Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study.

Background: Fostemsavir, a first-in-class attachment inhibitor that binds to the viral envelope protein gp120, is approved for heavily treatment-experienced persons with HIV-1 with limited treatment options. We explored changes in immunologic and coagulopathy parameters in the BRIGHTE study: a phase 3 trial that evaluated fostemsavir plus optimized background therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1.

Methods: CD4+ T-cell count, CD4+/CD8+ ratio, soluble CD14, soluble CD163, and D-dimer levels were measured through 96 weeks in participants with 1 or 2 fully active antiretroviral agents available at screening.

Long-term safety and impact of immune recovery in heavily treatment-experienced adults receiving fostemsavir for up to 5 years in the phase 3 BRIGHTE study.

Introduction: Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes.

Methods: The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021).

Week 240 Efficacy and Safety of Fostemsavir Plus Optimized Background Therapy in Heavily Treatment-Experienced Adults with HIV-1.

Introduction: Efficacy and safety of the attachment inhibitor fostemsavir + optimized background therapy (OBT) were evaluated through 48 and 96 weeks in the phase 3 BRIGHTE trial in heavily treatment-experienced (HTE) adults failing their current antiretroviral regimen. Here, we report 240-week efficacy and safety of fostemsavir + OBT in adults with multidrug-resistant human immunodeficiency virus (HIV)-1 in BRIGHTE.

Methods: Heavily treatment-experienced adults failing their current regimen entered the randomized cohort (RC; 1-2 fully active antiretrovirals available) or non-randomized cohort (NRC; no fully active antiretrovirals available) and received open-label fostemsavir + OBT (starting Day 8 in RC and Day 1 in NRC).

Evaluating caretaker satisfaction with same-day discharge after gastrostomy tube placement.

Background: Same-day discharge (SDD) after laparoscopic gastrostomy tube (G-tube) placement, using written and video-based preoperative education, has been our standard institutional practice since 2017. We aim to evaluate caretaker satisfaction with this protocol.

Methods: All patients planned for SDD after G-tube placement from February 2021-February 2022 were identified.

Influence of Light Phase Exposure to LED Lighting on Circadian Levels of Neuroendocrine Hormones in Sprague-Dawley Rats.

Light and lighting protocols of animal research facilities are critically important to the outcomes of biomedical research that uses animals. Previous studies from our laboratory showed that the wavelength (color) of light in animal housing areas affects the nocturnal melatonin signal that temporally coordinates circadian rhythms in rodents. Here, we tested the hypothesis that exposure to LED light enriched in the blue-appearing portion (460-480 nm) of the visible spectrum during the light phase (bLAD) influences circadian concentrations of select neuroendocrine hormones in adolescent Sprague-Dawley rats.

Week 96 Genotypic and Phenotypic Results of the Fostemsavir Phase 3 BRIGHTE Study in Heavily Treatment-Experienced Adults Living with Multidrug-Resistant HIV-1.

In the phase 3 BRIGHTE study in heavily treatment-experienced adults with multidrug-resistant HIV-1, fostemsavir plus optimized background therapy (OBT) resulted in sustained rates of virologic suppression through 96 weeks. HIV-1 RNA <40 copies/mL was achieved in 163/272 (60%) Randomized Cohort (RC) participants (with 1 or 2 remaining approved fully active antiretrovirals) and 37/99 (37%) Non-randomized Cohort (NRC) participants (with 0 fully active antiretrovirals). Here we report genotypic and phenotypic analyses of HIV-1 samples from 63/272 (23%) RC participants and 49/99 (49%) NRC participants who met protocol-defined virologic failure (PDVF) criteria through Week 96.

Patient-Reported Outcomes in the Phase III BRIGHTE Trial of the HIV-1 Attachment Inhibitor Prodrug Fostemsavir in Heavily Treatment-Experienced Individuals.

Introduction: Heavily treatment-experienced (HTE) people living with HIV-1 (PLWH) have limited viable antiretroviral regimens available because of multidrug resistance and safety concerns. The first-in-class HIV-1 attachment inhibitor fostemsavir demonstrated efficacy and safety in HTE participants in the ongoing phase III BRIGHTE trial.

Objectives: We describe patient-reported outcomes (PROs) through week 48.

Phase III/IV, Randomized, Fifty-Two-Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus.

Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self-identified Black race.

Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.

Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1.

Objectives: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens.

Design: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes).

Methods: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT.

Mortality and adverse events of special interest with intravenous belimumab for adults with active, autoantibody-positive systemic lupus erythematosus (BASE): a multicentre, double-blind, randomised, placebo-controlled, phase 4 trial.

Background: Belimumab is approved for the treatment of active systemic lupus erythematosus (SLE). Although clinical trials showed a favourable benefit-risk profile, numerical differences in the incidence of mortality and adverse events of special interest (AESIs) have been reported. We assessed the frequency of these events in patients with SLE receiving belimumab or placebo plus standard therapy.

Susceptibility of global HIV-1 clinical isolates to fostemsavir using the PhenoSense® Entry assay.

Background: Fostemsavir is a prodrug of a first-in-class HIV-1 attachment inhibitor, temsavir, that binds to gp120 and blocks attachment to the host-cell CD4 receptor, preventing entry and infection of the target cell. Previous studies using a limited number of clinical isolates showed that there was intrinsic variability in their susceptibility to temsavir.

Objectives: Here, an analysis was performed using all clinical isolates analysed in the Monogram Biosciences PhenoSense® Entry assay as part of the development programme.

Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study.

Background: Fostemsavir, a prodrug of the first-in-class attachment inhibitor, temsavir, is indicated for heavily treatment-experienced individuals with multidrug-resistant HIV-1. We previously reported superior efficacy of fostemsavir versus placebo in the randomised cohort of the BRIGHTE study after 8-day functional monotherapy (primary endpoint); here we report planned interim analyses through week 96.

Methods: BRIGHTE (NCT02362503) is an ongoing multicentre, two-cohort, phase 3 trial, done at 108 centres in 22 countries.

Same-day discharge for pediatric laparoscopic gastrostomy.

Background: Laparoscopic gastrostomy is a common procedure in children. We developed a same-day discharge (SDD) protocol for laparoscopic button gastrostomy.

Methods: We performed a prospective observational study of children undergoing laparoscopic button gastrostomy and were eligible for SDD from August 2017-September 2019.

Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection.

Background: Among some patients with human immunodeficiency virus type 1 (HIV-1) infection who have undergone multiple antiretroviral therapies and have limited options for treatment, new classes of antiretroviral drugs with novel mechanisms of action are needed. Fostemsavir is the prodrug of temsavir, a first-in-class investigational HIV-1 attachment inhibitor.

Methods: In this ongoing phase 3 trial in 23 countries, we enrolled patients with multidrug-resistant HIV-1 infection in two cohorts, according to their remaining treatment options.

Successful Brace Treatment of Pectus Carinatum in Osteogenesis Imperfecta Using the Dynamic Compression System.

Osteogenesis imperfecta (OI) is a genetic disorder of collagen resulting in a "fragile" skeleton with increased fracture risk and other complications, dependent on the specific variant. Pectus deformities of the chest wall, while not common, can be associated with OI. The use of a pectus carinatum brace in a patient with OI poses unknown risks for fractures and adverse treatment outcomes.

Outcomes Following Dynamic Compression Bracing for Pectus Carinatum.

Children with pectus carinatum (PC) are particularly vulnerable to psychosocial effects of poor body image, even though they may not experience physical symptoms. Nonoperative treatment with orthotic bracing is effective in PC correction. We describe our experience with dynamic compression bracing (DCB) for PC patients and their satisfaction with bracing.

Using Microphone Technology to Improve Speech Perception in Noise in Children with Cochlear Implants.

Background: Cochlear implant (CI) users are affected more than their normal hearing (NH) peers by the negative consequences of background noise on speech understanding. Research has shown that adult CI users can improve their speech recognition in challenging listening environments by using dual-microphone beamformers, such as adaptive directional microphones (ADMs) and wireless remote microphones (RMs). The suitability of these microphone technologies for use in children with CIs is not well-understood nor widely accepted.

A Single-Center Experience with Dynamic Compression Bracing for Children with Pectus Carinatum.

Objective:  Bracing for pectus carinatum (PC) has emerged as an alternative to surgical correction. However, predictive factors for bracing remain poorly understood, as much of the data have been reported from small series.

Materials And Methods:  We reviewed a prospective dataset in patients with PC who underwent dynamic compression bracing (DCB) from July 2011 to July 2016.

Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration.

Purpose: To evaluate pazopanib eye drops in subjects with active subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Design: Multicountry, randomized, parallel-group, double-masked, active and placebo-controlled, dose-ranging study of eye drops.

Participants: A total of 510 subjects (93% white; 58% female; mean age, 75.

A randomized, placebo-controlled phase 3 trial (Study SB-767905/012) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.

Unlabelled: Gastrointestinal (GI) side effects are common with opioid medication, and constipation affects ∼40% of patients. Such symptoms considerably impair patients' quality of life. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist approved in the US for short-term, in-hospital management of postoperative ileus in patients undergoing bowel resection.

A randomized, placebo-controlled phase 3 trial (Study SB-767905/013) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.

Unlabelled: The balance between the pain relief provided by opioid analgesics and the side effects caused by such agents is of particular significance to patients who take opioids for the long-term relief of non-cancer pain. The spectrum of signs and symptoms affecting the gastrointestinal (GI) tract associated with opioid use is known as opioid-induced bowel dysfunction. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist, approved in the US for the management of postoperative ileus in patients undergoing bowel resection (short-term, in-hospital use only).