Heart Foundation. A.J.C. reports personal fees/consulting fees from Bayer, Pfizer, BMS, Daiichi Sankyo, and Boehringer Ingelheim; reports royalties and/or editorial fees from Oxford University Press, Wiley, and Springer Verlag; and participates on DSMBs/Advisory Boards at Biotronik, Johnson and Johnson, and Allergan. G.S.C. receives grants from the NIHR, participates on DSMBs, and is a nonexecutive director at the MHRA. W.G. reports fees for participation in Advisory Board from Amgen, Novartis, Pfizer, Principia Biopharma Inc—a Sanofi Company, Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, and Hutchmed; lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, and Sanofi; and research grants from Bayer and BMS/Pfizer. M.T. reports Scientific Advisory Board personal fees from MorphogenIX and personal fees/honoraria from J&J/Actelion. R.A.-L. receives speaker’s honoraria from Philips Volcano, Medtronic, and Menarini. M.S.-S. has received honoraria from Pfizer (<£500). D.P.F., D.C., A.M., G.K., P.P., M.S., G.C., D.d.A.N., J.H., R.E., M.K., R.M., G.B., R.M.M., A.K., M.M., K.M., J.S., S.J.C., M.J.L., N.P., R.P., A.S.M.B., M.D., I.M., N.P., V.C. have no competing interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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183. Colonic Epithelial Angiotensin-Converting Enzyme 2 (ACE2) Expression in Blacks and Whites: Potential Implications for Pathogenesis Covid-19 Racial Disparities.
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De La Cruz M, Nunes DP, Bhardwaj V, Subramanyan D, Zaworski C, Roy P, and Roy HK
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- Black or African American, Humans, Inflammation, SARS-CoV-2, Angiotensin-Converting Enzyme 2 genetics, COVID-19
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Background: Covid-19 toll is disproportionate in Blacks although the mechanisms remain incompletely understood. From a biological perspective, several host proteins have received most attention as logical susceptibility targets. Specifically, angiotensin-converting enzyme 2 (ACE2) serves as the epithelial cell receptor and acts in concert with transmembrane protease serine 2 (TMPRSS2). Intriguingly, ACE2 can also suppress the inflammatory response and therefore may impact the severity of Covid-19 infections (from the exuberant immune response a.k.a. "cytokine storm"). We, therefore, assessed expression of ACE2 and TMPRSS2 in Blacks versus Whites., Methods: Archived mucosal biopsies from colonoscopic biopsies of visually normal rectal mucosa without concurrent neoplasia or inflammation were used for this study. Total mRNA was isolated and subjected to real-time polymerase chain reaction for ACE2, and TMPRSS2 was assessed from non-Hispanic Blacks (n = 45) and non-Hispanic Whites (n = 38). GAPDH and beta-actin were used for normalization. Multivariable analysis was performed using Analyse-IT software., Results: ACE2 and TMPRSS2 levels were not altered by gender, BMI, or age. ACE2 levels were lower in Blacks than Whites achieving statistical significance in multivariable (0.51-fold, p = 0.03) but not quite in univariable (p = 0.07) analysis. This downregulation was mirrored in TMRPSS2 in both univariable (p = 0.03) and multivariable analyses (0.41-fold, p = 0.02). Moreover, there was a strong correlation between ACE2 and TMPRSS2 levels (r-squared = 0.78)., Conclusions: To our knowledge, this is the first report on racial differences inACE2 and TMPRSS2 mucosal expression. This may provide potential biological underpinnings for the disproportionately higher mortality of Covid-19 in Blacks and should spur future studies., (© 2021. W. Montague Cobb-NMA Health Institute.)
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- 2022
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184. Herb-Induced Liver Injury-A Challenging Diagnosis.
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Nunes DRDCMA, Monteiro CSJ, and Dos Santos JL
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Herb-induced liver injury (HILI) can be caused by supplements containing herbs, natural products, and products used in traditional medicine. Herbal products' most common adverse reaction is hepatotoxicity. Almost every plant part can be used to make herbal products, and these products can come in many different forms, such as teas, powders, oils, creams, capsules, and injectables. HILI incidence and prevalence are hard to estimate and vary from study to study because of insufficient large-scale prospective studies. The diagnosis of HILI is a challenging process that requires not only insight but also a high degree of suspicion by the clinician. HILI presents with unspecific symptoms and is a diagnosis of exclusion. For diagnosis, it is necessary to make a causality assessment; the Council for International Organizations of Medical Sciences assessment is the preferred method worldwide. The most effective treatment is the suspension of the use of the suspected herbal product and close monitoring of liver function. The objective of this review is to highlight the necessary steps for the clinician to follow to reach a correct diagnosis of herb-induced liver injury. Further studies of HILI are needed to better understand its complexity and prevent increased morbidity and mortality.
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- 2022
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185. Drug Induced Liver Injury: Perspective of the Adverse Drug Reaction Reports to the Portuguese Pharmacovigilance System from 2010 to 2019.
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Nunes DRDCMA, Breton MC, Monteiro CSJ, and Dos Santos JL
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Background: Drug induced liver injury (DILI) is an adverse drug reaction that causes liver damage in a predictable (dose-dependent) or an unpredictable (idiosyncratic) fashion. We performed an assessment of DILI in Portugal, by analyzing the reports, sent to the Portuguese Pharmacovigilance System (PPS)., Methods: A search was performed on the PPS database, in a 10-year time frame, from 1 January 2010 to 31 December 2019., Results: There was not a prevalence of either sex in any age group. Most reports ( n = 1120, 55.0%) belonged to patients in the age group 19-64 years old. Hepatitis ( n = 626, 26.7%) was the most common adverse drug reaction in our study. Hepatotoxicity ( n = 362, 15.5%) and hepatitis ( n = 333, 14.2%) were more frequent in age group 19-64 years old. Cholestasis was more prevalent in adults independently of age. Hepatic fibrosis and encephalopathy were more common in the elderly. Most patients consumed between one and four suspected drugs ( n = 1867, 92%). Most patients in our study evolved to "cure" ( n = 796; 39%). Hepatotoxicity ( n = 23; 13.8%) and hepatitis ( n = 610; 25.9%) had a female predominancy while choluria ( n = 8; 4.8%) and splenomegaly ( n = 8; 4.8%) were of male predominance., Conclusions: DILI is rare but can be fatal. As such, an active search of DILI is necessary.
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- 2021
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186. Autoimmune Gastrointestinal Dysmotility in a Patient With HIV Treated With Methylprednisolone and Pyridostigmine.
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Gromisch CM, Machado MA, Satyam V, and Nunes D
- Abstract
Primary autoimmune gastrointestinal dysmotility is a limited form of autoimmune dysautonomia, driven by antiganglionic autoantibodies (AGAs) against enteric neurons. AGAs are observed in other autoimmune diseases, such as Guillain-Barré syndrome, before the development onset of gastrointestinal symptoms. Here, we report a case of a 57-year-old woman with human immunodeficiency virus, who previously developed Guillain-Barré syndrome, presenting with 6 months of intestinal dysmotility. Diagnosis was made by detecting AGAs to ganglionic acetylcholine receptor, alpha-3 subunit, radiographic evidence of duodenal dysmotility, and exclusion of other causes. The patient received high-dose methylprednisolone with low-dose pyridostigmine, which led to significant improvement of symptoms., (© 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)
- Published
- 2021
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187. Quantification of gastric mucosal microcirculation as a surrogate marker of portal hypertension by spatially resolved subdiffuse reflectance spectroscopy in diagnosis of cirrhosis: a proof-of-concept study.
- Author
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Mohanty A, Eshein A, Kamineni P, Avissar U, Bliss CM, Long MT, Lowe RC, Moore TC, Nunes DP, Backman V, and Roy HK
- Subjects
- Biomarkers, Gastric Mucosa, Humans, Liver Cirrhosis complications, Liver Cirrhosis diagnostic imaging, Microcirculation, Spectrum Analysis, Hypertension, Portal diagnostic imaging
- Abstract
Background and Aims: Portal pressure can be used to identify patients with chronic liver disease who have progressed to cirrhosis. Portal pressure can also provide accurate prognostication for patients with cirrhosis. However, there are no practical means for assessment of portal pressure. Although it is well established that the gastric mucosal blood supply increases in patients with cirrhosis, this has been difficult to quantify reproducibly. Our group has developed a novel spectroscopic technology called spatially resolved subdiffuse reflectance spectroscopy (SRSRS), which enables quantification of mucosal microcirculation. We aim to ascertain if quantification of the gastric mucosal microcirculation with SRSRS correlates with clinical evidence of portal hypertension., Methods: Patients undergoing EGD for clinical indications had 10 measurements taken in the endoscopically normal gastric fundus via SRSRS probe to assess the microcirculation. Cases were defined as patients with cirrhosis (n = 18), and controls were those without evidence of liver disease (n = 18); this was corroborated with transient elastography., Results: The blood volume fraction (P = .06) and subdiffuse reflectance (P = .02) from a shallow depth in the gastric fundus were higher in patients with cirrhosis than those without. These markers were combined to yield an overall optical marker that can differentiate patients with cirrhosis from controls with a sensitivity of 72% and specificity of 94% (area under receiver operating curve, 0.82)., Conclusions: Spectroscopic quantification of gastric fundal mucosal microcirculation is a promising surrogate of clinical correlates of portal hypertension. This approach may represent a less-intrusive surrogate biomarker for liver disease prognostication and potentially response to therapy., (Copyright © 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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188. Alcohol Consumption and Hepatitis C Virus (HCV) RNA Levels in HIV/HCV Coinfected Patients.
- Author
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Fuster D, Nunes D, Cheng DM, Saitz R, and Samet JH
- Subjects
- Adult, Cohort Studies, Female, Hepatitis C epidemiology, Humans, Male, Middle Aged, Risk Factors, Alcohol Drinking adverse effects, HIV Infections drug therapy, HIV Infections epidemiology, HIV Infections virology, Hepacivirus genetics, Hepatitis C virology, RNA, Viral, Viral Load
- Abstract
Background: The impact of Hepatitis C virus (HCV) RNA levels on the evolution of chronic HCV infection-related liver damage is controversial. Heavy alcohol use is believed to have a deleterious impact on the course of HCV disease, but current knowledge about the possible effect of alcohol use on HCV RNA levels in HIV/HCV coinfected patients is limited., Methods: We examined 107 HIV/HCV-infected individuals with current or past unhealthy alcohol use to assess the association between alcohol consumption (any drinking vs. abstinent) and HCV RNA levels., Results: Participants were 75% male, with a mean age of 43 years, and 63% were on antiretroviral therapy. Mean (SD) log HIV RNA was 3.1 (1.4) and mean (SD) log HCV RNA was 6.1 (0.8). Past-month alcohol use was present in 38% of participants. In a multivariable linear regression analysis we found no significant differences in mean log HCV RNA levels between those reporting alcohol use and those who were abstinent [β (95%CI): -0.04 (-0.34, 0.26), p = 0.79)]. There was no significant association between any heavy drinking day and HCV RNA level (0.07, 95% CI: (-0.24, 0.38), p = 0.66)., Conclusions: We did not detect significant associations between alcohol use and HCV RNA levels among HIV/HCV coinfected patients.
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- 2021
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189. Sustained Improvement in Type 2 Diabetes Mellitus is Common After Treatment of Hepatitis C Virus With Direct-acting Antiviral Therapy.
- Author
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Gilad A, Fricker ZP, Hsieh A, Thomas DD, Zahorian T, and Nunes DP
- Subjects
- Aged, Blood Glucose metabolism, Female, Glycated Hemoglobin metabolism, Humans, Male, Middle Aged, Retrospective Studies, Antiviral Agents therapeutic use, Diabetes Mellitus, Type 2, Hepatitis C, Chronic drug therapy
- Abstract
Goals: To determine whether diabetic patients with hepatitis C virus (HCV) treated with direct-acting antiviral agents have improved diabetes, accounting for change in both hemoglobin A1c (HbA1c) and diabetes medications, and whether any improvement was sustained., Background: HCV infection is associated with an increased risk of diabetes, with improvement in glycemic control after eradication. There remains uncertainty about the durability and magnitude of this effect., Study: HbA1c and diabetes medications were recorded at 6-month intervals for 1.5 years pretreatment and posttreatment for 122 patients. Subjects were classified as having improved diabetes if there was a decrease in HbA1c≥0.5% with no increase in diabetes medications or a decrease in diabetes medications with a stable HbA1c., Results: HbA1c at the nearest time point before treatment was 8.4%±1.9%, compared with 7.8%±1.7% after treatment, a mean difference of 0.6% [95% CI (0.2, 0.9), P<0.01]. A linear mixed effects model incorporating each subject's repeated measurements over time also demonstrated a reduction after treatment of 0.5% [95% CI, (0.3, 0.8), P<0.001]. Accounting for both HbA1c and diabetes medications, 42 of 122 (34%) had an improvement in diabetes after HCV treatment, and 20 of 28 (71%) of these subjects sustained improvement at 1.5 years follow-up. Prescription of insulin was associated with improved diabetes., Conclusions: Treatment of HCV with direct-acting antiviral agents was associated with improved diabetes in a significant portion of patients with an average reduction in HbA1c of clinically significant magnitude. Among responders, this effect was sustained over 1.5 years of follow-up.
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- 2019
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190. Improved Antibody Response to Three Additional Hepatitis B Vaccine Doses Following Primary Vaccination Failure in Patients with Inflammatory Bowel Disease.
- Author
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Pratt PK Jr, Nunes D, Long MT, and Farraye FA
- Subjects
- Adult, Biomarkers blood, Colitis, Ulcerative blood, Colitis, Ulcerative immunology, Crohn Disease diagnosis, Crohn Disease immunology, Female, Humans, Immunocompromised Host, Male, Middle Aged, Retrospective Studies, Time Factors, Treatment Failure, Adrenal Cortex Hormones adverse effects, Colitis, Ulcerative drug therapy, Crohn Disease drug therapy, Hepatitis B Antibodies blood, Hepatitis B Vaccines administration & dosage, Immunization, Immunogenicity, Vaccine, Immunosuppressive Agents adverse effects, Tumor Necrosis Factor Inhibitors adverse effects
- Abstract
Background: Studies have shown the efficacy of hepatitis B (HBV) vaccination in patients with inflammatory bowel disease (IBD) is impaired, but few data exist regarding the effectiveness of revaccination strategies following primary vaccination failure. Our aim was to analyze the association between administration of additional vaccine doses and hepatitis B surface antibody (HBsAb) seroconversion., Methods: This is a retrospective cohort study. Inclusion criteria are as follows: age ≥ 18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC), inadequate HBsAb < 10 IU/L following initial HBV vaccination series, subsequent administration of 1-3 additional doses of HBV vaccine with follow-up serum HBsAb measurements. Patients were stratified into groups of ≤ 2 or 3 doses received. Primary outcome was achieving HBsAb > 10 IU/L. Outcomes were stratified by age ≥ or < 40 years. We performed logistic and linear multivariable regression analyses for categorical and continuous data., Results: The study cohort consists of (n = 149) 54.4% women; 77.9% white; 72.6% with CD, with mean age: 46.2. Patients of all ages and age ≥ 40 years, who received 3 additional doses of vaccine, were more likely to achieve seroprotective HBsAb levels than patients who received 1 or 2 doses (OR 1.77, P = 0.01; OR 1.9, P = 0.03, respectively, after adjusting for age, sex, race, immunosuppressive medication exposure, time between vaccine/titer)., Conclusions: Following initial HBV vaccination failure, patients with IBD of all ages are more likely to develop seroprotective levels of HBsAb following 3 additional vaccine doses, rather than 1 or 2 alone. In patients who fail primary HBV vaccination, providers should consider a more aggressive revaccination strategy with an additional 3-dose series.
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- 2019
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191. CD4 recovery on antiretroviral therapy is associated with decreased progression to liver disease among hepatitis C virus-infected injecting drug users.
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Anderson JP, Horsburgh CR Jr, Williams PL, Tchetgen Tchetgen EJ, Nunes D, Cotton D, and Seage GR 3rd
- Abstract
Background. Human immunodeficiency virus (HIV) coinfection accelerates liver disease progression in individuals with chronic hepatitis C. We evaluated the associations of CD4, HIV RNA, and antiretroviral therapy (ART)-induced CD4 recovery with liver diagnoses in a prospective cohort of injecting drug users (IDUs). Methods. We evaluated 383 coinfected IDUs in the Boston area, prospectively observed for a median of 1.8 years. Liver disease progression included the first occurrence of hepatocellular carcinoma, variceal bleeding, ascites, encephalopathy, or death due to hepatic failure. Multivariable-adjusted extended Cox models were specified to estimate hazard ratios (HRs) for comparisons of CD4, change in CD4 (from nadir), and HIV RNA with respect to liver disease progression events. Results. Twenty-four persons experienced a liver disease progression event over 1155 person-years (2.1 per 100 person-years), including 20 deaths attributed to end-stage liver disease (1.7 per 100 person-years). CD4 at baseline and over follow-up strongly predicted liver disease progression (baseline CD4 <200 vs ≥200: HR = 5.23, 95% confidence interval [CI], 2.30-11.92; time-updated CD4 <200 vs ≥200: HR = 11.79, 95% CI, 4.47-31.07). Nadir CD4 was also a strong indicator (<100 vs ≥100: HR = 3.52, 95% CI, 1.54-8.06). A lack of CD4 recovery (failure to increase 100 cells over nadir) among ART initiators was associated with increased risk (HR = 7.69; 95% CI, 2.60-22.69). Human immunodeficiency virus RNA was not significantly associated with liver disease progression. Conclusions. Impaired immune function was highly predictive of liver disease progression in this cohort of IDUs, and a lack of CD4 recovery on ART was associated with increased risk of progression to HCV-associated liver disease.
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- 2015
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192. HIV infection does not affect the performance of noninvasive markers of fibrosis for the diagnosis of hepatitis C virus-related liver disease.
- Author
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Nunes D, Fleming C, Offner G, O'Brien M, Tumilty S, Fix O, Heeren T, Koziel M, Graham C, Craven DE, Stuver S, and Horsburgh CR Jr
- Subjects
- Adult, Alanine Transaminase blood, Aspartate Aminotransferases blood, Biopsy, Disease Progression, Female, Hepatitis C diagnosis, Humans, Liver pathology, Liver Function Tests, Male, Middle Aged, Platelet Count, ROC Curve, Sensitivity and Specificity, Biomarkers blood, HIV Infections complications, Hepatitis C complications, Liver Cirrhosis diagnosis, Liver Cirrhosis physiopathology
- Abstract
Background: Noninvasive markers of hepatic fibrosis hold great promise to stage liver fibrosis and to monitor disease progression. To date, few studies have assessed the performance of the currently available markers of hepatic fibrosis in HIV-infected cohorts. The aim of the current study was to compare the diagnostic performance and characteristics of a number of noninvasive markers of hepatic fibrosis in populations of hepatitis C virus (HCV)-infected patients with and without HIV infection., Methods: A sample of 97 subjects (40 HCV/HIV-coinfected, 57 HCV-infected) undergoing liver biopsy as part of an ongoing prospective cohort study was evaluated. Liver biopsies were assessed by a single hepatopathologist and scored according to Ishak criteria. Noninvasive markers of fibrosis studied included international normalized ratio, platelet count, aspartate aminotransferase (AST)/alanine aminotransferase ratio, AST platelet ratio index (APRI), Forns index, procollagen III N peptide, hyaluronic acid, and YKL-40., Results: The correlations between fibrosis markers with the stage of fibrosis and the diagnostic performance of each of the tests were similar in the groups with and without HIV infection. Although a trend to improved diagnostic performance in the HCV/HIV-coinfected group was observed, this may be related to the small sample size., Conclusions: The diagnostic performance of the evaluated noninvasive markers of liver fibrosis is equivalent in HCV/HIV-coinfected and HCV-infected subjects. These tests may be of value for the clinical evaluation of HCV/HIV-coinfected patients and warrant further study.
- Published
- 2005
- Full Text
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