1,721,011 research outputs found
Discontinued drugs in 2012 - 2013: Hepatitis C virus infection
No full textHepatitis C virus (HCV) chronically infects about 150 million people worldwide. Antiviral treatment can stop and even reverse the progression of the disease. Several antivirals have been developed. However, about 10,000 compounds are tested for each drug that eventually reaches the market. It would be useful to learn from these failures, for example, by reporting the candidate drugs that were discontinued and the reason for discontinuation.
Areas covered: This article focuses on the anti-HCV drug candidates discontinued between 1 January 2012 and 1 January 2014.
Expert opinion: In detail, 17 drugs were discontinued. Of these: 10 were NS5B inhibitors, 3 were NS5A inhibitors, 2 were immunostimulants, 1 was a therapeutic and prophylactic vaccine and 1 an NS3 inhibitor. Only 3 candidates were discontinued in the preclinical phase, and 14 were discontinued during clinical development (8 in Phase II and 6 in Phase I). Most discontinuations were attributed to corporate strategic decisions. The authors believe that learning from HCV drug development failures will help pharmaceutical companies and researchers to develop better strategies for the future. It is therefore important that this information is made available
Management of chronic viral hepatitis in the hematological patient
No full textInfection with HBV and HCV represents a growing challenge in the management of patients with hematological malignancies. Recently, hepatitis E (HEV) was recognized as an endemic infection in developed countries and as an emerging health problem in immunocompromised patients. Areas covered: We reviewed the current knowledge on the impact of chronic viral hepatitis in the hematological setting. Epidemiological features, screening strategies and indications for treatment and monitoring have been explored and commented. Expert commentary: Knowing patient's complete HBV serostatus is mandatory in order to choose between treatment, prophylaxis or a pre-emptive approach. Recent guidelines favor treatment with high barrier molecules in all patients with chronic HBV infection and long lasting prophylaxis with those with inactive or resolved one. With regard to HCV, the new direct-acting antiviral agents have been safely administered in the hematological setting. Their use as first-line single treatment in indolent lymphomas, and combined with chemotherapy in aggressive ones, should be considered. Due to the existing risk of chronic HEV infection in the immunocompromised, screening with serum HEV-RNA should be performed in case of signs and symptoms indicative of hepatitis. In the event of HEV infection, reduction of immunosuppression and, if not feasible or unsuccessful, ribavirin treatment should be prescribed
Does D-Dimer really help in the diagnosis of chronic periprosthetic joint infections (PJI)? A case-control study
No full textIntroduction
The differential diagnosis between aseptic and septic total joint arthroplasty (TJA) revision is fundamental in order to be successful in the surgical treatment. Several serum biomarkers have been proposed as gold standards in the diagnosis of Periprosthetic Joint Infections (PJI). The aim of the current study was (1) to evaluate serum levels of D-dimer in a retrospective series of PJIs diagnosed by traditional methods and (2) to compare the D-dimer performance as a diagnostic test with other well established PJI biomarkers in a case-control study.
Materials and methods
A total of 159 TJA revisions were included in the study database: 55 implants in 55 patients met the inclusion criteria. The final study group included 33 aseptic and 22 septic (with micro-organism isolation) TJA revisions; these two groups were not statistically different in terms of demographics. All patients were preoperatively tested with the following serologic tests: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, D-dimer and white blood cell (WBC) count. A standard univariate logistic analysis was performed in order to investigate the association between chronic PJI and the serologic tests.
Results
A gram-positive microorganism was isolated in 15 patients whereas a gram-negative microorganism was isolated in 7 patients. Univariate analysis showed that high D-dimer, ESR or fibrinogen were not associated with a PJI occurrence, whereas high CRP and WBC count >10.000 cells/mm3 were significantly elevated in chronic PJI patients. A multivariate analysis confirmed that leukocytosis was a significant predictor of PJI.
Conclusions
This study showed that D-dimer had a low sensitivity and specificity in diagnosing chronic PJI, especially when evaluated as a single diagnostic biomarker
Prevalence of human herpesvirus-6 and epstein barr virus infections in children with autistic spectrum disorders
No full textThe discovery of sofosbuvir: a revolution for therapy of chronic hepatitis C
No full textHepatitis C virus (HCV) infection is a worldwide health problem, whose management has been revolutionized after the availability of sofosbuvir, a direct-acting antiviral (DAAs). Sofosbuvir is a HCV NS5B polymerase inhibitor. Antiviral regimens including sofosbuvir are associated with success rates >90%, even in the case of "difficult-to-treat" patients such as subjects with liver cirrhosis as well as prior null response to IFN and ribavirin
Investigational direct-acting antivirals in hepatitis C treatment: The latest drugs in clinical development
No full textIntroduction: Therapeutic options for patients with HCV-related liver disease have increased over the last two decades. In fact, the old standard of care based on the combination of pegylated interferon and ribavirin did not result in satisfactory eradication rates, particularly in patients with liver cirrhosis. With the advent of direct-acting antivirals (DAAs), higher rates of viral clearance became possible and, patients with contraindications to interferon obtained access to treatment. However, several concerns have been raised regarding first-generation DAAs, namely their high costs, and the emergence of resistant-associated variants with low susceptibility to these drugs. Areas covered: In this review, the authors discuss the data about the efficacy and safety of the main anti-HCV direct-acting antivirals currently in the pipeline. Furthermore, they evaluate the impact of these drugs on the therapeutic options currently available for HCV patients. Expert opinion: The results of trials evaluating the effectiveness of new DAAs are encouraging. These new antivirals lead to high rates of viral eradication without relevant adverse reactions and seem to be effective regardless of viral genotypes, presence of resistant-associated variants or advanced liver disease. Consequently, with the advent of this new family of drugs, chronic HCV-related hepatitis may become a curable disease
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