Factors related to training time and achieving proficiency with visual-assistive mobile applications in visually impaired older adults.

SIGNIFICANCE: A majority of visually impaired older adults were able to learn to proficiently use visual-assistive iPhone applications (apps) following a median 1 hour and/or multiple training sessions, which should be considered when planning vision rehabilitation service delivery, including the option for remote telerehabilitation for those who prefer that modality. PURPOSE: Older adults with low vision are increasingly using technology to improve their visual functioning. We examined whether age-related comorbidities were potential barriers to success in learning to use visual-assistive apps on a smartphone. METHODS: A clinical trial assessed visual-assistive apps in 116 older adults aged 55+ years (mean [standard deviation], 72 [10] years). Subjects were randomized to use an app (SuperVision+, Seeing AI, or Aira) preloaded to a loaner iPhone and completed one-on-one training. App proficiency was measured by the participant's ability to use the iPhone/app without cueing at the end of training sessions. Training time was recorded for the initial session and totaled after subsequent sessions. Multiple regression models explored significant factors associated with training time and proficiency. RESULTS: Median initial and total training times were 45 and 60 minutes, respectively. Increased initial and total training times were both significantly related to increased age (p<0.001), legal blindness (p<0.007), Seeing AI versus SuperVision+ app (p<0.03), and participants from New England versus California (p<0.001). Most (71%) achieved proficiency after the initial training session; those odds were significantly greater among younger participants (p=0.04), those who opted for telerehabilitation (p=0.03), those who had higher cognitive scores (p=0.04), or those who were from New England (p=0.04). The majority (90%) was ultimately proficient with the app; those odds were significantly greater among participants who already had an optical magnifier (p=0.008), but were unrelated to other factors including study site. CONCLUSIONS: Following multiple, extensive training sessions, age, mild cognitive loss, or level of visual impairment did not preclude gaining proficiency with visual-assistive apps by visually impaired seniors, but those factors were associated with longer training times. Telerehabilitation can be a viable option to provide app training remotely for visually impaired seniors who choose that modality.

Epidural versus general anesthesia for laparo-endoscopic single-site cholecystectomy: a randomized controlled trial.

INTRODUCTION: This study compares outcomes after LESS cholecystectomy utilizing epidural versus general anesthesia. METHODS: Patients undergoing LESS Cholecystectomy were randomized into receiving epidural or general anesthesia by protocol. Patients used a Visual Analog Scale to rate pain from 0 (no pain) to 10 (severe pain). Data presented as median (mean ± standard deviation). RESULTS: 75 patients underwent LESS cholecystectomy with general anesthesia [32 patients (22% men) after five patients withdrew consent] or epidural anesthesia [23 patients (22% men) after 15 patients withdrew consent]. Respectively, they were of age 38 years (41 ± 15.1) and 47 years (48 ± 13.9), BMI 29 (28 ± 4.9) kg/m2 and 28 (28 ± 3.8) kg/m2, and ASA 2 (2 ± 0.5) and 2 (2 ± 0.3) (p > 0.05 for all). LOS for patients receiving general vs. epidural anesthesia was 72 min (122 ± 104.4) vs. 95 min (113 ± 77.5) (p = 0.25). On POD 0, patients receiving general anesthesia rated pain as 4 (4 ± 2.9) vs. 0 (1 ± 2.2) for epidural anesthesia (p = 0.02). On POD 1, they rated pain as 6 (5 ± 2.3) vs. 6 (6 ± 2.9) (p = 0.68). On POD 6, patients rated pain as 3 (3 ± 2.7) vs. 4 (3 ± 2.2) (p = 1.00). For patient satisfaction with incisional scars for those receiving general vs. epidural anesthesia, patients rated their scars to be 10 (8 ± 3.6) vs. 10 (9 ± 1.2) (p = 0.21). Total costs for the hospital using general vs. epidural anesthesia were found $6,909 (7,167 ± 2,083.8) vs. $6,225 (5,848 ± 1530.1) (p = 0.014), respectively. Patients self-assessed satisfaction on a scale of 1 (worst) to 5 (best) as a 5 (5 ± 0). CONCLUSIONS: Patients undergoing LESS cholecystectomy with general vs. epidural anesthesia had similar demographics, LOS, and pain scores. Patients that received epidural anesthesia reported less pain and incurred less cost. Utilization of epidural anesthesia in lieu of general anesthesia for LESS cholecystectomy is safe, reduces pain, and offers potential cost savings.

Outcomes of Telerehabilitation Versus In-Office Training With Magnification Devices for Low Vision: A Randomized Controlled Trial.

Purpose: An evidence basis is lacking but needed to compare reading ability outcomes after magnification device training remotely via telerehabilitation versus in office. Methods: A multicenter randomized controlled trial at academic centers and vision rehabilitation private practices randomized 61 visually impaired adults to telerehabilitation or in-office training 1 to 4 months after dispensing new portable electronic, hand-held, or stand optical magnifiers. Telerehabilitation included loaner equipment for Zoom videoconferencing with remote control access software. Using a multilevel regression model, changes in Activity Inventory responses using Rasch analysis estimated reading ability in dimensionless log odds units (logits) (0.14-logit change corresponds with ability change expected from a one-line change in visual acuity). Results: Across 47 participants who completed the trial, reading ability with new magnifiers improved significantly by 0.61 logits on average (95% confidence interval [CI], 0.36-0.86; P < 0.001) from baseline to 1 month, and by an additional 0.44 logits on average (95% CI, 0.19-0.69; P < 0.001) from 1 to 4months (i.e., after magnifier training), with very similar significant findings for both telerehabilitation (n = 29; mean improvement = 0.44 logits; 95% CI, 0.08-0.80; P = 0.018) and in-office training (n = 18; mean improvement = 0.43 logits; 95% CI, 0.15-0.71; P = .003), and no significant difference between randomized groups across both follow-ups (95% CI, -0.43 to 0.61; P = .73). Vision, demographics, and health factors were nonsignificantly related to reading ability changes from 1 to 4 months. Conclusions: Reading ability improved after the provision of newly dispensed magnifiers, with further improvements following additional magnifier training via either telerehabilitation or in-office usual care. Translational Relevance: These findings provide support for the use of telerehabilitation to enhance reading ability with newly prescribed magnifiers as an alternative modality of care delivery.

Transforming mental healthcare in higher education through scalable mental health interventions.

A significant number of young people throughout the world are experiencing mental health concerns. Many young people will develop their first mental health concerns or will be managing their symptoms while enrolled in institutions of higher education. Although many colleges and universities are aware of the significant mental health needs among their students, the mental health and psychosocial needs of students often exceed the availability of resources and cultural and contextual barriers, such as stigma, may further impede access to care. Such gaps and barriers in mental health may lead to poor prognosis as well as negative educational and social outcomes. We propose that non-specialist delivered mental health and psychosocial interventions may play a critical role in reducing the gaps in care for students in higher education. In particular, non-specialist delivered care can complement existing specialized services to provide stepped models of care. Importantly, the adaptation and implementation of non-specialist delivered mental health and psychosocial support interventions in higher education may lead to innovative strategies for increasing access to care in this context, but may lead to adaptations that could apply to contexts outside of higher education as well.

Insights Regarding Optometric Findings of CHARGE Syndrome in a Pediatric Low Vision Clinic.

SIGNIFICANCE: CHARGE, named for common findings-coloboma, heart defects, atresia of choanae, retardation of growth and development, genital hypoplasia, and ear anomalies-is a frequent etiology of deaf-blindness. A retrospective review in a pediatric low vision clinic presented the opportunity to investigate ocular findings in this syndrome with variable clinical presentations. PURPOSE: This retrospective study reviewed ocular findings and visual function measures from low vision evaluations of patients with CHARGE syndrome, which may influence their multidisciplinary management. METHODS: A retrospective chart review was conducted by three examiners of 60 patients presenting with CHARGE syndrome at a pediatric low vision clinic. Visual acuity and contrast sensitivity were obtained using standard measures. Ocular alignment and cycloplegic refractive error measurements were recorded. Refractive findings were analyzed using vector analysis. Anterior and posterior segment findings were recorded. RESULTS: Patients ranged in age from 1 to 29 years and were followed up for a mean of 4.3 years. Best-corrected visual acuity ranged from no light perception to 20/20 Snellen equivalent. Characteristics of strabismus, occurring in 82% of patients, were reported. Contrast sensitivity was reduced in 52% of patients. Chorioretinal colobomas were reported in 88% of patients. The most common ocular findings included nystagmus (43%), microphthalmia (27%), iris coloboma (27%), and facial nerve palsy (23%). Refractive vector analysis revealed significant myopic progression of the spherical equivalent with age and a tendency for with-the-rule astigmatism and minimal obliquity. CONCLUSIONS: This retrospective review of a relatively large sample size for this rare condition outlined the most common ocular manifestations of CHARGE syndrome. Decreased visual acuity, myopic refractive error, strabismus, and reduced contrast sensitivity were common. Thus, careful optometric evaluation in this population is required, as these findings must be considered in appropriate clinical and habilitative management.

Compassion and Trauma: Occupational Health Experiences of Certified Medical Interpreters in Five U.S. States.

Medical interpreters play a vital role in fostering understanding and ensuring safety and transparency in healthcare for patients with non-English language preference. Limited research describes work-related experiences of medical interpreters. The purpose of this research was to explore perceptions of occupational health and safety among medical interpreters. A structured, online survey was administered to all certified medical interpreters in Hawaii, New York, New Jersey, California, and Texas. Participants described occupational experiences as an interpreter via an open-ended question. Responses were coded using qualitative thematic analysis. Response text was reviewed, a codebook of descriptive themes developed, and data thematically coded and summarized. Of 981 potential participants, 199 responded (20.3% response rate). Four main themes were identified: Professionalism and Role, Work-Related Challenges, Approaches to Mitigate Vicarious Trauma, and The Rewarding Nature of the Job. Respondents described compassion fatigue, vicarious trauma, intentional emotional distancing from clients, and loneliness. Respondents identified needs for workplace support to ensure professionalism and safeguard interpreter safety. Medical interpreters appreciate their work, yet face challenges, including compassion fatigue and vicarious trauma. Employers and healthcare institutions should support the occupational and emotional needs of medical interpreters as a vital member of the healthcare team.

Incidence of asymptomatic COVID-19 positivity in cancer patients and effects on therapy.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic is posing unprecedented challenges for patient care, especially for cancer patients. This study looks at asymptomatic (AS) COVID-19 positivity in cancer patients and its effects on their care. METHODS: We conducted a retrospective chart review of AS patients testing positive for COVID-19 upon screening at Fox Chase Cancer Center between January 2020 and September 2020. Relationships between positive tests and demographics, clinical characteristics, and treatment delays were investigated using conditional logistic regression or Mantel-Haenszel tests. RESULTS: Among 4143 AS patients who underwent COVID-19 testing, 25 (0.6%) were COVID-19 positive (cases) and these were matched to 50 controls. The median age was lower in the cases compared to that of the controls (64 vs 70 years old, p = 0.04). Of the cases, 10 patients (40%) never underwent their planned oncologic intervention [6/10 (60%) did not require the planned intervention once deemed okay to proceed]. Of the controls, only 1 patient (2%) did not undergo the planned intervention. Of these 15 COVID-19 positive patients who underwent the planned intervention, 11 (73.3%) had a delay related to COVID-19, with a mean delay duration of 18 days (range: 0-49, SD: 16.72). CONCLUSION: Cancer patients had lower incidence of AS COVID-19 than general population. Delays that occur due to AS COVID screening are not very long and serve as a tool to limit spread of virus. Further studies will be important in addressing delays in cancer care and concerns of patient safety as the pandemic continues.

Telerehabilitation Training to Facilitate Improved Reading Ability with New Magnification Devices for Low Vision.

SIGNIFICANCE: This pilot study provides some insight about the potential benefits of telerehabilitation training to improve the reading ability of adults with low vision using magnifiers, to spur future work with larger groups. Telerehabilitation services can be implemented clinically to facilitate access to follow-up care for low vision. PURPOSE: A recent Cochrane systematic review revealed that there are no published visual function outcomes for telerehabilitation with handheld magnification devices for low vision; thus, this study aimed to provide evidence for its preliminary efficacy. METHODS: One to 4 months after receiving a new magnification device (i.e., handheld or stand optical magnifier or portable electronic magnifier), 14 adult low vision patients (with any visual acuity level or ocular diagnosis) received two training sessions at home via telerehabilitation with their vision rehabilitation provider located remotely in-office. Telerehabilitation included a loaner smartphone for Zoom videoconferencing with remote control access software. The Minnesota Low-Vision Reading Test was administered during each of the telerehabilitation sessions to assess near reading (acuity and speed) with the new magnifier. RESULTS: Mean reading acuity with the magnifier was 0.17 logMAR across subjects before training at telerehabilitation session 1, which significantly improved to 0.09 on average a few weeks later at telerehabilitation session 2 (95%confidence interval, -0.001 to -0.16; P = .047). Logarithm reading speed with the magnifier for the reading acuity level at session 1 improved significantly by 0.18 log words per minute on average for the same text size at session 2 (95% confidence interval, 0.06 to 0.29; P = .002). With the magnifier at session 2, 71% of participants gained at least 0.1 log unit in reading acuity, and half improved by >0.01 in log reading speed; all participants with increased reading speed also improved in reading acuity ( P = .02). CONCLUSIONS: These preliminary data support that telerehabilitation can enhance reading ability and efficiency with newly prescribed magnifiers as an alternative option to in-office vision rehabilitation.

Acceptability of Telerehabilitation for Magnification Devices for the Visually Impaired Using Various Approaches to Facilitate Accessibility.

Purpose: We examined different methods to reduce the burden of accessing technology for videoconferencing during telerehabilitation for magnification devices for the visually impaired. Methods: During telerehabilitation studies over the past 5 years, vision rehabilitation providers assessed and gave training to visually impaired participants with newly dispensed magnification devices at home who connected to Zoom videoconferencing via loaner tablets or smartphones with assistance from (phase 1; n = 10) investigators by phone, (phase 2; n = 11) local Lions Club volunteers in participants' homes, or (phase 3; n = 24) remote access control software in a randomized controlled trial with 13 usual care controls who received in-office training. All participants completed the same post-telerehabilitation phone survey. Results: A significantly greater proportion of phase 3 subjects indicated they strongly or mostly agreed that the technology did not interfere with the session (96%) compared to phase 1 (60%; 95% confidence interval [CI], 1.2-12.5; P = 0.03) or phase 2 (55%; 95% CI, 1.8-188; P = 0.01). The majority indicated telerehabilitation was as accurate as in person (68%), they were comfortable with telerehabilitation (91%) and interested in a future session (83%), and their magnifier use improved (79%), with no significant differences in these responses between phases (all P > 0.10), including comparisons of participants randomized to telerehabilitation or in-office training in phase 3 who reported similar overall satisfaction levels (P = 0.84). Conclusions: Participants across all phases reported high levels of acceptance for telerehabilitation, with least interference from technology using remote access control in phase 3. Translational Relevance: With accommodations for accessibility to videoconferencing technology, telerehabilitation for magnification devices can be a feasible, acceptable, and valuable option in countries with resources to support the technology.

Comparison of Higher-Than-Standard to D-Dimer Driven Thromboprophylaxis in Hospitalized Patients With COVID-19.

Introduction: Coronavirus disease 2019 is a global health threat often accompanied with coagulopathy. Despite use of thromboprophylaxis in this population, thrombotic event rates are high. Materials and methods: This was a multicenter, retrospective cohort study comparing the safety and effectiveness of thromboprophylaxis strategies at 2 institutions in hospitalized patients with coronavirus disease 2019. Regimen A utilized a higher-than-standard thromboprophylaxis dosage and Regimen B received full-dose anticoagulation for any D-dimer 3 mcg/mL or greater and prophylactic for less than 3 mcg/mL. The primary outcome compared the rate of thrombotic events between treatment groups. Secondary endpoints compared rates of major or clinically relevant non-major bleeding as well as the proportion of patients in each group experiencing thrombotic events within 30 days of discharge. Results: One-hundred fifty-three patients were included in the analysis, 64 receiving Regimen A and 89 receiving Regimen B. Seven (4.6%) thrombotic events occurred, 3 (4.7%) in patients receiving Regimen A, and 4 (4.5%) in Regimen B (P = 1.0). Twelve patients (13.5%) receiving Regimen B had a bleeding event versus 2 (3.1%) in Regimen A (P = .04), half of which were major in each group. All patients who bled in either treatment group were receiving mechanical ventilation, and 12 of 14 were receiving full-dose anticoagulation. One patient receiving Regimen A was readmitted with a pulmonary embolism. Conclusions: In this study, the thromboprophylactic regimen impacted bleeding, but no significant difference was seen with thrombotic outcomes. Almost all patients who experienced a bleed were mechanically ventilated and receiving full-dose anticoagulation. The use of full-dose anticoagulation should be cautioned in this population without an additional indication.

Incidence of asymptomatic COVID-19 positivity in cancer patients and effects on therapy.

Purpose The coronavirus disease 2019 (COVID-19) pandemic is posing unprecedented challenges for patient care, especially for cancer patients. This study looks at asymptomatic (AS) COVID-19 positivity in cancer patients and its effects on their care. Methods We conducted a retrospective chart review of AS patients testing positive for COVID-19 upon screening at Fox Chase Cancer Center between January 2020 and September 2020. Relationships between positive tests and demographics, clinical characteristics, and treatment delays were investigated using conditional logistic regression or Mantel-Haenszel tests. Results Among 4143 AS patients who underwent COVID-19 testing, 25 (0.6%) were COVID-19 positive (cases) and these were matched to 50 controls. The median age was lower in the cases compared to that of the controls (64 vs 70 years old, p = 0.04). Of the cases, 10 patients (40%) never underwent their planned oncologic intervention [6/10 (60%) did not require the planned intervention once deemed okay to proceed]. Of the controls, only 1 patient (2%) did not undergo the planned intervention. Of these 15 COVID-19 positive patients who underwent the planned intervention, 11 (73.3%) had a delay related to COVID-19, with a mean delay duration of 18 days (range: 0-49, SD: 16.72). Conclusion Cancer patients had lower incidence of AS COVID-19 than general population. Delays that occur due to AS COVID screening are not very long and serve as a tool to limit spread of virus. Further studies will be important in addressing delays in cancer care and concerns of patient safety as the pandemic continues.

Use and Perceptions of Advanced Driver Assistance Systems by Older Drivers With and Without Age-Related Macular Degeneration.

Purpose: Advanced driver assistance systems (ADAS) have been reported to improve the safety of elderly and normally sighted drivers. The purpose of this study was to assess exposure to, perceived safety of, comfort level with, and interest in using ADAS among drivers with age-related macular degeneration (AMD). Methods: Current drivers aged 60+ years were recruited at four US sites to complete a survey about ADAS and driving habits. Frequency of use and/or perceptions of eight ADAS were investigated. An avoidance score was generated using questions about difficult driving situations. Results: The survey was completed by 166 participants (80 with AMD vs. 86 without). Participants with AMD had worse self-rated vision than those without (34% vs. 2% poor or fair rating), and drove fewer weekly miles (median [interquartile range [IQR] 30 [15 to 75] vs. 60 [30 to 121] miles, P = 0.002). Participants with AMD reported more avoidance of difficult driving situations (P < 0.001). There was no difference in the number of ADAS used by AMD status (median [IQR for AMD = 2.5 [1 to 5] vs. 3 [2 to 4] without, P = 0.87). Greater reported number of ADAS used was associated with less avoidance of difficult situations (P = 0.02). The majority perceived improved safety with most ADAS. Conclusions: Many drivers with AMD utilize common ADAS, which subjectively improve their road safety and may help to reduce self-imposed restrictions for difficult situations and mileage. Translational Relevance: Drivers with AMD are adopting readily available ADAS, for which they reported potential benefits, such as safety and less restrictive driving.

Exploration of dynamic text presentations in bilateral central vision loss.

PURPOSE: Dynamic text presentation methods may improve reading ability in patients with central vision loss (CVL) by eliminating the need for accurate eye movements. We compared rapid serial visual presentation (RSVP) and horizontal scrolling text presentation (scrolling) on reading rate and reading acuity in CVL observers and normally-sighted controls with simulated CVL (simCVL). METHODS: CVL observers' (n = 11) central scotomas and preferred retinal loci (PRL) for each eye were determined with MAIA microperimetry and fixation analysis. SimCVL controls (n = 16) used 4° inferior eccentric viewing, enforced with an Eyelink eye-tracker. Observers read aloud 4-word phrases randomly drawn from the MNREAD sentences. Six font sizes (0.50-1.30 logMAR) were tested with the better near acuity eye and both eyes of CVL observers. Three font sizes (0.50-1.00 logMAR) were tested binocularly in simCVL controls. Text presentation duration of each word for RSVP or drift speed for scrolling was varied to determine reading rate, defined as 50% of words read correctly. In a subset of CVL observers (n = 7), relationships between PRL eccentricity, reading threshold and rate were explored. RESULTS: SimCVL controls demonstrated significantly faster reading rates for RSVP than scrolling text (p < 0.0001), and there was a significant main effect of font size (p < 0.0001). CVL patients demonstrated no significant differences in binocular reading rate between font sizes (p = 0.12) and text presentation (p = 0.25). Similar results were seen under monocular conditions. Reading acuity for RSVP and scrolling worsened with increasing PRL eccentricity (µ = 4.5°, p = 0.07). RSVP reading rate decreased significantly with increasing eccentricity (p = 0.02). CONCLUSIONS: Consistent with previous work, reading acuity worsened with increasing PRL eccentricity. RSVP and scrolling text presentations significantly affected reading rate in simCVL, but not in CVL observers, suggesting that simCVL results may not generalise to pathological CVL.

CCP1, a Tubulin Deglutamylase, Increases Survival of Rodent Spinal Cord Neurons following Glutamate-Induced Excitotoxicity.

Microtubules (MTs) are cytoskeletal elements that provide structural support and act as roadways for intracellular transport in cells. MTs are also needed for neurons to extend and maintain long axons and dendrites that establish connectivity to transmit information through the nervous system. Therefore, in neurons, the ability to independently regulate cytoskeletal stability and MT-based transport in different cellular compartments is essential. Posttranslational modification of MTs is one mechanism by which neurons regulate the cytoskeleton. The carboxypeptidase CCP1 negatively regulates posttranslational polyglutamylation of MTs. In mammals, loss of CCP1, and the resulting hyperglutamylation of MTs, causes neurodegeneration. It has also long been known that CCP1 expression is activated by neuronal injury; however, whether CCP1 plays a neuroprotective role after injury is unknown. Using shRNA-mediated knock-down of CCP1 in embryonic rat spinal cord cultures, we demonstrate that CCP1 protects spinal cord neurons from excitotoxic death. Unexpectedly, excitotoxic injury reduced CCP1 expression in our system. We previously demonstrated that the CCP1 homolog in Caenorhabditis elegans is important for maintenance of neuronal cilia. Although cilia enhance neuronal survival in some contexts, it is not yet clear whether CCP1 maintains cilia in mammalian spinal cord neurons. We found that knock-down of CCP1 did not result in loss or shortening of cilia in cultured spinal cord neurons, suggesting that its effect on survival of excitotoxicity is independent of cilia. Our results support the idea that enzyme regulators of MT polyglutamylation might be therapeutically targeted to prevent excitotoxic death after spinal cord injuries.

Mutation of NEKL-4/NEK10 and TTLL genes suppress neuronal ciliary degeneration caused by loss of CCPP-1 deglutamylase function.

Ciliary microtubules are subject to post-translational modifications that act as a "Tubulin Code" to regulate motor traffic, binding proteins and stability. In humans, loss of CCP1, a cytosolic carboxypeptidase and tubulin deglutamylating enzyme, causes infantile-onset neurodegeneration. In C. elegans, mutations in ccpp-1, the homolog of CCP1, result in progressive degeneration of neuronal cilia and loss of neuronal function. To identify genes that regulate microtubule glutamylation and ciliary integrity, we performed a forward genetic screen for suppressors of ciliary degeneration in ccpp-1 mutants. We isolated the ttll-5(my38) suppressor, a mutation in a tubulin tyrosine ligase-like glutamylase gene. We show that mutation in the ttll-4, ttll-5, or ttll-11 gene suppressed the hyperglutamylation-induced loss of ciliary dye filling and kinesin-2 mislocalization in ccpp-1 cilia. We also identified the nekl-4(my31) suppressor, an allele affecting the NIMA (Never in Mitosis A)-related kinase NEKL-4/NEK10. In humans, NEK10 mutation causes bronchiectasis, an airway and mucociliary transport disorder caused by defective motile cilia. C. elegans NEKL-4 localizes to the ciliary base but does not localize to cilia, suggesting an indirect role in ciliary processes. This work defines a pathway in which glutamylation, a component of the Tubulin Code, is written by TTLL-4, TTLL-5, and TTLL-11; is erased by CCPP-1; is read by ciliary kinesins; and its downstream effects are modulated by NEKL-4 activity. Identification of regulators of microtubule glutamylation in diverse cellular contexts is important to the development of effective therapies for disorders characterized by changes in microtubule glutamylation. By identifying C. elegans genes important for neuronal and ciliary stability, our work may inform research into the roles of the tubulin code in human ciliopathies and neurodegenerative diseases.

Pembrolizumab monotherapy in patients with previously treated metastatic high-grade neuroendocrine neoplasms: joint analysis of two prospective, non-randomised trials.

BACKGROUND: Metastatic high-grade neuroendocrine neoplasms (G3NENs) have limited treatment options after progression on platinum-based therapy. We addressed the role of Pembrolizumab in patients with previously treated metastatic G3NENs. METHODS: Two open-label, phase 2 studies enrolled patients with G3NEN (Ki-67 > 20%) to receive Pembrolizumab at 200 mg I.V. every 3 weeks. Radiographic evaluation was conducted every 9 weeks with overall response rate as the primary endpoint. RESULTS: Between November 2016 and May 2018, 29 patients (13 males/16 females) with G3NENs were enrolled. One patient (3.4%) had an objective response and an additional six patients (20.7%) had stable disease, resulting in a disease control rate of 24.1%. Disease control rate (DCR) at 18 weeks was 10.3% (3/29). There was no difference in the DCR, PFS or OS between the PD-L1-negative and -positive groups (p 0.56, 0.88 and 0.55, respectively). Pembrolizumab was well tolerated with only 9 grade 3, and no grade 4 events considered drug-related. CONCLUSIONS: Pembrolizumab can be safely administered to patients with G3NENs but has limited activity as a single agent. Successful completion of our trials suggest studies in G3NENs are feasible and present an unmet need. Further research to identify active combination therapies should be considered. CLINICAL TRIAL REGISTRATION NUMBER: NCT02939651 (10/20/2016).

U.S. Optometrists' Reported Practices and Perceived Barriers for Low Vision Care for Mild Visual Loss.

SIGNIFICANCE: Identification of modifiable barriers to low vision rehabilitation (LVR) can inform efforts to improve practice management of patients with low vision (LV), through, for example, targeted educational programs for optometrists who do not practice LVR. PURPOSE: Mild vision loss (20/25 to 20/70) is increasing in prevalence among the aging population, yet it is unclear whether near-reading complaints (the highest presenting chief complaint) are being addressed. Studies of LVR provision by U.S. optometrists are currently lacking. This study elucidated self-reported optometric practice patterns for patients with mild vision loss. METHODS: Anonymous surveys were completed by 229 actively practicing optometrists across the United States. The survey inquired about the frequency of providing LVR for mild vision loss patients and the top barriers that prevent them from offering LVR management (including optical aids or referral). RESULTS: Compared with those moderately actively practicing LVR, twice as many (2.08×) practitioners who do not practice any LVR reported that they never prescribe near-reading add power of 4 D or greater for mild vision loss (P < .001). Among those who do not practice LVR, 39 and 11% indicated that they never prescribe any LVR management strategies for patients with visual acuity of 20/25 to 20/40 and 20/50 to 20/70, respectively. The two most commonly reported barriers to LVR indicated by about half of respondents were "cost of the LV exam and/or devices" and that "patients are not interested or would not go to an LV exam." Nearly a third of providers reported that "it is not feasible to stock magnifiers in office." CONCLUSIONS: A sizable group of non-LVR providers in the United States may not be addressing the near-vision needs of patients with mild vision loss. Several of the reported top barriers are potentially modifiable through the development of targeted educational programs for providers.

Preliminary Evaluation of Two Digital Image Processing Strategies for Head-Mounted Magnification for Low Vision Patients.

PURPOSE: In an observational clinical outcome study, we tested the effectiveness and use of the combination of two innovative approaches to magnification: a virtual bioptic telescope and a virtual projection screen, implemented with digital image processing in a head-mounted display (HMD) equipped with a high-resolution video camera and head trackers. METHODS: We recruited 30 participants with best-corrected visual acuity <20/100 in the better-seeing eye and bilateral central scotomas. Participants were trained on the HMD system, then completed a 7- to 10-day in-home trial. The Activity Inventory was administered before and after the home trial to measure the effect of system use on self-reported visual function. A simulator sickness questionnaire (SSQ) and a system-use survey were administered. Rasch analysis was used to assess outcomes. RESULTS: Significant improvements were seen in functional ability measures estimated from goal difficulty ratings (Cohen's d = 0.79, P < 0.001), and reading (d = 1.28, P < 0.001) and visual information (d = 1.11, P < 0.001) tasks. There was no improvement in patient-reported visual motor function or mobility. One participant had moderately severe discomfort symptoms after SSQ item calibration. The average patient rating of the system's use was 7.14/10. CONCLUSIONS: Use of the system resulted in functional vision improvements in reading and visual information processing. Lack of improvement in mobility and visual motor function is most likely due to limited field of view, poor depth perception, and lack of binocular disparity. TRANSLATIONAL RELEVANCE: We determine if these new image processing approaches to magnification are beneficial to low vision patients performing everyday activities.

Oxaliplatin: Detection and Management of Hypersensitivity Reactions.

BACKGROUND: Oxaliplatin is used extensively for the treatment of gastrointestinal cancer and other malignancies, with increased frequency of use in recent years. Hypersensitivity reactions (HSRs) can pose a major problem in clinical practice because they can limit the use of oxaliplatin in the care of malignancies in which it has proven efficacy. Nurses play an integral role in the administration of oxaliplatin; therefore, they need to be well educated in the prevention, detection, and management of HSRs. OBJECTIVES: This article reviews the symptoms of HSRs associated with oxaliplatin, the specific management of HSRs associated with oxaliplatin, the role of desensitization, and the potential use of skin testing to better identify patients at risk for HSR. METHODS: This article reviews the literature related to the diagnosis, prevention, and management of HSRs associated with oxaliplatin and outlines nurses' role. FINDINGS: Oxaliplatin HSRs can occur at any cycle, but patients are at highest risk after they have received six prior infusions of oxaliplatin.