Research interests of family physicians applying for research training.

BACKGROUND: There is an ongoing need for research to support the practice of high quality family medicine. The Family Medicine Discovers Rapid Cycle Scientific Discovery and Innovation (FMD RapSDI) program is designed to build capacity for family medicine scientific discovery and innovation in the United States. Our objective was to describe the applicants and research questions submitted to the RapSDI program in 2019 and 2020. METHODS: Descriptive analysis for applicant characteristics and rapid qualitative analysis using principles of grounded theory and content analysis to examine the research questions and associated themes. We examined differences by year of application submission and the applicant's career stage. RESULTS: Sixty-five family physicians submitted 70 applications to the RapSDI program; 45 in 2019 and 25 in 2020. 41% of applicants were in practice for five years or less (n = 27), 18% (n = 12) were in in practice 6-10 years, and 40% (n = 26) were ≥ 11 years in practice. With significant diversity in questions, the most common themes were studies of new innovations (n = 20, 28%), interventions to reduce cost (n = 20, 28%), improving screening or diagnosis (n = 19, 27%), ways to address mental or behavioral health (n = 18, 26%), and improving care for vulnerable populations (n = 18, 26%). CONCLUSION: Applicants proposed a range of research questions and described why family medicine is optimally suited to address the questions. Applicants had a desire to develop knowledge to help other family physicians, their patients, and their communities. Findings from this study can help inform other family medicine research capacity building initiatives.

Transition to adult care in cystic fibrosis: The challenges and the structure.

In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics.

Innovations in Ventricular Assist Devices for End-Stage Heart Failure.

The number of patients with end-stage heart failure (HF) continues to increase over time, but there has been little change in the availability of organs for cardiac transplantation, intensifying the demand for left ventricular assist devices (LVADs) as a bridge to transplantation. There is also a growing number of patients with end-stage HF who are not transplant candidates but may be eligible for long-term support with an LVAD, known as destination therapy. Due to this increasing demand, LVAD technology has evolved, resulting in transformative improvements in outcomes. Additionally, with growing clinical experience patient management continues to be refined, leading to iterative improvements in outcomes. With outcomes continuing to improve, the potential benefit from LVAD therapy is being considered for patients earlier in their course of advanced HF. We review recent changes in technology, patient management, and implant decision making in LVAD therapy.

Honoring 50 Years of Clinical Heart Transplantation in Circulation: In-Depth State-of-the-Art Review.

Heart transplantation has become a standard therapy option for advanced heart failure. The translation of heart transplantation from innovative experiments to long-term clinical success has married prescient insights with discipline and organization in the domains of surgical techniques, organ preservation, immunosuppression, organ donation and transplantation logistics, infection control, and long-term graft surveillance. This review explores the key milestones of the past 50 years of heart transplantation and discusses current challenges and promising innovations on the clinical horizon.

Cost-effectiveness of soluble beta-glucan gel in hard-to-heal wounds: an evaluation.

OBJECTIVE: To evaluate the cost-effectiveness of a soluble beta-glucan-containing gel as short-term adjunct therapy in the treatment of hard-to-heal wounds in a UK community health-care setting. METHODS: A comparative clinical evaluation involving consecutive patients treated for up to eight weeks with a beta-glucan-containing gel as adjunct to standard care. This was compared with consecutive patients as retrospective controls, and using the same standard care protocol from a year previously. The inclusion criteria was wounds that were slow-healing or stalled (<40% healing in four weeks). RESULTS: A total of 300 patients took part. Complete follow-up at 24 weeks was available for 144 patients in the beta-glucan group, and 136 patients in the standard care group. At 24 weeks, the beta-glucan group had a 96% healing rate compared with 75% in the standard care group (p<0.001). The improvement in healing was associated with a reduction in the mean number of weeks of treatment per patient (7.2 and 10.7 for beta-glucan and standard care, respectively), and a reduction in the mean cost of treatment (£576 versus £685 for beta-glucan and standard care, respectively). Treatment costs included nursing time, prescription medications and dressings. In a subset of ulcer wounds (50% of the full sample), at 24 weeks the beta-glucan group had a 92% healing rate compared with 46% in the standard care group (p<0.001). Mean weeks of treatment were 10.4 versus 17.6, leading to a reduction in treatment cost of £388 per patient (£1227 versus £839) over 24 weeks. CONCLUSION: The results of this evaluation suggest that short-term use of the beta-glucan gel as an adjunct to standard care on slow-healing wounds can shorten healing times and reduce NHS costs.

Patient-Reported Outcomes Following Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir.

BACKGROUND & AIMS: Chronic infection with hepatitis C virus (HCV) has many hepatic and extrahepatic manifestations, measured by patient-reported outcomes (PROs). We measured changes in PROs during HCV treatment with recently developed pangenotypic regimens and from a sustained virologic response 12 weeks after treatment ended (SVR12). METHODS: We collected PRO data from 2 multi-center, blinded, international phase 3 trials of sofosbuvir, velpatasvir, and voxilaprevir, from 748 patients previously treated with direct-acting antivirals for chronic infection with HCV of any genotype (59% HCV genotype 1, 43% with compensated cirrhosis) (POLARIS-1 and POLARIS-4). The combination of sofosbuvir, velpatasvir, and voxilaprevir was given to 445 patients, the combination of sofosbuvir and velpatasvir to 151 patients, and placebo to 152 patients. Patients completed the SF-36, FACIT-F, CLDQ-HCV, and WPAI:SHP questionnaires at baseline, during treatment, and during the follow-up period. RESULTS: There was no difference in baseline clinical or demographic features or PRO scores among the groups (all P > .05). The group that received the combination of sofosbuvir, velpatasvir, and voxilaprevir had more gastrointestinal symptoms than the groups that received sofosbuvir and velpatasvir or placebo (P = .0001). An SVR12 was achieved by 90.1% of patients who received sofosbuvir and velpatasvir vs 96.9% of patients who received sofosbuvir, velpatasvir, and voxilaprevir (P = .0008). After 12 weeks of treatment, some PRO scores improved in both treatment groups (by 2.5 or by 9.1 points, on a 0-100 scale; P < .05) but not in the placebo group. All increases in PRO scores were sustained or increased after treatment ended (an increase of up to 11.1 points at 12 weeks after treatment and an increase of up to 16.6 points at 24 weeks after treatment ended) (P < .05 for all but 2 PROs). There were no differences in PROs between the sofosbuvir and velpatasvir group vs the sofosbuvir, velpatasvir, and voxilaprevir group (all P > .05). In multivariate analysis, after adjustment for clinical and demographic factors and baseline PRO scores, receiving treatment was associated with higher PROs scores than receiving placebo (beta as high as 5.1) (P < .05). CONCLUSIONS: In an analysis of data from 2 phase 3 clinical trials of patients with chronic HCV infection of any genotype, we found the combination of sofosbuvir, velpatasvir, with or without voxilaprevir, to increase PRO scores compared with placebo. These findings indicate the comprehensive benefit of these regimens during treatment and after SVR.

In an era of highly effective treatment, hepatitis C screening of the United States general population should be considered.

BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment with all oral direct acting antiviral agents (DAA's) achieve sustained virologic response (SVR) rates of 98%. Re-assessment of general US population screening for HCV is imperative. This study compared the cost-effectiveness (CE) of three HCV screening strategies: screen all (SA), screen Birth Cohort (BCS), and screen high risks (HRS). METHODS: Using a previous designed decision-analytic Markov model, estimations of the natural history of HCV and CE evaluation of the three HCV screening strategies over a lifetime horizon in the US population was undertaken. Based on age and risk status, 16 cohorts were modelled. Health states included: Fibrosis stages 0 to 4, decompensated cirrhosis, hepatocellular carcinoma, LT, post-LT, and death. The probability of liver disease progression was based on the presence or absence of virus. Treatment was with approved all-oral DAAs; 86% were assumed to be seen annually by a primary care provider; SVR rates, transition probabilities, utilities, and costs were from the literature. One-way sensitivity analyses tested the impact of key model drivers. RESULTS: SA cost $272.0 billion [$135 279 per patient] and led to 12.19 QALYs per patient. BCS and HRS cost $274.5 billion ($136 568 per patient) and $284.5 billion ($141 502 per patient) with 11.65 and 11.25 QALYs per patient respectively. Compared to BCS, SA led to an additional 0.54 QALYs per patient and saved $2.59 billion; compared to HRS, SA led to 0.95 additional QALYs per patient and saved $12.5 billion. CONCLUSIONS: Screening the entire US population and treating active viraemia was projected as cost-saving.

13C-Mixed Triglyceride Breath Test and Fecal Elastase as an Indirect Pancreatic Function Test in Cystic Fibrosis Infants.

BACKGROUND: The 'gold standard' test for the indirect determination of pancreatic function status in infants with cystic fibrosis (CF), the 72-hour fecal fat excretion test, is likely to become obsolete in the near future. Alternative indirect pancreatic function tests with sufficient sensitivity and specificity to determine pancreatic phenotype need further evaluation in CF infants. OBJECTIVE: Evaluation of the clinical utility of both the noninvasive, nonradioactive C-mixed triglyceride (MTG) breath test and fecal elastase-1 (FE1) in comparison with the 72-hour fecal fat assessment in infants with CF. METHODS: C-MTG breath test and the monoclonal and polyclonal FE1 assessment in stool was compared with the 72-hour fecal fat assessment in 24 infants with CF. Oral pancreatic enzyme substitution (PERT; if already commenced) was stopped before the tests. RESULTS: Sensitivity rates between 82% and 100% for CF patients with pancreatic insufficiency assessed by both the C-MTG breath test and the FE1 tests proved to be high and promising. The C-MTG breath test (31%-38%) as well as both FE1 tests assessed by the monoclonal (46%-54%) and the polyclonal (45%) ELISA kits, however, showed unacceptably low-sensitivity rates for the detection of pancreatic-sufficient CF patients in the present study. CONCLUSIONS: The C-MTG breath test with nondispersive infrared spectroscopy (NDIRS) technique, as well as both FE1 tests, are not alternatives to the fecal fat balance test for the evaluation of pancreatic function in CF infants during the first year of life.

Health-related Quality of Life in Adolescent Patients With Hepatitis C Genotype 1 Treated With Sofosbuvir and Ledipasvir.

OBJECTIVE: The aim of the study was to assess the effect of treatment with ledipasvir/sofosbuvir (LDV/SOF) on the health-related quality of life (HRQL) of pediatric patients with chronic hepatitis C virus (HCV) infection. METHODS: Adolescents (12-17 years) with HCV were treated with LDV/SOF (90/400 mg daily) for 12 weeks. HRQL was assessed using the PedsQLv4.0-SF15 completed by the children and caregivers before, during, and after treatment. RESULTS: We included 100 adolescents with HCV genotype 1 infection (14.7 ±â€Š2.0 years, 1% known cirrhosis, 80% treatment-naïve, 97% sustained virologic response-12). At baseline, HRQL the caregiver- perceived HRQL scores were lower than adolescents' self-reported scores (by 6.7-7.9 points, all P < 0.01). At the end of 12 weeks of treatment, however, the caregiver-reported HRQL scores showed a significant improvement (+all P < 0.04), whereas the adolescents' self-reported scores did not change from the baseline. HRQL scores reported by caregivers remained higher than baseline (by +4.7-+7.5, P < 0.01) through 12 weeks after treatment, as did the adolescents' self-reported Emotional Functioning scores (+4.3 from baseline, P = 0.0009); observed improvements were sustained after 24 weeks of follow-up (all P < 0.04). Multivariate analysis showed that, after adjustment for location, age, and sex, having a history of anxiety and panic disorders were consistent predictors of impaired HRQL in adolescents with HCV infection (P < 0.05). CONCLUSIONS: Treatment of HCV in adolescents with LDV/SOF is associated with some improvement in HRQL. Caregivers' reports of HRQL in adolescents with HCV significantly increased with treatment and were similar to the adolescent self-reported HRQL after sustained virologic response-12.

A clinical observation evaluation of bioactive soluble beta-glucan gel compared with standard care.

OBJECTIVE: Clinicians across all health-care settings are challenged daily by wounds that are slow or static in healing due to time constraints, reduced resources and the negative impact upon the patient's quality of life (QoL). Community settings are particularly challenging due to the varied environments, patient social, psychological and financial constraints, and multi-clinician wound care monitoring. The aim of this clinical evaluation is to clinically evaluate bioactive soluble beta-glucan gel (BSBG) on those wounds that have stalled at four weeks as an adjunct to normal standards of care. METHOD: A clinical observational evaluation was undertaken within a large community setting, reviewing patients who self-presented with stalled healing/chronic wounds, and the effects upon adding a BSBG gel twice a week for eight weeks as part of their set standard care. Formulary cleansing and dressing products were continued and results monitored by a designated clinician. All data was collected as part of the patient's normal wound review routine in relation to primary outcome of wound reduction with secondary outcomes relating to pain reduction, slough and necrosis reduction, exudate reduction and adverse events. RESULTS: At six months, analysis of data demonstrated >2-times a higher rate of healing in chronic wounds with eight weeks' initial treatment and >4-times a higher rate of healing over six months in those patients with ulceration (PU, VLU, DFU). A reduction of per patient care cost saving was achieved across the treatment group compared with the standard care retrospective group. CONCLUSION: The administration of a wound healing gel within a moderate size cohort of patients presenting with chronic wounds resulted in improved wound reduction and significant cost savings.

Assessment of clinical effectiveness of haemoglobin spray as adjunctive therapy in the treatment of sloughy wounds.

OBJECTIVE: To assess use of an adjunctive topical haemoglobin spray in the treatment of sloughy wounds. METHOD: In addition to a standard wound care regimen, consecutive patients with sloughy wounds self-administered haemoglobin spray treatment twice a week until the wound was healed. All patients were followed-up for 26 weeks. Results were compared with a retrospective cohort of 100 consecutive patients, treated during the same period the previous year with standard wound care alone. Data were collected on wound characteristics including percentage of slough, exudate levels, wound pain, and wound size. RESULTS: After 26 weeks, 94/100 patients (94%) treated with haemoglobin spray were completely healed compared with 63/100 control patients (63%). Positive results were evident as early as week one with 52% mean wound size reduction using the heamoglobin spray versus 11% in the retrospective control (p<0.001). At baseline, mean slough coverage was higher in the haemoglobin group, 58% versus 44% in the control group (p<0.001). By week four, mean slough coverage was 1% in the haemoglobin versus 29% in the control group (p<0.001). Reductions in exudate and pain levels (p<0.001) were also observed. CONCLUSION: Overall, results of this evaluation showed the addition of adjunctive haemoglobin spray to standard wound care treatment achieved positive clinical outcomes for patients self-managing complicated sloughy wounds, by supporting reduction of wound exudate and slough within the complex multifaceted process of wound healing.

Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis.

BACKGROUND & AIMS: The combination of sofosbuvir and velpatasvir is used to treat patients with hepatitis C virus (HCV) infection of different genotypes. We compared the effects of this treatment regimen, with and without ribavirin, on outcomes reported by patients (patient-reported outcomes [PROs]) with HCV infection, with or without cirrhosis. METHODS: We performed a post hoc analysis of data collected from phase 3 clinical trials (ASTRAL-1, -2, -3, and -4) of 1701 patients infected with HCV of different genotypes treated with sofosbuvir and velpatasvir with ribavirin for 12 weeks (n = 87), sofosbuvir with ribavirin for 12 or 24 weeks (n = 401), and ribavirin-free sofosbuvir and velpatasvir for 12 or 24 weeks (n = 1213). In all trials, participants completed 4 PRO questionnaires (while blinded to their HCV RNA levels): the Short Form-36, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Chronic Liver Disease Questionnaire-HCV Version, and the Work Productivity and Activity Impairment: Specific Health Problem, at multiple time points. We compared baseline PROs and changes in PROs following treatment in patients without cirrhosis (n = 1112), with compensated cirrhosis (n = 338), and with decompensated cirrhosis (n = 251). RESULTS: Baseline PRO scores were as much as 33.5% lower in patients with decompensated cirrhosis than in patients without cirrhosis (P < .05). Following treatment with ribavirin-containing regimens, changes in PRO scores were similar among patients with compensated and decompensated cirrhosis (all P > .01). Treatment with these regimens increased some PRO scores by as much as 11.8% from baseline (P < .05) and reduced others, by as much as 7.1% (P < .05). Despite this, by 12 weeks after cessation of treatment with ribavirin-containing regimens, all PRO decrements resolved; PRO scores increased by as much as 14.2%, and as much as 17.1% at 24 weeks after treatment, regardless of cirrhosis status (all P > .01 between cirrhosis groups). In contrast, treatment with ribavirin-free sofosbuvir and velpatasvir increased PRO scores for patients with compensated cirrhosis, and even more so in patients with decompensated cirrhosis starting at treatment Week 4; no statistically significant decrement was observed at any time point (all 1-sided P values > .05). In multivariate analysis, compensated cirrhosis was associated with a 2.3% to 5.0% greater increase in PRO scores following treatment with sofosbuvir and velpatasvir (P < .05); decompensated cirrhosis was associated with a 5.5%-9.1% greater increase (P < .002). Clinicaltrials.gov number, NCT02201940, NCT02220998, NCT02201953, NCT02201901. CONCLUSIONS: In an analysis of data from 4 phase 3 clinical trials, we found that patients with HCV infection (especially those with decompensated cirrhosis) have significant increases in their PRO scores during treatment with sofosbuvir and velpatasvir and after achieving a sustained virologic response.

The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. There is uncertainty around the economic burden of NAFLD. We constructed a steady-state prevalence model to quantify this burden in the United States and Europe. Five models were constructed to estimate the burden of NAFLD in the United States and four European countries. Models were built using a series of interlinked Markov chains, each representing age increments of the NAFLD and the general populations. Incidence and remission rates were calculated by calibrating against real-world prevalence rates. The data were validated using a computerized disease model called DisMod II. NAFLD patients transitioned between nine health states (nonalcoholic fatty liver, nonalcoholic steatohepatitis [NASH], NASH-fibrosis, NASH-compensated cirrhosis, NASH-decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, post-liver transplant, and death). Transition probabilities were sourced from the literature and calibrated against real-world data. Utilities were obtained from NAFLD patients using the Short Form-6D. Costs were sourced from the literature and local fee schedules. In the United States, over 64 million people are projected to have NAFLD, with annual direct medical costs of about $103 billion ($1,613 per patient). In the Europe-4 countries (Germany, France, Italy, and United Kingdom), there are ∼52 million people with NAFLD with an annual cost of about €35 billion (from €354 to €1,163 per patient). Costs are highest in patients aged 45-65. The burden is significantly higher when societal costs are included. CONCLUSION: The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577-1586).

Patient-reported outcomes in patients co-infected with hepatitis C virus and human immunodeficiency virus treated with sofosbuvir and velpatasvir: The ASTRAL-5 study.

BACKGROUND & AIM: The fixed-dose combination of sofosbuvir and velpatasvir (SOF/VEL) is a ribavirin-free pan-genotypic regimen with high efficacy. We assessed the impact of SOF/VEL on patient-reported outcomes (PRO) of HIV-HCV co-infected patients. METHODS: HIV-HCV co-infected patients were treated with 12 weeks of SOF/VEL (400 mg/100 mg daily). All subjects completed four PRO questionnaires [CLDQ-HCV, SF-36, FACIT-F and WPAI:SHP] before, during and post-treatment. RESULTS: ASTRAL-5 enrolled 106 HIV-HCV co-infected patients on stable antiretroviral therapy (age: 54.2±0.9 years, cirrhosis: 17.9%, HCV genotype 1: 73.6%). SVR-12 was achieved by 95.3% of subjects. By week 4 of treatment, PRO scores improved from the baselines levels in 12 out of 26 calculated PRO domains (on average, +1.9 to +7.4 points on a universal 0-100 PRO scale, all P<.05). By the end of treatment, improvements were seen in 20/26 PRO domains (+2.5% to +11.9%, P<.03). There were no significant decrements in any PRO domains during treatment. By follow-up week 12, patients who achieved SVR-12 experienced significant improvement in 19/26 of their PRO domains (+3.2% to +13.3%, P<.05). After controlling for baseline psychiatric co-morbidities, improvements in PRO scores during treatment with SOF/VEL were similar to those seen in matched HCV-mono-infected patients treated with the same regimen (ASTRAL-1 study). In multivariate analysis, pre-treatment anxiety and concomitant use of opioids were the most consistent significant (P<.05) predictors of PRO impairment in HIV-HCV patients. CONCLUSIONS: Patients with HIV-HCV treated with SOF/VEL experience very high efficacy accompanied by early and sustained improvement of patient-reported outcomes covering all aspects of patients' experience.

A disease-specific quality of life instrument for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: CLDQ-NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are the most common causes of chronic liver disease with known negative impact on patients' health-related quality of life. Our aim was to validate a disease-specific health-related quality of life instrument useful for efficacy trials involving patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. METHODS: From a long item selection questionnaire, we selected relevant items which, by factor analysis, were grouped into domains constituting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version. The developed instrument was subjected to internal validity, test-retest reliability and construct validity assessment using standard methods. RESULTS: For development of the Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument, a 75-item-long item selection questionnaire was administered to 25 patients with non-alcoholic fatty liver disease. After item reduction, factor analysis found that 98.7% of variance in the remaining items would be explained by six factors. Thus, the resulting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument had 36 items grouped into six domains: Abdominal Symptoms, Activity, Emotional, Fatigue, Systemic Symptoms, and Worry. The independent validation group included another 104 patients with non-alcoholic fatty liver disease. The Cronbach's alphas of 0.74-0.90 suggested good to excellent internal consistency of the domains. Furthermore, the presence of obesity and history of depression were discriminated best by Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version scores (P<.05). The domains' correlations with the most relevant domains of Short Form-36 exceeded 0.70. Test-retest reliability in a subgroup of patients (N=27) demonstrated no significant within-patient variability with multiple administrations (all median differences were zero, all P>.15, intraclass correlations .76-.88). CONCLUSION: The Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version is a disease-specific health-related quality of life instrument developed and validated using an established methodology and useful for clinical trials of non-alcoholic fatty liver disease.

Health utilities using SF-6D scores in Japanese patients with chronic hepatitis C treated with sofosbuvir-based regimens in clinical trials.

BACKGROUND: Health utilities are preference-based measures for health states which are typically used in economic analyses to estimate quality-adjusted life years. Our aim is to report the standard SF-6D health utility scores in Japanese patients with hepatitis C virus (HCV) during treatment with different regimens. METHODS: Japanese patients were enrolled in clinical trials of sofosbuvir (SOF) used in combination with or without ledipasvir (LDV) and/or ribavirin (RBV). The SF-6D health utility scores were calculated at multiple time points from the SF-36 instrument. RESULTS: Four hundred ninety-four patients with HCV (genotype 1 and 2) were enrolled: 19% with cirrhosis, 48% with a prior history of anti-HCV treatment. Of those, 153 received SOF + RBV, 170 received LDV/SOF + RBV, 171 received LDV/SOF for 12 weeks; the SVR rates were: 97, 98 and 100%, respectively. Patients treated with the three regimens had similar SF-6D scores before treatment (p = 0.87): 76.1 ± 11.5. During treatment with RBV containing regimen, patients experienced a decrement in their health utility scores to 74.3 ± 12.5 by the end of treatment (p = 0.03), while patients treated with RBV-free LDV/SOF had their SF-6D scores improved to 79.2 ± 12.8 after 12 weeks of treatment (p = 0.0004). At post-treatment week 12, in patients who achieved SVR-12, the SF-6D scores were similar between the treatment regimens (p = 0.36), and an average improvement of +1.4 points from baseline (p = 0.01) was noted. In multivariate analysis, the use of RBV was independently associated with lower utility score during treatment (beta = 4.7 ± 1.6, p < 0.0001). CONCLUSION: Health utilities are lower in Japanese HCV patients and tend to improve after clearance of infection.

Topical oxygenation therapy in wound care: are patients getting enough?

Wound management is a major burden on today's healthcare provider, both clinically with regard to available resources and financially. Most importantly, it has a significant impact on the patient's quality of life and experience. Within the field of wound care these pressures, alongside an ageing population, multiple comorbidities, disease processes and negative lifestyle choices, increase incidences of reduced skin integrity and challenging wounds. In an attempt to meet these challenges alternative, innovative therapies are being explored to support the wound healing process. Wound care experts are now exploring the scientific, biological aspects of wound healing at a cellular level. They are taking wound care back to basics with the identification of elements that, if introduced as an 'adjunct' or as a stand-alone device alongside gold-standard regimens, can positively impact the static or problematic wounds that pose the most challenges to clinicians on a daily basis. This article explores the phenomenon of oxygen, its place in tissue formation and the effect of depletion on the wound healing process and highlights ways in which patients may receive benefit from non-invasive intervention to improve wound care outcomes.

Ribavirin-Free Regimen With Sofosbuvir and Velpatasvir Is Associated With High Efficacy and Improvement of Patient-Reported Outcomes in Patients With Genotypes 2 and 3 Chronic Hepatitis C: Results From Astral-2 and -3 Clinical Trials.

BACKGROUND: Until recently, the approved treatment regimens for patients with hepatitis C virus (HCV) genotypes (GTs) 2 and 3 contain sofosbuvir (SOF) and ribavirin (RBV) for 12 or 24 weeks. The impact of RBV-free pan-genotypic regimen with SOF and velpatasvir (SOF/VEL) on patient-reported outcomes (PROs) of patients with genotype 2 and 3 has not been described. METHODS: PROs data were collected from participants of ASTRAL-2 and ASTRAL-3 studies before, during, and after treatment using 4 PRO instruments (Short Form-36, Chronic Liver Disease Questionnaire-HCV, Functional Assessment of Chronic Illness Therapy-Fatigue, and Work Productivity and Activity Index: Specific Health Problem), and compared between the SOF/VEL and SOF + RBV groups. RESULTS: A total of 818 HCV patients were included: 78% treatment naive, 25% cirrhosis. The rates of nearly all adverse events were lower in the RBV-free SOF/VEL group (all P < .03). The SOF/VEL group also experienced improvement of their PROs by treatment week 4 (+1.8% on average across all PROs), which continued throughout treatment (+4.1%) and post-treatment (+5.5%). In contrast, those in the SOF + RBV group had a modest decline in their PROs starting at treatment week 4 (up to -3.7%), which lasted until the end of treatment (up to -6.4%). In multiple regression analysis, the association of a treatment regimen with end-of-treatment PROs was significant for nearly all PROs; the average beta was +5.0% for the use of SOF/VEL (reference: SOF + RBV). CONCLUSIONS: Patients receiving ribavirin-free SOF/VEL reported significantly better PRO scores during treatment compared with those receiving the RBV-containing regimen. Furthermore, the interferon- and ribavirin-free SOF/VEL regimen resulted in a rapid improvement of PROs in HCV GTs 2 and 3 patients during treatment and after achieving sustained virologic response.

Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: Results from ASTRAL-1 placebo-controlled trial.

BACKGROUND & AIMS: The new pan-genotypic regimen [sofosbuvir (SOF) and velpatasvir (VEL)] for hepatitis C virus (HCV) has been associated with high efficacy. The aim of this study was to assess patient-reported outcomes (PROs) of this regimen. METHODS: The PRO data (CLDQ-HCV, SF-36, FACIT-F, WPAI) came from the ASTRAL-1 study, a multicenter multinational blinded placebo-controlled phase 3 clinical trial of a fixed dose combination of SOF 400mg and VEL 100mg for patients with genotype 1, 2, 4, 5, and 6 compared to placebo for 12weeks. RESULTS: 624 patients received active treatment [618 achieved sustained virologic response (SVR)], and 116 received placebo. The baseline PRO scores were similar. By treatment week 4, patients receiving SOF/VEL experienced improvements in general health (on average, +2.3points), emotional well-being (+3.4), FACIT-F (+1.3), and all domains of CLDQ-HCV (+2.1 to +7.3) (all p<0.005). On the other hand, the only PRO that improved in patients receiving placebo was the worry domain of CLDQ-HCV: +4.6 (p=0.002). By the end of treatment, improvement in PRO scores with SOF/VEL continued, and no improvement was noted in the placebo. Improvement in PROs were also noted 12 and 24weeks post-treatment: +3.7, on average, in patients with SVR-12 after SOF/VEL vs. -2.6, on average, in the placebo arm (p<0.005). Multivariate analysis showed that treatment-emergent changes in PROs were predicted by receiving SOF/VEL for some summary PRO score (p<0.005). CONCLUSIONS: This placebo-controlled trial shows that patients treated with SOF/VEL experience significant improvement of their PROs during treatment and after achieving SVR. LAY SUMMARY: In patients with chronic hepatitis C infection, health-related quality of life and work productivity are often impaired due to HCV-related fatigue. Treatment of hepatitis C with interferon-based regimens, which was the standard of care for all HCV patients until recently, had substantial and potentially debilitating side effects. These regimens caused additional impairment in health-related quality of life and work productivity during treatment and shortly after treatment cessation. The newly developed interferon-free combination of sofosbuvir and velpatasvir has been shown to improve health-related quality of life during treatment, and lead to an improvement in a number of indicators of patient-reported outcomes after successful clearance of HCV and achieving sustained virologic response.