Structural Limits of Orbital Compliance and Treatment Options for Pathologic Orbital Pressure.

PURPOSE: The integrity of the orbit has a finite structural limit due to the compliance of its tissue. The authors investigate these limits to quantify them and inform the treatment of heightened ocular and orbital pressure. METHODS: Cadaveric study with 12 orbits being volumized before randomization of treatment for pathologic levels of ocular and orbital pressure. First-line and second-line treatment was chosen randomly (lateral cantholysis, superior septolysis, inferior septolysis). Prior to treatment, IOP, orbital compartment pressure, and axial globe projection was measured after delivery of each 1cc aliquot and surgical treatment. RESULTS: Orbital compartment pressure and IOP were well correlated (r = 0.99). The average reduction in IOP after treatment averaged a 56.2 mm Hg reduction in IOP. All treatments were statistically equivalent ( p < 0.01). Loss of compliance (P LOC ) was determined when the mean plus 1 standard deviation of change in IOP/ml volume was achieved with simultaneous change in exophthalmometry of <0.5 mm change/ml added volume, indicating an acceleration in pressure in the face of a steady volume. This criteria was met for 11 of 12 orbits. The 12th orbit missed this threshold by 1 mm Hg in IOP. P LOC occurred at an average IOP of 43.0 mm Hg (±5.8 mm Hg, 90% CI) and after an average injection of 13 ml (±1.4 mm, 90% CI). Additionally, lateral cantholysis, superior septolysis, and inferior septolysis were statistically equivalent in reducing IOP after P LOC . CONCLUSIONS: IOP and orbital compartment pressure are excellent proxies for each other in the authors' model. Orbital compliance is a mathematic phenomenon that can be quantified, as evident in this investigation. P LOC can inform timing for orbital decompressions in the presence of heightened IOP. Multiple procedures can be used to extinguish dangerously high orbital compartment pressure.

Marginal Full Thickness Blepharotomy for Management of Orbital Compartment Syndrome.

PURPOSE: To assess the utility of a marginal full thickness blepharotomy (MFTB) for the treatment of orbital compartment syndrome. METHODS: An experimental study design employing a cadaver model for orbital compartment syndrome was used to assess the efficacy of an MFTB. Elevated orbital compartment pressures were created in 12 orbits of 6 fresh cadaver heads. Intraocular pressure, as an analog of orbital pressure, was measured before and after inferior and superior MFTBs were performed. Statistical analysis was performed on the collected data to assess the efficacy of the procedure. RESULTS: Both procedures were found to significantly lower the orbital compartment pressure. MFTB of the inferior lateral eyelid decreased orbital compartment pressure by an average of 62.2 mm Hg (95% CI, 56.9-67.5). MFTB of the superior lateral eyelid following MFTB of the inferior lateral eyelid decreased the orbital compartment pressure by an additional average of 10.3 mm Hg (total average reduction of 72.5 mm Hg; 95% CI, 68.1-76.9). CONCLUSIONS: Orbital compartment syndrome is a time-sensitive vision-threatening emergency that requires prompt diagnosis and intervention to prevent irreversible vision loss. The authors describe the MTFB, a simple one-step procedure that when performed correctly results in a significant decrease in orbital compartment pressure, making it a viable option when canthotomy and cantholysis fails or is unable to be performed.

Caffeine Gum Improves Reaction Time but Reduces Composure Versus Placebo During the Extra-Time Period of Simulated Soccer Match-Play in Male Semiprofessional Players.

This study aimed to determine whether caffeine gum influenced perceptual-cognitive and physical performance during the extra-time period of simulated soccer match-play. Semiprofessional male soccer players (n = 12, age: 22 ± 3 years, stature: 1.78 ± 0.06 m, mass: 75 ± 9 kg) performed 120-min soccer-specific exercise on two occasions. In a triple-blind, randomized, crossover design, players chewed caffeinated (200 mg; caffeine) or control (0 mg; placebo) gum for 5 min following 90 min of soccer-specific exercise. Perceptual-cognitive skills (i.e., passing accuracy, reaction time, composure, and adaptability) were assessed using a soccer-specific virtual reality simulator, collected pre- and posttrial. Neuromuscular performance (reactive-strength index, vertical jump height, absolute and relative peak power output, and negative vertical displacement) and sprint performance (15 and 30 m) were measured at pretrial, half-time, 90 min, and posttrial. Caffeine gum attenuated declines in reaction time (pre: 90.8 ± 0.8 AU to post: 90.7 ± 0.8 AU) by a further 4.2% than placebo (pre: 92.1 ± 0.8 AU to post: 88.2 ± 0.8 AU; p < .01). Caffeine gum reduced composure by 4.7% (pre: 69.1 ± 0.8 AU to post: 65.9 ± 0.8 AU) versus placebo (pre: 68.8 ± 0.8 AU to post: 68.3 ± 0.8 AU; p < .01). Caffeine gum did not influence any other variables (p > .05). Where caffeine gum is consumed by players prior to extra-time, reaction time increases but composure may be compromised, and neuromuscular and sprint performance remain unchanged. Future work should assess caffeine gum mixes with substances like L-theanine that promote a relaxed state under stressful conditions.

Penetrating colored pencil injury with Clostridium bifermentans pre-septal cellulitis: case report, literature review, and treatment algorithm.

The incidence of penetrating orbital injuries from writing instruments continues to rise in the pediatric population. Such injuries can cause significant visual morbidity and have a lifelong psychosocial impact. While the description of graphite pencil-related orbital trauma management is well demonstrated with over 40 reported cases, a lack of consistent management protocol for colored pencil-related injuries. Here, we report an inadvertent penetrating orbital colored pencil injury with progressive mechanical ptosis and pre-septal cellulitis necessitating urgent orbitotomy, debridement, and washout to reduce inflammatory and infectious burden. The wooden body serves as a nidus for polymicrobial infection, and the unique composition of colored pencil cores may lead to inflammatory processes that require vigilant multidisciplinary surgical and medical management reflected in our literature review.

nRCFV: a new, dataset-size-independent metric to quantify compositional heterogeneity in nucleotide and amino acid datasets.

MOTIVATION: Compositional heterogeneity-when the proportions of nucleotides and amino acids are not broadly similar across the dataset-is a cause of a great number of phylogenetic artefacts. Whilst a variety of methods can identify it post-hoc, few metrics exist to quantify compositional heterogeneity prior to the computationally intensive task of phylogenetic tree reconstruction. Here we assess the efficacy of one such existing, widely used, metric: Relative Composition Frequency Variability (RCFV), using both real and simulated data. RESULTS: Our results show that RCFV can be biased by sequence length, the number of taxa, and the number of possible character states within the dataset. However, we also find that missing data does not appear to have an appreciable effect on RCFV. We discuss the theory behind this, the consequences of this for the future of the usage of the RCFV value and propose a new metric, nRCFV, which accounts for these biases. Alongside this, we present a new software that calculates both RCFV and nRCFV, called nRCFV_Reader. AVAILABILITY AND IMPLEMENTATION: nRCFV has been implemented in RCFV_Reader, available at: https://github.com/JFFleming/RCFV_Reader . Both our simulation and real data are available at Datadryad: https://doi.org/10.5061/dryad.wpzgmsbpn .

Teprotumumab for the Treatment of Active Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).

Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation.

BACKGROUND: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. METHODS: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. RESULTS: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not-TX n = 59 (25%) and >1 Not-TX n = 64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p < .001) and more chronic changes on 1-year surveillance biopsy (p = .007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p < .001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. CONCLUSIONS: We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.

Barriers to Telehealth Utilization Among Patients of Limited Income with Chronic Conditions and a Gap in Care.

Objective: This study assessed barriers and facilitators to telehealth utilization among patients living in New York City public housing with chronic conditions and a gap in clinical care. Methods: Community health workers performed outreach to eligible patients by telephone between January and March 2021. Consenting respondents answered questions about telehealth barriers, including internet and cell phone access, ownership of digital devices, comfort with using digital devices, comfort with telehealth, cost, awareness, and availability of written materials in patients' preferred language. We obtained demographic and medical information from patients' electronic health records. We used multivariable logistic regression to estimate the association of barriers with the odds of self-reported prior telehealth utilization. Results: A total of 304 consenting patients participated in the program. The average patient had 3.1 telehealth barriers; 76% reported at least one barrier. Regression analysis showed sizable reductions in prior telehealth utilization associated with the barriers of unlimited cell phone minutes (odds ratio [OR]: 0.21 [0.05-0.88], p = 0.033), technological comfort (OR: 0.33 [0.13-0.82], p = 0.016), conceptual comfort with telehealth (OR: 0.15 [0.04-0.54], p = 0.004), and materials in the patient's preferred language (OR: 0.23 [0.07-0.79], p = 0.02). Discussion: With a high prevalence of telehealth barriers, patients with limited income, a chronic condition, and a care gap may benefit from greater technological access and supportive programs for awareness, telehealth comfort, and navigation support. Addressing telehealth barriers could increase the quality of medical care and improve health outcomes for this population.

A Critical Analysis of the Specific Pharmacist Interventions and Risk Assessments During the 12-Month TRANSAFE Rx Randomized Controlled Trial.

BACKGROUND: Medication safety issues have detrimental implications on long-term outcomes in the high-risk kidney transplant (KTX) population. Medication errors, adverse drug events, and medication nonadherence are important and modifiable mechanisms of graft loss. OBJECTIVE: To describe the frequency and types of interventions made during a pharmacist-led, mobile health-based intervention in KTX recipients and the impact on patient risk levels. METHODS: This was a secondary analysis of data collected during a 12-month, parallel-arm, 1:1 randomized clinical controlled trial including 136 KTX recipients. Participants were randomized to receive either usual care or supplemental, pharmacist-driven medication therapy monitoring and management using a smartphone-enabled app integrated with telemonitoring of blood pressure and glucose (when applicable) and risk-based televisits. The primary outcome was pharmacist intervention type. Secondary outcomes included frequency of interventions and changes in risk levels. RESULTS: A total of 68 patients were randomized to the intervention and included in this analysis. The mean age at baseline was 50.2 years; 51.5% of participants were male, and 58.8% were black. Primary pharmacist intervention types were medication reconciliation and patient education, followed by medication changes. Medication reconciliation remained high throughout the study period, whereas education and medication changes trended downward. From baseline to month 12, we observed an approximately 15% decrease in high-risk patients and a corresponding 15% increase in medium- or low-risk patients. CONCLUSION AND RELEVANCE: A pharmacist-led mHealth intervention may enhance opportunities for pharmacological and nonpharmacological interventions and mitigate risk levels in KTX recipients.

Opioid Prescribing Patterns of Optometrists in the Medicare Part D Database.

SIGNIFICANCE: This study aimed to determine the prescription rates and prescribing trends of opioids by optometrists in the Centers for Medicare & Medicaid Services (CMS) part D database from 2013 to 2017 and to assess opioid prescribing patterns of U.S. optometrists in the CMS part D database. METHODS: With internal review board approval, a retrospective observational cohort study was conducted on optometrists listed in the CMS part D database who prescribed opioids from 2013 to 2017. RESULTS: There was an average of 26,477 optometrists in the CMS database from 2013 to 2017, of which 5.9% prescribed opioids. Of those prescribing opioids, optometrists wrote an average of 5.9 opioid prescriptions per year. Those writing greater than 10 opioid prescriptions averaged 24.2 annually. Overall, of opioid prescribing optometrists, opioid prescriptions comprised 7% of prescriptions written per year. CONCLUSIONS: Most optometrists do not prescribe opioids, and the vast majority of those who do write few opioid prescriptions. The total number of optometrists prescribing opioids and the total number of opioid prescriptions declined from 2013 to 2017. Further investigation into the opioid prescribing practices by optometrists will help better understand specific pain needs, as opioid prescribing patterns may differ depending on patient population.

Significant Energy Deficit and Suboptimal Sleep During a Junior Academy Tennis Training Camp.

PURPOSE: To assess the training load, energy expenditure, dietary intake, and sleep quality and quantity of junior tennis players during a tennis training camp. METHODS: Ten junior academy tennis players (14 [1] y) completed a 6-day camp with daily morning and afternoon training. Players wore accelerometer watches to measure activity energy expenditure and sleep. Global positioning system units were worn to monitor external training load (distance covered, maximum velocity, and PlayerLoad™). Dietary intake was obtained from a food diary and supplementary food photography. RESULTS: Players covered significantly more distance and had higher PlayerLoad™ during morning sessions than afternoon sessions (5370 [505] m vs 4726 [697] m, P < .005, d = 3.2; 725 [109] a.u. vs 588 [96] a.u., P < .005, d = 4.0). Players also ran further (5624 [897] m vs 4933 [343] m, P < .05, d = 1.0) and reached higher maximum velocities (5.17 [0.44] m·s-1 vs 4.94 [0.39] m·s-1, P < .05, d = 0.3) during simulated match play compared with drill sessions. Mean daily energy expenditure was 3959 (630) kcal. Mean energy intake was 2526 (183) kcal, resulting in mean energy deficits of 1433 (683) kcal. Players obtained an average of 6.9 (0.8) hours of sleep and recorded 28 (7) nightly awakenings. CONCLUSIONS: Junior academy tennis players failed to achieve energy balance and recorded suboptimal sleep quantity and quality throughout the training camp.

Effect of Premature Tube Extrusion for Simple Congenital Nasolacrimal Duct Obstruction: A Comparison of Monocanalicular and Bicanalicular Intubation.

ABSTRACT: The objective of this article is to compare the incidence of premature dislocation of silicone tubes and the effect on treatment success between monocanalicular (MCI) and bicanalicular (BCI) intubation in pediatric patients with simple congenital nasolacrimal duct obstruction. Retrospective comparative case series of 108 eyes of 78 pediatric patients with simple congenital nasolacrimal duct obstruction who underwent probing with either BCI (n = 38 eyes) or MCI (n = 70 eyes) from 2017 to 2020. Premature tube extrusion was defined as any tube removed prior to the 3 month postoperative appointment. Success was defined as resolution of tearing 3 months post tube removal. Ages ranged from 10 months to 5.35 years (mean, 1.95 years; Standard deviation (SD), 0.91). Premature tube extrusion occurred in 15 eyes with BCI and 29 eyes with MCI. Success rates were not significantly different regardless of intubation type between the planned tube removal (90.6%) and the premature tube extrusion cohorts (84.1%), P = 0.89. There was no significant difference in treatment success between the planned tube removal (92.7% MCI, 87% BCI) and the premature tube extrusion cohorts (86.2% MCI, 80% BCI). Complications included 2 infections (1 MCI, 1 BCI) and 2 cases of tube related keratopathy (1 MCI, 1 BCI) that all resolved with tube removal. There were 2 BCI patients that presented to the emergency department for premature tube extrusion. Silicone intubation regardless of stent type is an effective treatment for simple congenital nasolacrimal duct obstruction. There was no significant difference in treatment success between tubes that extrude prematurely, and tubes removed at term based on type of intubation.

Long-acting opioid prescribing patterns of ophthalmic plastic surgeons in the medicare Part D database.

PURPOSE: To assess extended release/long acting (ER/LA) opioid prescribing patterns among ophthalmic plastic surgeons in the Centers for Medicare and Medicaid Services (CMS) Part D database. METHODS: A retrospective observational cohort study was conducted on oculoplastic surgeons in the CMS Part D database who prescribed ER/LA opioids from 2013 to 2017. American Society of Ophthalmic Plastics and Reconstructive Surgery (ASOPRS) and non-ASOPRS surgeons were analyzed as groups. Prescribers were also analyzed based on gender and practice experience. RESULTS: Oculoplastic surgeons (64 ASOPRS and 78 non-ASOPRS) were responsible for 1,177 ER/LA opioid prescriptions from 2013 to 2017. ASOPRS members accounted for 4.6% and non-ASOPRS members accounted for 7.5% of all ER/LA opioids prescribed by ophthalmologists over the study period (p= .02). The total number of ASOPRS and non-ASOPRS members prescribing ER/LA opioids decreased by 52% (p= .10) and 58% (p= .07) from 2013 to 2017 respectively. CONCLUSION: ER/LA opioids are indicated for treatment of chronic pain and may be appropriately prescribed by the oculoplastic surgeon in certain circumstances, however due to the higher risk of overdose injury, those circumstances must be defined and justified. While a relatively small number of oculoplastic surgeons (10.6% ASOPRS and 19.6% non-ASOPRS) prescribed ER/LA opioids from 2013 to 2017, non-ASOPRS oculoplastic surgeons wrote 23.5% more ER/LA opioid prescriptions over the study period. Over the 5-year study period there was a general decline in the prescribing of ER/LA opioids by oculoplastic surgeons. Reviewing the prescribing practices of oculoplastic specialists, regardless of professional affiliation, is necessary to understand the role of ER/LA opioids for all of ophthalmology.

Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors improve heart failure-related outcomes. The mechanisms underlying these benefits are not well understood, but diuretic properties may contribute. Traditional diuretics such as furosemide induce substantial neurohormonal activation, contributing to the limited improvement in intravascular volume often seen with these agents. However, the proximal tubular site of action of the sodium-glucose cotransporter-2 inhibitors may help circumvent these limitations. METHODS: Twenty patients with type 2 diabetes mellitus and chronic, stable heart failure completed a randomized, placebo-controlled crossover study of empagliflozin 10 mg daily versus placebo. Patients underwent an intensive 6-hour biospecimen collection and cardiorenal phenotyping at baseline and again after 14 days of study drug. After a 2-week washout, patients crossed over to the alternate therapy with the above protocol repeated. RESULTS: Oral empagliflozin was rapidly absorbed as evidenced by a 27-fold increase in urinary glucose excretion by 3 hours (P<0.0001). Fractional excretion of sodium increased significantly with empagliflozin monotherapy versus placebo (fractional excretion of sodium, 1.2±0.7% versus 0.7±0.4%; P=0.001), and there was a synergistic effect in combination with bumetanide (fractional excretion of sodium, 5.8±2.5% versus 3.9±1.9%; P=0.001). At 14 days, the natriuretic effect of empagliflozin persisted, resulting in a reduction in blood volume (-208 mL [interquartile range, -536 to 153 mL] versus -14 mL [interquartile range, -282 to 335 mL]; P=0.035) and plasma volume (-138 mL, interquartile range, -379 to 154±453 mL; P=0.04). This natriuresis was not, however, associated with evidence of neurohormonal activation because the change in norepinephrine was superior (P=0.02) and all other neurohormones were similar (P<0.34) during the empagliflozin versus placebo period. Furthermore, there was no evidence of potassium wasting (P=0.20) or renal dysfunction (P>0.11 for all biomarkers), whereas both serum magnesium (P<0.001) and uric acid levels (P=0.008) improved. CONCLUSIONS: Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in an improvement in blood volume. However, off-target electrolyte wasting, renal dysfunction, and neurohormonal activation were not observed. This favorable diuretic profile may offer significant advantage in the management of volume status in patients with heart failure and may represent a mechanism contributing to the superior long-term heart failure outcomes observed with these agents. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03027960.

Significant hospitalization cost savings to the payer with a pharmacist-led mobile health intervention to improve medication safety in kidney transplant recipients.

This was an economic analysis of a 12-month, parallel arm, randomized controlled trial in adult kidney recipients 6 to 36 months posttransplant (NCT03247322). All participants received usual posttransplant care, while the intervention arm received supplemental clinical pharmacist-led medication therapy monitoring and management, via a smartphone-enabled mHealth app, integrated with risk-based televisits. Hospitalization charges were captured from the study institution accounts payable and non-study institution hospitalization charges were estimated using multiple imputation. Multivariable modeling was used to assess the impact of the intervention on charges. The intervention significantly reduced rates of hospitalization (1.08 per patient-year in the control arm vs 0.65 per patient-year in the intervention arm, p = .007). The control arm had estimated hospitalization costs of $870,468 vs $390,489 in the intervention arm. Modeling demonstrated a 49% lower hospitalization charge risk in the intervention arm (RR 0.51, 95% CI 0.28-0.91; p = .022). From a payer or societal perspective, the net estimated cost savings, after accounting for intervention delivery costs, was $368,839, with a return on investment (ROI) of $4.30 for every $1 spent. These results demonstrate that a mHealth-enabled, pharmacist-led intervention significantly reduced hospitalization costs for payers over a 12-month period and has a positive ROI.

Teprotumumab in Clinical Practice: Recommendations and Considerations From the OPTIC Trial Investigators.

BACKGROUND: Thyroid eye disease (TED) is a vision-threatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)-approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials. METHODS: An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on. RESULTS: The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of >4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab. CONCLUSIONS: Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician.

Postoperative Clinical Outcomes Using Standard Variables Following Levator-Mullerectomy Advancement Blepharoptosis Surgery.

ABSTRACT: The Muller muscle-conjunctival resection is a common technique used to treat blepharoptosis, but there is variability with the target surgical resection and expected postoperative outcomes measured by marginal reflex distance-1 (MRD1). A Levator-Mullerectomy is a novel surgical approach described by Morris et al to incorporate the levator palpebrae superioris in the same incision as the classic Muller muscle-conjunctival resection in the treatment of blepharoptosis. This a retrospective study of patients who underwent Levator-Mullerectomy for ptosis repair showing the clinical outcomes based on MRD1. Statistical analysis was performed using analysis of variance and a nonparametric Kruskal-Wallis test. One hundred-twelve eyes of 83 patients (29 bilateral cases) with a mean age 64.6 years (7-92 years) were included. The types and prevalence of blepharoptosis were involutional (83%), neurogenic (8.0%), traumatic (3.6%), apraxia (2.7%), and congenital (2.7%). There was no significant difference in clinical outcome based on type of blepharoptosis (P = 0.7). Target resection lengths of 8 mm, 10 mm, and 12 mm were compared with postoperative MRD1 change. The mean change in MRD 1 between 8 mm and 10 mm was found to be statistically significant (P = 0.001 for both) but was not statistically significant for the 12 mm resection (P = 0.8). In patients with blepharoptosis and a positive response to 2.5% phenylephrine can benefit from Levator-Mullerectomy with either an 8 mm or 10 mm resection. This novel surgical approach allows surgeons to produce a more predictable and consistent clinical outcome.

Adjusting the need for speed: assessment of a visual interface to reduce fuel use.

Previous research has identified that fuel consumption and emissions can be considerably reduced if drivers engage in eco-driving behaviours. However, the literature suggests that individuals struggle to maintain eco-driving behaviours without support. This paper evaluates an in-vehicle visual interface system designed to support eco-driving through recommendations based on both feedforward and feedback information. A simulator study explored participants' fuel usage, driving style, and cognitive workload driving normally, when eco-driving without assistance and when using a visual interface. Improvements in fuel-efficiency were observed for both assisted (8.5%) and unassisted eco-driving (11%), however unassisted eco-driving also induced a significantly greater rating of self-reported effort. In contrast, using the visual interface did not induce the same increase of reported effort compared to everyday driving, but itself did not differ from unassisted driving. Results hold positive implications for the use of feedforward in-vehicle interfaces to improve fuel efficiency. Accordingly, directions are suggested for future research. Practitioner Summary: Results from a simulator study comparing fuel usage from normal driving, engaging in unassisted eco-driving, or using a novel speed advisory interface, designed to reduce fuel use, are presented. Whilst both unassisted and assisted eco-driving reduced fuel use, assisted eco-driving did not induce workload changes, unlike unassisted eco-driving. Abbreviations: CO-2: carbon dioxide; NASA-TLX: NASA task load index; RMS: root-mean-square; MD: mean difference.

Dietary Intake and Daily Distribution of Carbohydrate, Protein and Fat in Youth Tennis Players over a 7-Day Training and Competition Period.

During a 7-day training and/or competition period, macronutrient intake and distribution was assessed using food diaries, supported by remote food photography and 24-hr multiple pass recalls of youth tennis players categorised by under 12s, under 14s and under 16+ age groups (n = 27). Total energy did not differ between age groups nor type of day (training [TD], competition day [CD]), irrespective of a significant increase in body mass reported in the older players (U16+; p < 0.05). Average intakes were consistently below 2250 kcal·day-1 (range 1965 ± 317-2232 ± 612 kcal·day-1). Carbohydrate consumption was below guidelines for all groups (≤6g·kg-1). Conversely, protein intake met or exceeded guidelines throughout, with intakes ≥2 g·kg-1 for both the U12 and U14 age groups on both days. Protein intake was ~17% higher on TDs than CDs (p < 0.05), with protein intake at lunch significantly higher on TDs than CDs (p < 0.05). No further differences were observed between breakfast, lunch or dinner between group or day. Inconsistent snacking was reported, with players consuming snacks on less than half of the days reported (46 ± 12% of TDs and 43 ± 30% of CDs). In conclusion, youth tennis players present sub-optimal nutrition practices, appearing to under fuel and under consume carbohydrate for performance, adaptation, recovery and health.

Teprotumumab for Thyroid-Associated Ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).