Survey of Telehealth Adoption by Neuro-ophthalmologists During the COVID-19 Pandemic: Benefits, Barriers and Utility

Background: During the COVID-19 pandemic tele-health modalities have come to prominence as a strategy for providing patient care when in-person care provision opportunities are limited. The degree of adoption by neuro-ophthalmologists has not been quantified. Methods: Telehealth utilization pre- and peri-COVID-19 was surveyed among practicing neuro-ophthalmologists in and outside the US using an on-line platform. Demographics, perceived benefits, barriers, and utility for different neuro-ophthalmic conditions were collected. Data collection occurred over a 2-week period in May, 2020. Results: 208 practicing neuro-ophthalmologists (81.3% US, 50.2% female, age range 65, mode 35-44 years) participated in the survey. Utilization of all telehealth modalities increased from pre-COVID to peri-COVID (video visit 3.9% to 68.3%, p<0.0005, remote interpretation of testing 26.7% to 32.2%, p=0.09, on-line second opinion 7.9% to 15.3%, p=0.001, interprofessional e-consult 4.4% to 18.7%, p<0.0005, McNemar). The majority selected access, continuity, and patient efficiency of care as benefits and data quality as a barrier. Telehealth was felt to be most helpful for conditions relying on history, external exam, and previously collected ancillary testing and not helpful for conditions requiring funduscopic exam. Conclusions: Telehealth modality usage by neuro-ophthalmologists increased during the COVID-19 pandemic. Identified benefits have relevance both during and beyond COVID-19. Further work is needed to address barriers in their current and future states to maintain these modalities as viable care delivery options

The Impact of COVID-19 on Neuro-Ophthalmology Office Visits and Adoption of Telemedicine Services

Background: The COVID-19 public health emergency (PHE) has significantly changed medical practice in the U.S., including an increase in the utilization of telemedicine. Here, we characterize change in neuro-ophthalmic care delivery during the early COVID-19 PHE, including a comparison of care delivered via telemedicine and in office. Methods: Neuro-ophthalmology outpatient encounters from three practices in the United States (four providers) were studied during the early COVID-19 PHE (March 15, 2020-June 15, 2020) and during the same dates one year prior. For unique patient visits, patient demographics, visit types, visit format, and diagnosis were compared between years and between synchronous telehealth and in-office formats for 2020. Results: There were 1276 encounters for 1167 patients. There were 30% fewer unique patient visits in 2020 vs. 2019 (477 vs. 670) and 55% fewer in office visits (299 vs. 670). Compared to 2019, encounters in 2020 were more likely to be established, to occur via telemedicine and relate to an efferent diagnosis. In 2020, synchronous telehealth visits were more likely to be established compared with in-office encounters. Conclusions: In the practices studied, a lower volume of neuro-ophthalmic care was delivered during the early COVID-19 public health emergency than in the same period in 2019. The type of care shifted toward established patients with efferent diagnoses and the modality of care shifted toward telemedicine

Reduced cognitive deficits after FLASH irradiation of whole mouse brain are associated with less hippocampal dendritic spine loss and neuroinflammation

Aim To evaluate the impact of ultra-rapid FLASH mouse whole brain irradiation on hippocampal dendritic spines and neuroinflammation, factors associated with cognitive impairment after brain irradiation. Methods We administered 30 Gy whole brain irradiation to C57BL6/J mice in sub-second (FLASH) vs. 240 s conventional delivery time keeping all other parameters constant, using a custom configured clinical linac. Ten weeks post-irradiation, we evaluated spatial and non-spatial object recognition using novel object location and object recognition testing. We measured dendritic spine density by tracing Golgi-stained hippocampal neurons and evaluated neuroinflammation by CD68 immunostaining, a marker of activated microglia, and expression of 10 pro-inflammatory cytokines using a multiplex immunoassay. Results At ten weeks post-irradiation, compared to unirradiated controls, conventional delivery time irradiation significantly impaired novel object location and recognition tasks whereas the same dose given in FLASH delivery did not. Conventional delivery time, but not FLASH, was associated with significant loss of dendritic spine density in hippocampal apical dendrites, with a similar non-significant trend in basal dendrites. Conventional delivery time was associated with significantly increased CD68-positive microglia compared to controls whereas FLASH was not. Conventional delivery time was associated with significant increases in 5 of 10 pro-inflammatory cytokines in the hippocampus (and non-significant increases in another 3), whereas FLASH was associated with smaller increases in only 3. Conclusion Reduced cognitive impairment and associated neurodegeneration were observed with FLASH compared to conventional delivery time irradiation, potentially through decreased induction of neuroinflammation, suggesting a promising approach to increasing therapeutic index in radiation therapy of brain tumors

Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort

Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression

Multi-omic single-cell snapshots reveal multiple independent trajectories to drug tolerance in a melanoma cell line

The determination of individual cell trajectories through a high-dimensional cell-state space is an outstanding challenge for understanding biological changes ranging from cellular differentiation to epigenetic responses of diseased cells upon drugging. We integrate experiments and theory to determine the trajectories that single BRAF^(V600E) mutant melanoma cancer cells take between drug-naive and drug-tolerant states. Although single-cell omics tools can yield snapshots of the cell-state landscape, the determination of individual cell trajectories through that space can be confounded by stochastic cell-state switching. We assayed for a panel of signaling, phenotypic, and metabolic regulators at points across 5 days of drug treatment to uncover a cell-state landscape with two paths connecting drug-naive and drug-tolerant states. The trajectory a given cell takes depends upon the drug-naive level of a lineage-restricted transcription factor. Each trajectory exhibits unique druggable susceptibilities, thus updating the paradigm of adaptive resistance development in an isogenic cell population

Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: A Prospective Cohort Study

To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97). We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives