Shorter Duration Of Therapy Research Articles

Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia

BackgroundImatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy.MethodsIn this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events.ResultsThe median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment.ConclusionsAlmost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840.)

Allergen-specific immunotherapy prescription patterns in veterinary practice: a US population-based cohort study.

Poor adherence to continuing allergen-specific immunotherapy treatment (ASIT) may be an issue in veterinary medicine. No studies describe how allergen tests are used in general veterinary practice, including the percentage of patients that receive ASIT after allergen testing. Assess veterinary ASIT patterns in United States general practices. Dogs (n=2,557) and 121 cats allergen-tested at 177 hospitals (173 general practice and four specialty practices) in 44 states. Invoiced service descriptions of allergen tests and ASIT orders were retrieved from an aggregated database of veterinary practices. In general practice, 42% (992 of 2,360) of patients did not begin ASIT after allergen testing. ASIT was not refilled for 29% (398 of 1,368) of patients after the initial order. ASIT was initiated and refilled more often in dogs (56.6%, 71.4%, respectively) than cats (38%, 67.4%). Specialty practice patients had the highest ASIT initiation (94.4%) and refill (92.7%) percentages in comparison to general practices (P<0.001). Size, age, geographical region and type of practice were associated with whether dogs were started on ASIT. Geographical region was also associated with refilling a prescription for ASIT, which was considered to be evidence of adherence to continuing treatment. Almost one third of clients failed to continue ASIT beyond the initial order, which is a much shorter duration of therapy than the 12months recommended for determining ASIT efficacy. A large number of general practice patients did not begin ASIT after allergen testing, likely due to differences in how clinicians in general and dermatology practices use allergen tests.

Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 15 October 2016

Treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. Indication of therapy in patients with no contraindication is based on demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Therefore, expensive novel direct acting antiviral combinations as first line treatment are reimbursed only, if the freely available, but less effective and more toxic pegylated interferon plus ribavirin dual therapy deemed to prone high chance of adverse events and/or low chance of cure. Priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund and patient's organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv. Hetil., 2017, 158(Suppl. 1), 3-22.

Impact of the duration of antibiotics on clinical events in patients with Pseudomonas aeruginosa ventilator-associated pneumonia: study protocol for a randomized controlled study

BackgroundVentilator-associated pneumonia (VAP) accounts for 25% of infections in intensive care units. Compared to a long duration (LD) of antibiotic therapy, a short duration (SD) has a comparable clinical efficacy with less antibiotic use and less multidrug-resistant (MDR) pathogen emergence, with the exception of documented VAP of non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA). These results have led the American Thoracic Society to recommend SD therapy for VAP, except for PA-VAP. Thus the beneficial effect of SD therapy in PA-VAP is still a matter of debate. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) versus prolonged antibiotic therapy (15 days) in PA-VAP.Methods/designThe impact of the duration of antibiotics on clinical events in patients with Pseudomonas aeruginosa ventilator-associated pneumonia (iDIAPASON) trial is a randomized, open-labeled non-inferiority controlled trial, conducted in 34 French intensive care units (ICUs), comparing two groups of patients with PA-VAP according to the duration (8 days or 15 days) of effective antibiotic therapy against PA. The primary outcome is a composite endpoint combining day 90 mortality and PA-VAP recurrence rate during hospitalization in the ICU. Furthermore, durations of mechanical ventilation and hospitalization, as well as number and types of extrapulmonary infections or acquisition of MDR pathogens during the hospitalization in the ICU will be recorded. Recurrence with predefined criteria (clinical suspicion of VAP associated with a positive quantitative culture of a respiratory sample) will be evaluated by two independent experts.DiscussionDemonstrating that an SD (8 days) versus LD (15 days) therapy strategy in PA-VAP treatment is safe and not associated with an increased mortality or recurrence rate could lead to a change in practices and guidelines in the management of antibiotic therapy of this frequent ICU complication. This strategy could lead to decreased antibiotic exposure during hospitalization in the ICU and in turn reduce the acquisition and the spread of MDR pathogens.Trial registrationClinicalTrials.gov: NCT02634411. Registered on 19 November 2015.

Short duration of antibiotic therapy in hospitalized patients with community-acquired pneumonia: results from the CAPO International Cohort Study

Short duration of antibiotic therapy in hospitalized patients with community-acquired pneumonia: results from the CAPO International Cohort Study

Duración de la antiagregación dual postintervencionismo percutáneo

IntroductionWith the use of first-generation drug-eluting stents, the risk of thrombosis is of 1.9% at 18 months, with consequences that are usually severe and are potentially fatal. Dual antiaggregation therapy, that prevents such effects, entails a bleeding risk that is increased according to its duration, therefore, trying to achieve a balance between risk and benefit is the key goal. ObjectiveTo present current evidence of the optimal duration of dual antiaggregation therapy and to provide guidelines to establish the duration for patients.Dual antiaggregation therapy seeks to avoid the risk of early thrombosis and to reduce coronary events not related to the initial one, specially in patients with high risk of cardiovascular events or late thrombosis. Short duration therapy can be a safer alternative than the standard of one year and without a difference in patients with low cardiovascular risk. Long duration antiaggregation therapy reduces the risk of stent thrombosis and coronary events, but can increase the risk of a clinically important bleeding. ConclusionsUntil today literature does not allow to define an ideal time for dual antiaggregation therapy; this must be defined according to each particular case.

Utilization Patterns and Resource Use in Relapse/Refractory Hodgkin Lymphoma (rrHL) Patients Treated with Brentuximab Vedotin (BV)

Background: Real-world data on treatment patterns and economic burden associated with rrHL are limited. The study aimed to describe BV utilization, post-BV therapies, health care resource utilization (HCRU) and costs among rrHL patients treated with BV in US clinical practice.Methods: This is a retrospective database analysis of the Truven Health MarketScan Commercial and Medicare Database. Patients were included if they initiated BV treatment for HL between Jan 1, 2012 and Jun 30, 2014, were ≥18 yrs, and had ≥6 mos continuous enrollment before and after the 1st BV dose (index date). If two or more drugs were started within 30 days, they were considered as one regimen. Line of therapy (LOT) was defined when a new treatment was introduced or there was a treatment gap >60 days. Time to next treatment (TTNT) was defined from initiation of the LOT to initiation of subsequent LOT. Duration of treatment (DOT) and TTNT were evaluated based on Kaplan-Meier method. HCRU (events/person-months) and costs (per patient per month, PPPM) were calculated by LOT. The total costs included inpatient costs, outpatient costs and pharmacy costs.Results: A total of 219 patients were included in the study. On average, patients were observed for 2.7 yrs prior to and 1.1 yrs post to initiation of BV. During the observational period, 88 patients had transplant (SCT), including 50 having SCT prior to initiation of BV. Median age at index date was 46 yrs among all patients and 40 yrs among patients with SCT. For BV, median DOT was 2.1 mos and TTNT was 6.2 mos. Rate of outpatient visits, inpatient visits, ER visits and hospice care visits, per person-month, were 5.04, 0.08, 0.09, and 0.09, respectively. Mean total costs per person was $167,152, with outpatient costs being the largest cost driver ($144,583). Mean PPPM cost was $24,593. Of the 219 patients, 126 (57.5%) patients received subsequent systemic therapy (ST) after discontinuing BV. For subsequent ST post-BV, median DOT was 1.5 mos with BV (12.8%a), GVD/GV (10.5%), bendamustine (6.8%) gemcitabine (4.6%) and fludarabine (1.8%) being most common. Rate of outpatient visits, inpatient visits, ER visits and hospice care visits, per person-month, were 5.84, 0.18, 0.10, and 0.01, respectively. Mean total costs per person were $139,146, inpatient costs were $69,043, and outpatient costs were $65,233. Mean PPPM cost was $28,290.Conclusions: Short duration of therapy was observed for both BV and subsequent ST post-BV. Costs over $24K per month were incurred for each patient during BV treatment course and over $28K per month during subsequent ST post-BV course. Findings underscore substantial economic burden in rrHL patients treated with BV. [Display omitted] DisclosuresShao:Merck & Co., Inc.: Employment. Liu:Merck & Co., Inc.: Employment. Zhou:Merck & Co.: Employment. Raut:Merck & Co.: Employment. Monberg:Merck & Co.: Employment. Cao:Merck & Co.: Employment. Ricart:Pfizer: Equity Ownership; Merck & Co.: Employment. Balakumaran:Merck & Co.: Employment, Other: stock, stock options.

A Case of Acute Liver Failure during Ritonavir-Boosted Paritaprevir, Ombitasvir and Dasabuvir Therapy in a Patient with HCV Genotype 1b Cirrhosis

Background: Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir plus Ribavirin is one of the current recommended therapies for HCV genotype 1b monoinfected patients in compensated (Child-Pugh A) cirrhosis. Whether it is known that the worsening of liver function is a rare but possible complication of Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir therapy, to our knowledge no description of treatment-related acute liver failure is available in the literature.&#x0D; Case presentation: An 84-year-old Caucasian man with chronic compensated HCV genotype 1b cirrhosis received Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir plus Ribavirin therapy. After 13 days he developed grade 4 hyperbilirubinaemia and ascites. Even though treatment was promptly stopped, patient’s clinical condition worsened, and he underwent hospitalization, several paracentheses, and developed sub-acute kidney injury. The bilirubinemia returned under three times the upper normal limit only after five months. Notably, he achieved sustained virological response despite the very short duration of therapy.&#x0D; Conclusion: Hepatic decompensation and acute liver failure are rare but severe complications of Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir plus Ribavirin therapy in patients with compensated cirrhosis. Close monitoring for signs or symptoms of worsening of liver disease is mandatory, and further research for stratifying risk factors are required.&#x0D; Abbreviations: 3D: Ritonavir-boosted Paritaprevir, Ombitasvir and Dasabuvir; AKI: Acute Kidney Injury; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; GGT: gamma-glutamyl transpeptidase; GT1b: Genotype 1b; HCV: Hepatitis C Virus; INR: International Normalized Ratio; MELD: Model for End-Stage Liver Disease; RBV: Ribavirin; UNL: Upper Normal Limit.

Management of Premenstrual Syndrome: Green-top Guideline No. 48.

Management of Premenstrual Syndrome: Green-top Guideline No. 48.

Phase III trial comparing 3–6 months of adjuvant FOLFOX4/XELOX in stage II–III colon cancer: safety and compliance in the TOSCA trial

Six months of oxaliplatin-based adjuvant chemotherapy is standard of care for radically resected stage III colon cancer and an accepted option for high-risk stage II. A shorter duration of therapy, if equally efficacious, would be advantageous for patients and Health-Care Systems. TOSCA ['Randomized trial investigating the role of FOLFOX-4 or XELOX (3 versus 6 months) regimen duration and bevacizumab as adjuvant therapy for patients with stage II/III colon cancer] is an open-label, phase III, multicenter, noninferiority trial randomizing patients with high-risk stage II or stage III radically resected colon cancer to receive 3 months (arm 3 m) versus 6 months (arm 6 m) of FOLFOX4/XELOX. Primary end-point was relapse-free survival. We present here safety and compliance data. From June 2007 to March 2013, 3759 patients were accrued from 130 Italian sites, 64% receiving FOLFOX4 and 36% XELOX in either arm. Treatment completion rate without any modification was 35% versus 12% and with delays or dose reduction 52% versus 44% in arm 3 and 6 m. Treatment was permanently discontinued in 8% (arm 3 m) and 33% (arm 6 m). In arm 6 m, 50% of patients discontinuing treatment did so after completing 80% of planned program. Grade 3+ toxicities were higher in arm 6 m than that in 3 m. Grade 2+ neuropathy was 31.2% versus 8.8% (P < 0.0001) while grade 3+ was 8.4 versus 1.3 (P < 0.0001), in arm 3 and 6 m. Seven deaths within 30 days from last treatment administration in arm 6 m and three deaths in arm 3 m were observed (0.3% versus 0.1%, P = 0.34). TOSCA is the first trial comparing 3 versus 6 months of adjuvant chemotherapy completing accrual within the international initiative of treatment duration evaluation (International Duration Evaluation of Adjuvant, IDEA). High compliance to treatment in control arm will allow a correct assessment of potential differences between the two treatment durations. NCT00646607.

PIN88 - Value of Expanding Hcv Treatment Capacity in Germany Through Novel, Effective and Shorter Duration Therapies

PIN88 - Value of Expanding Hcv Treatment Capacity in Germany Through Novel, Effective and Shorter Duration Therapies

TCT-267 Clinical outcomes of diabetic patients treated with an amphilimus-eluting stent and a short duration of dual antiplatelet therapy in routine clinical practice: first results of the Utrecht Cre8 (U-Cre8) Registry

TCT-267 Clinical outcomes of diabetic patients treated with an amphilimus-eluting stent and a short duration of dual antiplatelet therapy in routine clinical practice: first results of the Utrecht Cre8 (U-Cre8) Registry

Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.

In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.

Prolonged vs Short Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With or Without Peripheral Arterial Disease

Patients with concomitant peripheral arterial disease (PAD) experience worse cardiovascular outcomes after percutaneous coronary intervention (PCI). To assess the efficacy and safety of prolonged (24 months) vs short (≤6 months) dual antiplatelet therapy (DAPT) in patients with PAD undergoing PCI. This subanalysis of the randomized Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) trial assessed unselected patients from tertiary care hospitals with stable coronary artery disease or acute coronary syndromes with or without concomitant PAD from December 2006 to December 2008. Data analysis was performed from January 7 to April 4, 2016. Percutaneous coronary intervention. Rates of the primary efficacy end point, composite of death, myocardial infarction, or cerebrovascular accidents, and occurrence of the key safety end point, a composite of Bleeding Academic Research Consortium type 2, 3, or 5. This analysis comprised 246 and 1724 patients with and without PAD, respectively. In the patients with PAD, mean (SD) age was 73.2 (9.2) in the prolonged group and 75.7 (8.7) years in the short DAPT group, and 97 (82.2%) were male in the prolonged group and 92 (71.9%) were male in the short DAPT group. In the patients without PAD, mean (SD) age was 67.1 (11.2) years in the prolonged group and 66.8 (11.3) years in the short DAPT group, and 667 (76.8%) were male in the prolonged group and 655 (76.6%) were male in the short DAPT group. Status of PAD was associated with a higher risk of death and ischemic events (hazard ratio [HR], 2.80; 95% CI, 2.05-3.83; P < .001). Prolonged vs short DAPT conveyed a lower risk of the primary efficacy end point in patients with PAD (19 [16.1%] vs 35 [27.3%]; HR, 0.54; 95% CI, 0.31-0.95; P = .03) but not in patients without PAD (81 [9.3%] vs 63 [7.4%]; HR, 1.28; 95% CI, 0.92-1.77; P = .15), with positive interaction (P = .01). The risk of definite or probable stent thrombosis was significantly lower in patients with PAD treated with prolonged compared with short DAPT (HR, 0.07; 95% CI, 0-1.21; P = .01). Bleeding Academic Research Consortium type 2, 3, or 5 bleeding occurred in 6 patients with PAD (5.2%) receiving prolonged DAPT relative to 8 (6.9%) of those receiving short DAPT (HR, 0.77; 95% CI, 0.27-2.21; P = .62), with a significant interaction (P = .04) compared with patients without PAD. Peripheral artery disease confers a poor prognosis in patients undergoing PCI in the setting of stable coronary artery disease or acute coronary syndromes. Prolonged DAPT lowers the risk of ischemic events with no apparent bleeding liability in this high-risk group. clinicaltrials.gov Identifier: NCT00611286.

Effect of virgin olive oil versus piroxicam phonophoresis on exercise-induced anterior knee pain.

The main purpose of this study was to evaluate the effects of virgin olive oil phonophoresis on female athletes' anterior knee pain (AKP). A double blinded randomized clinical trial was conducted. Ninety-three female athletes suffering from AKP voluntarily participated in this study. Patients were randomly assigned into olive oil (n=31), piroxicam (n=31) or base gel phonophoresis (n=31) groups. At the baseline visit, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was filled by subjects who were then treated with olive oil, piroxicam or pure phonophoresis for 12 sessions. After 6 and 12 sessions of physiotherapy, subjects filled the questionnaire again. Main outcomes were significant improvement in pain, stiffness, physical function, and total WOMAC scores. Although, there was a significant reduction in symptoms of AKP at the end of the therapy in all groups (p<0.05), but in olive oil group, this improvement was seen after 6 sessions of treatment (p<0.001). A significant difference between olive oil group and piroxicam and/or phonophoresis group was observed after 6 sessions of therapy (p<0.05). It could be proposed that phonophoresis with virgin olive oil is as effective as piroxicam gel on lowering WOMAC scores of AKP in female athletes and also has several beneficial properties including faster effect and shorter duration of therapy. The exact mechanism of beneficial action of virgin olive oil on AKP is not clear and requires further studies.

Adverse Event Reporting for Proton Pump Inhibitor Therapy: An Overview of Systematic Reviews.

To assist clinicians in counseling patients regarding the risk of adverse events from proton pump inhibitors (PPIs), by synthesizing evidence from published systematic reviews of antireflux therapy. Cochrane Library, CINAHL, PubMed, Web of Knowledge. Overview based on PRISMA reporting standards (preferred reporting items for systematic reviews and meta-analyses) of English-language meta-analyses and systematic reviews of PPI therapy for reflux disease through December 2014. Two independent investigators assessed study eligibility, rated the review quality with AMSTAR criteria (assessing the methodological quality of systematic reviews), and abstracted data for adverse events. Thirty-three systematic reviews met inclusion criteria. The most commonly reported adverse events were community-acquired pneumonia (odds ratios, 1.04-1.92), with a greater association noted with shorter duration of therapy and higher doses. Hip fractures were also associated with PPI use (odds ratios, 1.16-1.50), especially with long-term therapy. Last, enteric infection with Clostridium difficile was more common with PPI therapy (odds ratios, 1.69-1.33). Other less commonly reported adverse events included electrolyte and vitamin deficiency. Risk factors for adverse events are reported in the text. Our overview shows that PPI therapy is associated with significant and potentially serious adverse events that should be discussed with patients. The effect sizes and risk factors provided should facilitate this discussion and promote shared decision making.

Impact of Antimicrobial Stewardship on Outcomes in Hospitalized Veterans With Pneumonia

PurposeThe purpose of this study was to evaluate the impact of an antimicrobial stewardship program (ASP) on outcomes for inpatients with pneumonia, including length of stay, treatment duration, and 30-day readmission rates. MethodsA retrospective chart review comparing outcomes of veterans admitted with pneumonia before (2005–2006) and after (2013–2014) implementation of an ASP was conducted; pneumonia was defined according to International Classification of Diseases, Ninth Revision (ICD-9) codes. Infectious diseases physicians and pharmacist in the ASP provided appropriate recommendations to the primary medicine teams. Bivariate analysis of baseline characteristics and comorbid conditions were performed between the time frames. Least squares regression was used to analyze length of stay, time of IV to PO conversions, and duration of antibiotics. Multivariate logistic regressions were used to determine odds of 30-day readmission and odds of Clostridium difficile infections between time periods. FindingsThere were 86 patients in the pre-ASP period and 88 patients in the ASP period. Mean length of stay decreased from 8.1 to 6.6 days (P = 0.02), total duration of antibiotic therapy decreased from 12 to 8.5 days (P < 0.0001), and time of IV to PO antibiotic conversions decreased from 5.3 to 3.9 days (P = 0.0003), before ASP and during ASP, respectively. The odds ratio of 30-day readmission before ASP was 2.78 and 0.36 during the ASP (P = 0.05). The odds ratios of Clostridium difficile infections before ASP was 2.08 and 0.48 during the ASP (P = 0.37). ImplicationsThe ASP interventions were associated with shorter durations of therapy, shorter lengths of stay, and lower rates of readmission and Clostridium difficile infections within 30 days. Limitations of this study are retrospective cohort design, small study population, limited study population diversity, and non-concurrent cohort times periods.

Interferon-Free Treatments for Chronic Hepatitis C Genotype 1 Infection.

Hepatitis C virus (HCV) infection affects as many as 185 million people globally, many of whom are chronically infected and progress over time to cirrhosis, decompensated liver disease, hepatocellular carcinoma, and eventually death without a liver transplant. In the United States, HCV genotype 1 constitutes about 75% of all infections. While interferon and ribavirin therapy was the cornerstone of treatment for many years, interferon-free treatments have become the standard of care with the emergence of new direct-acting agents, resulting in more effective treatment, shorter duration of therapy, better tolerability, lower pill burden, and ultimately better adherence. This review will summarize the evidence for the currently available combination therapies as well as emerging therapies in phase 3 trials for treatment of HCV genotype 1.

Efficacy and safety of itraconazole use in infants.

Itraconazole has been used to treat fungal infections, in particular invasive fungal infections in infants or neonates in many countries. Literature search was conducted through Ovid EMBASE, PubMed, ISI Web of Science, CNKI and Google scholarship using the following key words: "pediatric" or "infant" or "neonate" and "fungal infection" in combination with "itraconazole". Based on the literature and our clinical experience, we outline the administration of itraconazole in infants in order to develop evidence-based pharmacotherapy. Of 45 articles on the use of itraconazole in infancy, 13 are related to superficial fungal infections including tinea capitis, sporotrichosis, mucosal fungal infections and opportunistic infections. The other 32 articles are related to systemic fungal infections including candidiasis, aspergillosis, histoplasmosis, zygomycosis, trichosporonosis and opportunistic infections as caused by Myceliophthora thermophila. Itraconazole is safe and effective at a dose of 5 mg/kg per day in a short duration of therapy for superficial fungal infections and 10 mg/kg per day for systemic fungal infections in infants. With a good compliance, it is cost-effective in treating infantile fungal infections. The profiles of adverse events induced by itraconazole in infants are similar to those in adults and children.

Spotlight on grazoprevir-elbasvir once-daily combination and its potential in the treatment of hepatitis C.

Chronic hepatitis C virus (HCV) infection is a leading cause of health care utilization in the USA. Incidence of cirrhosis from HCV is expected to rise in the near future, further increasing this burden. There is a high medical need for effective, tolerable, safe, all-oral, short-duration therapy. To this end, several new direct-acting antiviral agents have been developed and have shown excellent sustained virologic response rates. However, patients who have previously failed treatment or who have developed cirrhosis, renal failure, or human immunodeficiency virus coinfection remain difficult-to-treat subgroups. An all-oral agent that is effective in many of these subgroups would simplify treatment of HCV greatly. Here we review currently available data on the efficacy, treatment duration, tolerability, and safety of combination of grazoprevir and elbasvir.