Assuntos
Conjuntivite Alérgica/induzido quimicamente , Tamponamento Interno/efeitos adversos , Descolamento Retiniano/cirurgia , Óleos de Silicone/efeitos adversos , Adulto , Túnica Conjuntiva , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/cirurgia , Humanos , Masculino , Pupila , Reoperação , Descolamento Retiniano/diagnóstico , Óleos de Silicone/administração & dosagemRESUMO
PURPOSE/OBJECTIVE: A career in healthcare is built on the foundations of continuous self-reflection and self-assessment. Previous studies have solely compared student self-assessment to faculty grades in a single discipline. The objective of this study was to investigate whether associations of a student's self-assessment skills exist across multiple disciplines in the predoctoral setting. METHODS: Sixty-five students from two class years at the Harvard School of Dental Medicine completed preclinical competency exams in dental anatomy waxing and operative dentistry. The difference between the student's self-assessment score and average faculty grade for each exercise was calculated as the studentâfaculty (S-F) gap, which served as a proxy to determine how students evaluate their work. Regression analysis was performed to assess associations between wax-up and preclinical operative S-F gaps. RESULTS: Mean S-F gaps for waxing and preclinical operative procedures were positive (5.7 ± 6.1 and 7.6 ± 6.7, respectively). Additionally, students in the lower quartile tended to overestimate performance to a greater degree than their peers in the upper quartile. Furthermore, the waxing S-F gaps were positively associated with S-F gaps of each operative procedure, particularly with the combined operative exercise S-F gaps, where a statistically significant association was seen (coefficient = 0.28; p = 0.04). CONCLUSION(S): Previously, we identified a negative correlation between students' self-assessment skills (S-F gaps) and their preclinical performance. In this study, we further demonstrated an association of S-F gaps in two fundamental exercises: wax-up and operative dentistry. This underscores the roles of S-F gaps as possible indicators of students' preclinical and clinical performance, and it holds potential to become a widely standardized and applicable calculation that may help evaluate the effectiveness of the dental curricula and optimize student learning.
Assuntos
Anatomia , Dentística Operatória , Educação em Odontologia , Autoavaliação (Psicologia) , Estudantes de Odontologia , Estudantes de Odontologia/psicologia , Educação em Odontologia/métodos , Humanos , Dentística Operatória/educação , Anatomia/educação , Avaliação Educacional/métodos , Competência Clínica , Masculino , FemininoRESUMO
Spatial perception and psychomotor skills are critical components to clinical dentistry. However, measures within the dental school curricula have not been sufficiently studied and evaluated for their effectiveness in predicting preclinical performance. The objective of this study was to examine whether students' waxing skills are associated with preclinical operative performance. This study included 65 students from two class years at the Harvard School of Dental Medicine. Regression analysis was utilized to assess associations between waxing scores and operative exam scores. Waxing scores were found to be positively correlated with all operative practical exam scores and significantly associated with the class III resin composite restoration (coefficient, 0.42; P = 0.02) and the combined operative exam scores (coefficient, 0.33; P = 0.04). Wax-up assessments could serve as a predictor for preclinical performance and identify students who would benefit from additional assistance to help foster a more inclusive learning environment.
RESUMO
PURPOSE: This study aims to evaluate how student performance and perspectives changed when the Objective Structured Clinical Exam (OSCE) assessment system was changed from a composite score to discipline-specific grading at the Harvard School of Dental Medicine. METHODS: The retrospective study population consisted of all students (n = 349) who completed three OSCEs (OSCE 1, 2, and 3) as part of the predoctoral program during the years 2014-2023. Data on the students' OSCE scores were obtained from the Office of Dental Education, and data on students' race/ethnicity and gender were obtained from their admissions data. RESULTS: The likelihood of a student failing the OSCE after the assessment system change significantly increased with an adjusted odds ratio of 20.12. After the change, the number of failed subjects per student decreased with an adjusted mean ratio of 0.48. Students perceived the OSCE as being less useful after the change. Independent of the grading change, OSCEs 1 and 2 were seen as more useful compared to OSCE 3, which is administered in the last year of the Doctor of Dental Medicine program. CONCLUSION: The discipline-specific nature of the new assessment system helps focus on specific areas of remediation, rather than blanket remediation used previously, in order to isolate the actual areas of deficiency and to focus remediation efforts so that students can align their learning needs appropriately. Therefore, although the actual number of fails identified increased for the course, the assessment change has allowed for more directed, actionable information to be gained from the OSCE to prepare students to work toward competency standards.
RESUMO
Background/purpose: Self-assessment in dental education is considered a fundamental skill for proficient oral healthcare providers. While previous studies looked at self-assessment in education, few have done so at Japanese institutions. This study aimed to assess potential associations between gender and self-assessment skills in Japanese dental students. Materials and methods: Dental students from Niigata University (n = 301) completed preclinical prosthodontic exercises and self-assessed their practical exam performance. Three calibrated faculty evaluated students' work using the same rubric. The difference between student self-assessment score and mean faculty grade was defined as the student-faculty (S-F) gap, indicating how accurately students evaluated their work. The gap scores were stratified by quartiles by faculty grade and by gender. Regression analysis was used to investigate potential associations. Results: Students mean S-F gap was 2.9 ± 10.5 % with a significant negative association to faculty grades (coefficient, -0.32; P < 0.001). There was no significant difference between male and female students for faculty grades, self-assessment scores, and S-F gaps. When stratified by quartile, mean S-F gaps of bottom quartile students (5.7 ± 11.9 %) were significantly higher than the rest of the class (1.9 ± 9.8 %; P = 0.01), while the mean S-F gaps of students in the top quartile (-0.8 ± 10.2 %) were significantly lower than the rest of the class (4.2 ± 10.3 %; P < 0.001). Conclusion: Niigata University students generally overestimated their performance. Students with higher faculty grades self-assessed themselves more accurately than students with lower faculty grades. Gender did not influence S-F gaps, despite dentistry in Japan shifting toward a female-dominated field.
RESUMO
BACKGROUND & AIMS: A sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection is defined as the inability to detect HCV RNA 24 weeks after completion of treatment. Although small studies have reported that the SVR is durable and lasts for long periods, it has not been conclusively shown. METHODS: The durability of treatment responses was examined in patients originally enrolled in one of 9 randomized multicenter trials (n = 1343). The study included patients who received pegylated interferon (peginterferon) alfa-2a alone (n = 166) or in combination with ribavirin (n = 1077, including 79 patients with normal alanine aminotransferase levels and 100 patients who were coinfected with human immunodeficiency virus and HCV) and whose serum samples were negative for HCV RNA (<50 IU/mL) at their final assessment. Patients were assessed annually, from the date of last treatment, for a mean of 3.9 years (range, 0.8-7.1 years). RESULTS: Most patients (99.1%) who achieved an SVR had undetectable levels of HCV RNA in serum samples throughout the follow-up period. Serum samples from 0.9% of the patients contained HCV RNA a mean of 1.8 years (range, 1.1-2.9 years) after treatment ended. It is not clear if these patients were reinfected or experienced a relapse. CONCLUSIONS: In a large cohort of patients monitored for the durability of an SVR, the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin. In patients with chronic hepatitis C infection, the SVR is durable and these patients should be considered as cured.
Assuntos
Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Carga Viral/efeitos dos fármacos , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Relação Dose-Resposta a Droga , Portadores de Fármacos , Quimioterapia Combinada , Seguimentos , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , RNA Viral/análise , Proteínas Recombinantes , Estudos Retrospectivos , Ribavirina/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Assessing hepatitis C virus (HCV)-RNA levels is integral to response-guided therapy. Rules for early discontinuation and determination of treatment duration were mainly established with HCV-RNA assays with a detection limit of 50IU/ml (COBAS Amplicor HCV [CA]). The currently used real-time PCR-based COBAS Ampliprep/COBAS-TaqMan HCV (CAP-CTM) test has a detection limit of approximately 10IU/ml. It is unknown whether shortening of treatment duration to 16/24 weeks in patients with rapid virological response at week 4 (RVR) and viral loads between 10 and 50IU/ml is possible. METHODS: We reanalysed stored serum from two large, multinational, randomized trials in which patients were treated with peginterferon alfa-2a/ribavirin (n=962). Results of CAP-CTM with truly undetectable HCV RNA and those <15IU/ml, which includes patients with residual viraemia (<15), were compared with the originally obtained results using the CA assay. RESULTS: RVR rates were comparable for CA (<50) and CAP-CTM (<15) with 32% and 32% for genotype (gt) 1 and 50% and 49% for gt2/3 patients, respectively. A significantly smaller number of samples really had truly undetectable HCV RNA by the CAP-CTM assay (24% for gt1, 37% for gt2/3). However, sustained virological response rates after shortened treatment (16/24weeks) were not significantly different in patients with a RVR <50, a RVR <15 and RVR undetectable (82%, 83%, 83% for 24weeks gt1 and 95%, 95%, 94% for 16weeks gt2/3). CONCLUSIONS: Shortening the treatment duration to 16/24weeks can be performed on the basis of a RVR with HCV-RNA concentrations <15IU/ml by the CAP-CTM assay.
Assuntos
Monitoramento de Medicamentos/métodos , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Ribavirina/uso terapêutico , Antivirais/uso terapêutico , Farmacorresistência Viral , Quimioterapia Combinada , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Valor Preditivo dos Testes , RNA Viral/genética , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes , Recidiva , Carga Viral/efeitos dos fármacos , Viremia/tratamento farmacológico , Viremia/virologiaRESUMO
BACKGROUND: Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin. METHODS: We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV RNA level (<50 IU per milliliter) 24 weeks after the end of treatment. RESULTS: The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen. The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks (62% vs. 70%; odds ratio for 16 weeks vs. 24 weeks, 0.67; 95% confidence interval, 0.54 to 0.84; P<0.001). In addition, the rate of relapse (a detectable HCV RNA level during follow-up in patients who had undetectable HCV RNA at the end of treatment) was significantly greater in the 16-week group (31%, vs. 18% in the 24-week group; P<0.001). The sustained virologic response rates in patients with a pretreatment serum HCV RNA level of 400,000 IU per milliliter or less was 82% with the 16-week regimen and 81% with the 24-week regimen. Among patients with a rapid virologic response (an undetectable HCV RNA level by week 4), sustained virologic response rates were 79% in the 16-week group and 85% in the 24-week group (P=0.02). CONCLUSIONS: Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen. (ClinicalTrials.gov number, NCT00077636 [ClinicalTrials.gov].).
Assuntos
Antivirais/administração & dosagem , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Anemia/induzido quimicamente , Antivirais/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Polietilenoglicóis/efeitos adversos , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/efeitos adversos , Carga ViralRESUMO
UNLABELLED: Treatment response remains suboptimal for many patients with chronic hepatitis C, particularly those with genotype 1 and high levels of viremia. The efficacy of high-dose regimens of peginterferon alfa-2a and ribavirin was compared with conventional dose regimens in patients with features predicting poor treatment responses. Eligible treatment-naïve adults with genotype 1 infection, hepatitis C virus (HCV) RNA >800,000 IU/mL and body weight >85 kg were randomized to double-blind treatment with peginterferon alfa-2a at 180 or 270 microg/week plus ribavirin at 1200 or 1600 mg/day for 48 weeks (four regimens were evaluated). The primary endpoint was viral kinetics during the first 24 weeks of therapy. Among patients receiving peginterferon alfa-2a (270 microg/week) the magnitude of HCV RNA reduction was significantly greater than for patients randomized to the conventional dose of peginterferon alfa-2a (180 microg/week) for the pairwise comparison for ribavirin at 1600 mg/day (P = 0.036) and numerically greater for the pairwise comparison for ribavirin at 1200 mg/day (P = 0.060). Patients randomized to the highest doses of peginterferon alfa-2a (270 microg/week) and ribavirin (1600 mg/day) experienced the numerically highest rates of sustained virologic response (HCV RNA < 50 IU/mL) and the lowest relapse rate (47% and 19%, respectively). The arm with the higher doses of both drugs was less well-tolerated than the other regimens. CONCLUSION: Higher fixed doses of peginterferon alfa-2a (270 microg/week) and ribavirin (1600 mg/day) may increase sustained virologic response rates compared with lower doses of both drugs in patients with a cluster of difficult-to-treat characteristics.
Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Hepacivirus/genética , Hepatite C/sangue , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Polietilenoglicóis/efeitos adversos , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). The effect of steatosis on anti-HCV therapy efficacy is unclear. METHODS: We studied host and viral factors associated with steatosis and the effect of steatosis on treatment efficacy using the database of a large prospective trial in patients with HCV genotypes 2 and 3. RESULTS: Out of 885 patients assessed for steatosis, a total of 614 patients or 69% had steatosis. Patients with genotype 3 were more likely to have steatosis than those with genotype 2 (79 vs. 59%, P<0.001). Using the logistic regression model, steatosis was associated with genotype 3 (P<0.0001), older age (P=0.0025), heavier weight (P<0.0001), higher HCV RNA (P<0.0001), and higher ALT levels (P=0.015). By univariate analysis, steatosis was associated with lower sustained virological response (SVR) in patients with genotype 3, but not in patients with genotype 2. When all factors associated with steatosis and SVR were evaluated by logistic regression analysis; genotype, age, bodyweight, histological diagnosis, ALT quotient, baseline HCV RNA and treatment duration were associated with the probability of SVR, but gender, race and steatosis were not. Further analysis showed that steatosis remained a non-significant factor while baseline viral load was significantly associated with the probability of an SVR. CONCLUSIONS: Steatosis did not influence the efficacy of treatment in our study population. Baseline viral load is a confounding factor, particularly in patients infected with genotype 3 and once baseline viral load was accounted for, the association between steatosis and SVR was not relevant.
Assuntos
Fígado Gorduroso/fisiopatologia , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Fatores Etários , Peso Corporal , Fígado Gorduroso/etiologia , Genótipo , Hepatite C/genética , Humanos , Interferon alfa-2 , Interferon-alfa/farmacologia , Modelos Logísticos , Polietilenoglicóis/farmacologia , Proteínas Recombinantes , Ribavirina/farmacologia , Carga ViralRESUMO
Human papillomavirus (HPV) vaccination campaigns to prevent cervical cancer are being considered and implemented in countries around the world. While vaccination will protect future generations, it will not help the millions of women currently infected, leading to an estimated 311 000 deaths per year globally. This paper examines a selection of strategies that when applied to both existing and new technologies, could accelerate access to HPV testing. Authors from the US Agency for International Development, the National Institutes of Health, and the Bridge to Health Medical and Dental, a non-governmental organisation, joined forces to propose a scalable and country-directed solution for preventing cervical cancer using an end-to-end approach. Collectively, the authors offer seven evidence-based strategies, that when used alone or in combination have the ability to reduce HPV-caused cervical cancer deaths and disability. These strategies include (1) consistent HPV test intervals to decrease HPV DNA test costs; (2) exploring market shaping opportunities; (3) employing iterative user research methodologies like human-centred design; (4) target product profiles for new HPV tests; (5) encouraging innovation around cervical cancer screen and treat programmes; (6) developing national cancer control plans; and (7) integrating cervical cancer screen and treat services into existing infrastructure. By using the strategies outlined here, in combination with HPV vaccination campaigns, national governments will be able to scale and expand cervical cancer screening programmes and provide evidence-based treatment programmes for HPV-infected women.
RESUMO
Sustained virological response SVR is defined as undetectable HCV RNA in plasma 6 months after therapy has been discontinued. Relapse or re-emergence of viremia after SVR is rare. We report two patients that relapsed when immune suppressive therapy was given within a few weeks of achieving SVR. Patient 1 received prednisone for bronchitis and patient 2 relapsed soon after immune suppression was started post renal transplantation. These data suggest that the early phase of SVR might be associated with incomplete protective immunity. They suggest that sterilizing immunity with complete elimination of virus is unlikely. The cases also caution against the use of immune suppressive therapy in the immediate aftermath of SVR.
Assuntos
Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Imunossupressores/efeitos adversos , Viremia/imunologia , Viremia/virologia , Adulto , Antivirais/uso terapêutico , Bronquite/complicações , Bronquite/tratamento farmacológico , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Imunossupressores/administração & dosagem , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes , Recidiva , Insuficiência Renal/complicações , Insuficiência Renal/terapia , Resultado do Tratamento , Carga Viral , Viremia/complicações , Viremia/tratamento farmacológicoRESUMO
BACKGROUND: Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS: A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. RESULTS: A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than of patients who received interferon alfa-2b plus ribavirin (56 percent vs. 44 percent, P<0.001) or peginterferon alfa-2a alone (56 percent vs. 29 percent, P<0.001). The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent, 36 percent, and 21 percent, respectively, for the three regimens. Among patients with HCV genotype 1 and high base-line levels of HCV RNA, the proportions of those with sustained virologic responses were 41 percent, 33 percent, and 13 percent, respectively. The overall safety profiles of the three treatment regimens were similar; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin. CONCLUSIONS: In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Adulto , Antivirais/efeitos adversos , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/genética , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Polietilenoglicóis/efeitos adversos , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/efeitos adversos , Ribavirina/uso terapêuticoRESUMO
BACKGROUND: Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE: To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or standard dose of ribavirin. DESIGN: Randomized, double-blind trial. SETTING: 99 international centers. PATIENTS: 1311 patients with chronic hepatitis C. INTERVENTION: Peginterferon-alpha2a, 180 microg/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. MEASUREMENT: Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. RESULTS: Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-alpha2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. CONCLUSION: Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Antivirais/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes , Ribavirina/efeitos adversosRESUMO
BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS), which is also known by other names, including Gorlin-Goltz syndrome and multiple basal-cell carcinoma (BCC) syndrome, is a rare multi-systemic disease inherited in a dominant autosomal manner with complete penetrance and variable expressivity. The main clinical manifestations include multiple BCCs, odontogenic keratocysts of the jaw, hyperkeratosis of the palms and soles, skeletal abnormalities, intracranial calcifications and facial deformities. PATIENTS AND METHODS: A 31-year-old male diagnosed with Gorlin-Goltz syndrome with multiple unresectable facial BCCs was treated with the Hedgehog inhibitor vismodegib. RESULTS: After one month of therapy on vismodegib, there were significant reductions in the size of multiple BCCs on the patient's face. The patient remains on this therapy. CONCLUSION: Hedgehog pathway inhibition is an effective strategy to treat unresectable BCCs from Gorlin-Goltz syndrome. Although vismodegib shows some promising clinical results in the early phase of its use, there are concerns of possible resistance developing within months. Duration of therapy, role of maintenance treatment and drug modification to reduce resistance need to be explored in future case studies.
Assuntos
Anilidas/uso terapêutico , Síndrome do Nevo Basocelular/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Síndrome do Nevo Basocelular/patologia , Humanos , MasculinoRESUMO
BACKGROUND: Use of unmodified interferon alpha-2a in chronic hepatitis C is associated with impaired health-related quality of life during therapy. Treatment with peginterferon alpha-2a (40kD) provides an improved sustained response over unmodified interferon alpha-2a. OBJECTIVES: To compare health-related quality of life during treatment for patients receiving peginterferon alpha-2a (40kD) [Pegasys] versus unmodified interferon alpha-2a [Roferon]. DESIGN: A randomised, international, multicentre, open-label, parallel group study. SETTING: 36 centres worldwide. PATIENTS: Interferon-naïve patients (n = 531) with chronic hepatitis C. INTERVENTIONS: Peginterferon alpha-2a (40kD) 180 mirog once a week (n = 267) for 48 weeks or unmodified interferon alpha-2a 6 million IU three times a week for 12 weeks followed by 36 weeks of 3 million IU three times a week (n = 264). MEASUREMENTS: Fatigue Severity Scale and 36-item Short-Form Health Survey (SF-36). RESULTS: At weeks 2 and 12, differences favouring peginterferon alpha-2a (40kD) were seen on seven of eight domains and both summary scores of the SF-36 (p < 0.05 to p < 0.01). At weeks 2, 12 and 24, patients receiving peginterferon alpha-2a (40kD) had less disabling fatigue (p < 0.01) than those receiving unmodified interferon alpha-2a. CONCLUSION: Treatment with peginterferon alpha-2a (40kD) is associated with less disabling fatigue and less impairment in patient functioning and well-being during treatment than unmodified interferon alpha-2a. In addition to safety and efficacy, the impact on health-related quality of life may be an important consideration for physicians when selecting an optimal treatment regimen.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis , Adulto , Feminino , Nível de Saúde , Hepatite C Crônica/psicologia , Humanos , Interferon alfa-2 , Masculino , Qualidade de Vida , Proteínas Recombinantes , Resultado do TratamentoRESUMO
The combination of sucrose and starch in the presence of surface-adsorbed salivary α-amylase and bacterial glucosyltransferases increase the formation of a structurally and metabolically distinctive biofilm by Streptococcus mutans. This host-pathogen-diet interaction may modulate the formation of pathogenic biofilms related to dental caries disease. We conducted a comprehensive study to further investigate the influence of the dietary carbohydrates on S. mutans-transcriptome at distinct stages of biofilm development using whole genomic profiling with a new computational tool (MDV) for data mining. S. mutans UA159 biofilms were formed on amylase-active saliva coated hydroxyapatite discs in the presence of various concentrations of sucrose alone (ranging from 0.25 to 5% w/v) or in combination with starch (0.5 to 1% w/v). Overall, the presence of sucrose and starch (suc+st) influenced the dynamics of S. mutans transcriptome (vs. sucrose alone), which may be associated with gradual digestion of starch by surface-adsorbed amylase. At 21 h of biofilm formation, most of the differentially expressed genes were related to sugar metabolism, such as upregulation of genes involved in maltose/maltotriose uptake and glycogen synthesis. In addition, the groEL/groES chaperones were induced in the suc+st-biofilm, indicating that presence of starch hydrolysates may cause environmental stress. In contrast, at 30 h of biofilm development, multiple genes associated with sugar uptake/transport (e.g. maltose), two-component systems, fermentation/glycolysis and iron transport were differentially expressed in suc+st-biofilms (vs. sucrose-biofilms). Interestingly, lytT (bacteria autolysis) was upregulated, which was correlated with presence of extracellular DNA in the matrix of suc+st-biofilms. Specific genes related to carbohydrate uptake and glycogen metabolism were detected in suc+st-biofilms in more than one time point, indicating an association between presence of starch hydrolysates and intracellular polysaccharide storage. Our data show complex remodeling of S. mutans-transcriptome in response to changing environmental conditions in situ, which could modulate the dynamics of biofilm development and pathogenicity.
Assuntos
Biofilmes , Perfilação da Expressão Gênica , Amido/farmacologia , Streptococcus mutans/efeitos dos fármacos , Sacarose/farmacologia , Sequência de Bases , Primers do DNA , Genes Bacterianos , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Streptococcus mutans/genéticaRESUMO
BACKGROUND/AIMS: The current standard for the determination of sustained virologic response in patients treated for hepatitis C is undetectable hepatitis C virus (HCV) RNA 24 weeks following the completion of therapy. Sensitive molecular tests may permit earlier determination of sustained virologic response following the completion of therapy in end-of-treatment responders. METHODS: We examined this possibility in 1441 patients, who received 48 weeks of treatment with either standard or pegylated interferon alpha-2a. HCV RNA was determined by polymerase chain reaction assay (Amplicor HCV Monitor vs. 2.0) at baseline and monitored at 4-week intervals throughout the treatment and 24-week post-treatment follow-up periods. RESULTS: End-of-treatment and sustained response were achieved in 624 and 342 patients, respectively. For all treatments, relapse was most frequent at weeks 52 and 56 and became rare following week 60. Only six patients out of 348 patients (2%) became HCV RNA positive between weeks 60 and 72. Analysis of baseline characteristics failed to identify a specific set of parameters associated with early relapse. CONCLUSIONS: This finding suggests that determination of HCV RNA levels at 12 weeks of follow-up may be sufficient for making decisions related to the management of most patients treated with standard or pegylated interferon alpha.
Assuntos
Antivirais/administração & dosagem , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adulto , Feminino , Seguimentos , Hepacivirus/genética , Humanos , Interferon alfa-2 , Masculino , RNA Viral/análise , Proteínas Recombinantes , RecidivaRESUMO
BACKGROUND/AIMS: Baseline factors and early decline in serum hepatitis C virus RNA are predictive of sustained virological response to interferon therapy in patients with chronic hepatitis C. We evaluated the prognostic value of baseline factors and early viral RNA among patients treated with peginterferon alfa-2a (40KD). METHODS: Data were pooled from three randomized trials involving 814 patients treated with peginterferon alfa-2a (40KD) (90, 135, or 180 mirog). Stepwise and multiple logistic regression identified independent baseline factors associated with response. Receiver operating characteristic curves for both absolute values and log(10) decline in viral RNA at 4, 8, 12 and 24 weeks of therapy were created. RESULTS: Independent prognostic factors for sustained virological response included viral genotype non-1, low pretreatment viral load, age (<40 years), no cirrhosis and body weight (<85 kg). In addition, alanine aminotransferase quotient (>3) and histological activity index score (>10) were also independently prognostic. Receiver operating characteristic curves showed that detectable or less than 2-log(10) decline in viral RNA at week 12 predicted sustained virological non-response (negative predictive value is 98%) . CONCLUSIONS: In patients with chronic hepatitis C treated with peginterferon alfa-2a (40KD), the decision to continue or stop treatment can be made as early as week 12.