Quantitative Biomarkers of Diabetic Retinopathy Using Ultra-Widefield Fluorescein Angiography.

Introduction: Diabetic retinopathy (DR) is a leading cause of blindness. Retinal imaging is an important tool to monitor the progression of DR. While seven-standard retinal fields are the traditional method for evaluating DR, ultra-widefield (UWF) imaging allows for improved visualization of peripheral areas of nonperfusion (NP) and neovascularization (NV), which could be used as biomarkers to monitor and predict progression of DR. Methods: A retrospective, cross-sectional study was conducted on 651 eyes from 363 patients diagnosed with type 1 or type 2 diabetes who received UWF-FA over 10 years. Fluorescein Angiography (FA) images were segmented, and surface areas of NP and NV were analyzed using multivariate regression to determine if biomarkers of DR and DR severity are associated with increasing areas of NP and NV. Results: Each additional year with a diagnosis of DR was associated with a 10.75 mm2 increase in the total NP (95% CI, 1.94-19.56; P = 0.02) and 7.87 mm2 increase in NP far-periphery (95% CI, 1.62-14.13; P = 0.01). A one-unit change in severity as defined by the Early Treatment of Diabetic Retinopathy Study (ETDRS) classification was associated with a 25.75 mm2 increase in total NP (95% CI, 11.16-40.33; P = 0.001), a 13.15 mm2 increase in mid-periphery NP (95% CI, 6.93-19.38; P < 0.0001), and a 12.29 mm2 increase in far-periphery NP (95% CI, 3.62-20.97; P = 0.01). Discussion: Biomarkers identified through UWF imaging such as total and regional areas of NP can be used to monitor and predict the progression of DR. This may provide a quantitative method for prognostication in patients with DR.

Comparison of early and late norepinephrine administration in patients with septic shock: a systematic review and meta-analysis.

BACKGROUND: Vasopressor administration at an appropriate time is crucial but the optimal timing remains controversial. RESEARCH QUESTION: Does early versus late norepinephrine (NE) administration impact the prognosis of septic shock? STUDY DESIGN AND METHODS: Searches were conducted on PubMed, EMBASE, the Cochrane Library, and KMBASE. We included studies of adults with sepsis and categorized patients into early and late NE group according to specific time points or differences in norepinephrine use protocols. The primary outcome was overall mortality. The secondary outcomes included length of stay in the intensive care unit, days free from ventilator use, days free from renal replacement therapy, days free from vasopressor use, adverse events, and total fluid volume. RESULTS: Twelve studies (4 randomized controlled trials [RCTs], 8 observational) comprising 7,281 patients were analyzed. For overall mortality, no significant difference was found between the early NE group and late NE group in RCTs (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.19) or observational studies (OR, 0.83; 95% CI, 0.54-1.29). In the two RCTs without a restrictive fluid strategy that prioritized vasopressors and lower intravenous fluid volumes, the early NE group showed significantly lower mortality than the late NE group (OR 0.49, 95%, CI, 0.25-0.96). The early NE group demonstrated more mechanical ventilator-free days in observational studies (MD, 4.06; 95% CI, 2.82-5.30). The incidence of pulmonary edema was lower in the early NE group in the three RCTs that reported this outcome (OR 0.43; 95% CI, 0.25-0.74). No differences were found in the other secondary outcomes. INTERPRETATION: Overall mortality did not differ significantly between early and late NE administration for septic shock. However, early NE administration appeared to reduce pulmonary edema incidence, and mortality improvement was observed in studies without fluid restriction interventions, favoring early NE use.

Trends of Ophthalmic Surgery Cancellations at a County Hospital Before and During COVID-19: A 10-Year Retrospective Study.

PURPOSE: Despite several publications on ophthalmic surgical cancellations discussing preventative causes in academic institutions, there remains a paucity of similar studies for safety-net hospitals. This study analyzed cancellation rates at a county hospital over a 10-year period. METHODS: This retrospective, open cohort study investigated a total of 11,350 surgeries scheduled at a tertiary-level county hospital between January 1, 2012 and December 31, 2021. Surgical cancellation reasons were collected from chart review and categorized into eight groups to allow for analyses. Cancellation rates were then calculated per year and per subspecialty. The primary statistical analyses were paired, 2-tailed t test and χ2 test. RESULTS: The most common reason for cancellation overall was institution-related (1065 surgeries), which was also the most common reason per year from 2012 to 2019 (range: 37.4% - 60.6%). In 2020, during COVID-19 stay-at-home mandates, the most common reason became COVID-related rescheduling, and in 2021, it was patient-driven. The cancellation rate in 2020 was significantly higher than 2019 (+9.27%,95% CI:4.96%-13.6%,p = .05), and significantly lower from 2021 to 2020 (-22.8%,95% CI:-26.8%-(-)18.7%,p = .001). Pediatric surgery had the highest cancellation rate overall (36.4%), but oculoplastics had the highest cancellation rate in 2020 (48.9%). CONCLUSION: The most common reason for cancellation over the 10-year period was institution-related, in contrast to other publications based in academic centers. The study also had a higher cancellation rate than previously reported, again suggesting the difference between county and academic centers. The COVID-19 pandemic had a significant impact on cancellations, even after the COVID-19 stay-at-home orders were eased.

Ocular Ischemic Syndrome in the Setting of Normal Carotid Duplex Ultrasound.

PURPOSE: To describe two cases of ocular ischemic syndrome (OIS) that were initially ruled out due to a negative carotid duplex ultrasound (DUS) but eventually confirmed by angiography studies. METHODS: Case series. RESULTS: Case 1: A 67-year-old female presented with symptoms suggestive of OIS, but carotid DUS was negative, and the patient was diagnosed with occlusive retinal vasculitis due to retinal non-perfusion and vascular leakage on fluorescein angiography (FA). Immunosuppressive therapy was initiated but her symptoms did not improve. Computerized tomography angiography (CTA) was significant for severe osteal stenosis of the aortic arch vessels. Left common carotid angioplasty and stenting resulted in complete resolution of the symptoms and vascular leakage of the left eye. Case 2: A 41-year-old male with cryoglobulinemia-associated vasculitis complained of symptoms consistent with OIS, which was initially ruled out through a negative carotid DUS. FA revealed delayed arterial filling with poor retinal perfusion. Magnetic resonance angiography (MRA) revealed ophthalmic artery stenosis which was attributed to the underlying systemic vasculitis. CONCLUSION: CTA or MRA should be performed to rule out OIS if DUS is negative in the setting of high clinical suspicion. Carotid ostial and ophthalmic artery stenoses are rare but possible causes of OIS.

Deep learning for automated detection of neovascular leakage on ultra-widefield fluorescein angiography in diabetic retinopathy.

Diabetic retinopathy is a leading cause of blindness in working-age adults worldwide. Neovascular leakage on fluorescein angiography indicates progression to the proliferative stage of diabetic retinopathy, which is an important distinction that requires timely ophthalmic intervention with laser or intravitreal injection treatment to reduce the risk of severe, permanent vision loss. In this study, we developed a deep learning algorithm to detect neovascular leakage on ultra-widefield fluorescein angiography images obtained from patients with diabetic retinopathy. The algorithm, an ensemble of three convolutional neural networks, was able to accurately classify neovascular leakage and distinguish this disease marker from other angiographic disease features. With additional real-world validation and testing, our algorithm could facilitate identification of neovascular leakage in the clinical setting, allowing timely intervention to reduce the burden of blinding diabetic eye disease.

Prevalence of Carbon Monoxide Poisoning and Hyperbaric Oxygen Therapy in Korea: Analysis of National Claims Data in 2010-2019.

This study aimed to investigate the prevalence of carbon monoxide (CO) poisoning and the provision of hyperbaric oxygen therapy (HBOT) in South Korea. We used data from the Korea Health Insurance Review and Assessment service. In total, 44,361 patients with CO poisoning were identified across 10 years (2010-2019). The prevalence of CO poisoning was found to be 8.64/10,000 people, with a gradual annual increment. The highest prevalence was 11.01/10,000 individuals, among those aged 30-39 years. In 2010, HBOT was claimed from 15 hospitals, and increased to 30 hospitals in 2019. A total of 4,473 patients received HBOT in 10 years and 2,684 (60%) were treated for more than 2 hours. This study suggested that the prevalence of both CO poisoning and HBOT in Korea gradually increased over the past 10 years, and disparities in prevalence were observed by region.

Retinal neovascularization as self-organized criticality on ultra-widefield fluorescein angiography imaging of diabetic retinopathy.

BACKGROUND/OBJECTIVES: Do the distributions of surface area of non-perfusion (NP) and neovascularization (NV) on ultra-widefield fluorescein angiography (UWF FA) in patients with diabetic retinopathy (DR) differ significantly? SUBJECTS/METHODS: Inclusion criteria were patients who had a UWF FA taken for DR at the Kellogg Eye Center from January 2009 to May 2018. Exclusion criteria included previous panretinal photocoagulation and significant media opacity (e.g., vitreous haemorrhage or significant cataract). UWF FAs were manually segmented for surface areas of NP and NV. The total areas per patient were organized in a histogram, and logarithmically binned to test against power law and exponential distributions. Then, a computational model was constructed in Python 3.7 to suggest a mechanistic explanation for the observed distributions. RESULTS: Analysis of areas of NV across 189 images demonstrated a superior fit by the least squares method to a power law distribution (p = 0.014) with an R2 fit of 0.9672. Areas of NP over 794 images demonstrated a superior fit with an exponential distribution instead (p = 0.011). When the far periphery was excluded, the R2 fit for the exponential distribution was 0.9618. A computational model following the principles of self-organized criticality (SOC), akin to earthquake and forest fire models, matched these datasets. CONCLUSIONS: These distributions inform what useful statistics may be applied to study of these imaging characteristics. Further, the difference in event distribution between NV and NP suggests that the two phenomena are mechanistically distinct. NV may follow SOC, propagating as a catastrophic event in an unpredictable manner.

Quantitative contrast sensitivity test to assess visual function in central serous chorioretinopathy.

BACKGROUND: To characterise the contrast sensitivity function (CSF) in central serous chorioretinopathy (CSCR) compared with healthy controls using novel computerised contrast sensitivity (CS) testing with active learning algorithms. METHODS: Prospective observational study measuring CSF in CSCR eyes and controls using the Manifold Platform (Adaptive Sensory Technology, San Diego, California). Mixed effects multivariate regression models were used. Outcomes included area under the log CSF (AULCSF), CS thresholds at 1, 1.5, 3, 12 and 18 cycles per degree (cpd) and best-corrected visual acuity (BCVA). Associations of contrast outcomes with structural findings on optical coherence tomography (OCT) and subjective symptomatology were investigated. RESULTS: Forty CSCR eyes and 89 controls were included with median BCVA logarithm of median angle of resolution 0.10 (20/25) versus 0.00 (20/20), respectively (p=0.01). When accounting for age, CSCR was associated with significantly reduced median AULCSF (p=0.02, ß=-0.14) and reduced CS thresholds at 6 cpd (p=0.009, ß=-0.18), 12 cpd (p<0.001, ß=-0.23) and 18 cpd (p=0.04, ß=-0.09), versus controls. Within the CSCR group, subjectively perceived visual impairment (N=22) was associated with significantly decreased CS thresholds at all spatial frequencies and in AULCSF compared with asymptomatic CSCR eyes (N=18). Ellipsoid zone attenuation and subfoveal fluid on OCT were associated with decreased AULCSF and CS thresholds specifically at 3, 6 and 12 cpd, whereas presence of extrafoveal fluid at 1.5 and 3 cpd. CONCLUSION: Contrast sensitivity is significantly reduced in CSCR, and strongly correlates with subjective visual impairment. Different structural biomarkers correlate with contrast thresholds reductions at different spatial frequencies.

The Stanford Global Health Media Fellowship: Training the Next Generation of Physician Communicators to Fight Health Misinformation.

PROBLEM: The COVID-19 pandemic and the spread of related health misinformation, especially on social media, have highlighted the need for more health care professionals to produce and share accurate health information to improve health and health literacy. Yet, few programs address this problem by training health care professionals in the art of science writing and medical journalism. APPROACH: Created in 2011, the Stanford Global Health Media Fellowship aims to train medical students and residents in public communication strategies. Each year, 1 physician-in-training is selected to complete the fellowship, which includes 3 rotations: (1) 1 academic quarter at Stanford's Graduate Program in Journalism, (2) 3 to 5 months with a national news network (previously NBC and ABC, now CNN), and (3) a placement at an international site. During the year-long program, fellows also complete a capstone project tackling a global health equity issue. OUTCOMES: Since 2011, 10 fellows have completed the program, and they have acquired skills in reporting, writing, multimedia, social media, and medical communications. During the news network rotation, they have completed more than 200 medical news pieces and improved the quality of the health information in a myriad of other pieces. Alumni have continued to write and report on medical stories throughout residency, other fellowships, and as practicing physicians. One alumnus is now a medical news producer at CNN. NEXT STEPS: Expanding high-quality training in medical journalism for physicians through partnerships with journalism schools; communications departments; and local, national, and international journalists can greatly improve physicians' ability to communicate with the public. It also has the potential to greatly improve the health information the public receives. Educators should consider embedding mass health communications training in medical education curricula and increasing opportunities for physicians to engage with diverse public audiences.

Which Septic Shock Patients With Non-Overt DIC Progress to DIC After Admission? Point-of-Care Thromboelastography Testing.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a life-threatening complication of septic shock; however, risk factors for its development after admission are unknown. Thromboelastography (TEG) can reflect coagulation disturbances in early non-overt DIC that are not detected by standard coagulation tests. This study investigated the risk factors including TEG findings as early predictors for DIC development after admission in septic shock patients with non-overt DIC. METHODS: This retrospective observation study included 295 consecutive septic shock patients with non-overt DIC at admission between January 2016 and December 2019. DIC was defined as an International Society on Thrombosis and Hemostasis (ISTH) score ≥ 5. The primary outcome was non-overt DIC at admission that met the ISTH DIC criteria within 3 days after admission. RESULTS: Of the 295 patients with non-overt DIC, 89 (30.2%) developed DIC after admission. The DIC group showed a higher ISTH score and 28-day mortality rate than the non-DIC group (2 vs. 3, P < 0.001; 13.6% vs. 27.0%, P = 0.008, respectively). The DIC rate increased with the ISTH score (7.7%, 13.3%, 15.8%, 36.5%, and 61.4% for scores of 0, 1, 2, 3, and 4, respectively). Among TEG values, the maximum amplitude (MA) was higher in the non-DIC group (P < 0.001). On multivariate analysis, an MA < 64 mm was independently associated with DIC development (odds ratio, 2.311; 95% confidence interval, 1.298-4.115). CONCLUSIONS: DIC more often developed among those with admission ISTH scores ≥ 3 and was associated with higher mortality rates. An MA < 64 mm was independently associated with DIC development in septic shock patients.

Endoscope-Assisted Sutureless Intrascleral Haptic Fixation of a Posterior Chamber Intraocular Lens.

Purpose: In eyes with compromised capsule support, sutureless scleral fixation is a popular method of placing a posterior chamber intraocular lens (PCIOL). We describe an endoscope-assisted sutureless technique for intrascleral fixation of a 3-piece PCIOL. Methods: Eyes of patients who had endoscope-assisted scleral-fixated intraocular lens (SFIOL) implantation were examined retrospectively. The technique comprised direct capture of the IOL haptic with a forceps through a pars plana sclerotomy with subsequent haptic fixation into scleral tunnels created with a 26-gauge needle. The endoscope was used to visualize haptic positioning under the iris and ensure proper centration of the IOL. Results: Thirteen eyes of 13 patients were examined. The mean age of the patients was 68.2 years (range, 38-87 years), and the mean follow-up was 13.6 months (range, 5-23 months). The indications for surgery were a subluxated IOL (6 eyes), postoperative aphakia (5 eyes), and a subluxated cataract (2 eyes). The mean best-corrected visual acuity ± SD improved significantly from 1.2 ± 0.6 logMAR preoperatively to 0.6 ± 0.7 logMAR at last the follow-up (paired Welch t test; t10 = 2.69; P = .023). IOL stability and centration were maintained in all patients. Conclusions: Endoscopic visualization during sutureless SFIOL implantation helped improve haptic localization, minimize intraoperative complications, and achieve excellent IOL centration.

COMBINED PNEUMATIC AND ENZYMATIC VITREOLYSIS FOR SEVERE CASES OF VITREOMACULAR TRACTION.

PURPOSE: To evaluate the efficacy of combined pneumatic and enzymatic vitreolysis for treatment of severe cases of vitreomacular traction (VMT). METHODS: We analyzed a retrospective, consecutive series of five patients diagnosed with severe VMT refractory to pneumatic vitreolysis who then received an additional ocriplasmin injection while their gas bubble from pneumatic vitreolysis was still present between February 2015 and February 2019. Vitreomacular traction release was confirmed using spectral-domain optical coherence tomography. RESULTS: Four of the five patients treated with combined pneumatic and enzymatic vitreolysis achieved VMT release by Day 28, and all cases eventually achieved complete VMT release. In addition to having VMT refractory to pneumatic vitreolysis, patient characteristics included broad adhesion diameter (>1,500 µ m, n = 1), presence of epiretinal membrane (n = 2), age >65 years (n = 4), and pseudophakia (n = 1). The visual acuity improved by three or more lines at 6 months in both of the patients with initial vision worse than 20/50 on an Early Treatment Diabetic Retinopathy Study chart but not in those whose vision was already fairly good (i.e., visual acuity >20/60). None of the patients experienced the following complications after receiving this combined treatment: retinal tears or detachments, vitreous floaters, and ellipsoid zone changes. CONCLUSION: Sequential, combined pneumatic and enzymatic vitreolysis resulted in VMT release in all 5 cases (4 cases by 28 days) and may be a potentially useful alternative to surgical intervention for refractory VMT cases.

Hypercoagulability in Septic Shock Patients With Thrombocytopenia.

BACKGROUND: Despite thrombocytopenia, patients with sepsis often experience hypercoagulability. However, limited information is available on the prevalence and effect of hypercoagulability in patients with sepsis-induced thrombocytopenia. Hence, we evaluated the prevalence of hypercoagulability and the association between hypercoagulability and clinical outcomes in septic shock patients with thrombocytopenia. METHODS: Thromboelastography (TEG) was performed prospectively in 1294 patients with septic shock at the emergency department (ED) between January 2016 and December 2019. After excluding 405 patients who did not require resuscitation, refused enrollment, or developed septic shock after ED presentation, 889 patients were included. We defined thrombocytopenia as an admission platelet count lower than 150,000/µl according to SOFA score. We defined hypocoagulability and hypercoagulability as coagulation index (CI)< -3 and >3 on TEG, respectively. RESULTS: Of the 889 septic shock patients (mean age 65.6 ± 12.7 years, 58.6% male), 473 (53.2%) had thrombocytopenia. Eighty-five (18.0%) patients showed hypercoagulable TEG and73 (15.4%) patients showed hypocoagulable TEG. The hypercoagulable TEG group had a significantly higher fibrinogen level and a lower 28-day mortality rate than the normal and hypocoagulable TEG groups (518 vs. 347 and 315 mg/dL; 7.1% vs. 21.1% and 36.8%, P < 0.01, respectively). In multivariate analysis, hypercoagulable TEG was associated with a decreased mortality rate (odds ratio: 0.395; 95% confidence interval, 0.162-0.965). CONCLUSIONS: In septic shock patients with thrombocytopenia, hypercoagulability was not uncommon. TEG can quickly distinguish the hypercoagulability and hypocoagulability states and serve as a valuable tool for evaluating the degree and risk in septic shock patients with thrombocytopenia.

Active Learning of Contrast Sensitivity to Assess Visual Function in Macula-off Retinal Detachment.

PURPOSE: To characterize the contrast sensitivity function (CSF) in patients with successful repair of macula-off rhegmatogenous retinal detachment (RD) using an adaptive computerized contrast testing device. METHODS: CSF was prospectively measured in macula-off RD patients following successful repair and age-matched controls at W. K. Kellogg Eye Center and Massachusetts Eye and Ear, employing the active learning device Manifold Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA). Outcome measures included average area under the CSF curve (AULCSF), CS thresholds at 1-18 cycles per degree (cpd) and best correctd visual acuity (BCVA) in RD eyes fellow eyes and controls. A sub-analysis was performed in eyes with BCVA of 20/30 or better. RESULTS: Twenty-three macula-off RD eyes status post repair, fellow healthy eyes and 45 age-matched control eyes underwent CSF testing. The mean BCVA of the 23 RD eyes was 0.250 logMAR, significantly reduced compared to fellow eyes 0.032 (p<0.001) and controls 0.026 (p< 0.00001). There was a statistically significant reduction in AULCSF in RD eyes compared to the fellow eyes (p<0.0001) and to age-matched controls (Z-score -0.90, p<0.0001) and CSF reduction across all spatial frequencies. In the 15 RD eyes with BCVA of 20/30 or better, the mean CSF was significantly reduced compared to fellow eyes (p=0.0158) and controls (p=0.0453). CONCLUSIONS: CSF in macula-off RD eyes following repair was significantly reduced compared to fellow eyes and age-matched controls. CSF seems to be a promising visual function endpoint with potential applications in the clinical practice and future clinical trials.

Role of thromboelastography in the evaluation of septic shock patients with normal prothrombin time and activated partial thromboplastin time.

Coagulopathy is frequent in septic shock and plays a key role in multiple organ dysfunction. The aim of this study is to investigate application values of thromboelastography (TEG) for outcome in septic shock patients with a normal value of prothrombin time (PT) and active partial thromboplastin time (aPTT). Prospective observational study using 1298 consecutive septic shock patients with TEG at admission was conducted at the emergency department (ED) of a tertiary care hospital in South Korea between 2016 and 2019. After excluding overt-disseminated intravascular coagulation (DIC) defined by scoring system, we included patients with a normal value of international normalized ratio ≤ 1.3 and aPTT ≤ 34 s. The primary outcome was 28-day mortality. 893 patients were included and 129 patients with overt DIC were excluded. Of the 764 remaining patients, 414 (54.2%) patients showed normal PT and aPTT (28-day mortality rate, 11.4%). TEG values such as reaction time, kinetic time (K), alpha angle (α), maximum amplitude (MA) and lysis index (LY 30) showed no significant mean difference between the survivor and non-survivor groups. However, hypocoagulable TEG values such as α < 53° (12.0% vs. 23.4%; p = 0.039), and MA < 50 mm (6.3% vs. 21.3%; p = 0.002) were significantly higher in the non-survived group. In multivariate analysis, hypocoagulable state (defined as K > 3 and α < 53 and MA < 50) was independent factors associated with increased risk of death (OR 4.882 [95% CI, 1.698-14.035]; p = 0.003). In conclusion, septic shock patients with normal PT and aPTT can be associated with impaired TEG profile, such as hypocoagulability, associated with increased mortality.

The Michigan Retinal Degeneration Questionnaire: A Patient-Reported Outcome Instrument for Inherited Retinal Degenerations.

PURPOSE: To create a psychometrically validated patient-reported outcome measure for inherited retinal degenerations. DESIGN: Qualitative and quantitative patient-reported outcome (PROs) questionnaire development using item response theory validation. METHODS: One hundred twenty-eight patients with a diagnosis of an inherited retinal degeneration at the Kellogg Eye Center (University of Michigan) were recruited and administered a 166-item questionnaire comprising 7 expert-defined domains. The questionnaire was re-administered 4-16 days later to a subset of 25 participants to assess test-retest variability. Graded response models were fit by Cai's Metropolis-Hastings Robbins-Monro algorithm using the R (version 3.6.3) package mirt. Model data were fit to assess questionnaire dimensionality, to estimate item information, and to score participants. Poorly functioning items were removed, and the model was refit to create the final questionnaire. RESULTS: The psychometrically validated PROs measure was reduced to a 59-item questionnaire measuring 7 unidimesnional domains: central vision, color vision, contrast sensitivity, scotopic function, photopic peripheral vision, mesopic peripheral vision, and photosensitivity. A total of 39 items were removed because of poor factor loading, low item information, poor person-ability differentiation, or high item-level interdependence. This novel questionnaire produces a reliable domain score for person ability that does not show significant test-retest variability across repeated administration. CONCLUSIONS: The final PRO questionnaire, known as the Michigan Retinal Degeneration Questionnaire, is psychometrically validated and available for use in the evaluation of patients with inherited retinal degenerations.

The Michigan Vision-Related Anxiety Questionnaire: A Psychosocial Outcomes Measure for Inherited Retinal Degenerations.

OBJECTIVE: We sought to construct and validate a patient-reported outcome measure for screening and monitoring vision-related anxiety in patients with inherited retinal degenerations. DESIGN: Item-response theory and graded response modeling to quantitatively validate questionnaire items generated from qualitative interviews and patient feedback. METHODS: Patients at the Kellogg Eye Center (University of Michigan, Ann Arbor, Michigan, USA) with a clinical diagnosis of an inherited retinal degeneration (n = 128) participated in an interviewer-administered questionnaire. The questionnaire consisted of 166 items, 26 of which pertained to concepts of "worry" and "anxiety." The subset of vision-related anxiety questions was analyzed by a graded response model using the Cai Metropolis-Hastings Robbins-Monro algorithm in the R software mirt package. Item reduction was performed based on item fit, item information, and item discriminability. To assess test-retest variability, 25 participants completed the questionnaire a second time 4 to 16 days later. RESULTS: The final questionnaire consisted of 14 items divided into 2 unidimensional domains: rod function anxiety and cone function anxiety. The questionnaire exhibited convergent validity with the Patient Health Questionnaire for symptoms of depression and anxiety. This vision-related anxiety questionnaire has high marginal reliability (0.81 for rod-function anxiety, 0.83 for cone-function anxiety) and exhibits minimal test-retest variability (ρ = 0.81 [0.64-0.91] for rod-function anxiety and ρ = 0.83 [0.68-0.92] for cone-function anxiety). CONCLUSIONS: The Michigan Vision-Related Anxiety Questionnaire is a psychometrically validated 14-item patient-reported outcome measure to be used as a psychosocial screening and monitoring tool for patients with inherited retinal degenerations. It can be used in therapeutic clinical trials for measuring the benefit of an investigational therapy on a patient's vision-related anxiety.

Role of Thromboelastography as an Early Predictor of Disseminated Intravascular Coagulation in Patients with Septic Shock.

(1) Background: The currently proposed criteria for diagnosing overt disseminated intravascular coagulation (DIC) are not suitable for early detection of DIC. Thromboelastography (TEG) rapidly provides a comprehensive assessment of the entire coagulation process and is helpful as a guide for correcting consumptive coagulopathy in sepsis-induced DIC. This study aimed to investigate the role of TEG in the prediction of DIC in patients with septic shock. (2) Methods: TEG was conducted prospectively in 1294 patients with septic shock at the emergency department (ED) between January 2016 and December 2019. After exclusion of 405 patients with "do not attempt resuscitation" orders, those refusing enrollment, and those developing septic shock after ED presentation, 889 patients were included. DIC was defined as an International Society on Thrombosis and Hemostasis score ≥ 5 points within 24 h. (3) Results: Of the 889 patients with septic shock (mean age 65.6 ± 12.7 years, 58.6% male), 158 (17.8%) developed DIC. TEG values, except lysis after 30 min, were significantly different between the DIC and non-DIC groups. Among the TEG values, the maximal amplitude (MA) had the highest discriminating power for DIC, with an area under the curve of 0.814. An MA < 60 indicated DIC with 79% sensitivity, 73% specificity, and 94% negative predictive value. Based on multivariable analysis, MA < 60 was an independent predictor of DIC (odds ratio 5.616 (95% confidence interval: 3.213-9.818)). (4) Conclusions: In patients with septic shock, the MA value in TEG could be a valuable tool for early prediction of DIC.

Prognostic value of repeated thromboelastography measurement for favorable neurologic outcome during targeted temperature management in out-of-hospital cardiac arrest survivors.

BACKGROUND: Cardiac arrest can activate blood coagulation, which clinically manifests as obstruction of the microcirculation and multiple organ dysfunction. Thromboelastography (TEG) provides a rapid and comprehensive assessment of hemostatic processes, but there are limited data on the use of sequential TEG values during targeted temperature management (TTM) in out-of-hospital cardiac arrest (OHCA) survivors. The aim of this study was to investigate the prognostic value of coagulopathy assessed by repeated TEG to predict neurologically intact survival. METHODS: A prospective cohort of consecutive non-trauma OHCA patients who were successfully resuscitated and treated with TTM. Patients with a target temperature of 36 ℃, no TEG data, and who declined appropriate treatment were excluded. TEG was measured at three time points of TTM (initial phase, target phase, and rewarming phase). The primary outcome was 28 day favorable neurologic function, defined as a Cerebral Performance Category of 1 or 2. RESULTS: A total of 125 patients (mean age, 61 years; 63.2% male) were analyzed. A favorable neurologic outcome at 28 days was seen in 40 patients (32.0%). TEG values of R and LY30 in the initial phase were significantly lower in the favorable neurologic outcome group than in the unfavorable group (5.8 vs. 8.1 and 0.1 vs. 0.7, respectively; p < 0.01). TEG values of R < 5 or LY30 < 7.5 in the initial phase were more frequently seen in the favorable outcomes group than in the unfavorable group (37.5% vs. 12.9%, p = 0.002 and 95.0% vs. 72.9%, p = 0.004, respectively). However, no significant differences were seen between the two groups in other TEG values (R, K, alpha, and MA) in the target and rewarming phases (p > 0.05 for all). Univariate analysis showed higher D-dimer levels, prothrombin time, and activated partial thromboplastin time in the unfavorable outcome group. In the multivariable analysis, TEG values of combination of R < 5 and LY30 < 7.5 in the initial phase were the only coagulation profiles seen to be independently associated with favorable neurologic outcome (OR, 4.508, 95% CI, 1.254-16.210). CONCLUSION: TEG results are available within minutes, and shorted R values or the absence of prolonged LY30 values in the initial phase are an early predictor of neurologically intact survival in successfully resuscitated OHCA patients.