Treatment For Eligible Patients Research Articles

CJEM Debate Series: #TPA should be the initial treatment in eligible patients presenting with an acute ischemic stroke.

CJEM Debate Series: #TPA should be the initial treatment in eligible patients presenting with an acute ischemic stroke.

Abstract WP283: The Multiple-Encounter Multiply-Thrombolysed Telestroke Patient - A Unique Patient Population

Background: Thrombolysis with alteplase is the standard of care for the treatment of eligible patients presenting with acute ischemic stroke (AIS). Many hospitals do not have access to in-person cerebrovascular expertise, and utilize telestroke services for the remote diagnosis and treatment of AIS. Through this practice, an unusual subset of patients with multiple presentations having received thrombolysis several times has emerged. This study describes the largest known sample of this multiple-encounter population within a single teleneurology practice spanning 39 states over 4 years. Methods: A retrospective observational study of the experience of a single teleneurology practice serving over 400 hospitals from July 1, 2015 to June 30, 2019 was performed. The alteplase patient database was queried to identify patients with both multiple telestroke and multiple alteplase encounters. Demographic and clinical data were abstracted. Outcome analysis was restricted to those patients with available complete discharge data. Results: Within the queried period, 71 patients were identified to have had multiple encounters with the teleneurology practice, 46 males and 25 females. Of these, 36 patients were seen twice, 18 were seen three times, 10 were seen four times, and 7 had five or more encounters, with the maximum number of encounters of 26. Seven patients received care in multiple states. The overall alteplase rate was 58.2%. Alteplase was administered on more than one encounter in all 71 patients, with a maximum alteplase administration of 4 times in a single patient. The median NIHSS score in this population was 5. Of the 71 patients, all had stroke risk factors, 36.6% had noncerebrovascular neurological comorbidities, and 36.6% had psychiatric disease history. The symptomatic hemorrhage rate in this population was 0%. Conclusion: The observed phenomena of recurrent teleneurology encounters for patients presenting with suspected AIS symptoms and receiving alteplase at increased rates is not well-described and is poorly understood. Given the inherent risk and resource utilization associated with thrombolysis, further analysis of the characteristics of this patient population is warranted.

Comparison of Outcomes Post Autologous Stem Cell Transplant (ASCT) in Patients with Multiple Myeloma (MM) Based on Dosage of Melphalan (mel) As Part of Conditioning Therapy: Single Institutional Experience of a Large Study Group

<h3>Introduction</h3> High dose chemotherapy followed by ASCT is the standard of care in the treatment of eligible patients with MM. Melphalan has been the drug of choice for conditioning therapy at a dose of 200 mg/m² (mel 200). However, for elderly patients (older than 65 years) and renal dysfunction (serum creatinine>2), a reduced dose of 140 mg/m² (mel 140) is commonly used based on a prior retrospective study. We conducted a retrospective analysis comparing the outcomes of patients with MM who underwent ASCT at our institution at the standard dose of melphalan versus reduced dose. <h3>Objectives</h3> 1) Compare efficacy of melphalan 200mg/m² versus 140mg/m² for ASCT in MM. 2) Assess impact of age and renal dysfunction on the outcome in MM. 3) Compare the clinical characteristics of patients who underwent ASCT. <h3>Methods</h3> We performed a retrospective analysis of 1002 consecutive patients with newly diagnosed MM who underwent ASCT at The Ohio State University between 1992 through 2016. Data were collected regarding patient demographics, disease characteristics, therapy received, dose of melphalan conditioning and clinical outcomes. Progression-free survival (PFS) was defined from time of transplantation to disease progression or death, censoring those alive without progression at the last contact. Overall survival (OS) was calculated from the time of transplantation to death, censoring those alive at last contact. PFS and OS were estimated using Kaplan-Meier method. Log-rank tests were used to compare PFS and OS between the groups, and Cox proportional hazard models were used to estimate the hazard ratios (HR). <h3>Results</h3> 946 patients received high dose melphalan conditioning prior to ASCT, of which 807 patients received mel 200 while 126 patients received mel 140. Thirteen patients were excluded due to alternate dosing. Around 16% of patients in the mel 200 group were older than 65 years compared to 42.1% in the mel 140 group. More patients in the mel 140 group had ISS stage 3 MM compared to mel 200 (64.7% vs 24.6%). Renal dysfunction was seen in 69.8% of patients in the mel 140 group while 15.5% had it in the mel 200 group. PFS of patients who received mel 140 was not inferior to those who received mel 200 (p=0.29, figure 1). Overall survival of patients who received mel 200 was better than those who got mel 140 by univariate analysis (p=0.048, figure 1). However, after adjusting for age, ISS staging and renal dysfunction, the difference in OS was not significant. <h3>Conclusion</h3> Patients who got mel 140 did no worse than those who received mel 200 in terms of disease outcome as assessed by PFS and OS.

A US Budget Impact Model for Selinexor in Combination with Dexamethasone for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

BACKGROUND: Multiple myeloma is a relatively uncommon hematological cancer that occurs when the bone marrow produces malignant plasma cells that enter the blood stream. In the United States, the lifetime risk of getting multiple myeloma is 1 in 132 (0.76%). American Cancer Society estimates that about 32,110 new cases will be diagnosed and about 12,960 deaths are expected to occur among multiple myeloma patients. (American Cancer Society. Cancer Facts and Figures 2019). An increasing number of treatments are available for multiple myeloma, however, due to the highly refractory nature of the disease surviving patients must eventually resort to best supportive care (BSC). Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) for the treatment of relapsed or refractory multiple myeloma (RRMM). OBJECTIVE: To estimate the budget impact of Selinexor in combination with dexamethasone (Sel-dex) for the treatment of patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody in US. METHOD: An interactive budget impact model was developed to evaluate the addition of Selinexor for treatment of RRMM using a hypothetical health plan of 25 million lives over a time horizon of 3-years (2019-2021) after the introduction of Selinexor. The model compares the formulary without Selinexor to a formulary with Selinexor and considers direct cost only. The model was developed following guidelines from the International Society for Pharmacoeconomics and Outcomes Research. The key assumptions in the model are that there is no reasonable alternative to Selinexor besides BSC, the use of Selinexor will not meaningfully reduce the cost of BSC, and the number of patients eligible to receive Selinexor is expected to remain the same for each of the 3 years evaluated in the model. The assumed uptake rates for Selinexor were included. The average per-person drug cost for each year of treatment is calculated by accounting for the cost of the drug including dosage, frequency, and duration of treatment. The costs of treatment-emergent adverse events occurring at grade 3 or higher occurring in at least 5% of patients in the STORM trial (NCT02336815) were included. As Sel-dex is taken orally, wastage was not considered for this model. Total annual treatment costs included drug costs, AE costs, and BSC costs, and were calculated for each scenario to estimate the budget impact of making Selinexor available as a treatment for eligible patients. One-way sensitivity analysis was conducted to test the robustness of the model results and the sensitivity of the results to uncertainty in key model input parameters including time on treatment with Selinexor (weeks), uptake of Selinexor in year 1 after market entry and the drug cost of Selinexor. Results were calculated in terms of total plan, per-member-per-month (PMPM), and per-treated-member-per-month costs. RESULTS: In the hypothetical health plan of 25 million lives, the annual number of patients eligible for Selinexor was estimated to be 182. After the adoption of Selinexor, the base case results showed minimal budget impact with $0.01 per member per month incremental cost for year 1 and $0.02 for both year 2 and year 3. For Commercial and Medicare patients, the incremental cost was &lt; $0.02 per member per month for all three years. CONCLUSION: The results indicated that with limited treatment options in the later lines, Sel-dex for the treatment of multiple myeloma will have a minimal budget impact for a US health plan. Disclosures Gould: RTI International: Employment. Bassali:Karyopharm Therapeutics: Employment, Equity Ownership. Mehta:Karyopharm Therapeutics: Employment, Equity Ownership; Sanofi: Equity Ownership; Alkermes: Equity Ownership. Shah:Karyopharm Therapeutics: Employment, Equity Ownership. Mladsi:RTI International: Employment.

Prognostic Value of Right Ventricular Dysfunction and Tricuspid Regurgitation in Patients with Severe Low-Flow Low-Gradient Aortic Stenosis

Long and mid-term data in Low-Flow Low-Gradient Aortic Stenosis (LFLG-AS) are scarce. The present study sought to identify predictors of outcome in a sizeable cohort of patients with LFLG-AS. 76 consecutive patients with LFLG-AS (defined by a mean gradient <40 mmHg, an aortic valve area ≤1 cm2 and an ejection fraction ≤50%) were prospectively enrolled and followed at regular intervals. Events defined as aortic valve replacement (AVR) and death were assessed and overall survival was determined. 44 patients underwent AVR (10 transcatheter and 34 surgical) whilst intervention was not performed in 32 patients, including 9 patients that died during a median waiting time of 4 months. Survival was significantly better after AVR with survival rates of 91.8% (CI 71.1–97.9%), 83.0% (CI 60.7–93.3%) and 56.3% (CI 32.1–74.8%) at 1,2 and 5 years as compared to 84.3% (CI 66.2–93.1%), 52.9% (CI 33.7–69.0%) and 30.3% (CI 14.6–47.5%), respectively, for patients managed conservatively (p = 0.017). The presence of right ventricular dysfunction (HR 3.47 [1.70–7.09]) and significant tricuspid regurgitation (TR) (HR 2.23 [1.13–4.39]) independently predicted overall mortality while the presence of significant TR (HR 3.40[1.38–8.35]) and higher aortic jet velocity (HR 0.91[0.82–1.00]) were independent predictors of mortality and survival after AVR. AVR is associated with improved long-term survival in patients with LFLG-AS. Treatment delays are associated with excessive mortality, warranting urgent treatment in eligible patients. Right ventricular involvement characterized by the presence of TR and/or right ventricular dysfunction, identifies patients at high risk of mortality under both conservative management and after AVR.

The prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer in an unselected, consecutive population.

Little is known about prevalence of PD-L1 expression in tumor cells of unselected patients with all stages of non-small cell lung cancer. The objective of this study is to assess the prevalence of PD-L1 positivity in patients with non-small cell lung cancer, to analyze the association between PD-L1 positivity and patients' clinicopathological characteristics, and to assess the use of immune-oncologic treatment in eligible patients. All non-small cell lung cancer patients diagnosed in a 10-month period in an unselected population of 1.7 million Caucasian inhabitants were evaluated with the PD-L1 IHC 22C3 pharmDx kit. A total of 819 patients were diagnosed with non-small cell lung cancer. Samples analyzable for PD-L1 expression were obtained from 97% of patients. In a multivariate analysis with cut-off at tumor proportion score ≥50%, lower stage was associated with lower prevalence of PD-L1 positivity with an odds ratio of 0.31 for stage I vs. stage IV. A significant difference in PD-L1 expression between squamous-cell carcinoma and adenocarcinoma was observed with odds ratio for adenocarcinoma 1.8. With cut-off tumor proportion score ≥1%, attenuated effects of the same direction were seen. For neither cut-off did type and location of material used for PD-L1 analysis, age, sex, smoking history, or performance status have statistically significant impact on the PD-L1 expression. Fifty four percent of the patients who were eligible for immune-oncologic treatment were actually treated in first-line with pembrolizumab monotherapy. In conclusion, 97% of the patients had material analyzable for PD-L1. If a patient in need of immuno-oncologic treatment has shifted stage, a negative or low positive PD-L1 test performed on a biopsy taken in a lower stage might not mirror the PD-L1 expression in the new metastatic lesion. Therefore, a re-biopsy should be considered.

Frequency, Risk Factors, and Clinical Significance of Incorrect Dose of Alteplase Due to Weight Estimation in Acute Ischemic Stroke Patients: A Single-Center Retrospective Study.

Stroke is a clinical emergency requiring urgent recombinant tissue-type plasminogen activator treatment in eligible patients. The dosage of thrombolytic agent (alteplase) is weight dependent. However, many patients receive thrombolytic therapy based on weight estimation. Here, we assess the frequency of incorrect thrombolytic therapy dose as a result of weight estimation and evaluate the short-term safety and efficacy of alteplase misdose. Of 237 patients, weight was estimated in 147 (62%), of which 33 patients (22.4%) were treated with an erroneous dose of alteplase. An incorrect dose was associated with neither poor outcome nor a lower risk of hemorrhage. We conclude that hospitals should implement reliable methods for measuring patients' weight that could be easily applied and would not cause delays to the treatment of stroke patients.

Abstract TP279: The Multiple-Encounter Telestroke Patient - A Unique Patient Population

Background: Thrombolysis with alteplase is the standard of care for treatment of eligible patients presenting with acute ischemic stroke (AIS). Telestroke physicians must use available information to make timely treatment decisions remotely. Through this practice, an unusual subset of patients presenting multiple times with symptoms of AIS has emerged. This study describes the largest known sample of this multiple-encounter population within a single teleneurology practice spanning 34 states. Methods: A retrospective observational study of the experience of a single teleneurology practice serving over 400 hospitals from July 1, 2015 to August 1, 2018 was performed. The alteplase patient database was queried to identify patients with multiple telestroke encounters (n=56). Demographic and clinical data were abstracted. Results: Within the queried period, 56 patients were identified to have had multiple encounters with the teleneurology practice, 37 males and 19 females. Of these, 29 were seen twice, 10 were seen three times, 8 were seen four times, and 9 had five or more encounters. Four patients received care in multiple states. Alteplase was administered on more than one encounter in 45 patients, with a maximum alteplase administration of 4 times in a single patient. The overall alteplase rate was 54.6% (106 of 194 encounters). The median NIHSS score for patients seen in multiple encounters was 5. Of the 56 patients, 98.2% had stroke risk factors, 42.9% had noncerebrovascular neurological comorbidities, and 42.9% had psychiatric disease history. All patients presented with at least one motor symptom, while 64.3% presented with a sensory symptom, 26.8% presented with aphasia, and 55.4% presented with other neurological symptoms. Conclusions: The observance of multiple teleneurology encounters for patients presenting with AIS symptoms and receiving alteplase at high rates is anecdotal and not yet largely described. History of cerebrovascular disease is a risk factor for recurrent stroke, but the true composition of this patient population is undefined. Given the associated risks and resource utilization involved with alteplase, future study of the characteristics and disease mechanism of this population is warranted.

Long-Term Remission of Acquired von-Willebrand's Disease and Platelet Dysfunction after High-Dose Melphalan in a Patient with Multiple Myeloma

Background: Autologous stem cell transplantation is considered a standard of care treatment in eligible patients with multiple myeloma, but puts the patient at high risk for infections and bleeding complications. Acquired von-Willebrand's disease (AVWD) and acquired platelet dysfunction are rare bleeding disorders that are associated with lymphoproliferative disorders such as multiple myeloma. Patients with acquired bleeding disorders who are planned for ASCT to treat the underlying condition are considered at highest risk for bleeding complications, and optimal treatment strategies are not known. Materials and Methods: We summarized the diagnostic and therapeutic approach to a patient affected by AVWD and acquired platelet disorder related to multiple myeloma. The patient who was planned for ASCT presented with moderate to severe bleeding symptoms. Results: Acute bleeding episodes were successfully controlled and prevented during induction and consolidation therapy with immunoglobulins, whereas replacement of plasma-derived VW factor showed no clinical improvement. High-dose melphalan-based consolidation therapy supported with autologous stem-cell transplantation led to an immediate and sustainable rise of von-Willebrand antigen and activity and a subsequent normalization of platelet aggregation activity. After a follow-up of 40 weeks, the patient maintained normalized VW levels and platelet aggregation capacity. There were no further signs or symptoms of bleeding. Conclusion: This case report highlights the necessity for combined supportive and causal treatment in patients with AVWD and paraproteinemic PD. High-dose melphalan with autologous stem cell support may function as a treatment option in patients with myeloma-related AVWD.

Factors affecting complication rates of pneumonectomy in destroyed lung

This study aims to investigate the relationship between characteristics of patients who were performed pneumonectomy for destroyed lung and their surgical procedures with postoperative complications. Thirty-nine patients (19 males, 20 females; mean age 35 years; range, 6 to 71 years) who were performed pneumonectomy with a diagnosis of destroyed lung between February 2007 and October 2014 were retrospectively evaluated. Patients were divided into two as those who did not develop any postoperative complication (group 1) and those who developed a postoperative complication (group 2). Patients' characteristics and details of the surgical procedures were compared between the two groups. Twenty-nine patients (74%) were performed left pneumonectomy. Mean duration of hospital stay was nine days. During the postoperative three-month follow-up period, morbidity and mortality were reported for 13 patients (33.3%) and one patient (2.6%), respectively. No significant difference was found between groups 1 and 2 in terms of age, gender, concomitant diseases, spirometric findings, blood transfusion status, surgical resection width or methods of bronchial stump closure. Low albumin levels increased the risk of developing postoperative complications in patients who were performed surgical resection for destroyed lung. Postpneumonectomy morbidity and mortality rates were at acceptable levels. Pneumonectomy should not be avoided as surgical treatment in eligible patients with destroyed lung.

Sofosbuvir Plus Daclatasvir in Treatment of Chronic Hepatitis C Genotype 4 Infection in a Cohort of Egyptian Patients: An Experiment the Size of Egyptian Village.

Background and Aims As indicated by the World Health Organization (WHO), Egypt is positioned as the country with the world's highest prevalence of Hepatitis C virus (HCV). HCV is transmitted through unexamined blood transfusions, different employments of syringes, and poor cleansing, as per the WHO. Our study aimed at screening and management of chronic hepatitis C genotype 4 infected patients in Bardeen village, Sharkeya Governorate, Egypt, with Sofosbuvir plus Daclatasvir, as well as estimating the safety and efficacy of that regimen. Methods Screening of adult patients in Bardeen village was done from March 2016 till November 2016 using hepatitis C virus antibodies by third-generation ELISA testing. Positive results were confirmed by PCR. Patients eligible for treatment received Sofosbuvir 400 mg and Daclatasvir 60 mg daily for 12 weeks and were assessed for sustained virologic response at 12 weeks following the end of treatment (SVR 12). Results Out of 2047 subjects screened for hepatitis C virus, 249 (12.2%) showed positive results. 221 out of those 249 subjects (88.7%) had detectable RNA by PCR. Treatment of eligible patients (183 patients) with Sofosbuvir plus Daclatasvir for 12 weeks resulted in 96% achievement of sustained virologic response at week 12. Adverse events were tolerable. Conclusion Sofosbuvir plus Daclatasvir regimen is safe and effective for treatment of chronic hepatitis C Genotype 4 infected patients with minimal adverse events. HCV eradication program implemented in Egypt can be a model for other countries with HCV and limited resources. The availability of generic drugs in Egypt will help much in eradication of the virus.

Intravenous Thrombolysis for Acute Ischemic Stroke: Review of 97 Patients.

Background:Intravenous thrombolysis (IVT) has now become a standard treatment in eligible patients with acute ischemic stroke (AIS) who present within 4.5 h of symptom onset.Objective:To determine the usefulness of IVT and the subset of patients who will benefit from IVT in AIS within 4.5 h.Materials and Methods:Patients with AIS within 4.5 h of symptom onset who underwent IVT were studied prospectively. The study period was from October 2011 to October 2015.Results:A total of 97 patients were thrombolysed intravenously. The mean onset to needle time in all patients was 177.2 ± 62 min (range: 60–360). At 3 months follow-up, favorable outcome was seen in 65 patients (67.1%) and poor outcome including death in the remaining 32 patients (32.9%). Factors predicting favorable outcome was age <65 years (P = 0.02), the National Institute of Health Stroke Scale (NIHSS) <15 (P < 0.001), small vessel occlusion (P = 0.006), cardioembolism (P = 0.006), and random blood sugar (RBS) <250 mg/dl (P < 0.001). Factors predicting poor outcome was diabetes mellitus (P = 0.01), dyslipidemia (P = 0.01), NIHSS at admission >15 (P = 0.03), RBS >250 mg/dl (P = 0.01), Dense cerebral artery sign, age, glucose level on admission, onset-to-treatment time, NIHSS on admission score >5 (P = 0.03), and occlusion of large artery (P = 0.02).Conclusion:Milder baseline stroke severity, blood glucose <250 mg/dL, younger patients (<65 years), cardioembolic stroke, and small vessel occlusion benefit from recombinant tissue plasminogen activator.

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma.

High-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era predating targeted therapies and immune checkpoint inhibitors. The PROCLAIMSM registry was established to collect and analyze data for patients treated with HD IL-2 in the current era. This analysis includes 170 patients with mM and 192 patients with mRCC treated between 2005 and 2012 with survival data current as of July 27, 2015. For patients with mM, complete response (CR) was observed in 5 %, partial response (PR) in 10 %, stable disease (SD) in 22 %, and 63 % had progressive disease (PD). The median overall survival (mOS) for these patients was 19.6 months, with a median follow-up of 43.1 months. The mOS was not reached for patients achieving CR or PR, and was 33.4 months for patients with SD. For patients with mRCC, 6 % achieved CR, 9 % had PR, 22 % had SD, and 62 % had PD. The mOS was 41 months, with a median follow-up of 46.6 months. The mOS for patients who had CR and PR was not reached and was 49.6 months for patients with SD. There were no treatment-related deaths among 362 patients. The duration of mOS for patients with mM and mRCC is longer than historically reported. These data support a continued role for IL-2 in the treatment of eligible patients with mM or mRCC and warrant further evaluation of HD IL-2 in combination or sequence with other therapeutic agents.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-016-1910-x) contains supplementary material, which is available to authorized users.

SYSTEMATIC REVIEW OF COMPARATIVE STUDIES EXAMINING DIFFERENCES BETWEEN HMII AND HVAD CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICES

Cardiac transplantation remains the definitive treatment in eligible patients with end-stage heart failure. However, given the limited number of donor organs, left ventricular assist devices (LVADs) have become increasingly utilized in the management of these patients. There have been significant advancements in LVADs over the years but few studies have examined differences in clinical outcomes of the newer generation continuous flow (CF) LVADs. We therefore performed a systematic review to identify all studies conducting a comparative analysis of the newer generation CF LVADs. Specifically, we searched for comparisons between the HeartMate II (HMII) and the Heartware VAD (HVAD).

Limited Fibrosis Progression but Significant Mortality in Patients Ineligible for Interferon-Based Hepatitis C Therapy

Individuals ineligible for interferon-based hepatitis C therapy may have a worse prognosis than patients who have failed or not received treatment. To provide information about the limitations of medical treatment of hepatitis C in real-world patients. We studied 969 treatment-ineligible patients and 403 treated patients enrolled between 1/1/01 and 6/30/06; data were collected until 3/31/13. Treatment barriers were grouped into five categories and classified as health-related or health-unrelated. Fibrosis stage was assessed initially and at the end of follow-up. Mortality was determined by search of the Social Security database. Death certificates of treatment-ineligible patients were reviewed. Initially, 288 individuals had advanced fibrosis and compensated disease; 87 untreated patients developed advanced fibrosis during follow-up. Health-related treatment barriers were more commonly associated with fibrosis progression and worse survival. During follow-up, 247 untreated patients died: 47% of liver-related and 53% of liver-unrelated causes. Patients with significant comorbid illness had the worst five- (70%) and ten-year (50.5%) survival. Despite high mortality (47%) in persons with decompensated liver disease, no treatment barrier was associated with a greater incidence of liver-related death. Only significant comorbid medical illness was an independent predictor of disease progression; however, it was not associated with a greater incidence of liver-related death. Furthermore, treated patients had better 10-year survival than untreated patients on Kaplan-Meier analysis (80.3% vs. 74.5%, P=0.005). Many patients with hepatitis C will die of non-liver-related causes and may not be helped by anti-viral treatment.

New era in the treatment of chronic hepatitis C - novel direct acting antivirals

Chronic hepatitis C, without treatment, can cause liver cirrhosis, liver failure and liver cancer. The availability of new oral direct acting antivirals, such as the protease inhibitors simeprevir, asunaprevir and paritaprevir, the NS5A inhibitors daclatasvir, ledipasvir, and ombitasvir, the polymerase inhibitors Sofosbuvir and dasabuvir have resulted an enormous progress in the treatment of chronic hepatitis C, leading to >90% sustained viral response rates. Even the hard-to-treat or previously treatment ineligible patients can be cured with the combination of these drugs. Furthermore the treatment duration is much shorter, and the side effects are minimal. Today, treatment of all hepatitis C virus infected patients is recommended, and the best choices are the interferon-free options. Eradication of hepatitis C virus has become realistic, however, appropriate screening programs are mandatory to achieve this goal.

A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial

PurposeTo evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour infusion) in terms of safety, convenience and efficacy. Patients and methodsIn this randomised multicentre prospective dose-selection phase IIb superiority trial, 133 patients were randomised between doxorubicin (n=43), trabectedin (3-hour infusion, T3h) (n=47) and trabectedin (24-hour infusion, T24h) (n=43). PFS was defined as time from random assignment until objective progression by response evaluation criteria in solid tumours (RECIST 1.1), a global deterioration of the health status requiring discontinuation of the treatment, or death from any cause. ResultsThe study was terminated due to lack of superiority in both trabectedin treatment arms as compared to the doxorubicin control arm. Median PFS was 2.8months in the T3h arm, 3.1months in the T24h arm and 5.5months in the doxorubicin arm. No significant improvements in PFS were observed in the trabectedin arms as compared to the doxorubicin arm (T24h versus doxorubicin: hazard ratio (HR) 1.13, 95% confidence interval (CI) 0.67–1.90, P=.675; T3h versus doxorubicin: HR 1.50, 95% CI 0.91–2.48, P=.944). Only one toxic death occurred in the T3h arm, but treatment had to be stopped due to toxicity in 7 (15.2%) (T3h), 8 (19.5%) (T24h) and 1 (2.5%) doxorubicin patients. ConclusionDoxorubicin continues to be the standard treatment in eligible patients with advanced/metastatic soft-tissue sarcoma (STS). Trabectedin 1.5mg/m2/24-hour infusion is the overall proven approach to delivering this agent in the second-line setting for patients with advanced or metastatic STS.

Population health impact and cost-effectiveness of monitoring inactive chronic hepatitis B and treating eligible patients in Shanghai, China.

Inactive chronic hepatitis B (CHB) carriers make up the largest group of hepatitis B virus-infected patients, and China bears the largest total CHB burden of any country. We therefore assessed the population health impact and cost-effectiveness of a strategy of lifelong monitoring for inactive CHB and treatment of eligible patients in Shanghai, China. We used a computer simulation model to project health outcomes among a population cohort of CHB based on age-specific prevalence of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and cirrhosis. Using a Markov model we simulated patients' progression through a discrete series of health states, and compared current practice to a monitor and treat (M&T) strategy. We measured lifetime costs and quality-adjusted life years (QALYs) (both discounted at 3% per year), incremental cost-effectiveness ratios (ICERs), and clinical outcomes such as development of hepatocellular carcinoma (HCC). We estimated that there are 1.5 million CHB-infected persons in Shanghai. The M&T strategy costs US$20,730 per patient and yields a discounted QALY of 15.45, which represents incremental costs and health benefits of US$275 and 0.10 QALYs compared to current practice, and an ICER of US$2,996 per QALY gained. In the base case, we estimated that the M&T strategy will reduce HCC and CHB-related mortality by only around 1%. If variables such as adherence to monitoring and treatment could be substantially improved the M&T strategy could reduce HCC by 70% and CHB-related mortality by 83%. Lifelong monitoring of inactive CHB carriers is cost-effective in Shanghai according to typical benchmarks for value for money, but achieving substantial population-level health gains depends on identifying more CHB-infected cases in the population, and increasing rates of treatment, monitoring, and treatment adherence.

Comparable outcome of stem cell transplant versus bortezomib-based consolidation in myeloma patients after major response to induction

High-dose therapy with autologous stem cell transplant (ASCT) has been established as standard treatment for eligible patients with myeloma. However, whether this approach is still beneficial with new therapy is yet to be determined. Consolidation of effective therapy may be an alternative to ASCT following major response to initial induction. This retrospective case-series analysis included a total of 48 patients with newly diagnosed myeloma. All these patients achieved complete response or very good partial response to bortezomib-based induction and were eligible for ASCT; 24 of these patients proceeded with ASCT, and other 24 patients opted out of ASCT and received two additional cycles of bortezomib therapy as consolidation. With a median follow-up of 28.5 months in ASCT group and 29 months in non-ASCT group, no significant difference was seen in progression-free survival, 39 versus 32 months, P = 0.82. Median overall survival had not been reached, and the estimated 3-year overall survival rates were 87.5 and 67.5% in ASCT and non-ASCT, respectively, P = 0.97. This study provides an initial assessment of survival outcome of ASCT in comparison with non-ASCT consolidation. The additional study is required to establish the efficacy of non-ASCT consolidation.

Cost-effectiveness of Early Detection of Inactive and Treatment of Active Cases in a High Endemic Chronic Hepatitis B Region

Background: Persons with chronic hepatitis B (CHB) infection are at risk of developing cirrhosis and hepatocellular carcinoma (HCC). Early detection of active CHB through monitoring and treatment of eligible patients have the potential to prevent these diseases. Aims: We aimed to predict the disease progression in our baseline patient cohort by using risk prediction tools, and estimate the cost-effectiveness of a monitor and treat (M&T) strategy. Methods: The REVEAL-HBV study team has developed nomograms for predicting liver cirrhosis and HCC risk in patients with CHB. Baseline data such as gender, birth date, HBVDNA, ALT, HBeAg status, stage of liver disease, genotype, family history of HCC, and alcohol consumption were taken for 668 CHB patients. The cohort was divided into three subgroups according to the eligibility for treatment under the APASL guidelines; ineligible, borderline and eligible, and each were scored according to the REVEAL nomogram tools. Results: In the ineligible group, if inactive cases are being monitored and treated upon transition to active, the number of new cirrhotic and HCC cases will be reduced by 30% and 40%, respectively. For the borderline group, cirrhosis and HCC will be reduced by 63% and 72%, and for the eligible group, by 84% and 95%, respectively. If we were to implement the M&T strategy, the US$ per QALY gained, compared to do nothing strategy, for sub-groups eligible, borderline, and ineligible are $1,131, $500 and $97, respectively. Conclusions: To reduce the risk of cirrhosis and HCC, a monitor and treat strategy is cost-effective in allsubgroups.