d Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (C ss ) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n ‫؍‬ 150). The primary outcome was the attainment rate of the _target C ss of >700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n ‫؍‬ 118) or PCZ-tab (n ‫؍‬ 32) and had PCZ C ss assessment after at least 7 days of therapy were eligible. The median C ss in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the _target goal of >700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n ‫؍‬ 3) and 17% (n ‫؍‬ 2), respectively (P ‫؍‬ 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n ‫؍‬ 8) and 3% (n ‫؍‬ 1), respectively (P ‫؍‬ 0.68). We conclude that the use of PCZ-tab was associated with higher C ss and with the probability of achieving therapeutic goals without worsening of adverse effects. P osaconazole (PCZ) is a triazole antifungal agent that is approved for invasive fungal disease prophylaxis in high-risk patients. Oral formulations of PCZ are commercially available as a suspension (PCZ-susp) and as delayed-release tablets (PCZ-tab) (1). Several studies have shown that the gastrointestinal absorption and bioavailability of PCZ-susp are unpredictable and dependent on various factors, including food intake and concomitant acid suppressants (2-7). Due to its superior oral bioavailability, the PCZ-tab can be administered without regard to food intake and seems less likely to be affected by concomitant acid-suppressing medications (8-11).PCZ concentrations follow dose-dependent pharmacokinetics at steady state with saturation of absorption of the PCZ-susp occurring at 800 mg/day (12). The current guidelines recommend as a goal steady-state concentrations (C ss ) of Ն700 ng/ml in the prophylaxis setting (13). Comparative studies evaluating the PCZsusp and the newer PCZ-tab are not available. Herein, we report a retrospective analysis comparing the serum concentrations of the two formulations. MATERIALS AND METHODSPatient population. For this study, 152 consecutive patients with acute myelogenous leukemia (AML) or high-grade myelodysplastic syndrome (MDS) who were admitted to the inpatient hematologic malignancy service at West Virginia Unive...

No abstract

Long‐chain fatty acid oxidation disorders (LC‐FAOD) are autosomal recessive conditions that impair conversion of long‐chain fatty acids into energy, leading to significant clinical symptoms. Triheptanoin is a highly purified, 7‐carbon chain triglyceride approved in the United States as a source of calories and fatty acids for treatment of pediatric and adult patients with molecularly confirmed LC‐FAOD. CL202 is an open‐label, long‐term extension study evaluating triheptanoin (Dojolvi) safety and efficacy in patients with LC‐FAOD. Patients rolled over from the CL201 triheptanoin clinical trial (rollover); were triheptanoin‐naïve (naïve); or had participated in investigator‐sponsored trials/expanded access programs (IST/other). Results focus on rollover and naïve groups, as pretreatment data allow comparison. Primary outcomes were annual rate and duration of major clinical events (MCEs; rhabdomyolysis, hypoglycemia, and cardiomyopathy events). Seventy‐five patients were enrolled (24 rollover, 20 naïve, 31 IST/other). Mean study duration was 23.0 months for rollover, 15.7 months for naïve, and 34.7 months for IST/other. In the rollover group, mean annualized MCE rate decreased from 1.76 events/year pre‐triheptanoin to 0.96 events/year with triheptanoin (P = .0319). Median MCE duration was reduced by 66%. In the naïve group, median annualized MCE rate decreased from 2.33 events/year pre‐triheptanoin to 0.71 events/year with triheptanoin (P = .1072). Median MCE duration was reduced by 80%. The most common related adverse events (AEs) were diarrhea, abdominal pain/discomfort, and vomiting, most mild to moderate. Three patients had serious AEs (diverticulitis, ileus, rhabdomyolysis) possibly related to drug; all resolved. Two patients had AEs leading to death; neither drug related. Triheptanoin reduced rate and duration of MCEs. Safety was consistent with previous observations.

These results indicate that HCP may alleviate LPS induced lung inflammatory injury, which may be associated with its inhibitory effect on the over activation of complement and macrophages. This suggests a potential role to treat ALI.

Purpose. This study aims to evaluate dry eye and ocular surface conditions of myopic teenagers by using questionnaire and clinical examinations. Methods. A total of 496 eyes from 248 myopic teenagers (7–18 years old) were studied. We administered Ocular Surface Disease Index (OSDI) questionnaire, slit-lamp examination, and Keratograph 5M. The patients were divided into 2 groups based on OSDI dry eye standard, and their ocular surfaces and meibomian gland conditions were evaluated. Results. The tear meniscus heights of the dry eye and normal groups were in normal range. Corneal fluorescein scores were significantly higher whereas noninvasive break-up time was dramatically shorter in the dry eye group than in the normal group. All three meibomian gland dysfunction parameters (i.e., meibomian gland orifice scores, meibomian gland secretion scores, and meibomian gland dropout scores) of the dry eye group were significantly higher than those of the normal group (P < 0.0001). Conclusions. The prevalence of dry eye in myopic teenagers is 18.95%. Meibomian gland dysfunction plays an important role in dry eye in myopic teenagers. The Keratograph 5M appears to provide an effective noninvasive method for assessing ocular surface situation of myopic teenagers.