Telaprevir or boceprevir triple therapy in patients with chronic hepatitis C and varying severity of cirrhosis.

BACKGROUND: Risks and benefits of protease inhibitor (PI) (telaprevir or boceprevir) triple therapy in hepatitis C virus (HCV)-infected patients with mildly decompensated cirrhosis, including those wait-listed for liver transplantation (LT), are incompletely known. AIM: To assess virological responses and safety of PI triple therapy in patients with mildly decompensated Child-Pugh (CP) CP ≥6 vs. compensated (CP = 5) cirrhosis. METHODS: Multicentre cohort of 160 adults with cirrhosis treated with peginterferon/ribavirin (peg-IFN/RBV) plus telaprevir (69%) or boceprevir (31%), comparing outcomes between those with CP = 5 and CP ≥6. RESULTS: Patients, 47% with CP ≥6 cirrhosis (CP range 6-10), received PI triple therapy for a targeted duration of 48 weeks. The cohort was median age 59 years, 32% female, 59% genotype 1a, 35% previous null/partial responders. Sustained virological response at 12 weeks (SVR12) was achieved by 35% of patients with CP ≥6 vs. 54% of those with CP = 5 (P = 0.02). CP = 5, achievement of rapid virological response and genotype 1b/other, independently predicted SVR12. Compared to those with CP = 5, patients with CP ≥6 had more peg-IFN dose reductions, eltrombopag use, transfusions and hospitalisations to manage adverse events (all P < 0.05). Overall, 67 (42%) discontinued treatment early. Nine wait-listed patients were treated for a median of 97 days (IQR 60-160) prior to liver transplantation and five achieved post-LT SVR. CONCLUSIONS: In the presence of mild decompensation (Child-Pugh ≥6), SVR12 rates with protease inhibitor triple therapy are significantly reduced and adverse events increased. Thus, treatment with protease inhibitor triple therapy, if judged as necessary, should be undertaken with close monitoring and awareness of the significant risks.

Atorvastatin in the treatment of primary hypercholesterolemia and mixed dyslipidemias.

OBJECTIVE: To review the efficacy and safety of atorvastatin in the treatment of dyslipidemias. DATA SOURCES: A MEDLINE search (January 1960-April 1998), Current Contents search, additional references listed in articles, and unpublished data obtained from the manufacturer were used to identify data from scientific literature. Studies evaluating atorvastatin (i.e., abstracts, clinical trials, proceedings, data on file with the manufacturer) were considered for inclusion. STUDY SELECTION: English-language literature was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of atorvastatin. Additional relevant citations were used in the introductory material and discussion. DATA EXTRACTION: Open and controlled animal and human clinical studies published in the English-language literature were reviewed and evaluated. Clinical trials selected for inclusion were limited to those in human subjects and included data from animals if human data were not available. DATA SYNTHESIS: Atorvastatin is a recent hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia, mixed dyslipidemias, and homozygous familial hypercholesterolemia. In patients who have not met the low-density lipoprotein cholesterol (LDL-C) goal as recommended by the National Cholesterol Education Program Adult Treatment Panel II guidelines, atorvastatin 10-80 mg/d may be used as monotherapy or as an adjunct to other lipid-lowering agents and dietary modifications. In placebo-controlled clinical trials, atorvastatin 10-80 mg/d lowered LDL-C by 35-61% and triglyceride (TG) concentrations by 14-45%. In comparative trials, atorvastatin 10-80 mg/d showed a greater reduction of serum total cholesterol (TC), LDL-C, TG concentrations, and apolipoprotein B-100 (apo B) compared with pravastatin, simvastatin, or lovastatin. In comparison, currently available HMG-CoA reductase inhibitors (lovastatin, simvastatin, pravastatin, fluvastatin, cerivastatin) lower LDL-C concentrations by approximately 20-40% and TG concentrations by approximately 10-30%. In pooled placebo-controlled clinical trials of up to a duration of 52 weeks, atorvastatin in dosages up to 80 mg/d appeared to be well tolerated. The most common adverse effect of atorvastatin was gastrointestinal upset. The incidence of elevated serum hepatic transaminases may be greater at higher dosages of atorvastatin. The risk of myopathy and/or rhabdomyolysis is increased when an HMG-CoA reductase inhibitor is taken concomitantly with cyclosporine, gemfibrozil, niacin, erythromycin, or azole antifungals. CONCLUSIONS: Atorvastatin appears to reduce TC, LDL-C, TG concentrations, and apo B to a greater extent than do currently available HMG-CoA reductase inhibitors. Atorvastatin may be preferred in patients requiring greater than a 30% reduction in LDL-C or in patients with both elevated LDL-C and TG concentrations, which may obviate the need for combination lipid-lowering therapy. Adverse effects of atorvastatin appear to be similar to those of other HMG-CoA reductase inhibitors and should be routinely monitored. Long-term safety data (> 1 y) on atorvastatin compared with other HMG-CoA reductase inhibitors are still needed. Cost-effectiveness studies comparing atorvastatin with other HMG-CoA reductase inhibitors remain a subject for further investigation. Published clinical studies evaluating the impact of atorvastatin on cardiovascular morbidity and mortality are still needed. Additionally, clinical studies evaluating the impact of lipid-lowering therapy in a larger number of women, the elderly (> 70 y), and patients with diabetes for treatment of primary and secondary prevention of coronary heart disease are needed.

A review of the safety and efficacy of acarbose in diabetes mellitus.

Acarbose is a novel oral anti-hyperglycemic agent approved for the treatment of noninsulin-dependent diabetes mellitus. It inhibits alpha-glucosidases in the small intestine, an action that delays the digestion and absorption of complex carbohydrates. Subsequently, there is a smaller rise in the postprandial plasma glucose levels and an overall decrease in the glycosylated hemoglobin by 0.5-1.0%. Potential advantages of acarbose include a greater effectiveness in controlling postprandial hyperglycemia, a low risk of hypoglycemia, and a possible delay in initiating insulin therapy. Acarbose can potentiate the hypoglycemic effects of sulfonylureas or insulin. It has not been associated with weight gain and hyperinsulinemia, both of which can occur with sulfonylureas or insulin. Gastrointestinal adverse effects are common with acarbose, and may decrease with continued treatment. Although rare, elevated serum transaminase levels have been reported.

Common materials for emergency respiratory protection: leakage tests with a manikin.

In areas where respirators are not routinely used, emergencies (such as fires) may occur in which protection from airborne particles is necessary. The following readily available materials were tested on a manikin connected to a breathing simulator to determine the fraction of an approximately 2-micron diameter aerosol that would leak around the seal between the materials and the manikin's face: cotton/polyester shirt material, cotton handkerchief material, toweling (a wash cloth), a surgical mask (Johnson & Johnson Co., Model HRI 8137), and a NIOSH-approved disposable face mask (3M Corp., Model #8710). The leakage tests were done to supplement the measurements of penetration through the materials reported previously. Leakage fractions were determined by comparing the penetration of the same aerosol for the materials held to the face versus being fully taped to the face. At a breathing rate of 37 liters per minute, mean leakages for the materials ranged from 0.0 percent to 63 percent, depending on the material. Mean penetrations exclusive of leakage ranged from 0.6 percent to 39 percent. Use of nylon hosiery material ("panty hose") to hold the handkerchief material or the disposable face mask to the face was found to be very effective in preventing leakage. Such a combination could be expected to reduce leakage around the handkerchief to about 10 percent or less in practice, and around the mask to less than one percent, which suggests the adaptation and use of such an approach for industrial hygiene.