Paulina Deming

Outcomes of Treatment for Hepatitis C Virus Infection by Primary Care Providers

BACKGROUND The Extension for Community Healthcare Outcomes (ECHO) model was developed to improve access to care for underserved populations with complex health problems such as hepatitis C virus (HCV) infection. With the use of video-conferencing technology, the ECHO program trains primary care providers to treat complex diseases. METHODS We conducted a prospective cohort study comparing treatment for HCV infection at the University of New Mexico (UNM) HCV clinic with treatment by primary care clinicians at 21 ECHO sites in rural areas and prisons in New Mexico. A total of 407 patients with chronic HCV infection who had received no previous treatment for the infection were enrolled. The primary end point was a sustained virologic response. RESULTS A total of 57.5% of the patients treated at the UNM HCV clinic (84 of 146 patients) and 58.2% of those treated at ECHO sites (152 of 261 patients) had a sustained viral response (difference in rates between sites, 0.7 percentage points; 95% confidence interval, -9.2 to 10.7; P=0.89). Among patients with HCV genotype 1 infection, the rate of sustained viral response was 45.8% (38 of 83 patients) at the UNM HCV clinic and 49.7% (73 of 147 patients) at ECHO sites (P=0.57). Serious adverse events occurred in 13.7% of the patients at the UNM HCV clinic and in 6.9% of the patients at ECHO sites. CONCLUSIONS The results of this study show that the ECHO model is an effective way to treat HCV infection in underserved communities. Implementation of this model would allow other states and nations to treat a greater number of patients infected with HCV than they are currently able to treat. (Funded by the Agency for Healthcare Research and Quality and others.).

Expanding access to hepatitis C virus treatment—Extension for Community Healthcare Outcomes (ECHO) project: Disruptive innovation in specialty care†

The Extension for Community Healthcare Outcomes (ECHO) Model was developed by the University of New Mexico Health Sciences Center as a platform to deliver complex specialty medical care to underserved populations through an innovative educational model of team‐based interdisciplinary development. Using state‐of‐the‐art telehealth technology, best practice protocols, and case‐based learning, ECHO trains and supports primary care providers to develop knowledge and self‐efficacy on a variety of diseases. As a result, they can deliver best practice care for complex health conditions in communities where specialty care is unavailable. ECHO was first developed for the management of hepatitis C virus (HCV), optimal management of which requires consultation with multidisciplinary experts in medical specialties, mental health, and substance abuse. Few practitioners, particularly in rural and underserved areas, have the knowledge to manage its emerging treatment options, side effects, drug toxicities, and treatment‐induced depression. In addition, data were obtained from observation of ECHO weekly clinics and database of ECHO clinic participation and patient presentations by clinical provider. Evaluation of the ECHO program incorporates an annual survey integrated into the ECHO annual meeting and routine surveys of community providers about workplace learning, personal and professional experiences, systems and environmental factors associated with professional practice, self‐efficacy, facilitators, and barriers to ECHO. The initial survey data show a significant improvement in provider knowledge, self‐efficacy, and professional satisfaction through participation in ECHO HCV clinics. Clinicians reported a moderate to major benefit from participation. We conclude that ECHO expands access to best practice care for underserved populations, builds communities of practice to enhance professional development and satisfaction of primary care clinicians, and expands sustainable capacity for care by building local centers of excellence. (HEPATOLOGY 2010)

Partnering Urban Academic Medical Centers And Rural Primary Care Clinicians To Provide Complex Chronic Disease Care

Many of the estimated thirty-two million Americans expected to gain coverage under the Affordable Care Act are likely to have high levels of unmet need because of various chronic illnesses and to live in areas that are already underserved. In New Mexico an innovative new model of health care education and delivery known as Project ECHO (Extension for Community Healthcare Outcomes) provides high-quality primary and specialty care to a comparable population. Using state-of-the-art telehealth technology and case-based learning, Project ECHO enables specialists at the University of New Mexico Health Sciences Center to partner with primary care clinicians in underserved areas to deliver complex specialty care to patients with hepatitis C, asthma, diabetes, HIV/AIDS, pediatric obesity, chronic pain, substance use disorders, rheumatoid arthritis, cardiovascular conditions, and mental illness. As of March 2011, 298 Project ECHO teams across New Mexico have collaborated on more than 10,000 specialty care consultations for hepatitis C and other chronic diseases.

Site of infection rather than vancomycin MIC predicts vancomycin treatment failure in methicillin-resistant Staphylococcus aureus bacteraemia

BACKGROUND Therapeutic use of vancomycin is characterized by decreased susceptibilities and increasing reports of clinical failures. Few studies have examined the clinical outcomes of patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia treated with vancomycin. The primary objective was to compare clinical outcomes of patients with MRSA bacteraemia treated according to standard of care practices. METHODS Patients were included if: (i) admitted to University of New Mexico Hospital between 2002 and 2009; (ii) ≥18 years of age; (iii) had one blood culture positive for MRSA; and (iv) received vancomycin. Clinical outcomes were defined as cure, failure (relapse of infection 30 days after completion of therapy, death or change in therapy) or unevaluable. Patient demographics, source of bacteraemia, treatment regimen, and microbiological characteristics were determined. RESULTS Two hundred patients with MRSA bacteraemia were included. Sixty-one patients were unevaluable, leaving 139 patients for the final analysis. Seventy-two (51.8%) patients were cured and 67 (48.2%) experienced vancomycin failure. Vancomycin MIC(90) was 2 mg/L for both groups by Etest. Patients with endocarditis (P = 0.02) or pneumonia (P = 0.02) were more likely to fail therapy. Panton-Valentine leucocidin, loss of agr functionality and strain type were not predictors of outcomes in this study. CONCLUSIONS High failure rates were observed in patients with MRSA bacteraemia treated with vancomycin, despite high vancomycin troughs and low rates of nephrotoxicity. Predictors of vancomycin failure included endocarditis and pneumonia. In these situations, vancomycin provides suboptimal therapy.

Provision of clinical pharmacist services for individuals with chronic hepatitis C viral infection: Joint opinion of the GI/liver/nutrition and infectious diseases practice and research networks of the American College of Clinical Pharmacy

The objective of this opinion paper was to identify and describe potential clinical pharmacists’ services for the prevention and management of patients infected with the hepatitis C virus (HCV). The goals of this paper are to guide the establishment and development of pharmacy services for patients infected with HCV and to highlight HCV research and educational opportunities. Recommendations were based on the following: a review of published data on clinical pharmacist involvement in the treatment and management of HCV‐infected patients; a consensus of clinical pharmacists who provide direct patient care to HCV‐infected patients and practice in different pharmacy models, including community‐based and academic settings; and a review of published guidelines and literature focusing on the treatment and management of HCV infections. The recommendations provided in this opinion paper define the areas of clinical pharmacist involvement and clinical pharmacy practice in the treatment and management of patients with HCV. Clinical pharmacists can promote preventive measures and education about reducing HCV transmission, improve medication adherence, assist in monitoring clinical and adverse effects, recommend treatment strategies to minimize adverse effects and drug interactions, and facilitate medication acquisition and logistics that positively improve patient outcomes and reduce the health care system costs.

Therapeutic Advances in HCV Genotype 1 Infection: Insights from the Society of Infectious Diseases Pharmacists

Hepatitis C virus (HCV) is the most common blood‐borne infection in the United States. The high morbidity and mortality due to untreated infection have prompted updated screening recommendations that now include one‐time HCV screening for all patients born between 1945 and 1965, in addition to risk factor–based screening. Current guidelines recommend treatment for all patients with chronic HCV. Treatment for HCV genotype 1 has evolved dramatically since the approval of the direct‐acting antivirals. The approval of ledipasvir‐sofosbuvir, ombitasvir‐paritaprevir‐ritonavir and dasabuvir, and simeprevir with sofosbuvir has dramatically altered the treatment landscape. High sustained virologic response (SVR) rates favor treatment, yet access to care poses a challenge for patients and providers. Current and emerging data with new therapies indicate high SVR rates in treatment‐naïve and treatment‐experienced patients, including patients with cirrhosis and in other special populations. Additional data suggest the addition of ribavirin can decrease treatment duration without compromising SVR rates. Resistance is an increasing area of interest in HCV, with baseline mutations identified and the potential for the development of resistance‐associate variants in patients undergoing treatment. Due to the rapid evolution of HCV treatment, pharmacists should address challenges and play an integral role in agent selection, dosing, drug interaction screening, adverse effect monitoring, and the coordination of treatment. Clinical application of the latest information will reduce patient risk and improve outcomes.

Coinfection with human immunodeficiency virus and hepatitis C virus: challenges and therapeutic advances. Insights from the Society of Infectious Diseases Pharmacists.

In the United States, approximately 30% of all human immunodeficiency virus (HIV)-positive patients are also infected with hepatitis C virus (HCV). Both viruses share similar routes of transmission. Unlike HIV or hepatitis B virus, HCV is curable if treated and the patient achieves a sustained virologic response. The impact of coinfection includes greater morbidity and mortality, with higher rates of opportunistic disease, development of cirrhosis, and death. The standard of treatment for HIV-HCV coinfection is similar to that for HCV monoinfection and consists of pegylated interferon alfa and ribavirin. As with HCV monoinfection, the best predictor of response to therapy for HIV-HCV coinfection is infection with an HCV genotype other than genotype 1 or 4. Adherence to treatment is critical for improving response to HCV therapy. However, considerable toxicities are associated with pegylated interferon alfa and ribavirin and pose particular problems in the coinfected patient. Coinfected patients are more likely to experience significant weight loss with HCV therapy. Neutropenia and anemia are both common laboratory abnormalities that necessitate dosage reductions and are concerns for development of acquired immunodeficiency syndrome-defining events. The effect of CD4+ cell count has been evaluated both as a factor in response to HCV therapy and in stratification of risk for infection. Immunosuppression is not a contraindication to HCV therapy, although CD4+ counts above 350 cells/mm3 are associated with increased response rates in patients with HCV genotype 1 coinfection. Antiretroviral therapy does need to be adjusted to minimize adverse effects. Concomitant use of zidovudine is contraindicated because of its profound exacerbation of bone marrow suppression. The use of didanosine is also not indicated during HCV therapy because of the risks of hepatic decompensation. Controversy exists regarding the use of abacavir. Newer agents for HCV include the protease inhibitors telaprevir and boceprevir. Although results with the protease inhibitors are highly encouraging, their effects in coinfected patients have not been evaluated. Treatment for HCV in patients with HIV poses potential obstacles to success, but the benefits of viral eradication warrant the challenge of therapy.In the United States, approximately 30% of all human immunodeficiency virus (HIV)‐positive patients are also infected with hepatitis C virus (HCV). Both viruses share similar routes of transmission. Unlike HIV or hepatitis B virus, HCV is curable if treated and the patient achieves a sustained virologic response. The impact of coinfection includes greater morbidity and mortality, with higher rates of opportunistic disease, development of cirrhosis, and death. The standard of treatment for HIV‐HCV coinfection is similar to that for HCV monoinfection and consists of pegylated interferon alfa and ribavirin. As with HCV monoinfection, the best predictor of response to therapy for HIV‐HCV coinfection is infection with an HCV genotype other than genotype 1 or 4. Adherence to treatment is critical for improving response to HCV therapy. However, considerable toxicities are associated with pegylated interferon alfa and ribavirin and pose particular problems in the coinfected patient. Coinfected patients are more likely to experience significant weight loss with HCV therapy. Neutropenia and anemia are both common laboratory abnormalities that necessitate dosage reductions and are concerns for development of acquired immunodeficiency syndrome‐defining events. The effect of CD4+ cell count has been evaluated both as a factor in response to HCV therapy and in stratification of risk for infection. Immunosuppression is not a contraindication to HCV therapy, although CD4+ counts above 350 cells/mm3 are associated with increased response rates in patients with HCV genotype 1 coinfection. Antiretroviral therapy does need to be adjusted to minimize adverse effects. Concomitant use of zidovudine is contraindicated because of its profound exacerbation of bone marrow suppression. The use of didanosine is also not indicated during HCV therapy because of the risks of hepatic decompensation. Controversy exists regarding the use of abacavir. Newer agents for HCV include the protease inhibitors telaprevir and boceprevir. Although results with the protease inhibitors are highly encouraging, their effects in coinfected patients have not been evaluated. Treatment for HCV in patients with HIV poses potential obstacles to success, but the benefits of viral eradication warrant the challenge of therapy.

Taribavirin in the treatment of hepatitis C

Introduction: Treatment of chronic hepatitis C virus (HCV) is limited by substantial side effects including ribavirin-induced hemolytic anemia. Taribavirin, a ribavirin prodrug, was designed to concentrate within the liver to target HCV-infected hepatocytes while minimizing distribution within red blood cells (RBCs) and the subsequent development of hemolytic anemia. Areas covered: The objective of the review is to evaluate the efficacy and safety of taribavirin as compared with ribavirin in the treatment of chronic HCV infections. A PubMed search was performed using the following key words: viramidine, taribavirin and ribavirin analog. Additional sources included press releases on preliminary results of clinical trials of taribavirin and abstracts presented at international meetings. The literature suggests that weight-based dosing of taribavirin at 25 mg/kg demonstrates lower rates of hemolytic anemia with comparable rates of sustained virologic response (SVR) and is the optimum dose for further studies comparing the efficacy of taribavirin with weight-based dosing of ribavirin. Expert opinion: Failure to eradicate HCV may be associated with extrahepatic viral replication. The dosing strategy of taribavirin favors concentration within the liver to reduce treatment-limiting rates of anemia but may be insufficient to prevent virologic relapse.

Closing the Gap: The Challenges of Treating Hepatitis C Virus Genotype 3 Infection

The efficacy of hepatitis C virus (HCV) treatment has increased over the last 5 years to nearly 100% for many patient groups. Patients with genotype (GT) 3 HCV infection, however, and specifically cirrhotic or treatment‐experienced patients, have lower sustained virologic response (SVR) rates than patients with other GTs. Because GT 3 presents more clinical challenges than other GTs, this review focuses on the evolution and efficacy of direct‐acting antiviral (DAA) treatment options for HCV GT 3 infection after the historical standard of care with pegylated interferon and ribavirin. Our objective was to review the SVR rates with available and late‐pipeline DAAs for HCV GT 3 infection and discuss challenges with successful GT 3 treatment. Authors performed a literature search of the PubMed/MEDLINE database (inception to March 27, 2017) and narrowed the field to clinical trials published in English. Trials that evaluated alternative treatments, non‐DAA historical treatment, and DAAs not currently indicated for HCV were excluded. Trials only involving patients with human immunodeficiency virus/HCV coinfection were also excluded. Additional trials were identified from a review of the ClinicalTrials.gov database. Authors further identified references from a review of literature citations and reviewed annual meeting abstracts from the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver for pipeline and real‐world GT 3 data. Phase III trial data were not available to support all GT 3 treatment recommendations found in the guidelines. The SVR rates were lower in treatment‐experienced and cirrhotic patients with GT 3 than other HCV populations. Treatment failure was associated with resistance to current treatment regimens. Clinical studies included patients with various levels of advanced liver disease, but few patients with decompensated cirrhosis were represented. Recent advances in pharmacologic treatment with DAAs have greatly increased SVR rates in patients with all HCV GTs, but SVR rates for treatment‐experienced cirrhotic patients with GT 3 are lower than for other GTs. Given the limited data and observed SVR rates in this patient population, the optimal therapy for patients with decompensated cirrhotic GT 3 HCV infection is not yet established. Newer agents and recommendations regarding baseline resistance are likely to evolve treatment strategies in the near future.

Project ECHO: a Revolutionary Approach to Expanding Access to Modern Treatments for Hepatitis C

Despite the introduction of direct-acting antivirals which simplified treatment and significantly increased cure rates, hepatitis C virus (HCV) treatment barriers persist. The number of HCV specialists is limited, particularly in rural and medically underserved areas, and patients often do not have access to care and treatment. Project ECHO was developed to increase the number of patients optimally treated for HCV through their local primary care clinics. Since its inception, the ECHO model has been used to improve HCV access across the USA and globally. Project ECHO and the ECHO model represent a revolutionary approach to expanding access to treatment for HCV.