A phase 2, randomized, blinded, dose-finding, controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of a 24-valent pneumococcal conjugate vaccine (VAX-24) in healthy adults 65 years and older.

Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression.

Immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO®) in African clinical trial participants by age, sex, and baseline GP-ELISA titer: A post hoc analysis of three Phase 2/3 trials.

Background: ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was advanced through clinical development by Merck & Co., Inc., Rahway, NJ, USA in collaboration with multiple partners to prevent Ebola virus disease (EVD) and has been approved for human use in several countries.

Attenuation and recovery of an avoidance response to a chemical antipredator cue in an invasive fish: implications for use as a repellent in conservation.

The detection of predation risk without direct engagement with a predator is an important driver of prey movement strategies. Consequently, the application of alarm cues may prove an effective tool in guiding the movements of fishes targeted for control or conservation. However, failure to contemplate the sensory, physiological and cognitive outcomes of repeated or persistent exposure to the cue will likely lead to poor performance of management practices.

Development of Pandemic Vaccines: ERVEBO Case Study.

Preventative vaccines are considered one of the most cost-effective and efficient means to contain outbreaks and prevent pandemics. However, the requirements to gain licensure and manufacture a vaccine for human use are complex, costly, and time-consuming. The 2013-2016 Ebola virus disease (EVD) outbreak was the largest EVD outbreak to date and the third Public Health Emergency of International Concern in history, so to prevent a pandemic, numerous partners from the public and private sectors combined efforts and resources to develop an investigational (EBOV) vaccine candidate (rVSVΔG-ZEBOV-GP) as quickly as possible.

Corrigendum to: Renal Impairment, Recurrence, and the Differential Effect of Bezlotoxumab: A Post Hoc Analysis of Pooled Data From 2 Randomized Clinical Trials.

[This corrects the article DOI: 10.1093/ofid/ofaa248.].

Renal Impairment, Recurrence, and the Differential Effect of Bezlotoxumab: A Post Hoc Analysis of Pooled Data From 2 Randomized Clinical Trials.

Background: Renal impairment is not a consistently cited risk factor for recurrent infection (rCDI). We examined the association between renal impairment and rCDI and the effect of bezlotoxumab, an anti-toxin B monoclonal antibody, in reducing rCDI in participants with renal impairment.

Methods: We pooled data from 2 randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials conducted in participants receiving bezlotoxumab or placebo infusion during oral antibacterial drug treatment for CDI.

Imaging features of disseminated xanthogranulomatous inflammation in eclectus parrots (Eclectus roratus).

Xanthogranulomatous disease is a rare condition, which can be caused by infection, inflammation, hemorrhage, immunologic disease, or inherited lysosomal disorders. It is characterized by non-intracellular lipid and cholesterol deposits among an inflammatory infiltrate of vacuolated macrophages and giant cells. The diagnosis of xanthogranulomatous disease is challenging, with nonspecific imaging findings often misinterpreted as aggressive neoplastic processes in humans.

Thermal injury initiates pervasive fibrogenesis in skeletal muscle.

Severe burn injury induces a myriad of deleterious effects to skeletal muscle, resulting in impaired function and delayed recovery. Following burn, catabolic signaling and myofiber atrophy are key fiber-intrinsic determinants of weakness; less well understood are alterations in the interstitial environment surrounding myofibers. Muscle quality, specifically alterations in the extracellular matrix (ECM), modulates force transmission and strength.

Bezlotoxumab Is Associated With a Reduction in Cumulative Inpatient-Days: Analysis of the Hospitalization Data From the MODIFY I and II Clinical Trials.

Background: Patients with recurrent infection (rCDI) are more likely to have a hospital readmission and spend increased time in inpatient settings compared with patients with primary CDI. MODIFY I and II demonstrated that bezlotoxumab significantly reduced rCDI vs placebo. A post hoc within-trial analysis assessed whether bezlotoxumab was associated with a reduction in cumulative inpatient-days.

Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment for Clostridium difficile Infection.

NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

Antiplatelet Therapy and Clinical Outcomes Following Myocardial Infarction Among Patients in a U.S. Employer-Based Insurance Database.

Background: Estimates of residual cardiovascular risks among patients who have experienced a recent acute myocardial infarction (MI) are predominantly derived from secondary prevention trial populations, patient registries, and population-based cohorts.

Objective: To generate real-world evidence of antiplatelet treatment and recurrent events following MI in patients on antiplatelet treatment among commercial, employer-based insured patients in a large administrative database.

Methods: This was a retrospective cohort claims database study using the Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental databases between 2007-2011.

Geographic variation and risk factors for systemic and limb ischemic events in patients with symptomatic peripheral artery disease: Insights from the REACH Registry.

Background: Patients with symptomatic peripheral artery disease (PAD) are at high risk of ischemic events. However, data about predictors of this risk are limited.

Hypothesis: We analyzed baseline characteristics and 4-year follow-up of patients enrolled in the international REduction of Atherothrombosis for Continued Health (REACH) Registry with symptomatic PAD and no history of stroke/transient ischemic attack to describe annual rates of recurrent ischemic events globally and geographically.

Effect on Fasting Serum Glucose Levels of Adding Ezetimibe to Statins in Patients With Nondiabetic Hypercholesterolemia.

Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy.

Residual Ischemic Risk and Its Determinants in Patients With Previous Myocardial Infarction and Without Prior Stroke or TIA: Insights From the REACH Registry.

Background: Although the rate of in-hospital ischemic events after myocardial infarction (MI) has dramatically decreased, long-term residual risk may remain substantial. However, most of the information on current residual risk is derived from highly selected randomized trials.

Hypothesis: In patients with previous MI and no prior ischemic stroke/transient ischemic attack (TIA), residual ischemic risk increases over time.

Randomized trial assessing the safety and efficacy of sitagliptin in Chinese patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea alone or combined with metformin.

Background: Type 2 diabetes mellitus (T2DM) is a significant burden in China, where approximately 114 million patients have been diagnosed with diabetes. Chinese patients present with prominent β-cell failure, with resulting deficiency in insulin secretion, particularly early phase insulin secretion leading to postprandial hyperglycemia. Sitagliptin, a selective once-daily oral dipeptidyl peptidase-4 inhibitor, has been shown to improve glycemic control as monotherapy and in combination with other antihyperglycemic agents, including sulfonylureas and metformin.

A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma.

This study was undertaken to evaluate safety and pharmacokinetics and to determine treatment doses of vorinostat plus bortezomib in Japanese patients with relapsed or refractory multiple myeloma (MM). Of 9 originally enrolled patients, 2 were refractory to bortezomib, and both experienced dose-limiting toxicity (DLT), prompting a protocol amendment to exclude bortezomib-refractory individuals. Patients not considered bortezomib refractory (N = 7) received 21-day cycles of 1.

A randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia.

Background: Recent evidence points to an increased incidence of new-onset diabetes and a negative impact on glucose parameters with statin use. This study examined the safety of ezetimibe vs placebo for change from baseline to week 24 in HbA1c (primary endpoint), glycoalbumin, and fasting plasma glucose (secondary endpoints) in Japanese subjects with type 2 diabetes and hypercholesterolemia.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multi-site trial.

Variability of the LDL-C lowering response to ezetimibe and ezetimibe + statin therapy in hypercholesterolemic patients.

Objective: We compared the variability of LDL-C-lowering responses to treatment with ezetimibe + statins versus statins in hypercholesterolemic patients.

Methods: An analysis of patient-level data pooled from 27 double-blind, placebo and/or active-controlled studies in 21,671 patients treated with ezetimibe + statins versus statins on first-line (statin-naïve/wash-out) or second-line (on statin, randomized to ezetimibe versus placebo [add-on] or ezetimibe versus uptitrated statin [uptitrate]) for 6-24 wks. Variances (standard deviation [SD], coefficient of variation [CV], and root mean squared error [RMSE] adjusted for various factors) for % change from baseline in LDL-C were compared.

Vorapaxar, an oral PAR-1 receptor antagonist, does not affect the pharmacokinetics of rosiglitazone.

Purpose: To evaluate the potential effects of vorapaxar on the pharmacokinetics and safety of rosiglitazone.

Methods: This was an open-label, two-period, two-treatment, fixed-sequence study in 18 healthy subjects. On Day 1, Period 1, subjects received a single dose of rosiglitazone 8 mg.

Evaluation of blood pressure reduction response and responder characteristics to fixed-dose combination treatment of amlodipine and losartan: a post hoc analysis of pooled clinical trials.

Data from four clinical trials compared reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among patients treated with amlodipine/losartan 5/50 mg vs 5/100 mg and amlodipine/losartan 5/50 mg vs amlodipine 5 mg and 10 mg. Response rate was assessed as reduction in SBP or DBP (>20/10 mm Hg) and proportion of patients achieving SBP <140 mm Hg or DBP <90 mm Hg. Patients were grouped into quartiles based on baseline SBP and DBP.

Efficacy and safety of losartan 100 mg/hydrochlorothiazide 12.5 mg in Japanese subjects with essential hypertension: two randomized, controlled trials.

Two randomized studies were designed to assess the safety, tolerability and efficacy of losartan 100 mg (L100) plus hydrochlorothiazide 12.5 mg (H12.5) in a single fixed-dose combination.

An evaluation of the systemic bioavailability of mometasone furoate (MF) after oral inhalation from a MF/formoterol fumarate metered-dose inhaler versus an MF dry-powder inhaler in healthy subjects.

Purpose: This randomized, open-label, multiple-dose, two-period, crossover study compared the systemic bioavailability of mometasone furoate (MF) administered from a metered-dose inhaler containing MF and formoterol fumarate (F) (MF/F-MDI) versus MF administered from a single-ingredient dry-powder inhaler (MF-DPI).

Methods: Healthy, non-smoking adults, 18-65 years with body mass index 18-29 kg/m(2) (N = 12) received MF 800 µg/F 20 µg via MF/F-MDI or MF 800 µg via MF-DPI twice daily for 5 days separated by a 7-day period. MF pharmacokinetics (AUC(0-12 hour) , Cmax , and Tmax ) were measured at Day 1 and 5 after each treatment.