Comparison of clinical note quality between an automated digital intake tool and the standard note in the emergency department.

BACKGROUND: Medical encounters require an efficient and focused history of present illness (HPI) to create differential diagnoses and guide diagnostic testing and treatment. Our aim was to compare the HPI of notes created by an automated digital intake tool versus standard medical notes created by clinicians. METHODS: Prospective trial in a quaternary academic Emergency Department (ED). Notes were compared using the 5-point Physician Documentation Quality Instrument (PDQI-9) scale and the Centers for Medicare & Medicaid Services (CMS) level of complexity index. Reviewers were board certified emergency medicine physicians blinded to note origin. Reviewers received training and calibration prior to note assessments. A difference of 1 point was considered clinically significant. Analysis included McNemar's (binary), Wilcoxon-rank (Likert), and agreement with Cohen's Kappa. RESULTS: A total of 148 ED medical encounters were charted by both digital note and standard clinical note. The ability to capture patient information was assessed through comparison of note content across paired charts (digital-standard note on the same patient), as well as scores given by the reviewers. Reviewer agreement was kappa 0.56 (CI 0.49-0.64), indicating moderate level of agreement between reviewers scoring the same patient chart. Considering all 18 questions across PDQI-9 and CMS scales, the average agreement between standard clinical note and digital note was 54.3% (IQR 44.4-66.7%). There was a moderate level of agreement between content of standard and digital notes (kappa 0.54, 95%CI 0.49-0.60). The quality of the digital note was within the 1 point clinically significant difference for all of the attributes, except for conciseness. Digital notes had a higher frequency of CMS severity elements identified. CONCLUSION: Digitally generated clinical notes had moderate agreement compared to standard clinical notes and within the one point clinically significant difference except for the conciseness attribute. Digital notes more reliably documented billing components of severity. The use of automated notes should be further explored to evaluate its utility in facilitating documentation of patient encounters.

Retroillumination Photography Analysis Enhances Clinical Definition of Severe Fuchs Corneal Dystrophy.

PURPOSE: Retroillumination photography analysis (RPA) provides an objective assessment of the number and distribution of guttae in Fuchs corneal dystrophy. Here, we assess its correlation with clinical grading using slit-lamp biomicroscopy across varying levels of severity. METHODS: Retroillumination photographs were conducted for 95 affected corneas with slit-lamp flash photography after pupillary dilation. Individual guttae were counted manually and the position of individual points recorded. Clinical grading using the Krachmer scale was documented for each eye during examination, and regression analyses were performed to identify the strength of association with number of guttae. We assessed range at each stage of clinical grading and used the Mann-Whitney U test to assess whether clinical grading levels demonstrated successively higher numbers of guttae. RESULTS: Krachmer score ranged from 1 to 5, with mean of 2.6. Mean numbers of guttae at each level of severity were 289 (1+), 999 (2+), 2669 (3+), 5474 (4+), and 7133 (5+). Each stage demonstrated significantly higher numbers of guttae than its preceding level except from 4+ to 5+ (P = 0.30), consistent with the definition of 4+ as the highest level defined by the presence of guttae. Higher levels of clinical grading were associated with larger ranges of guttae (P < 0.01). A linear regression model resulted in a strong fit between RPA and Krachmer score (r = 0.81). CONCLUSIONS: In this largest study of RPA data and comparison with subjective clinical grading of Fuchs dystrophy severity, RPA correlates strongly and demonstrates enhanced definition of severity at advanced stages of disease.

Central adenosine receptor signaling is necessary for daily torpor in mice.

When calorically restricted at cool ambient temperatures, mice conserve energy by entering torpor, during which metabolic rate (MR), body temperature (T(b)), heart rate (HR), and locomotor activity (LMA) decrease. Treatment with exogenous adenosine produces a similar hypometabolic state. In this study, we conducted a series of experiments using the nonspecific adenosine receptor antagonists aminophylline and 8-sulfophenyltheophylline (8-SPT) to test the hypothesis that adenosine signaling is necessary for torpor in fasted mice. In the first experiment, mice were subcutaneously infused with aminophylline while T(b), HR, and LMA were continuously monitored using implanted radiotelemeters. During a 23-h fast, saline-treated mice were torpid for 518 ± 43 min, whereas aminophylline-treated mice were torpid for significantly less time (54 ± 20 min). In a second experiment, aminophylline was infused subcutaneously into torpid mice to test the role of adenosine in the maintenance of torpor. Aminophylline reversed the hypometabolism, hypothermia, bradycardia, and hypoactivity of torpor, whereas saline did not. In the third and fourth experiments, the polar adenosine antagonist 8-SPT, which does not cross the blood-brain barrier, was infused either subcutaneously or intracerebroventricularly to test the hypothesis that both peripheral and central adenosine receptor signaling are necessary for the maintenance of torpor. Intracerebroventricular, but not subcutaneous, infusion of 8-SPT causes a return to euthermia. These findings support the hypothesis that adenosine is necessary for torpor in mice and further suggest that whereas peripheral adenosine signaling is not necessary for the maintenance of torpor, antagonism of central adenosine is sufficient to disrupt torpor.

Mutations in LOXHD1, a recessive-deafness locus, cause dominant late-onset Fuchs corneal dystrophy.

Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHD1 mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico analyses predicted that these mutations reside on the surface of the protein and are likely to affect the protein's interface and protein-protein interactions. Finally, expression of the familial LOXHD1 mutant allele as well as two sporadic mutations in cells revealed prominent cytoplasmic aggregates reminiscent of the corneal phenotype. All together, our data implicate rare alleles in LOXHD1 in the pathogenesis of FCD and highlight how different mutations in the same locus can potentially produce diverse phenotypes.

Prevalence and severity of fuchs corneal dystrophy in Tangier Island.

PURPOSE: To investigate the clinical and genetic features of late-onset Fuchs corneal dystrophy (FCD) on Tangier, an island in the Chesapeake Bay with an isolated population of approximately 500 individuals. DESIGN: Observational, cross-sectional study. METHODS: A total of 156 individuals born to inhabitants of Tangier Island volunteered to undergo ophthalmic evaluation. Medical history was ascertained prior to examination. All participants underwent anterior segment examination with slit-lamp biomicroscopy. Retroillumination photographs were acquired from affected individuals and the disease severity was compared with individuals from large families ascertained previously. Genomic DNA samples were investigated for the presence of the recently identified risk allele rs613872, an intronic variant of TCF4. RESULTS: Of the 148 examined individuals who were at least 30 years of age, 32 showed the classical symptoms of late-onset FCD (21.6%), providing a minimum prevalence of 11% among individuals over the age of 50 years. Severity was significantly lower compared to 51 cases from unlinked families, among individuals either 50 to 70 or above 70 years of age (P = .05 and P = .01, respectively). Retroillumination photography analyses were suggestive of mild severity when compared with the disease phenotype associated with FCD1- and FCD2-linked families. The rs613872 variant was associated with a higher affectation rate (P = .01), while the wild-type allele was correlated with a higher proportion of subclinical disease (P = .01). CONCLUSIONS: In this study population in Tangier, late-onset FCD manifests clinically with a mild phenotype and increased prevalence. The rs613872 variant correlates with increased affectation and a clinical disease phenotype.

A single-base substitution in the seed region of miR-184 causes EDICT syndrome.

PURPOSE: To investigate the cause of the syndrome characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT). METHODS: Previously a multigenerational family was reported that comprised 10 individuals affected by syndromal anterior segment dysgenesis. Blood samples were re-collected from eight affected and two unaffected individuals, and genomic DNA was extracted. A total of 24 candidate genes and 4 microRNAs residing within the critical interval were sequenced bidirectionally. In silico analyses were performed to examine the effect of the causal variant on the stability of the pre-microRNA structure. RESULTS: Bidirectional sequencing identified the single-base substitution +57C>T in miR-184. This variation segregated with the disease phenotype and was absent in the 1000 Genomes project, 1130 control chromosomes, and 28 nonhuman vertebrates. CONCLUSIONS: The single-base-pair substitution in the seed region of miR-184 is responsible for the disease phenotype observed in EDICT syndrome.

The genetics of Fuchs' corneal dystrophy.

Fuchs' corneal dystrophy (FCD) is a common late-onset genetic disorder of the corneal endothelium. It causes loss of endothelial cell density and excrescences in the Descemet membrane, eventually progressing to corneal edema, necessitating corneal transplantation. The genetic basis of FCD is complex and heterogeneous, demonstrating variable expressivity and incomplete penetrance. To date, three causal genes, ZEB1, SLC4A11 and LOXHD1, have been identified, representing a small proportion of the total genetic load of FCD. An additional four loci have been localized, including a region on chromosome 18 that is potentially responsible for a large proportion of all FCD cases. The elucidation of the causal genes underlying these loci will begin to clarify the pathogenesis of FCD and pave the way for the emergence of nonsurgical treatments.

Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction.

Dietary supplementation with resveratrol may produce calorie restriction-like effects on metabolic and longevity endpoints in mice. In this study, we sought to determine whether resveratrol treatment elicited other hallmark changes associated with calorie restriction, namely bradycardia and decreased body temperature. We found that during short-term treatment, wild-type mice on a calorie-restricted diet experienced significant decreases in both heart rate and body temperature after only 1 day whereas those receiving resveratrol exhibited no such change after 1 wk. We also used ob/ob mice to study the effects of long-term treatment because previous studies had indicated the therapeutic value of resveratrol against the linked morbidities of obesity and diabetes. After 12 wk, resveratrol treatment had produced no changes in either heart rate or body temperature. Strikingly, and in contrast to previous findings, we found that resveratrol-treated mice had significantly reduced endurance in a treadmill test. Quantitative reverse transcriptase-polymerase chain reaction suggested that a proposed target of resveratrol, Sirt1, was activated in resveratrol-treated ob/ob mice. Thus, we conclude that the bradycardia and hypothermia associated with calorie restriction occur through mechanisms unaffected by the actions of resveratrol and that further studies are needed to examine the differential effects of resveratrol in a leptin-deficient background.