Efficacy and safety of twice per year depemokimab in chronic rhinosinusitis with nasal polyps (ANCHOR-1 and ANCHOR-2): phase 3, randomised, double-blind, parallel trials.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) symptoms are frequently driven by type 2 inflammation. Depemokimab is the first ultra-long-acting biological drug engineered with enhanced interleukin-5 binding affinity, high potency, and an extended half-life, enabling twice per year dosing and sustained type 2 inflammation inhibition. The ANCHOR-1 and ANCHOR-2 trials investigated the efficacy and safety of depemokimab in people with CRSwNP.

Changes in respiratory symptoms during 48-week treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies.

It is not known if inhaled antibiotics improve respiratory symptoms in patients with bronchiectasis. In the recent phase-3 ORBIT trials, 48 weeks' treatment with ARD-3150 (inhaled liposomal ciprofloxacin) did not significantly improve symptoms using the prespecified method of analysis comparing baseline symptoms to those after 48 weeks, when patients had been off treatment for 28 days. This method of analysis does not take account of possible improvements in symptoms while on active treatment.

Detection of alpha-1 antitrypsin deficiency: the past, present and future.

Background: Most patients with alpha-1 antitrypsin deficiency remain undiagnosed and therefore do not benefit from current therapies or become eligible for research studies of new treatments under development. Improving the detection rate for AATD is therefore a high priority for the Alpha-1 Foundation. A workshop was held on June 23, 2019 in Orlando, Florida during which stakeholders from the research, pharmaceutical, and patient communities focused on the topic of alpha-1 antitrypsin deficiency detection.

Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic lung infection with Pseudomonas aeruginosa (ORBIT-3 and ORBIT-4): two phase 3, randomised controlled trials.

Background: In patients with non-cystic fibrosis bronchiectasis, lung infection with Pseudomonas aeruginosa is associated with frequent pulmonary exacerbations and admission to hospital for treatment, reduced quality of life, and increased mortality. Although inhaled antibiotics are conditionally recommended for long-term management of non-cystic fibrosis bronchiectasis with frequent exacerbations, there is no approved therapy. We investigated the safety and efficacy of inhaled liposomal ciprofloxacin (ARD-3150) in two phase 3 trials.

Impact of a Health Management Program on Healthcare Outcomes among Patients on Augmentation Therapy for Alpha 1-Antitrypsin Deficiency: An Insurance Claims Analysis.

Introduction: Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder which reduces serum alpha 1-antitrypsin (AAT or alpha1-proteinase inhibitor, A1PI) and increases the risk of chronic obstructive pulmonary disease (COPD). Management strategies include intravenous A1PI augmentation, and, in some cases, a health management program (Prolastin Direct; PD).

Objectives: This study compared clinical and economic outcomes between patients with and without PD program participation.

Engineering Chinese hamster ovary (CHO) cells for producing recombinant proteins with simple glycoforms by zinc-finger nuclease (ZFN)-mediated gene knockout of mannosyl (alpha-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (Mgat1).

While complex N-linked glycoforms are often desired in biotherapeutic protein production, proteins with simple, homogeneous glycan structure have implications for X-ray crystallography and for recombinant therapeutics targeted to the mannose receptor of antigen presenting cells. Mannosyl (alpha-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (Mgat1, also called GnTI) adds N-acetylglucosamine to the Man5GlcNAc2 (Man5) N-glycan structure as part of complex N-glycan synthesis. Here, we report the use of zinc-finger nuclease (ZFN) genome editing technology to create Mgat1 disrupted Chinese hamster ovary (CHO) cell lines.

Once-daily fluticasone furoate is efficacious in patients with symptomatic asthma on low-dose inhaled corticosteroids.

Background: Fluticasone furoate (FF) is an inhaled corticosteroid (ICS) with 24-hour activity in development as a once-daily treatment for the long-term management of asthma.

Objective: To assess the efficacy and safety of 4 doses of once-daily FF administered using a dry powder inhaler in patients (≥12 years) with moderate asthma, uncontrolled on low-dose ICS (fluticasone propionate [FP] 200 μg/day or equivalent).

Methods: This double-blind, placebo-controlled, dose-ranging study randomized 622 patients to 1 of 6 treatments: FF (100, 200, 300, or 400 μg) once daily in the evening, FP 250 μg twice daily (active control), or placebo for 8 weeks.

Dose effect of once-daily fluticasone furoate in persistent asthma: a randomized trial.

Background: This randomized, double-blind, multicenter study was designed to evaluate the efficacy of inhaled once-daily fluticasone furoate (FF) administered in the evening in patients with persistent asthma not controlled by short-acting beta(2) agonists, and to determine the dose(s) suitable for further development.

Methods: Of 1459 patients screened, 598 received one of six treatments: placebo, FF (25 μg, 50 μg, 100 μg or 200 μg) once daily each evening, or fluticasone propionate (FP) 100 μg twice daily for 8 weeks. The primary endpoint was change from baseline in pre-dose evening forced expiratory volume in 1 s (FEV(1)).

Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial.

Background: Fluticasone furoate (FF) is a novel inhaled corticosteroid with 24 h activity. FF is being developed as a once-daily treatment in combination with the long-acting β(2) agonist vilanterol trifenatate for asthma and chronic obstructive pulmonary disease.

Objectives: To determine the optimal dose(s) of FF for treating patients with asthma.

Using the electronic medical record to improve asthma severity documentation and treatment among family medicine residents.

Background And Objectives: Use of electronic medical records (EMRs) is being advocated to improve quality of care. The objectives of this study were (1) to determine the effect of EMR template use on family medicine residents' documentation of the severity classification of asthma and (2) to determine if documentation leads to appropriate treatment.

Methods: We reviewed the charts of patients with asthma seen by residents in the Center for Family Medicine (CFM) between July 1, 2007, and December 31, 2007.

Repeat dosing of albuterol via metered-dose inhaler in infants with acute obstructive airway disease: a randomized controlled safety trial.

Background: Airway obstruction and bronchial hyperactivity often times lead to emergency department visits in infants. Inhaled short-acting beta2-agonist bronchodilators have traditionally been dispensed to young children via nebulizers in the emergency department. Delivery of bronchodilators via metered-dose inhalers (MDIs) in conjunction with holding chambers (spacers) has been shown to be effective.

Safety of daily albuterol in infants with a history of bronchospasm: a multi-center placebo controlled trial.

Introduction: Inhaled short-acting bronchodilators are recommended for the quick relief of bronchospasm symptoms in children including those less than five years of age. However, limited safety data is available in this young population.

Methods: Safety data were analyzed from a randomized, double-blind, parallel group, placebo-controlled multicenter, study evaluating albuterol HFA 90microg or 180microg versus placebo three times a day for 4 weeks using a valved holding chamber, Aerochamber Plus and facemask in children birth View Article and Find Full Text PDF

Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus.

Selective estrogen receptor modulators (SERMs) are potentially useful in treating various endometrial disorders, including endometrial cancer, as they block some of the detrimental effects of estrogen. It remains unclear whether each SERM regulates a unique subset of genes and, if so, whether the combination of a SERM and 17beta-estradiol has an additive or synergistic effect on gene expression. We performed microarray analysis with Affymetrix Mouse Genome 430 2.

The contrasting effects of ad libitum and restricted feeding of a diet very high in saturated fats on sex ratio and metabolic hormones in mice.

Skewing of the sex ratio towards males occurs among pups born to mice fed a very high saturated fat (VHF) diet. In the present study, we tested whether the fat content of the VHF diet rather than the number of calories consumed is responsible for this effect. Eight-week-old NIH Swiss mice were placed on the VHF diet either ad libitum (VHF) or in a restricted manner (VHF-R).

The effects of the selective estrogen receptor modulators, methyl-piperidino-pyrazole (MPP), and raloxifene in normal and cancerous endometrial cell lines and in the murine uterus.

Since estrogens have vital functions in the uterus but might also contribute to endometrial cancer, we sought to determine the in vitro effects of methyl-piperidino-pyrazole (MPP), raloxifene, and beta-estradiol on Ishikawa and RL-95 endometrial cancer, and ovine luminal endometrial (oLE) cell lines and the in vivo effects of these compounds in the rodent uterus. MPP and raloxifene (1 nM) induced significant apoptosis in the endometrial cancer and oLE cell lines compared to beta-estradiol treated and control cells (P View Article and Find Full Text PDF

Effects of prostaglandin F2alpha and latanoprost on phosphoinositide turnover, myosin light chain phosphorylation and contraction in cat iris sphincter.

The effects of the ocular hypotensive agents prostaglandin F(2alpha) (PGF(2alpha)) and its analog latanoprost on intraocular pressure (IOP) in both animals and human have been investigated extensively in the last two decades. While there is general agreement that application of these PGs to the eye alters IOP by altering the aqueous humor outflow of the eye via the uveoscleral and trabecular meshwork pathways, the mechanism of action of these agents on IOP lowering remains unclear. There is evidence which suggests that myosin light kinase (MLC kinase) may be involved in the IOP-lowering effects of these agents.

A curriculum based on social learning theory emphasizing fruit exposure and positive parent child-feeding strategies: a pilot study.

This study examined the effectiveness of a nutrition intervention program to enhance children's knowledge, preference, and intake of whole fruit and to decrease parents' use of controlling child-feeding behaviors. Subjects were fifth- and sixth-grade students (children aged 10-12 years) from Cincinnati, Ohio. Nine parent-child pairs completed the study.