Search

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.

Chronic HCV infection has been associated with impairment of HRQL in both adults and paediatric patients. Our aim was to assess the HRQL of HCV-positive children treated with SOF + RBV. The data for this post hoc analysis were collected in a phase 2 open-label multinational study that evaluated safety and efficacy of SOF (400 mg/day) plus RBV (weight-based up to 1400 mg/day) for 12 or 24 weeks in adolescents with chronic HCV (GS-US-334-1112). Patients and their parents/guardians completed the PedsQL-4.0-SF-15 questionnaire at baseline, at the end of treatment and in post-treatment follow-up. We included 50 adolescents with HCV genotype 2 and 3 without cirrhosis (14.8 ± 1.9 years; male: 58%; treatment-naive: 82%; vertically transmitted HCV: 70%). After treatment, 100% of patients with HCV genotype 2 and 95% with genotype 3 achieved SVR-12. During treatment with SOF + RBV, there were no significant decrements in any of patients' self-reported or parent-proxy-reported PRO scores regardless of treatment duration (all P > .05). After treatment cessation, we recorded a statistically significant improvement in patients' self-reported Social Functioning score by post-treatment week 12: on average, +4.8 points on a 0-100 scale (P = .02). By post-treatment week 24, parent-proxy-reported School Functioning score increased by, on average, +13.0 points (P = .0065). In multivariate analysis, history of abdominal pain and psychiatric disorders were predictive of impaired HRQL in adolescents with HCV (P

Zusammenfassung Zielsetzung Die Behandlung des diabetischen Fuß-Ulkus (DFU) ist klinisch problematisch und mit hohen Kosten verbunden. Die ergänzende topische Applikation des Hämoglobinsprays Granulox® zusätzlich zum etablierten Therapiestandard der lokalen Wundversorgung erreicht einen schnelleren und häufigeren Wundverschluss insbesondere bei stagnierender Wundheilung. Die Auswirkung der zusätzlichen Gabe des Hämoglobinsprays auf die Kosten aus Sicht der Krankenversicherung soll untersucht werden. Methodik Auf Basis von klinischen Studiendaten wurde ein 28-Wochen-Markov-Modell mit den Modellzuständen „unterbrochene Wundheilung“, „normale Wundheilung“, „infizierte Wunde“, „Amputation“, „verstorben“ und „geheilt“ programmiert. Die inkrementellen Kosten-Unterschiede wurden analysiert und mit einer Sensitivitätsanalyse überprüft. Ergebnisse Patienten in der Standardtherapie des DFU verursachten über 28 Wochen Durchschnittskosten in Höhe von 1737 €, für DFU-Patienten mit zusätzlicher Gabe von Hämoglobin-Spray fielen Gesamtkosten in Höhe von 1028 € an. Behandlungspflege war der größte Kostenfaktor mit durchschnittlich 806 € in der Standardversorgung und 474 € in der um den Hämoglobin-Spray erweiterten Behandlungsstrategie. Die Kostenreduktion von insgesamt durchschnittlich 709 € bestätigte sich in dieser Größenordnung auch bei der Variation der Modellannahmen in der Sensitivitätsanalyse. Schlussfolgerung Durch eine zusätzliche Gabe des Hämoglobinsprays Granulox® können beträchtliche Kosteneinsparungen aus Sicht der Krankenversicherung im Rahmen der Wundversorgung des diabetischen Fuß-Ulkus in Deutschland erreicht werden.

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.

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.

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

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.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.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).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.

The human leukocyte antigen (HLA) genes may play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH). The aim of this study was to assess the association of HLA class I and II alleles with NASH and its histological features. Deoxyribonucleic acid (DNA) was extracted from 140 subjects (85 biopsy-proven NAFLD and 55 controls) and genotyped for HLA (-A, -B, -C, -DR1, -DR3, -DQ, and -DP). Liver biopsies were assessed for presence of NASH, degree of fibrosis and inflammation. Multivariate analysis was performed to assess associations between HLA genes and different histologic features of NAFLD. Our data for HLA class I showed that HLA-C∗4 was associated with lower risk for histologic NASH and HLA-C∗6 was protective against portal fibrosis. Conversely, HLA-B∗27 was associated with high-grade hepatic steatosis, while HLA-A∗31 was associated with increased risk for advanced fibrosis. Among HLA class II alleles, HLA-DQA1∗01 was associated with lower risk for NASH while HLA-DRB1∗03 was associated with increased risk for NASH. Our findings indicate that HLA class I and II gene polymorphism may be associated with susceptibility to NASH, fibrosis and other pathologic features and may be involved in the pathogenesis of NAFLD.

Summary Background Hepatitis C virus (HCV) treatment regimens with direct-acting antivirals have not been extensively studied in patients with decompensated cirrhosis. We assessed patient-reported outcomes (PROs) in patients with decompensated cirrhosis given a fixed-dose combination of sofosbuvir and velpatasvir with and without ribavirin. Methods This study was an exploratory analysis of data collected in a randomised, open-label phase 3 trial (ASTRAL-4) in which patients with HCV-related decompensated cirrhosis were randomly assigned to an all-oral fixed-dose combination of sofosbuvir (400 mg) and velpatasvir (100 mg) once daily for 12 weeks, sofosbuvir and velpatasvir plus oral ribavirin (weight-based 1000 mg or 1200 mg) for 12 weeks, or sofosbuvir and velpatasvir for 24 weeks. Eligible patients were aged 18 years or older with any HCV genotype and decompensated cirrhosis at screening. PROs were collected for the intention-to-treat population using four questionnaires, Short Form (36) Health Survey version 2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), the Chronic Liver Disease Questionnaire-HCV Version (CLDQ-HCV), and the Work Productivity Activity Index:HCV (WPAI), which were given prospectively to patients before, during, and after treatment. The ASTRAL-4 study is registered with ClinicalTrials.gov, number NCT02201901. Findings Patients were enrolled at 47 hepatology outpatient practices in the USA from Aug 19, 2014, to Dec 19, 2014. 267 patients with HCV-related decompensated cirrhosis were included. In patients given sofosbuvir and velpatasvir for 12 weeks (n=90), clinically significant improvements in PROs started 4 weeks after treatment initiation (+4·4 to +7·5 points on a 0–100 scale at treatment week 4). By the end of treatment, mean improvements in PROs of +5·3 to +16·0 points were noted in all PROs except for role emotional, mental component summary, and social wellbeing scores and work productivity metrics by WPAI:HCV. Similar end-of-treatment improvements (+3·8 to +17·0 points) were observed in patients given sofosbuvir and velpatasvir for 24 weeks (n=90). In patients given sofosbuvir and velpatasvir plus ribavirin (n=87), PRO scores decreased within 4 weeks of treatment (−3·6 to −6·9 points), although scores returned to the baseline levels by the end of treatment. After treatment cessation, significant improvements in all PROs were similar between the treatment groups (all p>0·01) and, by post-treatment week 24, improvements were between +4·9 and +21·2 points. In multivariate analysis, predictors of PRO impairment were treatment naivety, anxiety, use of anxiolytics, use of antidepressants, use of opioids, ribavirin use, the presence of ascites, encephalopathy, insomnia, and depression. Interpretation A clinically significant early (within 4 weeks) and sustained improvement in PROs was observed in patients with HCV-related decompensated cirrhosis who were given sofosbuvir and velpatasvir without ribavirin. A similar regimen with ribavirin resulted in a temporary decrease in PROs, which completely resolved after 8 weeks of treatment. Accompanied by high efficacy, the favourable effect of treatment on PROs improves patients' experience in this difficult-to-treat population with HCV. Funding Gilead Sciences.

It is estimated that around one in 500 people in the UK are living with a stoma, with approximately 21 000 operations that result in stoma formation being performed each year ( Colostomy Association, 2016 ). These people face a unique set of challenges in maintaining the integrity of their peristomal skin. This article explores the normal structure and function of skin and how the care and management of a stoma presents challenges for maintaining peristomal skin health. Particular focus is paid to the incidence of skin problems for those living with a stoma, whether it is temporary or permanent, and the factors that contribute to skin breakdown in this population. Wider factors such as the central role of the clinical nurse specialist and the impact of product usage on positive outcomes and health economics are also considered.

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.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.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).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.

A recent multi-centre observational evaluation investigated the effect of a topical haemoglobin spray (Granulox, Infirst), used as an adjunct to standard care, on wound size reduction in 17 patients (4 females/13 males) with 20 chronic diabetic foot ulcers (DFUs) over a 4-week period. In 14 of the 18 wounds that completed the evaluation (one patient dropped out due to an infection) there was a mean reduction of 53.8% (range: 11.9–100%). The product was acceptable to both patients and clinicians, who all found it easy to use. This article describes the outcomes for the remaining 13 patients (with 15 wounds) who continued using the spray after the 4-week evaluation ended. (Data are not available for two patients and the one patient who healed during the 4-week evaluation.) By 12 weeks, three wounds (20%) had healed, eight (53%) were progressing towards healing, three (20%) increased in size and one (7%) was slow healing.

Hepatitis C virus (HCV) modulates host lipid metabolism for its replication and lifecycle. Our aims were to assess changes in the serum lipid and distal (post-squalene) cholesterol biosynthesis metabolite profile of HCV genotypes (GT) 2 and 3 patients treated with sofosbuvir+ribavirin.Serum samples [baseline, treatment week 12, 4weeks post-treatment] were analyzed for apolipoproteins B and E (apoB/E), total cholesterol, HDL, LDL, and 11 post-squalene sterol metabolites using a GC/MS platform.We selected 127 patients (GT2 n=50, GT3 n=77), 50% cirrhotic patients, and 42% who experienced a virological relapse. At baseline, GT3 patients had lower level of serum lipids, apoB/E, 7-dehydrocholesterol, desmosterol, lathosterol, compared to GT2 (p0.006). Baseline lathosterol was lower in relapsers with cirrhosis compared to cirrhotic patients with SVR (p=0.003). From baseline to treatment week 12, serum lipids, apoB/E, and key sterol pathway metabolites (7-dehydrocholesterol, desmosterol, lathosterol, lanosterol) increased in GT3. In contrast, in GT2 patients, apoB/E and dihydrolanosterol decreased with viral suppression (p0.025). At follow-up week 4, cirrhotic SVR patients showed substantially greater increases in apoB and total sterols compared to cirrhotic relapsers regardless of HCV genotype. After adjustment for genotype and gender, baseline lathosterol was independently associated with virologic response (p=0.04).HCV GT3 is associated with reduced circulation of lipids involved in the distal cholesterol biosynthesis pathway, resulting in relative hypocholesterolemia. HCV suppression during sofosbuvir+ribavirin restores distal sterol metabolites indicating viral interference with de novo lipogenesis or selective retention by hepatocytes.

Patients with Hepatitis C virus (HCV) have a higher risk of developing mental and emotional health (MEH) issues compared with the general population.Our aim was to assess the relationship between MEH and work productivity (WP) in patients with HCV.Patients with HCV enrolled in multinational clinical trials completed 4 questionnaires (Short Form 36 [SF-36], the Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F], Chronic Liver Disease Questionnaire-Hepatitis C Virus [CLDQ-HCV], and the WP and Activity-Specific Health Problem [WPAI:SHP]) while they were not under treatment. The emotional domain (EM) of CLDQ-HCV, the role emotional, mental health, and the mental summary score of the SF-36 were used as the MEH indicators. We compared patients with an EM score of less than 4.66 (range: 1-7), which is the lowest quartile of emotional health, and those with an EM score of more than 6.33, which is the topmost quartile.A total of 4333 patients were enrolled. Of those, 3,888 had MEH issues and WP data available. Patients were 52.3 ± 9.9 years old, 65.8% of them were male, 63.7% were treatment naïve, 19.7% were cirrhotic, 29.0% reported having a history of depression, and 18.7% had a history of anxiety. Patients at the top quartile of the EM were older, were more likely to be men, had less anxiety and depression, and were less likely to be cirrhotic and fatigued, but they were more likely to be employed as compared with the patients at the lowest quartile of the EM domain (all p0.0001). Furthermore, these patients had less WP impairment (0.023 ± 0.101 vs. 0.310 ± 0.288, p0.05). Multivariate regression analysis revealed that RE and EM were both predictive of WP scores (all p0.0001), presenteeism, and absenteeism (all p0.003).In patients with HCV, impairment in MEH is predictive of lower WP.

This chapter reviews the history of heart transplantation, with emphasis on the early progress and advances which made the current state of the art possible, and reviews the evolution of the clinical field of transplant cardiology.

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.

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.

Background & Aims New interferon-free anti-HCV regimens are highly efficacious with a favorable safety profile. We assessed health-related quality of life (HRQL) and work productivity in patients with different stages of hepatic fibrosis treated with sofosbuvir+ledipasvir. Methods Four questionnaires [Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index:Specific Health Problem (WPAI:SHP)] were administered at baseline, during, and after treatment with sofosbuvir+ledipasvir+ribavirin or sofosbuvir+ledipasvir (ION-1,2,3 clinical trials). Metavir fibrosis stage was determined from pre-treatment liver biopsies. Results There were 1005 patients included (stage F0: n=94; F1: n=311; F2: n=301; F3: n=197; F4: n=102). At baseline, patients with more advanced fibrosis had more HRQL impairments, predominantly related to physical functioning (stage 0 vs. stage 4 by up to 0.126 on a normalized 0–1 scale p p >0.05 across fibrosis stages). In multivariate analysis, advanced fibrosis was independently associated with impairment of HRQL and work productivity (beta up to −0.056 in comparison with none-to-mild fibrosis, p p >0.05). Conclusions Although advanced hepatic fibrosis is associated with HRQL and work productivity impairment, viral eradication with sofosbuvir+ledipasvir leads to HRQL improvement regardless of fibrosis stage. HCV patients with early fibrosis experience similar improvement of patient reported outcomes as those with advanced fibrosis.

Background and Aim A significant number of autoantibodies have been reported in patients with non-alcoholic fatty liver disease (NAFLD) patients. In the present study, our aim was to assess the role of disease and cell-specific antibodies, namely anti-adipocyte antibodies (anti-AdAb) in patients with NAFLD and non-alcoholic steatohepatitis (NASH). Methods Flow cytometry was used to detect the presence of anti-AdAb (immunoglobulin M [IgM] and immunoglobulin G [IgG]) in sera from patients with biopsy-proven NAFLD (n = 98) and in controls (n = 49) without liver disease. Univariate and multivariate analysis was performed to draw associations between anti-AdAb IgM and IgG levels and the different clinical variables. Results Patients with NAFLD had significantly higher levels of anti-AdAb IgM and significantly lower levels of AdAb IgG when compared with controls (P = 0.002 and P

Background. Sofosbuvir-containing regimens have been approved for treatment of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients. We assessed the effect of treatment with sofosbuvir and ribavirin on patient-reported outcomes (PROs) in individuals with HIV/HCV coinfection. Methods. HIV/HCV-coinfected patients were treated for 12 or 24 weeks with sofosbuvir and ribavirin. Matched HCV-monoinfected controls were also evaluated. All subjects completed standard PRO questionnaires before, during, and after treatment. Results. Included were 497 participants from the PHOTON-1 and PHOTON-2 clinical trials. At baseline, more impairment in PRO scores was noted in HIV/HCV-coinfected patients, compared with HCV-monoinfected patients. During treatment, moderate decrements in PRO scores (change, up to −6.8% on a 0%–100% scale; P = .0053) were experienced regardless of treatment duration and were similar to those for HCV-monoinfected patients (all P > .05). In 413 HIV/HCV-coinfected patients with a virologic response sustained for 12 weeks after treatment cessation, most PRO scores improved (change, up to +7.6%; P .05). Conclusions. Patients with HIV/HCV coinfection tolerate interferon-free sofosbuvir-based anti-HCV regimens well and, despite the presence of some baseline impairment, have treatment-emergent changes in PRO scores that are similar to those of patients with HCV monoinfection. Clinical Trials Registration. {"type":"clinical-trial","attrs":{"text":"NCT01667731","term_id":"NCT01667731"}}NCT01667731 (PHOTON-1), {"type":"clinical-trial","attrs":{"text":"NCT01783678","term_id":"NCT01783678"}}NCT01783678 (PHOTON-2), {"type":"clinical-trial","attrs":{"text":"NCT01604850","term_id":"NCT01604850"}}NCT01604850 (FUSION), and {"type":"clinical-trial","attrs":{"text":"NCT01682720","term_id":"NCT01682720"}}NCT01682720 (VALENCE).

The proposed new United States allocation system incorporates extensive research into an elegant plan designed to reduce wait list mortality while preserving post-transplant outcomes. All architects are to be congratulated. However, the future cannot be reliably modeled from the past as listing practices will evolve in response to new criteria. The new system should provide a major advance if and only if it is combined with a commitment to limit the number of listed patients overall and within each high priority status to the number that could reasonably undergo timely transplantation.

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.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.We included 100 adolescents with HCV genotype 1 infection (14.7 ± 2.0 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).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.

Supplemental Digital Content is available in the text, Patient-reported outcomes (PROs) such as quality of life and work productivity are important for measuring patient's experience. We assessed PROs during and after treatment of hepatitis C virus (HCV) patients. Data were obtained from a phase 3 open label study of sofosbuvir and ribavirin (SOF + RBV) with and without interferon (IFN). Patients completed 4 PRO assessment instruments (SF-36, Functional Assessment of Chronic Illness Therapy—Fatigue, Chronic Liver Disease Questionnaire— HCV, Work Productivity and Activity—Specific Health Problem) before, during, and after treatment. A total of 533 patients with chronic HCV were enrolled; 28.9% treatment-naïve, 23.1% cirrhotic, 219 received IFN + SOF + RBV and 314 received IFN-free SOF + RBV. At baseline, there were no differences in PROs between the IFN-free and IFN-containing treatment arms (all P > 0.05). During treatment, patients receiving IFN + SOF + RBV had a substantial impairment in their PROs (up to −24.4% by treatment week 12, up to −8.3% at week 4 post-treatment). The PRO decrements seen in the SOF + RBV arm were smaller in magnitude (up to −7.1% by treatment week 12), and all returned to baseline or improved by post-treatment week 4. By 12 weeks after treatment cessation, patients who achieved sustained viral response-12 showed some improvement of PRO scores regardless of the regimen (up to +7.1%, P

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

Background and Aim Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD). A liver biopsy is considered the “gold standard” for diagnosing/staging NASH. Identification of NAFLD/NASH using non-invasive tools is important for intervention. The study aims were to: develop/validate the predictive performance of a non-invasive model (index of NASH [ION]); assess the performance of a recognized non-invasive model (fatty liver index [FLI]) compared with ION for NAFLD diagnosis; determine which non-invasive model (FLI, ION, or NAFLD fibrosis score [NFS]) performed best in predicting age-adjusted mortality. Methods From the National Health and Nutrition Examination Survey III database, anthropometric, clinical, ultrasound, laboratory, and mortality data were obtained (n = 4458; n = 861 [19.3%] NAFLD by ultrasound) and used to develop the ION model, and then to compare the ION and FLI models for NAFLD diagnosis. For validation and diagnosis of NASH, liver biopsy data were used (n = 152). Age-adjusted Cox proportional hazard modeling estimated the association among the three non-invasive tests (FLI, ION, and NFS) and mortality. Results FLI's threshold score > 60 and ION's threshold score > 22 had similar specificity (FLI = 80% vs ION = 82%) for NAFLD diagnosis; FLI 50 predicted histological NASH (92% specificity); the FLI model did not predict NASH or mortality. The ION model was best in predicting cardiovascular/diabetes-related mortality; NFS predicted overall or diabetes-related mortality. Conclusions The ION model was superior in predicting NASH and mortality compared with the FLI model. Studies are needed to validate ION.

Many children who undergo heart transplantation will survive into adulthood. We sought to examine the QOL and capacity for achievement in long-term adult survivors of pediatric heart transplantation. Adults >18 yr of age who received transplants as children (≤18 yr old) and had survived for at least 10 yr post-transplant completed two self-report questionnaires: (i) Ferrans & Powers QLI, in which life satisfaction is reported as an overall score and in four subscale domains and is then indexed from 0 (very dissatisfied) to 1 (very satisfied); and (ii) a “Metrics of Life Achievement” questionnaire regarding income, education, relationships, housing status, and access to health care. A total of 20 subjects completed the survey. The overall mean QLI score was 0.77 ± 0.16. Subjects were most satisfied in the family domain (0.84 ± 0.21) and least satisfied in the psychological/spiritual domain (0.7 ± 0.28). Satisfaction in the domains of health/functioning and socioeconomic were intermediate at 0.78 and 0.76, respectively. Most respondents had graduated from high school, reported a median annual income >$50 000/yr, and lived independently. Adult survivors of pediatric heart transplant report a good QOL and demonstrate the ability to obtain an education, work, and live independently.

Recent advances in the management of heart transplant recipients have resulted in improved survival, particularly in the early post-transplant period. Although graft rejection, infection, malignancy, and allograft vasculopathy remain important challenges to the long-term management of heart transplant recipients, active research in these fields continues to advance our understanding and improve outcomes. This review will provide an overview of modern heart transplantation, summarize our current understanding of best practices for the management of heart transplant recipients, and describe recent advances in the field and areas of active research.

The prevalence of advanced liver disease and its complications may be on the rise within the Medicare population. The study aim was trend assessment for prevalence, mortality and resource utilization of patients with advanced liver disease. A retrospective, cross-sectional design was used to analyze a national sample of non-institutionalized Medicare in/outpatients from 2005 to 2009. Cases were ascertained by International Classification of Diseases, 9th Edition. Outcomes were overall mortality (within 1 year) and resource utilization [hospital length of stay (LOS/days) and institutional costs to Medicare]. Multivariate analyses were used to estimate the odds ratios for mortality predictors; linear regression was used for resource utilization predictors. A total of 21,913 beneficiaries with advanced liver disease were identified in the Medicare inpatient and outpatient administrative data sets from 2005 to 2009. Over 70 % of the beneficiaries with advanced liver disease died during study time period with 17 % dying while hospitalized. Predictors of mortality were: admission to the intensive care unit (ICU) and increasing Charlson Comorbidity Index. Predictors for increased LOS and cost were: ICU admission and having a thoracentesis procedure (both indicators of the levels of illness). Advanced liver disease and its related complication are increasing in the Medicare population and are associated with very high mortality. Further study is warranted to understand the drivers of the increased prevalence of advanced liver disease for earlier identification and treatment.

Summary Background Type 2 diabetes is known to negatively impact the outcome of chronic liver disease. Aim To evaluate the impact of diabetes on the outcomes of liver transplants (LT). Methods Study cohort included adults (>18 years) who received LT in the US between 1994 and 2013 (The Scientific Registry of Transplant Recipients). Pre- and post-transplant diabetes was recorded in patients with mortality follow-up. Results We included 85 194 liver transplant recipients. Of those, 11.2% had history of pre-transplant diabetes. The most common indications for liver transplant were hepatitis C (36.4%), alcohol-related liver disease (20.6%), primary liver malignancy of unspecified aetiology (14.7%), cryptogenic cirrhosis (8.0%), hepatitis B (4.6%) and non-alcoholic steatohepatitis (3.9%). A total of 96.5% transplants were from deceased donors, and 7.9% donors had history of diabetes. During an average 6.5 years of follow-up, 31.3% recipients died and 8.8% had a graft failure. In multivariate survival analysis [at least 5 years of cohort follow-up (N = 35 870)], after adjustment for age, ethnicity, insurance type, history of chronic diseases, HCV infection and noncompliance, independent predictors of recipient mortality included the presence of pre-transplant diabetes [adjusted hazard ratio (95%CI) = 1.21 (1.12–1.30)] and developing diabetes post-transplant [1.06 (1.02–1.11)]. Donor's history of diabetes was also independently associated with higher mortality [1.10 (1.02–1.19)]. Furthermore, donor's history of diabetes was also associated with an increased the risk of liver graft failure [1.35 (1.24–1.47)]. Conclusions Presence of type 2 diabetes pre- and post-transplant, as well as presence of type 2 diabetes in the donors, are all associated with an increased risk of adverse post-transplant outcomes.

Background Non-alcoholic fatty liver disease (NAFLD) has been associated with coronary artery disease (CAD) and cardiac-related mortality. Aim To assess the association between endothelial dysfunction markers (Endocan, high mobility group box 1 [HMGB1], and anti-endothelial cell antibodies [AECAs]) and the risk of CAD in NAFLD. Methods Ninety-one patients scheduled for coronary angiography for chest pain were included. Of these, 77 had NAFLD (85% with documented CAD). NAFLD was diagnosed after exclusion of other causes of liver diseases and by hepatic ultrasound and/or fatty liver index. Diagnosis and severity of CAD were established with coronary angiography. Endocan (ng/mL) and HMGB1 (ng/mL) concentrations were determined in the serum using enzyme-linked immunosorbent assay technique. AECAs were quantified in sera using flow cytometry. Results NAFLD patients with CAD had higher serum endocan level as compared with NAFLD without CAD (P = 0.006). Furthermore, levels of endocan (odds ratio [OR] 38.66 [95% confidence interval {CI} 1.10–999.99]) and hyperlipidemia (OR 5.62 [95% CI 1.36–23.19]) were significantly associated with the risk of CAD and high serum high-density lipoprotein cholesterol level (OR 0.92 [95% CI 0.87–0.97]) was protective against CAD. On the other hand, serum level of HMGB1 was significantly lower in NAFLD patients with CAD than NAFLD patients without CAD (P = 0.0003). Interestingly, in our NAFLD cohort, serum endocan levels positively correlated the severity of CAD (r = 0.27; P

Whether the presence of cirrhosis influences patient-reported outcomes (PROs), including health-related quality of life, during treatment with newly available anti-HCV (hepatitis C virus) regimens is unclear. Our aim was to assess the association of cirrhosis with PROs in patients treated with sofosbuvir (SOF)-containing regimens. Four PRO questionnaires (Short Form-36 [SF-36], Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F], Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), and the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem [WPAI-SHP]) were administered to subjects receiving SOF and ribavirin (RBV; FUSION trial, N=201, 34% cirrhosis; VALENCE trial: N=333, 21% cirrhosis) and SOF, RBV, and pegylated interferon (Peg-IFN; NEUTRINO trial: N=327, 17% cirrhosis). HCV patients with cirrhosis showed significant impairment of PROs before initiation of treatment. During treatment, patients with cirrhosis treated with the IFN-free regimen experienced moderate decline in their PRO scores (0.6%-5.2% on a normalized scale of the summary scores; all P0.02). In contrast, patients with cirrhosis treated with IFN-containing regimen showed decline in PRO scores that ranged from 3.4% to 16.0% (all P0.005). Nevertheless, by follow-up week 12, no PRO decrement from baseline was observed in patients with cirrhosis regardless of the treatment regimen. Furthermore, in patients with cirrhosis with HCV who achieved sustained virological response at 12 weeks (SVR-12), some improvement in PROs from baseline was observed. During treatment, changes in PRO scores were similar between patients with and without cirrhosis for both treatment regimens (all P0.05). Independent predictors of lower PROs in patients with cirrhosis included baseline depression, anxiety, fatigue, high HCV viral load, female gender, and receiving IFN-containing treatment.Treatment with SOF+RBV with or without Peg-IFN is tolerated by HCV patients with and without cirrhosis in terms of their PRO scores. After achieving SVR-12 with the IFN-free regimen, patients with cirrhosis showed improvement in some aspects of their PROs.

Interferon (IFN) negatively impacts patients' well-being and patient-reported outcomes (PROs). Our aim was to assess PROs during treatment with an IFN-free regimen [sofosbuvir (SOF)+ribavirin (RBV)]. Four PRO questionnaires [Short Form-36 (SF-36), Chronic Liver Disease Questionnaire-HCV (CLDQ-HCV), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Work Productivity and Activity Index: Specific Health Problem (WPAI:SHP)] were administered at baseline, end-of-treatment and post-treatment to 334 HCV genotype 2 and 3 patients (naïve or treatment-experienced) enrolled in the VALENCE study. Of these, 250 genotype 3 patients were treated for 24 weeks while 73 genotype 2 and 11 genotype 3 patients received 12 weeks of treatment. Baseline PRO scores were similar between the two arms of the study. Throughout and after treatment, patients receiving 12 or 24 weeks had similar FACIT-F, CLDQ-HCV, SF-36 and WPAI:SHP scores (all p>0.05). Compared to their own baseline scores, patients receiving SOF+RBV experienced modest declines in some aspects of SF-36, CLDQ-HCV, fatigue and WPAI:SHP scores (p = 0.04 to 0.05). In patients achieving SVR-12 (regardless of the regimen), significant improvements were noted in general health (p = 0.0004), CLDQ-HCV (p

Ventilator-associated pneumonia is associated with high mortality and morbidity and significantly increases intensive care unit length of stay and costs of care. In a pre- and postintervention study, we found that the majority of patients (63%) had an antecedent condition that necessitated emergent intubation prior to surgery. Efforts should be directed to developing strategies to minimize the risk of ventilator-associated pneumonia in emergent intubations, decrease reintubations, and reduce the use of blood products.

Summary Background As baby boomers age, chronic hepatitis C (CHC) will become increasingly important in Medicare eligible group. Aim To evaluate trends in Medicare resource utilisation for CHC. Methods We analysed the Medicare in-patient and out-patient data from 2005 to 2010. For each patient, all claims with CHC as a principal diagnosis were added up and yearly CHC-related spending was calculated. Results A total of 48 880 out-patient claims for 21 655 CHC patients and 4884 hospital admission claims for 3092 patients were included. The number of in-patient (1.5–1.6/year) or out-patient (2.2–2.3/year) visits per patient did not change over time, nor did the demographic characteristics of the CHC population. The majority of this population was eligible for Medicare based on disability and the average number of diagnoses per in-patient claim (from 8.11 in 2005 to 8.60 in 2010) and per out-patient claim (from 2.18 in 2005 to 2.71 in 2010) increased (both P

Patients with atrial fibrillation (AF) undergoing cardiac surgery have higher morbidity and decreased survival. Recent data revealed that surgical ablation (SA) is performed in only 39% of these patients, with variability among surgeons. The aim of this study was to determine the impact of clinical presentation and surgeon experience when making the decision to treat AF concomitantly with another cardiac surgical procedure.Since 2005, we identified 983 nonemergent patients with preoperative AF at our institution with 41% (n=401) having a concomitant SA. Logistic regression identified independent predictors for SA. The number of SAs performed captured surgeon experience in AF ablation.Major growth in the percent of SA performed for AF was noted (31% in 2005 vs 49% in 2010; p0.001). Independent predictors (χ2=283.5, p0.001, area under the curve=0.80) for SA were found, including concomitant mitral valve surgery (odds ratio [OR]=5.81) and lower creatinine (OR=4.34). Surgeon experience predicted SA with 6% greater odds for every 10 SA cases performed (OR=1.06, p0.001). The group of surgeons with 50 or greater SA cases ablated, 57% of AF patients (301 of 526), compared with those with less than 50 cases ablated, 22% (101 of 457; p0.001).We demonstrated that patient acuity and surgeon experience are significantly associated with the decision to perform concomitant SA for AF. Only the most experienced surgeons performed SA in patients with more complex clinical presentation. These findings, together with the negative impact of AF on patient outcomes, should prompt a comprehensive approach to educate and train surgeons in the performance of SA for AF when clinically justified.

Objective Atrial fibrillation (AF) management suggests that women do not tolerate medication rhythm control strategies as well as men do; however, AF percutaneous catheter ablation has been found to be favorable. The study purpose was to compare the sex-based outcomes for patients who undergo the Cox-Maze procedure for AF. Methods Data were collected through our AF surgical ablation registry. Rhythm was verified by electrocardiogram and 24-hour holter at 6 and 12 months. General health-related quality of life (Short-Form 12) and specific AF symptom burden (Atrial Fibrillation Symptom Checklist: Frequency and Severity, version 3) were obtained at baseline and 12 months. Results Since 2005, a total of 540 patients have undergone a Cox-Maze procedure (34% were women). The women presented with higher operative risk [additive European System for Cardiac Operative Risk Evaluation (EuroSCORE), 6.71 ± 2.61 vs 5.25 ± 2.80, t = 5.85, P < 0.001], higher rates of congestive heart failure (49% vs 32%, P < 0.001), and more concomitant mitral valve procedures (32% vs 19%, P = 0.001). Perioperative outcomes were similar. Return to sinus rhythm off antiarrhythmics were not different at 6 and 12 months (78% vs 75%, P = 0.53, and 81% vs 80%, P = 1.00, respectively). Cumulative 2-year survival (93.9% for the men and 89.3% for the women) was not different for all-cause mortality (hazard ratio, 1.47; confidence interval, 0.68–3.21; P = 0.33) and cardiac-related mortality [women: 10/14 (71%) vs men 7/11 (64%), P = 1.00]. Health-related quality of life showed significant improvement; AF symptoms significantly decreased across the sexes. Conclusions Outcomes after the Cox-Maze procedure are similar across sex. Atrial fibrillation surgical ablation should be considered a treatment option for women—it is safe and effective, improves general health-related quality of life, and reduces AF symptom burden.

Steven R. Bailey, MD, FACC, FSCAI, FAHA, Moderator Andrea M. Russo, MD, FACC, FHRS, Writing Group Liaison [⁎][1] Suraj Kapa, MD, Writing Group Liaison Michael B. Alexander, MD, FACC[§][2] Steven R. Bailey, MD, FACC, FSCAI, FAHA[∥][3] Ulrika Birgersdotter-Green, MD, FHRS[∥][3] Alan S.

Background The presentation, mechanisms, and incidence of ST elevation myocardial infarction (STEMI) in heart transplant recipients have been characterized only to a limited degree in the current literature. Herein, we present a unique case of STEMI years after heart transplantation with a focus on the salient features of its diagnosis and interventions. We also provide a review of the epidemiology of this phenomenon. Case Report A 33-year-old woman who was status post cardiac transplantation for dilated cardiomyopathy presented to the clinic with mild nonspecific fatigue and concern after having noticed relative bradycardia compared with her posttransplantation baseline heart rate. Electrocardiogram (ECG) showed junctional rhythm and inferior ST elevations, likely reflecting nodal ischemia. Troponins were grossly positive and echocardiogram showed marked right ventricular dysfunction. Results Successful percutaneous coronary intervention (PCI) with aspiration thrombectomy and drug-eluting stent placement was emergently performed. The heart's rhythm soon returned to sinus tachycardia. Right ventricular wall-motion abnormalities resolved. The patient suffered no clinical sequelae of her STEMI. Conclusion This case illustrated that “classic” symptoms of STEMI may not occur at all in the setting of heart transplantation. To our knowledge, this is the first case of posttransplantation STEMI presenting as asymptomatic bradycardia, and highlights the importance of maintaining high clinical suspicion for ischemia in transplant recipients with subtle changes. In reviewing the epidemiology of this case, we locate and bundle different types of studies that have directly or indirectly looked at STEMI in heart transplantation. For a variety of putative pathophysiological reasons, STEMI is indeed a rare manifestation of the common transplant phenomenon of coronary artery vasculopathy (CAV).