Challenges in posterior uveitis-tips and tricks for the retina specialist.

PURPOSE: Posterior uveitis is a common chorioretinal pathology affecting all ages worldwide and is a frequent reason for referral to the retina clinic. The spectrum of etiologies for uveitis is very broad and includes infectious and auto-immune diseases. Inflammation can be confined to the eye or may be a part of systemic disease. A useful outline is therefore proposed to aid in the correct diagnosis of these challenging entities. The situation is further complicated by the fact that many neoplastic conditions resemble features of posterior uveitis; they are known as "masqueraders of uveitis". Here, we summarize different posterior uveitides that present with rare findings, along with masqueraders that can be difficult to distinguish. These conditions pose a diagnostic dilemma resulting in delay in treatment because of diagnostic uncertainty. METHODS: An extensive literature search was performed on the MEDLINE/PUBMED, EBSCO and Cochrane CENTRAL databases from January 1985 to January 2022 for original studies and reviews of predetermined diagnoses that include posterior uveitic entities, panuveitis and masquerade syndromes. RESULTS: We described conditions that can present as mimickers of posterior uveitis (i.e., immune check-points inhibitors and Vogt-Koyanagi-Harada-like uveitis; leukemia and lymphoma associated posterior uveitis), inflammatory conditions that present as mimickers of retinal diseases (i.e., Purtscher-like retinopathy as a presentation of systemic lupus erythematosus; central serous chorioretinopathy masquerading inflammatory exudative retinal detachment), and uveitic conditions with rare and diagnostically challenging etiologies (i.e., paradoxical inflammatory effects of anti-TNF-α; post vaccination uveitis; ocular inflammation after intravitreal injection of antiangiogenic drugs). CONCLUSION: This review of unique posterior uveitis cases highlights the overlapping features of posterior uveitis (paradoxical inflammatory effects of anti -TNF α and uveitis; Purtscher-like retinopathy as a presentation of systemic lupus erythematosus, …) and the nature of retinal conditions (ischemic ocular syndrome, or central retinal vein occlusion, amyloidosis, inherited conditions like retinitis pigmentosa, autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), etc.…) that may mimic them is represented. Careful review of past uveitis history, current medications and recent vaccinations, detailed examination of signs of past or present inflammation, eventually genetic testing and/ or multimodal retinal imaging (like fluorescein angiography, EDI-OCT, OCT-angiography for lupus Purtscher-like retinopathy evaluation, or ICG for central serous retinopathy, or retinal amyloid angiopathy) may aid in correct diagnosis.

Herpes zoster ophthalmicus: frequency and risk factors for developing uncommon ocular manifestations.

OBJECTIVE: To determine the frequency of herpes zoster ophthalmicus (HZO) and assess risk factors for developing uncommon ocular manifestations of laboratory-verified HZO. DESIGN: Retrospective cohort study. METHODS: The frequency of HZO out of all herpes zoster cases was calculated using International Classification of Diseases codes for patients seen at the University of Pittsburgh Medical Center from January 1, 2004 to October 31, 2021. We also collected demographic and clinical data of patients with HZO identified by polymerase chain reaction (PCR) detection of varicella zoster virus from January 1, 2011 to December 31, 2020. RESULTS: The frequency of HZO from 2004 to 2021 in all ages was 4.2% and ranged from 2.7% to 6.7% annually, with a consistent increase of 2.9% from 2012 to 2021. After the live zoster vaccine became available in 2008, the frequency of HZO decreased by 5.1% from 2008 to 2012 in patients aged 60 and older. Among 50 cases of PCR-verified HZO, 62% represented clinically-common ocular manifestations, mostly comprised of 13 cases of keratitis and 10 cases of anterior uveitis. Fifteen cases of acute retinal necrosis (ARN) represented the majority of uncommon HZO manifestations (38%), which were significantly more likely to occur in immunosuppressed patients (unadjusted odds ratio 4.55, 95% confidence interval 1.29-13.83). CONCLUSIONS: The overall frequency of HZO from 2004 to 2021 was 4.2% and has increased annually since 2012. Uncommon ocular manifestations of PCR-verified HZO, mostly comprised of ARN, were more likely to occur in immunosuppressed patients.

A Retrospective Analysis of Clinical Utilization Between Patients Who Used Telemedicine and Office Visits in Outpatient Physical Medicine and Rehabilitation Clinics During the COVID-19 Pandemic.

OBJECTIVE: To describe the demographic characteristics of patients who used telemedicine and office visits in physical medicine and rehabilitation during the COVID-19 pandemic and to quantify differences in clinical utilization between groups. Clinical utilization was defined as emergency department, urgent care, and hospital visits. DESIGN: This was a retrospective cohort study of 1096 patients who used telemedicine and 1171 patients who used office visits from April to June 2020 in the outpatient physical medicine and rehabilitation clinics at University of Pittsburgh Medical Center for musculoskeletal-related complaints. RESULTS: The telemedicine groups contained proportionally more people of color and higher comorbidities than the office visit groups. Patients who were seen in the telemedicine groups were more likely to be prescribed opioids than the office visit group. There were no differences in clinical utilizations between the telemedicine and office visit groups. CONCLUSIONS: The higher use of telemedicine in patients of color suggests a need for studying long-term outcomes to evaluate differences in care standards. There is an urgent need to understand how telemedicine affects opioid prescribing practices. Lastly, future studies are needed to understand why there were no differences in clinical utilization between the telemedicine and office visit groups.

Impact of Bamlanivimab Monoclonal Antibody Treatment on Hospitalization and Mortality Among Nonhospitalized Adults With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Monoclonal antibody treatment may prevent complications of coronavirus disease 2019 (COVID-19). We sought to quantify the impact of bamlanivimab monoclonal antibody monotherapy on hospitalization and mortality among outpatients at high risk of COVID-19 complications. METHODS: In this observational study we compared outpatients who received bamlanivimab monoclonal antibody from December 9, 2020 to March 3, 2021 to nontreated patients with a positive polymerase chain reaction or antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the same period who were eligible for monoclonal antibody treatment. The primary outcome was 28-day hospitalization or all-cause mortality, and the secondary outcome was hospitalization or emergency department visit without hospitalization. The risk-adjusted odds of study outcomes comparing bamlanivimab treated and untreated patients was determined using 1:5 propensity matching and multivariable logistic regression. RESULTS: Among 232 patients receiving bamlanivimab matched with 1160 comparator patients, the mean age was 67 years, 56% were female, and 196 (14%) of patients experienced hospitalization or mortality. After adjustment for propensity to receive treatment, bamlanivimab treatment was associated with a significantly reduced risk-adjusted odds of hospitalization or mortality within 28 days (odds ratio [OR], 0.40; 95% confidence interval [95% CI], 0.24-0.69; P < .001). Bamlanivimab treatment was also associated with a significantly lower risk adjusted odds of hospitalization or emergency department visit without hospitalization (OR, 0.54; 95% CI, 0.35-0.82; P = .004). The results were most strongly associated with patients age 65 years and older. CONCLUSIONS: Bamlanivimab monoclonal antibody monotherapy was associated with reduced hospitalizations and mortality within 28 days among outpatients with mild to moderate COVID-19.Use of bamlanivimab monotherapy for outpatients with mild to moderate COVID-19 infection was associated with reductions in hospitalizations and mortality within 28 days. Benefit was strongest in those age 65 years or older.

The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization.

OBJECTIVES: The primary objective is to evaluate the comparative effectiveness of COVID-19 specific monoclonal antibodies (mABs) with US Food and Drug Administration (FDA) Emergency Use Authorization (EUA), alongside UPMC Health System efforts to increase patient access to these mABs. TRIAL DESIGN: Open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization PARTICIPANTS: We will evaluate patients who meet the eligibility criteria stipulated by the COVID-19 mAB EUAs who receive mABs within the UPMC Health System, including infusion centers and emergency departments. EUA eligibility criteria include patients with mild to moderate COVID-19, <10 days of symptoms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization (elderly, obese, and/or with specific comorbidities). The EUA criteria exclude patients who require oxygen for the treatment of COVID-19 and patients already hospitalized for the treatment of COVID-19. We will use data collected for routine clinical care, including data entered into the electronic medical record and from follow-up calls. INTERVENTION AND COMPARATOR: The interventions are the COVID-19 specific mABs authorized by the EUAs. All aspects of mAB treatment, including eligibility criteria, dosing, and post-infusion monitoring, are as per the EUAs. As a comparative effectiveness trial, all patients receive mAB treatment, and the interventions are compared against each other. When U.S. government mAB policies change (e.g., FDA grants or revokes EUAs), UPMC Health System policies and the evaluated mAB interventions will accordingly change. From November 2020 to February 2021, FDA issued EUAs for three mAB treatments (bamlanivimab; bamlanivimab and etesevimab; and casirivimab and imdevimab), and at trial launch on March 10, 2021 we evaluated all three. Due to a sustained increase in SARS-CoV-2 variants in the United States resistant to bamlanivimab administered alone, on March 24, 2021 the U.S. Government halted distribution of bamlanivimab alone, and UPMC accordingly halted bamlanivimab monotherapy on March 31, 2021. On April 16, 2021, FDA revoked the EUA for bamlanivimab monotherapy. At the time of manuscript submission, we are therefore evaluating the two mAB treatments authorized by EUAs (bamlanivimab and etesevimab; and casirivimab and imdevimab). MAIN OUTCOMES: The primary outcome is total hospital free days (HFD) at 28 days after mAB administration, calculated as 28 minus the number of days during the index stay (if applicable - e.g., for patients admitted to hospital after mAB administration in the emergency department) minus the number of days readmitted during the 28 days after treatment. This composite endpoint captures the number of days from the day of mAB administration to the 28 days thereafter, during which the patient is alive and free of hospitalization. Death within 28 days is recorded as -1 HFD, as the worst outcome. RANDOMISATION: We will start with equal allocation. Due to uncertainty in sample size, we will use a Bayesian adaptive design and response adaptive randomization to ensure ability to provide statistical inference despite variable sample size. When mABs are ordered by UPMC physicians as a generic referral order, the order is filled by UPMC pharmacy via therapeutic interchange. OPTIMISE-C19 provides the therapeutic interchange via random allocation. Infusion center operations teams and pharmacists use a mAB assignment application embedded in the electronic medical record to determine the random allocation. BLINDING (MASKING): This trial is open-label. However, outcome assessors conducting follow-up calls at day 28 are blinded to mAB assignment, and investigators are blinded to by-mAB aggregate outcome data until a statistical platform trial conclusion is reached. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size will be determined by case volume throughout the course of the pandemic, supply of FDA authorized mABs, and by that needed to reach a platform trial conclusion of inferiority, superiority, or futility of a given mAB. The trial will continue as long as more than one mAB type is available under EUA, and their comparative effectiveness is uncertain. TRIAL STATUS: Protocol Version 1.0, February 24, 2021. Recruitment began March 10, 2021 and is ongoing at the time of manuscript submission. The estimated recruitment end date is February 22, 2022, though the final end date is dependent on how the pandemic evolves, mAB availability, and when final platform trial conclusions are reached. As noted above, due to U.S. Government decisions, UPMC Health System halted bamlanivimab monotherapy on March 31, 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04790786 . Registered March 10, 2021 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Outcomes After Sentinel Lymph Node Biopsy and Radiotherapy in Older Women With Early-Stage, Estrogen Receptor-Positive Breast Cancer.

Importance: Overtreatment of early-stage breast cancer with favorable tumor biology in older patients may be harmful without affecting recurrence and survival. Guidelines that recommend deimplementation of sentinel lymph node biopsy (SLNB) (Choosing Wisely) and radiotherapy (RT) (National Comprehensive Cancer Network) have been published. Objective: To describe the use rates and association with disease recurrence of SLNB and RT in older women with breast cancer. Design, Setting, and Participants: This cohort study obtained patient and clinical data from an integrated cancer registry and electronic health record of a single health care system in Pennsylvania. The cohort was composed of consecutive female patients 70 years or older who were diagnosed with early-stage, estrogen receptor-positive, ERBB2 (formerly HER2)-negative, clinically node-negative breast cancer from January 1, 2010, to December 31, 2018, who were treated at 15 community and academic hospitals within the health system. Exposures: Sentinel lymph node biopsy and adjuvant RT. Main Outcomes and Measures: Primary outcomes were 5-year locoregional recurrence-free survival (LRFS) rate and disease-free survival (DFS) rate after SLNB and after RT. Secondary outcomes included recurrence rate, subgroups that may benefit from SLNB or RT, and use rate of SLNB and RT over time. Propensity scores were used to create 2 cohorts to separately evaluate the association of SLNB and RT with recurrence outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HRs). Results: From 2010 to 2018, a total of 3361 women 70 years or older (median [interquartile range {IQR}] age, 77.0 [73.0-82.0] years) with estrogen receptor-positive, ERBB2-negative, clinically node-negative breast cancer were included in the study. Of these women, 2195 (65.3%) received SLNB and 1828 (54.4%) received adjuvant RT. Rates of SLNB steadily increased (1.0% per year), a trend that persisted after the 2016 adoption of the Choosing Wisely guideline. Rates of RT decreased slightly (3.4% per year). To examine patient outcomes and maximize follow-up time, the analysis was limited to cases from 2010 to 2014, identifying 2109 patients with a median (IQR) follow-up time of 4.1 (2.5-5.7) years. In the propensity score-matched cohorts, no association was found between SLNB and either LRFS (HR, 1.26; 95% CI, 0.37-4.30; P = .71) or DFS (HR, 1.92; 95% CI, 0.86-4.32; P = .11). In addition, RT was not associated with LRFS (HR, 0.33; 95% CI, 0.09-1.24; P = .10) or DFS (HR, 0.99; 95% CI, 0.46-2.10; P = .97). Subgroup analysis showed that stratification by tumor grade or comorbidity was not associated with LRFS or DFS. Low absolute rates of recurrence were observed when comparing the groups that received SLNB (3.5%) and those that did not (4.5%) as well as the groups that received RT (2.7%) and those that did not (5.5%). Conclusions and Relevance: This study found that receipt of SLNB or RT was not associated with improved LRFS or DFS in older patients with ER-positive, clinically node-negative breast cancer. Despite limited follow-up time and wide 95% CIs, this study supports the continued deimplementation of both SLNB and RT in accordance with the Choosing Wisely and National Comprehensive Cancer Network guidelines.

Use of healthcare resources in patients with low back pain and comorbid depression or anxiety.

BACKGROUND CONTEXT: Psychological comorbidities are important prognostic factors for low back pain (LBP). To develop improved treatment paradigms, it is first necessary to characterize and determine current patterns of treatment in this population. PURPOSE: Identify how comorbid depression or anxiety in patients with LBP is related to use of healthcare resources. STUDY DESIGN/SETTING: Retrospective cohort study using electronic health records from outpatient offices at a large multisite academic medical center. PATIENT SAMPLE: Data from 513,088 unique patients seen between January 2010 and July 2020 (58.0% female, 52.6±19.5 years) with a diagnosis of LBP, indicated by predetermined ICD-9 and ICD-10 codes. OUTCOME MEASURES: Average self-reported pain scores, absolute differences and unadjusted risk ratios to compare opioid use, emergency department visits, hospitalizations, advanced imaging orders, spinal injections, and back surgeries between cohorts. METHODS: Clinical characteristics and data regarding use of healthcare resources were extracted from the electronic health record. Clinical features and patterns in healthcare utilization were determined for patients with depression or anxiety compared to those without. RESULTS: Depression or anxiety was coded for 21.4% of patients at first LBP visit. Those with depression or anxiety were more likely to be on opioids (unadjusted risk ratio: 1.22, CI: [1.22,1.23]), go to the emergency department (1.31 [1.30-1.33]), be hospitalized (1.15 [1.13, 1.17]), receive advanced imaging (1.09 [1.08, 1.11]), receive an epidural steroid injection (1.16 [1.15, 1.18]), and less likely to have back surgery (0.74 [0.72, 0.77]). Differences in pain scores for those with depression/anxiety compared to those without were not clinically significant. CONCLUSIONS: Depression/anxiety is associated with increased use of healthcare resources, and is not associated with clinically meaningful elevated pain scores. Limitations come from use of an aggregate data set and reliance on administrative coding.

Persistent sex disparities in implantable cardioverter-defibrillator therapy.

BACKGROUND: Clinical guidelines recommend cardioverter defibrillator implantation for patients with heart failure and reduced ejection fraction. Despite this, women and minorities have been less likely to receive implantable cardioverter-defibrillator (ICD) therapy than white men. We examined race and sex differences in ICD implantation in a recent cohort. METHODS: Using cross-sectional, retrospective analyses, we mined our health system's outpatient electronic medical records to assess age, race, sex, medications, and comorbidities for patients aged ≥18 years with ejection fraction ≤ 35% during 2014. While adjusting for confounding variables such as medications, age, and comorbidities, we conducted a multivariable logistic regression assessing whether racial and sex differences in ICD therapy persist. RESULTS: Among 5,156 outpatients with ejection fraction ≤35%, 1,681 (32.6%) patients had an ICD present at the time of their index outpatient visit in 2014. Women were less likely to have an ICD than men (25.0% vs 36.3%, P < 0.01), and black patients were less likely to have an ICD than white patients (28.0% vs 33.2%, P  =  0.02). In adjusted multivariable analyses, women were less like to have ICDs (adjusted odds ratio [OR]  =  0.68, 95% confidence interval [CI], 0.58-0.79, P < 0.01) but the race difference dissipated (adjusted OR for black race  =  0.86, 95% CI, 0.68-1.08, P  =  0.18). CONCLUSIONS: In this large, outpatient cohort, we have shown that sex differences in ICD therapy continue to exist, but the difference in ICD prevalence by race was attenuated. Dedicated studies are required to fully understand the causes of persistent sex differences in ICD therapy.

Reducing Surgical Infections and Implant Costs via a Novel Paradigm of Enhanced Physician Awareness.

BACKGROUND: Studies have demonstrated that physicians are often unaware of prescription drug, laboratory, diagnostic, and surgical supply costs. OBJECTIVE: To investigate the effects of increased physician awareness on infection incidence and surgical device cost containment. METHODS: Within our institution, physicians were informed of individual, independently adjudicated, craniotomy and ventricular shunt infection incidence and rankings among peers, after which a protocol aimed at reducing skin bacterial burden was implemented for craniotomies. Physicians were also made aware of the costs for shunts and dural substitutes as well as available alternatives. RESULTS: The combined craniotomy and ventricular shunt infection incidence significantly decreased by 37.5% from 3.2% over May 2011 to April 2015 (132 infections/4137 procedures) to 2.1% over May 2015 to April 2016 (26 infections/1250 procedures; P = .041). The average annual cost savings was $234 175 from preventing postoperative craniotomy infections and $121 125 from preventing postoperative ventricular shunt infections. Total supply costs of ventricular shunts significantly decreased by 26% from $2345 per procedure in fiscal year 2015 to $1747 per procedure in fiscal year 2016 (P < .001). Total supply cost of dural grafts significantly decreased by 54% from $191 per procedure in fiscal year 2015 to $88 per procedure in fiscal year 2016 (P < .001). In total, all initiatives in this study resulted in an estimated annual savings of $567 062. CONCLUSION: Physician awareness of outcomes and costs resulted in increasing the quality of care, while at the same time reducing the cost.