ASSESSMENT OF RETINAL MICROVASCULAR ALTERATIONS IN INDIVIDUALS WITH AMNESTIC AND NONAMNESTIC MILD COGNITIVE IMPAIRMENT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess retinal microvascular alterations in individuals with amnestic mild cognitive impairment (MCI) and nonamnestic MCI. METHODS: One hundred twelve eyes of 59 amnestic MCI participants, 32 eyes of 17 nonamnestic MCI participants, and 111 eyes of 56 controls with normal cognition were included. Optical coherence tomography angiography vessel density and perfusion density in the Early Treatment Diabetic Retinopathy Study 3-mm circle and ring were assessed. Retinal thickness parameters including retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness were also analyzed. Multivariable generalized estimating equations were used for statistical analysis. RESULTS: Perfusion density in the 3-mm inner ring was significantly lower in amnestic MCI patients when compared with nonamnestic MCI participants (0.29 ± 0.03 vs. 0.34 ± 0.09, P = 0.025) and controls with normal cognition (0.29 ± 0.03 vs. 0.39 ± 0.02, P < 0.001), after adjustment for age and sex as covariates. Vessel density, retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness did not differ among or between diagnostic groups. CONCLUSION: Perfusion density was significantly reduced in individuals with amnestic MCI, compared with those with nonamnestic MCI and controls with normal cognition.

A Disease Identification Algorithm for Medical Crowdfunding Campaigns: Validation Study.

BACKGROUND: Web-based crowdfunding has become a popular method to raise money for medical expenses, and there is growing research interest in this topic. However, crowdfunding data are largely composed of unstructured text, thereby posing many challenges for researchers hoping to answer questions about specific medical conditions. Previous studies have used methods that either failed to address major challenges or were poorly scalable to large sample sizes. To enable further research on this emerging funding mechanism in health care, better methods are needed. OBJECTIVE: We sought to validate an algorithm for identifying 11 disease categories in web-based medical crowdfunding campaigns. We hypothesized that a disease identification algorithm combining a named entity recognition (NER) model and word search approach could identify disease categories with high precision and accuracy. Such an algorithm would facilitate further research using these data. METHODS: Web scraping was used to collect data on medical crowdfunding campaigns from GoFundMe (GoFundMe Inc). Using pretrained NER and entity resolution models from Spark NLP for Healthcare in combination with targeted keyword searches, we constructed an algorithm to identify conditions in the campaign descriptions, translate conditions to International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes, and predict the presence or absence of 11 disease categories in the campaigns. The classification performance of the algorithm was evaluated against 400 manually labeled campaigns. RESULTS: We collected data on 89,645 crowdfunding campaigns through web scraping. The interrater reliability for detecting the presence of broad disease categories in the campaign descriptions was high (Cohen κ: range 0.69-0.96). The NER and entity resolution models identified 6594 unique (276,020 total) ICD-10-CM codes among all of the crowdfunding campaigns in our sample. Through our word search, we identified 3261 additional campaigns for which a medical condition was not otherwise detected with the NER model. When averaged across all disease categories and weighted by the number of campaigns that mentioned each disease category, the algorithm demonstrated an overall precision of 0.83 (range 0.48-0.97), a recall of 0.77 (range 0.42-0.98), an F1 score of 0.78 (range 0.56-0.96), and an accuracy of 95% (range 90%-98%). CONCLUSIONS: A disease identification algorithm combining pretrained natural language processing models and ICD-10-CM code-based disease categorization was able to detect 11 disease categories in medical crowdfunding campaigns with high precision and accuracy.

Investigation of the adolescent female breast transcriptome and the impact of obesity.

BACKGROUND: Early life environmental exposures affect breast development and breast cancer risk in adulthood. The breast is particularly vulnerable during puberty when mammary epithelial cells proliferate exponentially. In overweight/obese (OB) women, inflammation increases breast aromatase expression and estrogen synthesis and promotes estrogen-receptor (ER)-positive breast cancer. In contrast, recent epidemiological studies suggest that obesity during childhood decreases future breast cancer risk. Studies on environmental exposures and breast cancer risk have thus far been limited to animal models. Here, we present the first interrogation of the human adolescent breast at the molecular level and investigate how obesity affects the immature breast. METHODS: We performed RNA-seq in 62 breast tissue samples from adolescent girls/young women (ADOL; mean age 17.8 years) who underwent reduction mammoplasty. Thirty-one subjects were non-overweight/obese (NOB; mean BMI 23.4 kg/m2) and 31 were overweight/obese (OB; BMI 32.1 kg/m2). We also compared our data to published mammary transcriptome datasets from women (mean age 39 years) and young adult mice, rats, and macaques. RESULTS: The ADOL breast transcriptome showed limited (30%) overlap with other species, but 88% overlap with adult women for the 500 most highly expressed genes in each dataset; only 43 genes were shared by all groups. In ADOL, there were 120 differentially expressed genes (DEG) in OB compared with NOB samples (padj < 0.05). Based on these DEG, Ingenuity Pathway Analysis (IPA) identified the cytokines CSF1 and IL-10 and the chemokine receptor CCR2 as among the most highly activated upstream regulators, suggesting increased inflammation in the OB breast. Classical ER targets (e.g., PR, AREG) were not differentially expressed, yet IPA identified the ER and PR and growth factors/receptors (VEGF, HGF, HER3) and kinases (AKT1) involved in hormone-independent ER activation as activated upstream regulators in OB breast tissue. CONCLUSIONS: These studies represent the first investigation of the human breast transcriptome during late puberty/young adulthood and demonstrate that obesity is associated with a transcriptional signature of inflammation which may augment estrogen action in the immature breast microenvironment. We anticipate that these studies will prompt more comprehensive cellular and molecular investigations of obesity and its effect on the breast during this critical developmental window.

Testis-specific ATP synthase peripheral stalk subunits required for tissue-specific mitochondrial morphogenesis in Drosophila.

BACKGROUND: In Drosophila early post-meiotic spermatids, mitochondria undergo dramatic shaping into the Nebenkern, a spherical body with complex internal structure that contains two interwrapped giant mitochondrial derivatives. The purpose of this study was to elucidate genetic and molecular mechanisms underlying the shaping of this structure. RESULTS: The knotted onions (knon) gene encodes an unconventionally large testis-specific paralog of ATP synthase subunit d and is required for internal structure of the Nebenkern as well as its subsequent disassembly and elongation. Knon localizes to spermatid mitochondria and, when exogenously expressed in flight muscle, alters the ratio of ATP synthase complex dimers to monomers. By RNAi knockdown we uncovered mitochondrial shaping roles for other testis-expressed ATP synthase subunits. CONCLUSIONS: We demonstrate the first known instance of a tissue-specific ATP synthase subunit affecting tissue-specific mitochondrial morphogenesis. Since ATP synthase dimerization is known to affect the degree of inner mitochondrial membrane curvature in other systems, the effect of Knon and other testis-specific paralogs of ATP synthase subunits may be to mediate differential membrane curvature within the Nebenkern.

Academic versus Community Retinal Surgery for Primary Retinal Detachment: Characteristics, Duration, and Value Analysis of Teaching Modifier.

PURPOSE: To compare operative time and case characteristics of primary rhegmatogenous retinal detachment (RRD) repairs between academic and community vitreoretinal surgeons. DESIGN: A retrospective, observational clinical study. SUBJECTS: Patients who underwent primary RRD repair surgeries at Massachusetts Eye and Ear between 2019 and 2021. METHODS: A random sample of 20 vitreoretinal surgeons distributed evenly among the academic or community setting was selected. Fifteen consecutive cases of primary RRD repair surgeries were included from each surgeon. A cost analysis was performed for the teaching modifier for the physician fee and for hospital costs. MAIN OUTCOME MEASURES: Length of surgery. RESULTS: Of 300 primary RRD repairs, fellows were present in 75%, which comprised all academic surgeon cases and 50% of community surgeon cases, P < 0.001. Mean operation length was shorter for community surgeon cases without fellows (55.0 ± 24.1) than either academic (73.0 ± 30.8) or community surgeon cases with fellows (75.7 ± 32.5) (P < 0.001). There was a higher percentage of macula-off RRDs in academic versus community surgeon cases (52.7% vs. 38.0%, P = 0.002) and higher rates of combined scleral buckle (SB)/pars plana vitrectomy (PPV) repairs (14% vs. 3%, P < 0.001). When excluding combined SB/PPV cases, there was no difference in operative time between academic and community surgeon cases. Among RRDs repaired by PPV only, there was a 31.4% (16.6 minutes) greater procedure duration in cases with fellows compared with cases without fellows (P < 0.001). Covariates associated with greater surgery time: addition of an SB (ß = 32.6), membrane peel (ß = 18.5), presence of a fellow (ß = 14.5), proliferative vitreoretinopathy (ß = 12.8), and greater number of retinal breaks (ß = 2.4). The teaching modifier adds 16% extra reimbursement ($184.16) to the physician fee, which is 50.9% of what is necessary to cover the percentage increase in surgeon time (31.4%). Using a time-driven activity-based costing for hospital costs, the extra 16.6 minutes leads to an additional $1038.00, which is 5.6 times more than the reimbursement for the modifier. CONCLUSIONS: Retinal detachment repair cases performed by academic surgeons are more likely to be macula-off and include the addition of an SB, which drive longer operative times. Medicare's reimbursement of the assistant modifier in a teaching facility significantly undercompensates the time-driven activity-based costing of trainee participation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intrasession Repeatability of OCT Angiography Parameters in Neurodegenerative Disease.

Purpose: To assess the intrasession repeatability of macular OCT angiography (OCTA) parameters in Alzheimer's disease (AD), mild cognitive impairment (MCI), Parkinson's disease (PD), and normal cognition (NC). Design: Cross sectional study. Subjects: Patients with a clinical diagnosis of AD, PD, MCI, or NC were imaged. Images with poor quality and of those with diabetes mellitus, glaucoma, or vitreoretinal disease were excluded from analysis. Methods Intervention or Testing: All participants were imaged using the Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Software Version 11.0.0.29946) and repeat OCTA images were obtained for both eyes. Perfusion density (PFD), vessel density (VD), and Foveal avascular zone (FAZ) area were measured from 3 × 3 mm and 6 × 6 mm OCTA images centered on the fovea using an ETDRS grid overlay. Main Outcome Measures: Intraclass correlation coefficients were used to quantify repeatability of PFD, VD, and FAZ area measurements obtained from imaging. Results: 3 × 3 mm scans of 22 AD, 40 MCI, 21 PD, and 26 NC participants and 6 × 6 mm scans of 29 AD, 44 MCI, 29 PD, and 30 NC participants were analyzed. Repeatability values ranged from 0.64 (0.49-0.82) for 6 × 6 mm PFD in AD participants to 0.87 (0.67-0.92) for 3 × 3 mm PFD in AD participants. No significant differences were observed in repeatability between NC participants and those with neurodegenerative disease. Conclusions: Overall, similar OCTA repeatability was observed between NC participants and those with neurodegeneration. Regardless of diagnostic group, macular OCTA metrics demonstrated moderate to good repeatability. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Deciding Whether to Take Sacubitril/Valsartan: How Cardiologists and Patients Discuss Out-of-Pocket Costs.

Background Out-of-pocket costs have significant implications for patients with heart failure and should ideally be incorporated into shared decision-making for clinical care. High out-of-pocket cost is one potential reason for the slow uptake of newer guideline-directed medical therapies for heart failure with reduced ejection fraction. This study aims to characterize patient-cardiologist discussions involving out-of-pocket costs associated with sacubitril/valsartan during the early postapproval period. Methods and Results We conducted content analysis on 222 deidentified transcripts of audio-recorded outpatient encounters taking place between 2015 and 2018 in which cardiologists (n=16) and their patients discussed whether to initiate, continue, or discontinue sacubitril/valsartan. In the 222 included encounters, 100 (45%) contained discussions about cost. Cost was discussed in a variety of contexts: when sacubitril/valsartan was initiated, not initiated, continued, and discontinued. Of the 97 cost conversations analyzed, the majority involved isolated discussions about insurance coverage (64/97 encounters; 66%) and few addressed specific out-of-pocket costs or affordability (28/97 encounters; 29%). Discussion of free samples of sacubitril/valsartan was common (52/97 encounters; 54%), often with no discussion of a longer-term plan for addressing cost. Conclusions Although cost conversations were somewhat common in patient-cardiologist encounters in which sacubitril/valsartan was discussed, these conversations were generally superficial, rarely addressing affordability or cost-value judgments. Cardiologists frequently provided patients with a course of free sacubitril/valsartan samples without a plan to address the cost after the samples ran out.

Intracanalicular Dexamethasone Insert or Topical Prednisolone Following iStent and Hydrus Surgery for Glaucoma.

PRCIS: Using an intracanalicular dexamethasone insert or topical prednisolone following iStent and Hydrus surgery provided similar short-term control of postoperative inflammation. PURPOSE: The purpose of this study was to compare postoperative inflammation in patients who received an intracanalicular dexamethasone insert or topical prednisolone after iStent or Hydrus insertion during cataract surgery. PATIENTS AND METHODS: Patients receiving a dexamethasone insert after iStent or Hydrus insertion were included and compared with age-matched controls who received topical prednisolone. Preoperative data were recorded. Postoperative inflammatory cell and the proportion of patients with zero anterior chamber cells was recorded at month 1. Postoperative intraocular pressure (IOP) and rate of cystoid macular edema were recorded at months 1 and 3. RESULTS: Forty eyes receiving topical prednisolone were compared with 35 eyes receiving a dexamethasone insert after iStent or Hydrus insertion. The mean postoperative inflammatory cell for the topical group at month 1 was 0.2±0.3, and the dexamethasone group, 0.3±0.5 ( P =0.816). Overall, 70% of patients in the topical group had zero anterior chamber cell at postoperative month 1 compared with 75.8% in the dexamethasone group ( P =0.583). The mean preoperative IOP for the topical group was 18.8±5.5 and the dexamethasone group was 17.1±4.1 ( P =0.064). Mean postoperative IOP for the topical group at months 1 and 3 was 17.6±6.4 and 15.1±3.1, respectively and the dexamethasone group, 17.5±4.8 and 15.0±3.4, respectively ( P =0.772 and 0.884). One patient developed cystoid macular edema in each group. CONCLUSION: There was no statistically significant difference in the proportion of patients who had zero anterior chamber cell at postoperative month 1 between groups receiving intracanalicular dexamethasone insert or topical prednisolone.

Perceptions of Respect From Clinicians by Patients in Racial and Ethnic Minority Groups With Eye Disease.

IMPORTANCE: The perception of being treated with respect by clinicians may be a driver of disparities in individuals in racial and ethnic minoritie groups with eye diseases. Understanding these drivers may help identify potential interventions to reduce eye health disparities to prevent vision loss and blindness. OBJECTIVE: To evaluate the association between racial and ethnic minority status and the perception of being treated with respect by clinicians. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis of a nationally representative cohort study using data from the National Health Interview Survey (NHIS) included participants in the 2017 survey with complete data on outcomes, associated factors, and covariates. Data analysis took place from January 2021 to February 2021. Using a population-based survey conducted in the US in 2017 by the US census bureau on behalf of the National Center for Health Statistics, NHIS study participants (age ≥18 years) who self-reported having an eye disease (macular degeneration, diabetic retinopathy [DR], glaucoma, cataracts) were included, and patients who self-reported as Black, Asian, other/multiple races, or Hispanic ethnicity were considered to be in racial and ethnic minority groups. MAIN OUTCOMES AND MEASURES: Multivariable logistic regression models were used to evaluate the association of minority status with self-reported "always" being treated with respect by clinicians and self-reported "always" being asked about opinions/beliefs about medical care. RESULTS: Participants in racial and ethnic minority groups had 23% lower odds of reporting being treated with respect compared with non-Hispanic White patients (adjusted odds ratio [AOR], 0.77; 95% CI, 0.61-0.97; P = .03). A minority of participants had 66% higher odds of reporting being asked about their beliefs (AOR, 1.66; 95% CI, 1.39-1.98; P < .001). For all patients, being asked about opinions/beliefs by their clinician was associated with a 5.8 times higher odds of reporting being treated with respect (AOR, 5.80; 95% CI, 4.35-7.74; P < .001). CONCLUSIONS AND RELEVANCE: In this nationally representative US population of patients with eye diseases, being a patient in a racial or ethnic minority group was associated with feeling less respected by health care professionals compared with non-Hispanic White patients. Asking about opinions and beliefs, regardless of race or ethnicity, is associated with patients feeling that they are treated with respect.

Substance Use Disorder Education in Medical Schools: A Scoping Review.

PURPOSE: As medical schools adapt their curricula to prepare future physicians for the opioid crisis and for treating patients with substance use disorders (SUDs), educators should refer to courses described in the literature. This scoping review aimed to (1) provide a comprehensive evaluation and summation of peer-reviewed literature reporting on SUD education in medical schools globally and (2) appraise the research quality and educational outcomes reported in SUD education studies in medical schools. METHOD: The authors searched 6 databases (3 Ovid MEDLINE databases, Embase, ERIC, and Web of Science) from inception through May 25, 2018. Original English-language research studies focusing on medical students and describing SUD education in medical schools were included. The Medical Education Research Study Quality Instrument (MERSQI) was used to assess included studies. RESULTS: Of 3,178 articles identified, 43 met inclusion criteria. Studies were conducted in 9 countries. Most reported on educational interventions for tobacco (n = 20; 47%); others reported on interventions for SUDs broadly (n = 15; 35%), alcohol (n = 8; 19%), and opioids (n = 1; 2%). The mean MERSQI score was 12.27 (standard deviation 2.30). Four studies (9%) reported on educational outcomes at the level of behaviors or patient or health care outcomes. The majority (n = 39; 91%) reported significant benefits. CONCLUSIONS: Educational interventions relating to SUDs were effective in improving medical students' knowledge, skills, and attitudes. Educators should develop courses that achieve higher-level educational outcomes, increase education on opioid use disorders, and focus on the greatest public health concerns.