Ribavirin revisited in the era of direct‐acting antiviral therapy for hepatitis C virus infection

Over the past two decades, ribavirin has been an integral component of treatment for hepatitis C virus (HCV) infection, where it has been shown to improve the efficacy of (pegylated) interferon. However, because of treatment‐limiting side effects and its additive toxicity with interferon, the search for interferon‐ and ribavirin‐free regimens has been underway. The recent approvals of all‐oral direct acting antivirals (DAAs) have revolutionized the HCV therapeutic landscape, and initially it was expected that the role of ribavirin with DAA regimens would be eliminated. On the contrary, what we have witnessed is that ribavirin retains an important role in the optimal treatment of some subgroups of patients, particularly those that historically have been considered the most difficult to cure. Fortunately, it has also been recognized that the safety profile of ribavirin is improved when co‐administered with all‐oral DAA combinations in the absence of interferon. Despite the antiviral mechanism of action of ribavirin being poorly understood, we now have a range of novel insights into the potential role of ribavirin in all‐oral DAA HCV treatment and greater insight into the antiviral mechanism by which it continues to provide clinical benefit for defined patient groups.     

Transfusion-associated graft-versus-host disease: risk due to homozygous HLA haplotypes

BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) may occur in transfusions of blood from HLA-homozygous persons to HLA- heterozygous persons who share a haplotype. STUDY DESIGN AND METHODS: Two mathematical models were developed to calculate the upper and lower limit of the associated risks in various populations using a combination of serology- and DNA sequence-based HLA haplotype frequencies. RESULTS: For nondirected transfusion, the range of the estimated risk in United States whites is 1 of 17,700 to 39,000 (1/6,900-48,500 in Germans; 1/1,600-7,900 in Japanese). The risk in directed donation between parents and children is increased at least 21- fold for US whites, 18-fold for Germans, and 11-fold for Japanese. CONCLUSION: For nondirected transfusions, the estimates of TA-GVHD risk derived in this model are lower than estimates of previously published models, are in better agreement with the clinical experience, and explain in part the observed discrepancy between TA-GVHD incidence in the United States and that in Japan. Most notably for US whites, the relative increase in risk in directed transfusion is larger than previously thought.     

AIDS trends in Europe: decrease in the west,increase in the east

In 1996, 24 920 AIDS cases were reported in the WHO European Region, bringing the cumulative total to 185 808 cases including 6969 (4%) paediatric cases (<13 years). For the first time since the start of the epidemic, the annual number of cases reported d     

Pulmonary angiography with iopamidol: patient comfort, image quality, and hemodynamics

The choice of a contrast agent for pulmonary angiography has important implications for patient comfort, image quality, and perhaps the safety of the procedure, particularly for "high-risk" patients. In a prospective study the nonionic, low-osmolality agent iopamidol eliminated the problem of image degradation due to coughing, and patients showed excellent tolerance for it. However, pressure measurements obtained within 3-5 minutes of injection of iopamidol and diatrizoate sodium meglumine 76% showed no significant difference in the hemodynamic effects of the two contrast agents, either for normotensive or for pulmonary hypertensive patients. Contrary to a common presumption, pulmonary hypertension by itself did not appear to increase the risk of pulmonary angiography. The theoretic presumption of greater hemodynamic stability with low-osmolality contrast agents was not clinically evident in this trial with iopamidol. At present, enhanced patient comfort and improved image quality remain the only confirmed bases for choosing this contrast agent for pulmonary angiography.     

Patterns of disease in patients at a tertiary referral centre requiring reoperative parathyroidectomy

Introduction

Reoperative parathyroidectomy is required when there is persistent or recurrent hyperparathyroidism following the initial surgery (at least 5% of parathyroidectomies nationally). By convention, ‘persistent disease’ is defined as the situation where the patient has not been cured by the first operation. The term ‘recurrent hyperparathyroidism’ is used when the patient was confirmed to be biochemically cured for six months from the first operation but has hyperparathyroidism after this date. Reoperative surgery is associated with higher rates of postoperative complications as well as a greater rate of failure to cure. The aim of our study was to review our departmental experience of reoperative parathyroidectomy, with a view to identify patterns of disease persistence and recurrence.

Methods

Using a departmental database, patients were identified who had undergone reoperative parathyroidectomy between 2006 and 2014. All the pre, intra and postoperative information was documented including the operative note so as to record the location of the abnormal parathyroid gland found at reoperation.

Results

Almost two-thirds (63%) of patients had negative, equivocal or discordant conventional imaging so secondary investigative tools were required frequently. The majority of abnormal glands were found in eutopic locations. The most common locations for ectopic glands were intrathyroidal, mediastinal and intrathymic. A third (33%) of the patients had multigland disease and over a quarter (28%) had coexisting thyroid disease.

Conclusions

Persistent hyperparathyroidism represents a challenging patient subgroup for which access to all radiological modalities and intraoperative parathyroid hormone monitoring are required. Patient selection for reintervention is a key determinant in the reoperation cure rate.     

Viral-guided hepatitis C therapy

Predicting hepatitis C treatment outcomes is of great benefit to patient and clinician. Baseline predictors of response or failure can set the appropriate expectations for the patient and may aid in decision making about starting therapy. An accurate assessment of the potential for treatment success involves using rapid and early viral kinetics at weeks 4 and 12. These time points are useful to set up stopping rules and to provide motivation for the patient and health care provider to continue when appropriate. Relapse is an unfortunate consequence of therapy in a significant number of patients. Baseline and on-treatment viral assessments are useful in helping predict and perhaps reduce this phenomenon.