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1.
Artigo em Inglês | MEDLINE | ID: mdl-38943454

RESUMO

OBJECTIVE: To evaluate patients' satisfaction with opioid versus opioid-sparing postoperative analgesia in patients undergoing outpatient head and neck surgery. STUDY DESIGN: Prospective randomized trial. SETTING: Tertiary care academic hospital. METHODS: Adult patients undergoing outpatient head and neck surgery were randomly assigned to 1 of 3 analgesic regimens. First- and second-line medications were the following by group (1) Hydrocodone-acetaminophen with ibuprofen, (2) ibuprofen with hydrocodone-acetaminophen, and (3) ibuprofen with acetaminophen. Preoperative counseling was provided to patients regarding expected pain and proper medication use. Postoperative questionnaires were administered to assess satisfaction. RESULTS: One hundred three patients were enrolled in the study (mean age, 56.5 years; women, 75 [73%]). The mean satisfaction score with the pain regimen assigned was similar between the 3 groups (scale 0-10, [7.7, 8.3, 8.5, P = .46]). A similar percentage of patients in each group reported that surgery was more painful than anticipated (25%, 32%, 26%, P = .978), and a similar percentage of patients reported willingness to utilize the same analgesic regimen following future surgeries (75%, 83%, 76%, P = .682). Additional questions evaluating the side effect profile, maximum and minimum pain scores, and difficulty of recovery were not statistically different between the 3 groups. CONCLUSION: In the postoperative population for outpatient head and neck surgeries, there was no significant difference in patient satisfaction and pain control between the opioid and nonopioid arms. Providers should discuss opioid-sparing regimens preoperatively with patients and describe them as effective in providing adequate pain control without a significant impact on patient's perception of care.

2.
NPJ Precis Oncol ; 8(1): 130, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851780

RESUMO

Oral squamous cell carcinoma (OSCC) biomarker studies rarely employ multi-omic biomarker strategies and pertinent clinicopathologic characteristics to predict mortality. In this study we determine for the first time a combined epigenetic, gene expression, and histology signature that differentiates between patients with different tobacco use history (heavy tobacco use with ≥10 pack years vs. no tobacco use). Using The Cancer Genome Atlas (TCGA) cohort (n = 257) and an internal cohort (n = 40), we identify 3 epigenetic markers (GPR15, GNG12, GDNF) and 13 expression markers (IGHA2, SCG5, RPL3L, NTRK1, CD96, BMP6, TFPI2, EFEMP2, RYR3, DMTN, GPD2, BAALC, and FMO3), which are dysregulated in OSCC patients who were never smokers vs. those who have a ≥ 10 pack year history. While mortality risk prediction based on smoking status and clinicopathologic covariates alone is inaccurate (c-statistic = 0.57), the combined epigenetic/expression and histologic signature has a c-statistic = 0.9409 in predicting 5-year mortality in OSCC patients.

3.
J Biol Chem ; 298(12): 102597, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36244454

RESUMO

Most eukaryotic secretory proteins are cotranslationally translocated through Sec61 into the endoplasmic reticulum (ER). Because these proteins have evolved to fold in the ER, their mistargeting is associated with toxicity. Genetic experiments have implicated the ER heat shock protein 70 (Hsp70) Hspa13/STCH as involved in processing of nascent secretory proteins. Herein, we evaluate the role of Hspa13 in protein import and the maintenance of cellular proteostasis in human cells, primarily using the human embryonic kidney 293T cell line. We find that Hspa13 interacts primarily with the Sec61 translocon and its associated factors. Hspa13 overexpression inhibits translocation of the secreted protein transthyretin, leading to accumulation and aggregation of immature transthyretin in the cytosol. ATPase-inactive mutants of Hspa13 further inhibit translocation and maturation of secretory proteins. While Hspa13 overexpression inhibits cell growth and ER quality control, we demonstrate that HSPA13 knockout destabilizes proteostasis and increases sensitivity to ER disruption. Thus, we propose that Hspa13 regulates import through the translocon to maintain both ER and cytosolic protein homeostasis. The raw mass spectrometry data associated with this article have been deposited in the PRIDE archive and can be accessed at PXD033498.


Assuntos
Proteínas de Choque Térmico , Proteostase , Humanos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Pré-Albumina/metabolismo , Citosol/metabolismo , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Transporte Proteico , Canais de Translocação SEC/metabolismo
4.
Medicine (Baltimore) ; 101(37): e30577, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36123845

RESUMO

Endoscopic screening is used widely to minimize the rates of colorectal cancer cases and deaths. During highly virulent infectious disease pandemics such as the coronavirus disease 2019 (COVID-19) pandemic, it is essential to weigh the risks and benefits of receiving endoscopy, especially in regions with moderately high viral infection rates. An observational study was conducted to assess the number of patients seen for endoscopic procedure at 2 of our surgery centers. Reasons for their procedure were collected in addition to information regarding any positive COVID-19 cases. This study considers the rate of severe acute respiratory syndrome coronavirus 2 infection along with the number of colorectal cancer cases encountered at a community endoscopy center to suggest that the benefits of undergoing endoscopic evaluation may outweigh the risks of attending an endoscopy procedure during the COVID-19 pandemic. One of the main reasons patients underwent endoscopic procedure was for colon cancer screenings (41.9%), and 5 of 1020 patients seen during the observation period were diagnosed with cancer. Of these 1020 patients, 8 were found to have positive tests for COVID-19 within 2 to 4 weeks after their procedure.


Assuntos
COVID-19 , Neoplasias do Colo , COVID-19/epidemiologia , Neoplasias do Colo/cirurgia , Detecção Precoce de Câncer , Endoscopia Gastrointestinal , Humanos , Pandemias/prevenção & controle
5.
ACS Chem Biol ; 17(7): 1963-1977, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35675579

RESUMO

The proper trafficking of eukaryotic proteins is essential to cellular function. Genetic, environmental, and other stresses can induce protein mistargeting and, in turn, threaten cellular protein homeostasis. Current methods for measuring protein mistargeting are difficult to translate to living cells, and thus the role of cellular signaling networks in stress-dependent protein mistargeting processes, such as ER pre-emptive quality control (ER pQC), is difficult to parse. Herein, we use genetically encoded peroxidases to characterize protein import into the endoplasmic reticulum (ER). We show that the ERHRP/cytAPEX pair provides good selectivity and sensitivity for both multiplexed protein labeling and for identifying protein mistargeting, using the known ER pQC substrate transthyretin (TTR). Although ERHRP labeling induces formation of detergent-resistant TTR aggregates, this is minimized by using low ERHRP expression, without loss of labeling efficiency. cytAPEX labeling recovers TTR that is mistargeted as a consequence of Sec61 inhibition or ER stress-induced ER pQC. Furthermore, we discover that stress-free activation of the ER stress-associated transcription factor ATF6 recapitulates the TTR import deficiency of ER pQC. Hence, proximity labeling is an effective strategy for characterizing factors that influence ER protein import in living cells.


Assuntos
Estresse do Retículo Endoplasmático , Retículo Endoplasmático , Retículo Endoplasmático/metabolismo , Proteínas de Choque Térmico , Transporte Proteico , Proteostase
6.
Cancer ; 128(1): 192-202, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34460935

RESUMO

BACKGROUND: Little is known about cancer survivors who discontinue survivorship care. The objective of this study was to characterize patients with head and neck cancer who discontinue survivorship care with their treating institution and identify factors associated with discontinuation. METHODS: This was a retrospective cohort study of patients diagnosed with head and neck cancer between January 1, 2014, and December 31, 2016, who received cancer-directed therapy at the University of Iowa Hospitals and Clinics (UIHC). Eligible patients achieved a cancer-free status after curative-intent treatment and made at least 1 visit 90+ days after treatment completion. The primary outcome was discontinuation of survivorship care, which was defined as a still living survivor who had not returned to a UIHC cancer clinic for twice the expected interval. Demographic and oncologic factors were examined to identify associations with discontinuation. RESULTS: Ninety-seven of the 426 eligible patients (22.8%) discontinued survivorship care at UIHC during the study period. The mean time in follow-up for those who discontinued treatment was 15.4 months. Factors associated with discontinuation of care included an unmarried status (P = .036), a longer driving distance to the facility (P = .0031), and a single-modality cancer treatment (P < .0001). Rurality was not associated with discontinuation (24.3% vs 21.6% for urban residence; P = .52), nor was age, gender, or payor status. CONCLUSIONS: The study results indicate that a sizeable percentage of head and neck cancer survivors discontinue care with their treating institution. Both demographic and oncologic factors were associated with discontinuation at the treating institution, and this points to potential clinical and care delivery interventions.


Assuntos
Sobreviventes de Câncer , Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Estudos Retrospectivos , Sobreviventes , Sobrevivência
7.
Front Cell Infect Microbiol ; 11: 752899, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34976853

RESUMO

The continued proliferation of superbugs in hospitals and the coronavirus disease 2019 (COVID-19) has created an acute worldwide demand for sustained broadband pathogen suppression in households, hospitals, and public spaces. In response, we have created a highly active, self-sterilizing copper configuration capable of inactivating a wide range of bacteria and viruses in 30-60 seconds. The highly active material destroys pathogens faster than any conventional copper configuration and acts as quickly as alcohol wipes and hand sanitizers. Unlike the latter, our copper material does not release volatile compounds or leave harmful chemical residues and maintains its antimicrobial efficacy over sustained use; it is shelf stable for years. We have performed rigorous testing in accordance with guidelines from U.S. regulatory agencies and believe that the material could offer broad spectrum, non-selective defense against most microbes via integration into masks, protective equipment, and various forms of surface coatings.


Assuntos
Anti-Infecciosos , COVID-19 , Antibacterianos , Humanos , Equipamento de Proteção Individual , SARS-CoV-2
8.
Anal Bioanal Chem ; 411(19): 4987-4998, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31254054

RESUMO

Influenza infection requires viral escape from early endosomes into the cytosol, which is enabled by an acid-induced irreversible conformational transformation in the viral protein hemagglutinin. Despite the direct relationship between this conformational change and infectivity, label-free methods for characterizing this and other protein conformational changes in biological mixtures are limited. While the chemical reactivity of the protein backbone and side-chain residues is a proxy for protein conformation, coupling this reactivity to quantitative mass spectrometry is a challenge in complex environments. Herein, we evaluate whether electrophilic amidination coupled with pseudo-parallel reaction monitoring is an effective label-free approach to detect the fusion-associated conformational transformation in recombinant hemagglutinin (rHA). We identified rHA peptides that are differentially amidinated between the pre- and post-fusion states, and validated that this difference relies upon the fusion-associated conformational switch. We further demonstrate that we can distinguish the fusion profile in a matrix of digested cellular lysate. This fusion assay can be used to evaluate fusion competence for modified HA. Graphical abstract.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Orthomyxoviridae/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Virais/metabolismo , Amidas/metabolismo , Células HEK293 , Humanos , Limite de Detecção , Peptídeos/metabolismo , Ligação Proteica , Conformação Proteica , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Proteínas Virais/química , Proteínas Virais/classificação
9.
Otolaryngol Head Neck Surg ; 160(5): 839-846, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30832548

RESUMO

OBJECTIVE: To compare the efficacy of pain control and opioid consumption between patients who receive opioid as primary analgesic therapy and those who receive ibuprofen. STUDY DESIGN: Prospective randomized trial. SETTING: Tertiary care academic hospital. SUBJECT AND METHODS: Adult patients undergoing outpatient otolaryngology surgery were assigned to take hydrocodone/acetaminophen or ibuprofen for postoperative analgesia. Patient-recorded pain scores and analgesic consumption were analyzed. RESULTS: Out of 185 recruits, 108 (58%) completed responses. Fifty-six patients (52%) received opioid medication for primary analgesic treatment versus 52 (48%) who received ibuprofen. There was no difference in reported pain scores between the treatment groups. Those who received ibuprofen as primary therapy reported a significantly lower consumption of opioid medication at 2.04 tablets/pills (95% CI, 0.9-3.1) versus 4.86 (3.6-6.1; P = .001). Based on multivariate analysis, male sex and older age exhibited lower reported pain scores, while older age and use of ibuprofen as primary therapy exhibited lower opioid requirements. CONCLUSION: For postoperative pain management in outpatient otolaryngology procedures, ibuprofen as primary therapy can provide equally effective pain control as compared with hydrocodone/acetaminophen while decreasing overall opioid requirement. Prescription pill counts are further described to help guide physician practices in the era of an opioid epidemic.


Assuntos
Acetaminofen/uso terapêutico , Procedimentos Cirúrgicos Ambulatórios/efeitos adversos , Analgésicos Opioides/uso terapêutico , Hidrocodona/uso terapêutico , Ibuprofeno/uso terapêutico , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Estudos Prospectivos , Método Simples-Cego , Adulto Jovem
10.
Clin Gastroenterol Hepatol ; 17(5): 957-967.e7, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30326298

RESUMO

BACKGROUND & AIMS: The American Association for the Study of Liver Diseases (AASLD) guidelines for treatment of chronic hepatitis B virus (HBV) infection have changed with time. We assessed rates of treatment evaluation and initiation in patients with chronic HBV infection from different practice settings in the past 14 years. METHODS: Treatment-naive patients with chronic HBV infection were recruited from different practice settings in California from January 2002 through December 2016. The study population comprised 4130 consecutive, treatment-naive patients with chronic HBV infection seen by community primary care physicians (n = 616), community gastroenterologists (n = 2251), or university hepatologists (n = 1263). Treatment eligibility was assessed using data from the first 6 months after initial presentation based on AASLD criteria adjusted for changes over time. RESULTS: Within the first 6 months of care, the proportions of patients evaluated by all 3 relevant tests (measurements of alanine aminotransferase, hepatitis B virus e antigen, and HBV DNA levels) were as follows: 36.69% in community primary care, 59.80% in gastroenterologist care, and 79.97% in hepatology care (P < .0001 among the 3 groups). Higher proportions of patients were eligible for treatment in specialty practices: 12.76% in community primary care, 24.96% in gastroenterologist care, and 29.43% in hepatology care (P < .0001). Among treatment-eligible patients, there was no significant difference in the proportions of patients who began antiviral therapy between those receiving treatment from a gastroenterologist (55.65%) vs a hepatologist (57.90%; P = .56). Of 243 evaluable patients receiving community primary care, only 31 were eligible for treatment and only 12 of these (38.71%) received treatment. CONCLUSIONS: In an analysis of patients receiving care for chronic HBV infection, we found the proportions evaluated and receiving treatment to be suboptimal, according to AASLD criteria, in all practice settings. However, rates of evaluation and treatment were lowest for patients receiving community primary care.


Assuntos
Gerenciamento Clínico , Fidelidade a Diretrizes/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Atenção Primária à Saúde/métodos , Atenção Secundária à Saúde/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , California , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
J Agric Food Chem ; 66(28): 7256-7264, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-29924601

RESUMO

Poplar hybrids can be used for selenium (Se) and boron (B) phytoremediation under saline conditions. The phenolic antioxidant stress response of two salt and B tolerant poplar hybrids of parentage Populus trichocarpa × nigra × deltoides was studied using high-performance liquid chromatography (HPLC) and absorption-based assays to determine the antioxidant capacity, total phenolic content, hydroxycinnamic acid levels, and the enzyme activity of l-phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), phenol peroxidase (POD), and laccase. Most remarkable was the contrasting response of the two poplar clones for PPO activity and phenolic levels to irrigation with high salt/B water. To cope with stressful growing conditions, only one clone increased its phenolic antioxidant level, and each clone displayed different PPO isoform patterns. Our study shows that poplar hybrids of the same parentage can differ in their salt/B stress coping mechanism.


Assuntos
Antioxidantes/análise , Boro/análise , Catecol Oxidase/metabolismo , Fenóis/análise , Proteínas de Plantas/metabolismo , Populus/enzimologia , Populus/genética , Cloreto de Sódio/metabolismo , Antioxidantes/metabolismo , Boro/metabolismo , Fenóis/metabolismo , Populus/química , Populus/crescimento & desenvolvimento , Cloreto de Sódio/análise
13.
BMJ Open Gastroenterol ; 2(1): e000060, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26543565

RESUMO

BACKGROUND AND AIMS: Despite available effective therapies, only a minority of patients with chronic hepatitis B (CHB) receive treatment. Our goal is to study treatment rates and time to treatment initiation in patients who meet treatment criteria on long-term follow-up. METHODS: We performed a retrospective cohort study of 608 consecutive treatment-eligible patients with CHB (by 2008 US Panel or 2009 American Association for the Study of Liver Disease (AASLD) criteria) at a US community gastroenterology clinic and a university liver clinic between 2007 and 2011. Patients were observed until they started treatment or last follow-up if untreated. RESULTS: Mean age was 44 and most were Asian (96%) with community patients being younger and having lower alanine aminotransferase (ALT) levels. A total of 62% started treatment, and 38% remained untreated after median follow-up of 17 months (IQR=1-40 months). Overall, treatment rate was significantly higher at university liver clinic than in the community (66.7% vs 59.9%, p=0.01). In multivariate analysis, older age (HR 1.02, p=0.002), male gender (HR 1.37, p=0.02), and baseline ALT >45 U/L for males and >29 U/L for females (HR 2.24, p<0.0001) were significant predictors of treatment initiation, but not practice setting. CONCLUSIONS: Approximately 40% of treatment-eligible patients still have not started treatment on longer follow-up. Treatment rates were higher at university clinics, but practice setting was not a predictor for treatment, but older age, male gender, and higher ALT levels were. Further studies are needed to determine the barriers for treatment initiation and to improve treatment rates in treatment-eligible patients.

14.
J Gastroenterol Hepatol ; 30(1): 43-50, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25168842

RESUMO

BACKGROUND AND AIM: Suboptimal viral suppression with adefovir (ADV) poses a challenge in managing chronic hepatitis B. Few studies have evaluated the efficacy of entecavir (ETV) in ADV-experienced patients. Our aim is to assess treatment effectiveness of ETV in ADV-experienced patients. METHODS: ADV-experienced patients switched to ETV were enrolled from six US clinics. Patients completed a median of 24 months of ETV after switch. Patients were categorized into partial responders (detectable HBV-DNA at switch) or complete responders (undetectable HBV-DNA at switch) to ADV. Primary and secondary outcome measurements were complete viral suppression (CVS, HBV-DNA < 60 IU/mL) and biochemical response (BR, alanine aminotransferase [ALT] < 40 U/L), respectively. RESULTS: A total of 120 patients were included in the analysis (80 ADV partial responders; 40 ADV complete responders). In partial responders, CVS rate was 84% after 24 months of ETV. BR rate was 58% at switch to ETV and increased to 90% after 24 months. All complete responders continued to experience CVS after switch. On multivariate analysis inclusive of age, male gender, ALT level at switch, and history of lamivudine (LAM) exposure, we identified positive, hepatitis B e antigen status before ADV and higher HBV-DNA level at time of switch as significant independent negative predictors of CVS. In eight patients with ADV resistance, seven achieved CVS after 24 months of ETV, and all achieved BR. CONCLUSION: In ADV-experienced patients, high rates of CVS and BR can be achieved/sustained after switching to ETV, including those with ADV resistance or with prior exposure to LAM.


Assuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Adulto , Alanina Transaminase/sangue , Biomarcadores/sangue , Substituição de Medicamentos , Feminino , Seguimentos , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Tempo , Resultado do Tratamento , Carga Viral
15.
Dig Dis Sci ; 59(1): 168-73, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24248420

RESUMO

BACKGROUND AND AIMS: The dose recommendation for entecavir (ETV) is 0.5 mg daily for treatment-naïve chronic hepatitis B (CHB) patients and 1.0 mg daily for lamivudine-refractory patients; however, few data are available for the efficacy of a 1.0-mg daily dose in treatment-naïve CHB patients. Our goal is to examine the treatment outcome of treatment-naïve patients placed on ETV 0.5 mg or ETV 1.0 mg daily through week 48. METHODS: Cases were 40 consecutive hepatitis B e antigen (HBeAg)-positive CHB patients treated with ETV 1.0 mg daily between January 2005 and September 2010, and controls were 40 consecutive CHB patients treated with ETV 0.5 mg daily between January 2005 and September 2010 at three US gastroenterology/liver clinics. Controls were matched for age (±5 years), sex, HBeAg, and baseline hepatitis B virus (HBV) DNA (±0.5 log10 IU/ml). Complete viral suppression was defined as undetectable HBV DNA by polymerase chain reaction (<100 IU/ml). RESULTS: Both groups had similar distributions of age (38 ± 11 years), male patients (55 %), and mean HBV DNA (7.7 ± 1.1 log10 IU/ml). The complete viral suppression rate was similar in both cases and controls through week 24 (15 vs. 15 %, p = 1.00) and week 48 (22 vs. 36 %, p = 0.17). Non-adherence was reported in three patients in the ETV 1.0 mg daily cohort at week 48. CONCLUSIONS: There were no significant differences in the proportion of patients with complete viral suppression in patients treated with ETV 0.5 mg daily or the higher daily dose of 1.0 mg.


Assuntos
Antivirais/administração & dosagem , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Adulto , Feminino , Guanina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
16.
Dig Dis Sci ; 58(11): 3342-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24081641

RESUMO

BACKGROUND AND AIMS: The Centers for Disease Control and Prevention recommend screening for hepatitis C virus (HCV) in patients with injection drug use, blood transfusion before 1992, stigmata of liver disease, or born between 1945 and 1965. The purpose of this study was to examine risk factors for HCV acquisition in Asian Americans. METHODS: This was a case-controlled study, with 471 consecutive patients testing positive for anti-HCV between January 2001 and December 2008. Controls included 471 patients with negative HCV matched at a one-to-one ratio for sex, age (±5 years), and ethnicity. RESULTS: For Asian patients, the most common risk factors were blood transfusion and acupuncture or exposure to dirty needles (27 and 20 %, respectively). On multiple logistic regression, potential predictors for a positive anti-HCV test in Asians were acupuncture or exposure to dirty needles (OR = 12.9, P < 0.0001), body tattoo (OR = 12.0, P = 0.001), and history of blood transfusion (OR = 5.7, P < 0.0001). DISCUSSION: Acupuncture and exposure to dirty needles are independent risk factors of HCV infection. Asians coming from endemic areas should be screened for HCV even when commonly-known risk factors for Western patients are not present.


Assuntos
Asiático , Hepacivirus/isolamento & purificação , Hepatite C/epidemiologia , Hepatite C/etiologia , Terapia por Acupuntura/efeitos adversos , Adulto , Idoso , Anticorpos Antivirais , Estudos de Casos e Controles , Feminino , Hepatite C/etnologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Tatuagem/efeitos adversos , Reação Transfusional , Estados Unidos/epidemiologia
17.
J Gastroenterol Hepatol ; 28(5): 855-60, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23278507

RESUMO

BACKGROUND AND AIM: Treatment end-point of therapy for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) includes HBeAg seroconversion, which ranges from 15% to 22% after 1 year of oral nucleos(t)ides according to clinical trials. Our goal was to determine the incidence and predictors of HBeAg seroconversion in such patients in routine clinical practice because they may differ than reported rates. METHODS: We conducted a retrospective cohort study of 333 consecutive treatment-naïve HBeAg-positive patients who were treated for CHB between 1/2000 and 6/2010 at three gastroenterology and liver clinics in the USA. Primary study end-point was HBeAg seroconversion-loss of HBeAg and antibody to HBeAg (anti-HBe) development. RESULTS: The majority of patients were Asian (96%). Median treatment duration prior to HBeAg seroconversion was 50 (range 26-52) weeks. Of the 333 study patients, 25% received lamivudine, 16% adefovir, 51% entecavir, and 8% tenofovir. HBeAg seroconversion at month 12 was 8.2%. On multivariate analysis inclusive of age, gender, and antiviral agents, independent predictors for HBeAg seroconversion at month 12 were hepatitis B virus DNA < 7.5 log10 IU/mL (hazard ratio [HR] = 2.59 [1.04-6.44]), P = 0.041) and alanine transaminase (ALT) > 1.5 × upper normal limit (HR = 2.86 [1.05-7.81], P = 0.040), but not the choice of nucleos(t)ides. CONCLUSIONS: The HBeAg seroconversion rate seen in clinical settings for oral nucleos(t)ides appears much lower than those reported in pivotal trials, especially in patients with lower ALT and higher HBV DNA levels. HBeAg-positive patients should be counseled about the high possibility of the long treatment duration required to achieve recommended treatment end-points.


Assuntos
Antígenos E da Hepatite B , Vírus da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Nucleotídeos/administração & dosagem , Administração Oral , Adulto , Antivirais/administração & dosagem , DNA Viral/metabolismo , Quimioterapia Combinada , Determinação de Ponto Final , Feminino , Anticorpos Anti-Hepatite B , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
18.
Eur J Gastroenterol Hepatol ; 25(3): 338-43, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23169311

RESUMO

AIM: Data from registration trials with highly selective patients have shown that hepatitis B envelope antigen (HBeAg)-positive patients with chronic hepatitis B respond well to entecavir (ETV) 0.5 mg daily, with an HBeAg seroconversion rate of 21% at 12 months. However, there are varying data on the treatment outcomes of ETV 0.5 mg daily in routine clinical settings, with seroconversion rates at 12 months ranging from 8 to 48% in studies limited to 44-90 patients from centers in Asia, Europe, and South America. MATERIALS AND METHODS: In the present study, we examined long-term treatment efficacy and tolerability in 136 consecutive treatment-naive HBeAg-positive chronic hepatitis B patients treated between January 2005 and January 2011 with ETV 0.5 mg daily at community clinics and tertiary centers in the USA. The primary study end point was HBeAg seroconversion. RESULTS: Sixty-one percent of HBeAg-positive patients were men, mean age 39 ± 12 years, median hepatitis B virus DNA 7.48 (3.7-9.8) log10 IU/ml, median alanine aminotransferase 67 (14-1077) U/l, and median treatment duration 18 (6-60) months. At months 12, 24, and 36, complete viral suppression rates were 41, 66, and 85% and HBeAg seroconversion rates were 4.8, 20, and 30%, respectively. No patients experienced adverse events or developed genotypic resistance to ETV. CONCLUSION: In clinical settings, ETV is highly tolerable and potent at suppressing hepatitis B viremia; however, the rates of HBeAg seroconversion appear to be much lower than those reported, highlighting the importance of appropriate counseling and planning for long-term therapy.


Assuntos
Antivirais/administração & dosagem , Guanina/análogos & derivados , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Adulto , Alanina Transaminase/sangue , Antivirais/efeitos adversos , Biomarcadores/sangue , California , Distribuição de Qui-Quadrado , Centros Comunitários de Saúde , Esquema de Medicação , Feminino , Guanina/administração & dosagem , Guanina/efeitos adversos , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento
19.
J Clin Gastroenterol ; 47(4): 367-71, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23090039

RESUMO

GOALS AND BACKGROUND: Besides United States population born between 1945 and 1965, screening for hepatitis C virus (HCV) is not recommended for the general US population. However, HCV may be more prevalent in certain subgroups and screening may be warranted. The goal of this study was to examine the proportion of HCV in a large sample of community Asian American patients presenting for non-liver-related complaints. STUDY: We conducted a cross-sectional study of 1246 patients tested for hepatitis C virus antibodies (anti-HCV) referred to 2 gastroenterology clinics for non-liver-related gastrointestinal reasons between January 2001 and February 2011. We determined HCV status and patient history via electronic medical record review. RESULTS: Of the 1246 study patients tested for anti-HCV, the majority were Asian (81.4%) and 29 Asian patients (2.9%) had positive anti-HCV. HCV proportion in the remaining 232 non-Asians (non-Hispanic whites and Hispanics) was 1.7%. Asians with positive anti-HCV were more likely to have had blood transfusions (31.0% vs. 6.6%, P<0.0001) or acupuncture (10.3% vs. 1.5%, P<0.0001). Of the 976 Asian patients with hepatitis B surface antigen testing, 38 (3.9%) also had detectable hepatitis B surface antigen. CONCLUSIONS: Among patients seen at community gastroenterology clinics for non-liver-related reasons, HCV proportion was 1.7% for non-Asians and 2.9% for Asians. Screening for HCV should be offered to high-risk patients presenting to gastroenterology clinics with unrelated gastrointestinal complaints.


Assuntos
Asiático/estatística & dados numéricos , Hepatite C/etnologia , Terapia por Acupuntura/efeitos adversos , Adulto , Idoso , Biomarcadores/sangue , California/epidemiologia , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C/sangue , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Reação Transfusional , População Branca/estatística & dados numéricos
20.
J Clin Gastroenterol ; 47(5): 461-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23090046

RESUMO

BACKGROUND: Despite its high potency against hepatitis B virus (HBV), entecavir (ETV) 0.5 mg daily may not be sufficient to induce complete viral suppression in some patients with very high pretreatment viremia. It is not clear whether ETV 1.0 mg daily would have additive effect in such patients. GOALS: Our goal was to examine virologic outcome of ETV 1.0 mg daily in patients with partial response to ETV 0.5 mg daily. METHODS: We retrospectively studied 31 consecutive treatment-naive patients who were switched to ETV 1.0 mg daily after partial response [reduction of HBV DNA ≥2 log10 IU/mL but with detectable HBV DNA levels (>100 IU/mL) after 24 weeks of therapy or longer] with ETV 0.5 mg daily from January 2005 to January 2010 at 2 clinics. RESULTS: All patients were Asians and 90% had positive hepatitis B e antigen. Mean HBV DNA was 8.04±0.65 log10 IU/mL before therapy and 3.64±0.91 log10 IU/mL at the time of switch. Overall rate of complete viral suppression were 29% (n=9/31) after 24 weeks of ETV 1.0 mg daily and 22% (n=5/23) after 48 weeks. Complete viral suppression after 24 weeks with ETV 1.0 mg daily was significantly higher in patients with lower HBV DNA (<3 log10 IU/mL) at time of switch: 75% versus 5%, P<0.0001. CONCLUSIONS: The majority of patients with partial response to ETV 0.5 mg daily did not achieve complete viral suppression with the higher dose of ETV 1.0 mg daily except those with minimal residual viremia (HBV DNA <3 log10 IU/mL).


Assuntos
Antivirais/administração & dosagem , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Carga Viral/efeitos dos fármacos , Viremia/tratamento farmacológico , Adulto , DNA Viral/sangue , Relação Dose-Resposta a Droga , Feminino , Guanina/administração & dosagem , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Viremia/virologia , Adulto Jovem
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