A case of Staphylococcus epidermidis osteomyelitis in the absence of spine hardware.

Staphylococcus epidermidis is a typically indolent pathogen that is often considered a blood culture contaminant. It is a rare and unexpected cause of osteomyelitis, especially in the absence of recent surgical intervention or orthopedic implants. We highlight a case in which a 90-year-old Caucasian male with no recent spine surgery was found to have osteomyelitis of the lumbar spine and repeat positive blood cultures for methicillin resistant Staphylococcus epidermidis (MRSE). Further investigation revealed a history of mitral valve replacement and a new diagnosis of endocarditis leading to persistent bacteremia and seeding of his lumbar vertebrae. This case demonstrates that S. epidermidis can cause vertebral osteomyelitis resulting in severe complications that are more similar to highly pathogenic bacteria. We describe the steps to diagnosing this chronic undetected infection and related comorbidities.

Correction: Associations between healthcare utilization and access and diabetic retinopathy complications using All of Us nationwide survey data.

[This corrects the article DOI: 10.1371/journal.pone.0269231.].

Review of glaucoma medication adherence monitoring in the digital health era.

Current glaucoma treatments aim to lower intraocular pressure, often with topical ocular hypotensive medications. Unfortunately, the effectiveness of these medications depends on sustained patient adherence to regimens which may involve instilling multiple medications several times daily. Patient adherence to glaucoma medications is often low. Recent innovations in digital sensor technologies have been leveraged to confirm eyedrop medication usage in real-time and relay this information back to providers. Some sensors have also been designed to deliver medication reminders and notifications as well as assist with correct eyedrop administration technique. Here, we review recent innovations targeted at improving glaucoma medication adherence and discuss their limitations.

Social Determinants of Health Data Availability for Patients with Eye Conditions.

Purpose: To quantify and characterize social determinants of health (SDoH) data coverage using single-center electronic health records (EHRs) and the National Institutes of Health All of Us research program. Design: Retrospective cohort study from June 2014 through June 2021. Participants: Adults 18 years of age or older with a diagnosis of diabetic retinopathy, glaucoma, cataracts, or age-related macular degeneration. Methods: For All of Us, research participants completed online survey forms as part of a nationwide prospective cohort study. In local EHRs, patients were selected based on diagnosis codes. Main Outcome Measures: Social determinants of health data coverage, characterized by the proportion of each disease cohort with available data regarding demographics and socioeconomic factors. Results: In All of Us, we identified 23 806 unique adult patients, of whom 2246 had a diagnosis of diabetic retinopathy, 13 448 had a diagnosis of glaucoma, 6634 had a diagnosis of cataracts, and 1478 had a diagnosis of age-related macular degeneration. Survey completion rates were high (99.5%-100%) across all cohorts for demographic information, overall health, income, education, and lifestyle. However, health care access (12.7%-29.4%), housing (0.7%-1.1%), social isolation (0.2%-0.3%), and food security (0-0.1%) showed significantly lower response rates. In local EHRs, we identified 80 548 adult patients, of whom 6616 had a diagnosis of diabetic retinopathy, 26 793 had a diagnosis of glaucoma, 40 427 had a diagnosis of cataracts, and 6712 had a diagnosis of age-related macular degeneration. High data coverage was found across all cohorts for variables related to tobacco use (82.84%-89.07%), alcohol use (77.45%-83.66%), and intravenous drug use (84.76%-93.14%). However, low data coverage (< 50% completion) was found for all other variables, including education, finances, social isolation, stress, physical activity, food insecurity, and transportation. We used chi-square testing to assess whether the data coverage varied across different disease cohorts and found that all fields varied significantly (P < 0.001). Conclusions: The limited and highly variable data coverage in both local EHRs and All of Us highlights the need for researchers and providers to develop SDoH data collection strategies and to assemble complete datasets.

Novel Association between Opioid Use and Increased Risk of Retinal Vein Occlusion Using the National Institutes of Health All of Us Research Program.

Purpose: To assess for risk factors for retinal vein occlusion (RVO) among participants in the National Institutes of Health All of Us database, particularly social risk factors that have not been well studied, including substance use. Design: Retrospective, case-control study. Participants: Data were extracted for 380 adult participants with branch retinal vein occlusion (BRVO), 311 adult participants with central retinal vein occlusion (CRVO), and 1520 controls sampled among 311 640 adult participants in the All of Us database. Methods: Data were extracted regarding demographics, comorbidities, income, housing, insurance, and substance use. Opioid use was defined by relevant diagnosis and prescription codes, with prescription use > 30 days. Controls were sampled at a 4:1 control to case ratio from a pool of individuals aged > 18 years without a diagnosis of RVO and proportionally matched to the demographic distribution of the 2019 U.S. census. Multivariable logistic regression identified medical and social determinants significantly associated with BRVO or CRVO. Statistical significance was defined as P < 0.05. Main Outcome Measure: Development of BRVO or CRVO based on diagnosis codes. Results: Among patients with BRVO, the mean (standard deviation) age was 70.1 (10.5) years. The majority (53.7%) were female. Cases were diverse; 23.7% identified as Black, and 18.4% identified as Hispanic or Latino. Medical risk factors including glaucoma (odds ratio [OR], 3.29; 95% confidence interval [CI], 2.22-4.90; P < 0.001), hypertension (OR, 2.15; 95% CI, 1.49-3.11; P < 0.001), and diabetes mellitus (OR, 1.68; 95% CI, 1.18-2.38; P = 0.004) were re-demonstrated to be associated with BRVO. Black race (OR, 2.64; 95% CI, 1.22-6.05; P = 0.017) was found to be associated with increased risk of BRVO. Past marijuana use (OR, 0.68; 95% CI, 0.50-0.92; P = 0.013) was associated with decreased risk of BRVO; however, opioid use (OR, 1.98; 95% CI, 1.41-2.78; P < 0.001) was associated with a significantly increased risk of BRVO. Similar associations were found for CRVO. Conclusions: Understanding RVO risk factors is important for primary prevention and improvement in visual outcomes. This study capitalizes on the diversity and scale of a novel nationwide database to elucidate a previously uncharacterized association between RVO and opioid use.

Associations between healthcare utilization and access and diabetic retinopathy complications using All of Us nationwide survey data.

PURPOSE: Inadequacies in healthcare access and utilization substantially impact outcomes for diabetic patients. The All of Us database offers extensive survey data pertaining to social determinants that is not routinely available in electronic health records. This study assesses whether social determinants were associated with an increased risk of developing proliferative diabetic retinopathy or related complications (e.g. related diagnoses or procedures). METHODS: We identified 729 adult participants in the National Institutes of Health All of Us Research Program data repository with diabetic retinopathy (DR) who answered survey questions pertaining to healthcare access and utilization. Electronic health record data regarding co-morbidities, laboratory values, and procedures were extracted. Multivariable logistic regression with bi-directional stepwise variable selection was performed from a wide range of predictors. Statistical significance was defined as p<0.05. RESULTS: The mean (standard deviation) age of our cohort was 64.9 (11.4) years. 15.2% identified as Hispanic or Latino, 20.4% identified as Black, 60.6% identified as White, and 19.3% identified as Other. 10-20% of patients endorsed several reasons for avoiding or delaying care, including financial concerns and lack of access to transportation. Additional significant social determinants included race and religion discordance between healthcare provider and patient (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.41, p = 0.03) and caregiver responsibilities toward others (OR 3.14, 95% CI 1.01-9.50, p = 0.04). CONCLUSIONS: Nationwide data demonstrate substantial barriers to healthcare access among DR patients. In addition to financial and social determinants, race and religion discordance between providers and patients may increase the likelihood of PDR and related complications.

Delayed Facial Nerve Palsy Following Resection of Vestibular Schwannoma: Clinical and Surgical Characteristics.

OBJECTIVE: Analyze delayed facial nerve palsy (DFNP) following resection of vestibular schwannoma (VS) to describe distinct characteristics and facial nerve (FN) functional course. STUDY DESIGN: Prospective cohort with retrospective review. SETTING: Academic medical center. PATIENTS: Consecutive patients undergoing VS resection 11/2017 to 08/2020. Exclusion criteria: preoperative House-Brackmann (HB) ≥ III, postoperative HB ≥ III without delayed palsy, <30 days follow-up. INTERVENTIONS: VS resection with intraoperative electromyographic monitoring. MAIN OUTCOME MEASURES: FN outcomes utilizing the HB scale; comparison between patients with DFNP (deterioration greater than one HB grade 24 hours to 30 days postoperatively) vs. those with HBI-II throughout. RESULTS: Two hundred eighty-eight patients met criteria: mean age 47.6 years, 36.1% male; 24.0% middle cranial fossa, 28.5% retrosigmoid, 47.6% translabyrinthine. DFNP occurred in 31 (10.8%) patients with average time to onset of 8.1 days. Of these, 22 (71.0%) recovered HBI-II and 3 (9.7%) recovered HBIII. Patients who experienced DFNP, on average, had larger maximum tumor diameter (23.4 vs. 18.7 mm, p = 0.014), lower rate of gross-total resection (54.8% vs. 75.5%, p = 0.014), and lower rate of ≥100 µV FN response to 0.05 mA stimulus intraoperatively (80.6% vs. 94.9%, p = 0.002). Compared to overall incidence of DFNP, translabyrinthine approach demonstrated higher incidence (15.3%, p = 0.017) while retrosigmoid lower (3.7%, p = 0.014). In multivariable logistic regression, patients with FN response ≥100 µV to 0.05 mA stimulus were 72.0% less likely to develop DFNP (p = 0.021). CONCLUSIONS: Intraoperative electromyographic facial nerve response, tumor size, surgical approach, and extent of resection may play a role in development of DFNP following resection of VS. Most patients who develop DFNP recover near-normal function.

Geographic Trends in the Otolaryngology Match (2016-2020).

OBJECTIVE: Presenting geographic matching trends over 5 match cycles (2016-2020) to serve as a context for changes in residency match outcomes due to the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: Retrospective review. SETTING: Single academic institution-affiliated otolaryngology-head and neck surgery residency program. METHODS: Residency match outcomes for all applicants to our institution (2015-2019) were collected from the National Residency Matching Program, including medical school and matched program. Matches were categorized as home program, home region, or out of region and sorted by US geographic region. Statistical analysis included frequencies, totals, χ2 testing, and binary logistic regression. RESULTS: From 2016 to 2020, the US MD senior match rate was 84.9%: 18.9% to home programs, 35.7% to home region, and 45.3% to out of region. Rates were similar across regions and decreased over time. Westerners matched to home programs more than Southerners or Midwesterners (27.5% vs 16.0% and 16.0%, P < .01). Southerners and Westerners were more likely to match within their regions (South: 63.1%, P = .011, odds ratio [OR] = 1.296, 95% CI, 1.060-1.584; West: 42.0%, P = .018, OR = 1.462, 95% CI, 1.066-2.004). Matching from out of region was more likely in the West and less likely in the South (West: 58.0%, P = .017, OR = 1.379, 95% CI, 1.059-1.796; South: 36.9%, P < .001, OR = 0.584, 95% CI, 0.47-0.727). CONCLUSION: From 2016 to 2020 in otolaryngology-head and neck surgery, about 1 in 5 matches were to home institutions, a trend that appeared to be more common in the West. Over 4 out of 5 trainees match to nonhome programs, and nearly half relocate to a new region for training. Changes to travel, rotations, and interviews due to COVID-19 may influence these trends.

Assessment of patient recognition of coronavirus disease 2019 (COVID-19)-associated olfactory loss and recovery: a longitudinal study.

BACKGROUND: The clinical course of coronavirus disease 2019 (COVID-19) olfactory dysfunction remains poorly characterized, often limited by self-reported measures. Given the logistical challenges of psychophysical testing, understanding the longitudinal relationship between self-reported and quantitative measures can help accurately identify patients with persistent olfactory dysfunction. This study aimed to longitudinally correlate measured and subjective olfactory function in COVID-19 subjects. METHODS: A prospective, longitudinal study evaluating subjective and measured olfaction was conducted on ambulatory COVID-19 subjects. Olfaction scores were obtained using a visual analogue scale (VAS) (0 = anosmia, 10 = normosmia) and the validated 12-item Brief Smell Identification Test (BSIT). Weekly testing was performed until recovery (BSIT ≥ 9/12 and/or VAS = 10/10) or study completion. RESULTS: Eighty-six polymerase chain reaction (PCR)-positive COVID-19 subjects were recruited ≤3 days from diagnosis and 52 completed longitudinal testing. Among those with self-reported smell loss at recruitment, similar levels (75.8%) of objective (BSIT ≥ 9/12) and subjective recovery were obtained using a VAS cutoff ≥8, yet only 30.3% reported complete subjective recovery (VAS = 10). Median times to objective and complete subjective olfactory recovery were 12 ± 2.3 and 24 ± 3.5 days, respectively. Although both measures showed chemosensory improvement, the distributions of objective and full subjective olfactory recovery differed significantly (log rank test χ2 = 6.46, degrees of freedom [df] = 1, p = 0.011). Overall correlation between BSIT and VAS scores was moderate to strong across longitudinal follow-up (rs = 0.41-0.65). CONCLUSION: Self-reported and psychophysically measured COVID-19 olfactory dysfunction improve at similar levels and are moderately correlated longitudinally, yet there is a significant delay in complete subjective recovery. Psychophysical testing in conjunction with qualitative assessments may be considered for counseling and follow-up of patients with COVID-19 smell loss.

Pre-clinical remote undergraduate medical education during the COVID-19 pandemic: a survey study.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic has necessitated a sudden transition to remote learning in medical schools. We aimed to assess perceptions of remote learning among pre-clinical medical students and subsequently to identify pros and cons of remote learning, as well as uncover gaps to address in ongoing curricular development. METHODS: A survey was distributed to first- and second-year medical students at the University of California San Diego School of Medicine in March 2020. Frequencies of responses to structured multiple-choice questions were compared regarding impacts of remote learning on quality of instruction and ability to participate, value of various remote learning resources, living environment, and preparedness for subsequent stages of training. Responses to open-ended questions about strengths and weaknesses of the remote curriculum and overall reflections were coded for thematic content. RESULTS: Of 268 students enrolled, 104 responded (53.7% of first-year students and 23.9% of second-year students). Overall, students felt that remote learning had negatively affected the quality of instruction and their ability to participate. Most (64.1%) preferred the flexibility of learning material at their own pace. Only 25.5% of respondents still felt connected to the medical school or classmates, and feelings of anxiety and isolation were noted negatives of remote learning. Most second-year students (56.7%) felt their preparation for the United States Medical Licensing Examination Step 1 exam was negatively affected, and 43.3% felt unprepared to begin clerkships. In narrative responses, most students appreciated the increased flexibility of remote learning, but they also identified several deficits that still need to be addressed, including digital fatigue, decreased ability to participate, and lack of clinical skills, laboratory, and hands-on learning. CONCLUSIONS: Videocasted lectures uploaded in advance, electronic health record and telehealth training for students, and training for teaching faculty to increase technological fluency may be considered to optimize remote learning curricula.

Student Perspectives on Remote Medical Education in Clinical Core Clerkships During the COVID-19 Pandemic.

PURPOSE: To assess student perceptions of remote learning curricula implemented by clinical clerkships at a single US medical school during the COVID-19 pandemic. METHOD: Students enrolled in core clinical clerkships at the UC San Diego School of Medicine from March to April 2020 were sent an anonymous online survey, assessing components of remote learning curricula via quantitative rating and free-response questions. RESULTS: Of 132 students enrolled, 96 (73%) completed the survey. Online question banks, remote progress reviews, and telehealth sessions were rated as the most valuable resources, while textbooks were rated least valuable. Most students felt that the number of resources was adequate (69/94, 74%), the quantity of required content was appropriate (77/93, 83%), and there was a good balance of rigidity versus flexibility in the schedule (81/94, 86%). Most students felt "prepared" or "somewhat prepared" for the shelf examination (61/91, 67%) and for the next year of medical training (73/94, 78%). In narrative reflections, students valued the flexibility afforded by remote curricula but desired some weekly structure. Students enjoyed expanded access to learning resources and participating in interactive remote sessions. Students expressed anxiety about the pandemic and uncertainty regarding medical education, but transparent communication from clerkship directors helped assuage these concerns. CONCLUSIONS: Student participation in direct patient care is fundamental to medical school core clerkships and was negatively impacted by the COVID-19 pandemic. Strategic incorporation of select remote learning components into clinical clerkships may permit a favorable student experience even when opportunities for on-site participation are limited.

Association of subjective olfactory dysfunction and 12-item odor identification testing in ambulatory COVID-19 patients.

BACKGROUND: Acute loss of smell and taste are well-recognized symptoms of coronavirus disease 2019 (COVID-19), yet the correlation between self-reported and psychophysical olfactory function remains unclear. Understanding the reliability of self-reported smell loss in ambulatory cases can assess the utility of this screening measure. METHODS: A prospective, longitudinal study evaluating patient-reported and measured olfactory function using the validated 12-item Brief Smell Identification Test (BSIT) was conducted on adult outpatients with COVID-19. Patient-reported olfaction scores using a visual analog scale (VAS) were obtained at baseline, time of COVID-19 testing, and time of BSIT completion. Linear associations between VAS and BSIT were evaluated using Spearman's correlation coefficient and the sensitivity, specificity, and accuracy of VAS scores were calculated. Logistic regression identified characteristics associated with accurate assessment of olfactory function. RESULTS: A total of 81 polymerase chain reaction (PCR)-confirmed COVID-19 positive subjects, of whom 54 self-reported smell loss, were prospectively recruited ≤5 days from diagnosis date between May 8, 2020, and July 8, 2020. Self-reported smell loss had good discriminative ability in identifying abnormal BSIT (area under receiver operating curve [AUC] 0.82, 95% confidence interval [CI], 0.71 to 0.92). A VAS <5 demonstrated sensitivity of 0.62 and specificity of 0.94 for predicting hyposmia (BSIT ≤8) with accuracy of 82.7%, whereas a VAS <9 had highest sensitivity at 0.86. Moderate bivariate linear associations were found between VAS and BSIT scores (rs = 0.59, p < 0.001). CONCLUSION: Self-reported olfactory loss associated with COVID-19 has a strong ability to predict abnormal olfactory function though the 2 measures are moderately correlated. Subjective olfactory assessment is useful in screening olfactory dysfunction at early disease time points when psychophysical testing cannot be conducted.

Pre-Clinical Remote Undergraduate Medical Education During the COVID-19 Pandemic: A Survey Study .

Background : The COVID-19 pandemic has necessitated a sudden transition to remote learning in medical schools. We aimed to assess student perceptions of remote learning during the pre-clinical curricular training phase. Methods: A survey was distributed to first- and second-year medical students enrolled at the University of California San Diego School of Medicine in March 2020. Frequencies of responses to structured multiple-choice questions were compared regarding impacts of remote learning on quality of instruction and ability to participate, value of various remote learning resources, living environment, and preparedness for subsequent stages of training. Responses to open-ended questions about strengths and weaknesses of the remote curriculum and overall reflections were coded for thematic content. Results: Of 268 students enrolled, 104 responded (53.7% of first-year students and 23.9% of second-year students). Overall, students felt the quality of instruction and their ability to participate had been negatively affected. Most (64.1%) preferred the flexibility of learning material at their own pace. Only 25.5% of respondents still felt connected to the medical school or classmates. Most second-year students (56.7%) felt their preparation for the USMLE Step 1 exam was negatively affected and 43.3% felt unprepared to begin clerkships. In narrative responses, most appreciated the increased flexibility of remote learning but recognized that digital fatigue, decreased ability to participate, and lack of clinical skills and hands-on lab learning were notable deficits. Conclusions: Videocasted lectures uploaded in advance, electronic health record and telehealth training for students, and training for teaching faculty to increase technological fluency may be considered to optimize remote learning curricula.

Inhibition of Escherichia coli CTP Synthetase by NADH and Other Nicotinamides and Their Mutual Interactions with CTP and GTP.

CTP synthetases catalyze the last step of pyrimidine biosynthesis and provide the sole de novo source of cytosine-containing nucleotides. As a central regulatory hub, they are regulated by ribonucleotide and enzyme concentration through ATP and UTP substrate availability, CTP product inhibition, GTP allosteric modification, and quaternary structural changes including the formation of CTP-inhibited linear polymers (filaments). Here, we demonstrate that nicotinamide redox cofactors are moderate inhibitors of Escherichia coli CTP synthetase (EcCTPS). NADH and NADPH are the most potent, and the primary inhibitory determinant is the reduced nicotinamide ring. Although nicotinamide inhibition is noncompetitive with substrates, it apparently enhances CTP product feedback inhibition and GTP allosteric regulation. Further, CTP and GTP also enhance each other's effects, consistent with the idea that NADH, CTP, and GTP interact with a common intermediate enzyme state. A filament-blocking mutation that reduces CTP inhibitory effects also reduced inhibition by GTP but not NADH. Protein-concentration effects on GTP inhibition suggest that, like CTP, GTP preferentially binds to the filament. All three compounds display nearly linear dose-dependent inhibition, indicating a complex pattern of cooperative interactions between binding sites. The apparent synergy between inhibitors, in consideration with physiological nucleotide concentrations, points to metabolically relevant inhibition by nicotinamides, and implicates cellular redox state as a regulator of pyrimidine biosynthesis.