Keratinocytes are an essential component of the epidermis that undergoes constant proliferation and differentiation. However, the dysregulation of keratinocyte differentiation has been implicated in various skin disorders such as psoriasis. Imiquimod, otherwise known as IMQ, is a topical immunomodulator often used to induce psoriasis-like lesions in murine models for research purposes.
View Article and Find Full Text PDFLong-chain fatty acid oxidation disorders (LC-FAODs) result in life-threatening energy metabolism deficiencies/energy source depletion. Triheptanoin is an odd-carbon, medium chain triglyceride (that is an anaplerotic substrate of calories and fatty acids) for treating pediatric and adult patients with LC-FAODs. Study CL202 (NCT02214160), an open-label extension study of study CL201 (NCT01886378), evaluated the long-term safety/efficacy of triheptanoin in patients with LC-FAODs (N = 94), including cohorts who were triheptanoin naïve (n = 33) or had received triheptanoin in study CL201 (n = 24) or in investigator-sponsored trials/expanded access programs (IST/EAPs; n = 37).
View Article and Find Full Text PDFBackground: Relationships between gut microbiomes and airway immunity have been established in murine and human studies of allergy and asthma. Early life Lactobacillus supplementation alters the composition and metabolic productivity of the gut microbiome. However, little is known of how Lactobacillus supplementation impacts the gut microbiota in children with cystic fibrosis (CF) and whether specific microbiota states that arise following gut microbiome manipulation relate to pulmonary outcomes.
View Article and Find Full Text PDFLong-chain fatty acid oxidation disorders (LC-FAOD) are a group of inborn errors of metabolism wherein patients are unable to process long-chain fatty acids into useable energy in the mitochondria. LC-FAOD commonly affects organ systems with high energy demand, manifesting as hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, rhabdomyolysis, and skeletal myopathy, as well as peripheral neuropathy and retinopathy in some subtypes. Collectively, LC-FAOD have a high mortality rate, especially in cases of early onset disease, and in the presence of cardiomyopathy.
View Article and Find Full Text PDFPurpose: Community-level interventions in cluster randomized controlled trials may alter the gut microbiome of individuals. The current method of estimating community diversities uses microbiome data obtained from multiple individual's specimens. Here we propose randomly pooling a number of microbiome samples from the same community into one sample before sequencing to estimate community-level microbiome diversity.
View Article and Find Full Text PDFPurpose: To determine if there is a benefit to adjuvant corneal crosslinking (CXL) and to compare natamycin versus amphotericin B for filamentous fungal keratitis.
Design: Outcome-masked, 2×2 factorial design, randomized controlled clinical trial.
Participants: Consecutive patients presenting with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India.
Background: The MORDOR I trial (Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance) showed that in Niger, mass administration of azithromycin twice a year for 2 years resulted in 18% lower postneonatal childhood mortality than administration of placebo. Whether this benefit could increase with each administration or wane owing to antibiotic resistance was unknown.
Methods: In the Niger component of the MORDOR I trial, we randomly assigned 594 communities to four twice-yearly distributions of either azithromycin or placebo to children 1 to 59 months of age.
Background: Mass azithromycin distributions have been shown to reduce mortality among pre-school children in sub-Saharan Africa. It is unclear what mediates this mortality reduction, but one possibility is that antibiotics function as growth promoters for young children.
Methods And Findings: 24 rural Ethiopian communities that had received biannual mass azithromycin distributions over the previous four years were enrolled in a parallel-group, cluster-randomized trial.
Purpose: To compare longitudinal outcomes of visual acuity after fungal corneal ulcers with those of bacterial ulcers.
Design: Prospective cohort study.
Methods: This study was conducted in a tertiary eye hospital in South India.
Background: Exposure to antibiotics may result in alterations to the composition of intestinal microbiota. However, few trials have been conducted, and observational studies are subject to confounding by indication. We conducted a randomized controlled trial to determine the effect of 3 commonly used pediatric antibiotics on the intestinal microbiome in healthy preschool children.
View Article and Find Full Text PDFBackground: Mass azithromycin distribution reduces under-5 child mortality. Trachoma control programs currently treat infants aged 6 months and older. Here, we report findings from an infant adverse event survey in 1-5 month olds who received azithromycin as part of a large community-randomized trial in Niger.
View Article and Find Full Text PDFOpen Forum Infect Dis
August 2018
Background: Mass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community's gut microbiome at 6 months after the last distribution.
View Article and Find Full Text PDFObjective: To compare oral voriconazole vs placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis.
Design: Non-prespecified, secondary case-control analysis from a multicenter, double-masked, randomized placebo-controlled clinical trial.
Methods: Study Participants: Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 or worse who eventuated to therapeutic penetrating keratoplasty (TPK).
Purpose: We compare results from regression discontinuity (RD) analysis to primary results of a randomized controlled trial (RCT) utilizing data from two contemporaneous RCTs for treatment of fungal corneal ulcers.
Methods: Patients were enrolled in the Mycotic Ulcer Treatment Trials I and II (MUTT I & MUTT II) based on baseline visual acuity: patients with acuity ≤ 20/400 (logMAR 1.3) enrolled in MUTT I, and >20/400 in MUTT II.
Background: We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the Sustainable Development Goals of the United Nations.
Methods: In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial.
Purpose: To identify fungal keratitis patients who are at risk of a poor outcome and may benefit from closer follow-up or more aggressive treatment.
Design: Secondary analysis of randomized clinical trial data.
Methods: We compared the clinical outcomes of patients who had positive 6-day fungal cultures with those who did not, using backward stepwise regression with covariates for all baseline clinical characteristics.
Importance: Identifying patients with infectious keratitis who are at risk of experiencing a poor outcome may be useful to allocate resources toward high-risk patients, particularly in resource-poor settings.
Objective: To determine baseline patient and ulcer characteristics that predict a high risk of developing corneal perforation and/or the need to undergo therapeutic penetrating keratoplasty (TPK).
Design, Setting, And Participants: This is a secondary analysis of Mycotic Ulcer Treatment Trial II, a multicenter, double-masked, placebo-controlled randomized clinical trial that enrolled 240 patients with smear-positive filamentous fungal corneal ulcers who enrolled between May 2010 and August 2015.
Importance: Common pathophysiological mechanisms may be responsible for immune dysregulation in both thyroid disease and uveitis. Studies investigating a possible association are limited.
Objective: To determine the association between thyroid disease and uveitis.
Importance: Fusarium keratitis is common and often results in poor outcomes. No new treatments since natamycin have become available.
Objective: To explore the role of adjuvant oral voriconazole on clinical outcomes in Fusarium keratitis.
Background: Antibiotic exposure can alter the gut microbiome. We evaluate the effects of azithromycin on the gut microbiome diversity of children from an antibiotic-naive community in Niger.
Methods: A population-based sample of 80 children aged 1-60 months in the Dosso region of Niger was randomized to receive a single dose of either oral azithromycin or placebo.
Purpose: To determine whether patients who had a positive repeated culture was predictive of worse clinical outcome than those who achieved microbiological cure at 6 days in the Mycotic Ulcer Treatment Trial I (MUTT-I).
Design: Secondary analysis from a multicenter, double-masked, randomized clinical trial.
Methods: setting: Multiple hospital sites of the Aravind Eye Care System, India.
Titanium root form dental implants are among the major advances modern dentistry can offer patients. Occasionally, in spite of all precautions and best operator intentions, implants are inadvertently placed in positions that do not permit their use for high-quality esthetic dental restorations. Salvaging these implants to permit their use is a challenge for practitioners.
View Article and Find Full Text PDFObjective: To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis.
Design, Setting, And Participants: The Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.
The Steroids for Corneal Ulcers Trial (SCUT) was a multicenter, international study of bacterial keratitis in which 101 Pseudomonas aeruginosa infections were treated. Twenty-two of 101 P. aeruginosa isolates collected had a colony morphology characteristic of a loss-of-function mutation in lasR, the gene encoding a quorum-sensing master regulator.
View Article and Find Full Text PDFObjective: The aim of this study was to look for differences between patients with an increased pain response as compared with those with a decreased pain response.
Methods: Data were collected from consecutive new patients with lumbar or lumbopelvic pain in a chiropractic clinic. A pelvic tilt exercise was included in the initial examination, and pain response was noted.