Ericksonmcfadden1848
Uncomplicated urinary tract infections are one of the most common bacterial infections in the United States. Clinical practice guidelines from the Infectious Diseases Society of America recommend nitrofurantoin, trimethoprim-sulfamethoxazole, and Fosfomycin as first-line antibiotic treatments and discourage the use of fluoroquinolone antibiotic agents. US Food and Drug Administration released several black box warnings about fluoroquinolones over the past decade owing to antibiotic resistance and a high burden of adverse events. Historically, uncomplicated urinary tract infections have high rates of guideline-discordant treatment with past studies noting substantial use of fluoroquinolones, directly contradicting clinical practice guidelines.
This study aimed to assess the current concordance of physician prescribing practices with Infectious Diseases Society of America guidelines for the treatment of uncomplicated urinary tract infections in women and identify patient and physician predictors of guidelinto the growing rates of antibiotic resistance. Actions such as educating physicians about antibiotic resistance and clinical practice guidelines and providing feedback on prescription habits are needed to increase guideline concordance and therefore reduce the use of fluoroquinolones, especially for physicians in family and internal medicine.Synapses in the outer retina are the first information relay points in vision. Here, photoreceptors form synapses onto two types of interneurons, bipolar cells and horizontal cells. Because outer retina synapses are particularly large and highly ordered, they have been a useful system for the discovery of mechanisms underlying synapse specificity and maintenance. Understanding these processes is critical to efforts aimed at restoring visual function through repairing or replacing neurons and promoting their connectivity. We review outer retina neuron synapse architecture, neural migration modes, and the cellular and molecular pathways that play key roles in the development and maintenance of these connections. We further discuss how these mechanisms may impact connectivity in the retina.
Hypothalamic melanocortin 4 receptors (MC4R) are a key regulator of energy homeostasis. Brain-penetrant MC4R agonists have failed, as concentrations required to suppress food intake also increase blood pressure. However, peripherally located MC4R may also mediate metabolic benefits of MC4R activation. Mc4r transcript is enriched in mouse enteroendocrine L cells and peripheral administration of the endogenous MC4R agonist, α-melanocyte stimulating hormone (α-MSH), triggers the release of the anorectic hormones Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in mice. This study aimed to determine whether pathways linking MC4R and L-cell secretion exist in humans.
GLP-1 and PYY levels were assessed in body mass index-matched individuals with or without loss-of-function MC4R mutations following an oral glucose tolerance test. Immunohistochemistry was performed on human intestinal sections to characterize the mucosal MC4R system. Static incubations with MC4R agonists were carried out on humion on L cells in an autocrine and paracrine fashion. Outcomes from this study have direct implications for targeting mucosal MC4R to treat human metabolic disorders.
To identify common causes of emergency department-treated eye injury among older adults in the United States and to characterize fall-related ocular trauma in this population.
Retrospective cohort study.
Data from the National Electronic Injury Surveillance System, a nationally representative database of US emergency department-treated injuries, was used to assemble a cohort of adults ≥65 years of age with eye injuries between January 1, 2000 and December 31, 2019. Demographic information, diagnosis, disposition, injury location, and the consumer product associated with injury were collected. Narrative descriptions of all injuries were reviewed to identify eye injuries caused by falls.
Four thousand nine hundred fifty-three eye injuries among older adults were reported from 2000-2019, a stratified probability sample representing approximately 238,162 injuries, with an average annual frequency of 12,000 injuries. Falls accounted for 11.5% of these injuries. Fall-related eye injuries commonly presented from home (66.5%) and were more likely to occur in the winter than eye injuries from other causes (28.1% vs 18.4%, P < .01). Risk factors for fall-related eye injury included older age (odds ratio [OR] 1.11 [95% confidence interval CI 1.10-1.13 per year), female sex (OR 2.3 [95% CI 1.6-3.1] vs male), black race (OR 2.4 [95% CI 1.3-4.5] vs white), and presentation from a nursing home (OR 12.7 [95% CI 4.9-32.8] vs other locations). Older adults with fall-related injuries were more likely to be hospitalized (OR 22.8 [95% CI 15.3-33.9]) and to have a ruptured globe (OR 14.1 [95% CI 6.5-30.6]) than those with fall-unrelated injury.
Falls are an important mechanism of ocular trauma in older adults and are associated with worse outcomes compared with eye injuries from other causes.
Falls are an important mechanism of ocular trauma in older adults and are associated with worse outcomes compared with eye injuries from other causes.To identify geographic and socioeconomic variables predictive of residential proximity to neovascular age-related macular degeneration (nAMD) clinical trial locations.
Retrospective, cross-sectional study.
Census tract-level data from public datasets and trial-level data from ClinicalTrials.gov were analyzed. We calculated the driving distance (>60 miles) and time (>60 minutes) from the population-weighted US census tract centroid to the nearest clinical trial site.
We identified 42 trials studying nAMD across 829 unique clinical trial sites in the United States. In a multivariable model, driving distance >60 miles had a significant association with rural location (adjusted odds ratio [aOR] 5.54; 95% confidence interval [CI] 3.86-7.96, P < .0001) and with Midwest (aOR 2.30; 95% CI 1.21-4.38, P=.01) and South (aOR 2.43; 95% CI 1.21-4.91, P=.01) as compared to the Northeast region, and with some college or an associate's degree, as compared to a bachelor's degree (aOR 1.02; 95% CI 1.01-1.04, P=.0007, and aOR 1.05; 95% CI 1.00-1.10, P=.04, respectively). Lower odds of traveling >60 miles to the nearest nAMD trial site were associated with census tracts with a higher percentage of blacks (aOR 0.98; 95% CI 0.97-0.99, P < .0001), Hispanics (aOR 0.97; 95% CI 0.95-0.99, P=.002), and Asians (aOR 0.90; 95% CI 0.88-0.93, P < .0001), as compared to whites, and with a lower percentage of the population <200% of the federal poverty level. Similar predictors were found in time traveled >60 minutes.
There are geographic access disparities of clinical trial sites for nAMD in the United States.
There are geographic access disparities of clinical trial sites for nAMD in the United States.
To develop classification criteria for 25 of the most common uveitides.
Machine learning using 5,766 cases of 25 uveitides.
Cases were collected in an informatics-designed preliminary database. Using formal consensus techniques, a final database was constructed of 4,046 cases achieving supermajority agreement on the diagnosis. Cases were analyzed within uveitic class and were split into a training set and a validation set. Machine learning used multinomial logistic regression with lasso regularization on the training set to determine a parsimonious set of criteria for each disease and to minimize misclassification rates. The resulting criteria were evaluated in the validation set. Accuracy of the rules developed to express the machine learning criteria was evaluated by a masked observer in a 10% random sample of cases.
Overall accuracy estimates by uveitic class in the validation set were as follows anterior uveitides 96.7% (95% confidence interval [CI] 92.4, 98.6); intermediate uveitides 99.3% (95% CI 96.1, 99.9); posterior uveitides 98.0% (95% CI 94.3, 99.3); panuveitides 94.0% (95% CI 89.0, 96.8); and infectious posterior uveitides / panuveitides 93.3% (95% CI 89.1, 96.3). Accuracies of the masked evaluation of the "rules" were anterior uveitides 96.5% (95% CI 91.4, 98.6) intermediate uveitides 98.4% (91.5, 99.7), posterior uveitides 99.2% (95% CI 95.4, 99.9), panuveitides 98.9% (95% CI 94.3, 99.8), and infectious posterior uveitides / panuveitides 98.8% (95% CI 93.4, 99.9).
The classification criteria for these 25 uveitides had high overall accuracy (ie, low misclassification rates) and seemed to perform well enough for use in clinical and translational research.
The classification criteria for these 25 uveitides had high overall accuracy (ie, low misclassification rates) and seemed to perform well enough for use in clinical and translational research.
To assess both the safety and efficacy, in terms of symptomatic improvement, of botulinum toxin injections distributed in the bowel patch and the bladder remnant of failed augmented bladders.
A retrospective study was performed on patients with augmented bladders who had presented with clinical and/or urodynamic failure and had received an onabotulinum
toxin-A (BTX-A) injection at both the bowel and the bladder level due to refractoriness to oral treatment. The primary variable tested was safety, which was assessed by analysing the adverse effects according to the Clavien-Dindo classification. Subjective improvement was assessed by means of the Treatment Benefit Scale (TBS) as a secondary variable.
Eight patients who underwent a total of 23 procedures were analysed. The mean age at first injection was 23 years. The mean interval between bladder augmentation and first BTX-A injection was 65.11 months. read more The mean interval between BTX-A injections was 11.6 months. No adverse effects due to systemic absorption were recorded. link2 The only postoperative complication was an afebrile urinary infection (Clavien-Dindo 2) in 2 out of 23 procedures (8.7%). Eighty-six percent (19/22) of the procedures yielded a symptomatic benefit (TBS 1 and 2).
Injection of onabotulinum toxin-A in both the bowel patch and the bladder remnant appears to be a safe and efficient technique for the symptomatic treatment of patients with bladder augmentation who have shown clinical and/or urodynamic failure in response to a conservative treatment. This procedure allows bladder re-augmentation to be delayed or even avoided.
Injection of onabotulinum toxin-A in both the bowel patch and the bladder remnant appears to be a safe and efficient technique for the symptomatic treatment of patients with bladder augmentation who have shown clinical and/or urodynamic failure in response to a conservative treatment. This procedure allows bladder re-augmentation to be delayed or even avoided.UVR and immunosuppression are major risk factors for cutaneous squamous cell carcinoma (cSCC). Regulatory T cells promote cSCC carcinogenesis, and in other solid tumors, infiltrating regulatory T cells and CD8+ T cells express ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) (also known as CD39), an ectoenzyme that catalyzes the rate-limiting step in converting extracellular adenosine triphosphate (ATP) to extracellular adenosine (ADO). We previously showed that extracellular purine nucleotides influence DNA damage repair. In this study, we investigate whether DNA damage repair is modulated through purinergic signaling in cSCC. We found increased ENTPD1 expression on T cells within cSCCs when compared with the expression on T cells from blood or nonlesional skin, and accordingly, concentrations of derivative extracellular adenosine diphosphate (ADP), adenosine monophosphate (AMP), and ADO are increased in tumors compared with those in normal skin. link3 Importantly, ENTPD1 expression is significantly higher in human cSCCs that metastasize than in those that are nonmetastatic.
