Patterns of Care in Maintenance Therapy in US Patients Undergoing Definitive Chemoradiation for Stage 3 Non-Small Cell Lung Cancer (NSCLC).

OBJECTIVE: The recommended treatment for patients with unresectable stage 3 non-small cell lung cancer (NSCLC) is definitive chemoradiation followed by 1 year of maintenance durvalumab. Our objective was to assess the rate of maintenance durvalumab use after chemoradiation. METHODS: Analyses were conducted in both open claims (IQVIA pharmacy and medical claims data) and adjudicated closed claims (IQVIA PharMetrics Plus Health Plan Claims Database). Patients with a lung cancer diagnosis between November 2017 and November 2020 who received definitive chemoradiation were included. RESULTS: Of the 5802 NSCLC patients included in the open claims source, 1794 (31%) received durvalumab, 1403 (24%) received maintenance chemotherapy, and 2605 (45%) did not receive any maintenance therapy. Of the 239 NSCLC patients included in the closed claims source, 127 (53%) received durvalumab, 40 (17%) received maintenance chemotherapy, and 72 (30%) did not receive any maintenance therapy. The most common maintenance chemotherapy agents patients received were carboplatin, pemetrexed, and paclitaxel. CONCLUSIONS: The rate of durvalumab utilization was overall low in both the open and closed claims data sources (31% and 53%, respectively). It remains unknown what percent of eligible patients end up receiving durvalumab, as our analysis was unable to filter out patients who were unfit for durvalumab or if they had progression after chemoradiation. Future efforts are needed to increase maintenance durvalumab utilization and to determine how best to manage patients who are unfit for durvalumab.

Leveraging unstructured data to identify hereditary angioedema patients in electronic medical records.

BACKGROUND: The epidemiologic impact of hereditary angioedema (HAE) is difficult to quantify, due to misclassification in retrospective studies resulting from non-specific diagnostic coding. The aim of this study was to identify cohorts of patients with HAE-1/2 by evaluating structured and unstructured data in a US ambulatory electronic medical record (EMR) database. METHODS: A retrospective feasibility study was performed using the GE Centricity EMR Database (2006-2017). Patients with ≥ 1 diagnosis code for HAE-1/2 (International Classification of Diseases, Ninth Revision, Clinical Modification 277.6 or International Classification of Diseases, Tenth Revision, Clinical Modification D84.1) and/or ≥ 1 physician note regarding HAE-1/2 and ≥ 6 months' data before and after the earliest code or note (index date) were included. Two mutually exclusive cohorts were created: probable HAE (≥ 2 codes or ≥ 2 notes on separate days) and suspected HAE (only 1 code or note). The impact of manually reviewing physician notes on cohort formation was assessed, and demographic and clinical characteristics of the 2 final cohorts were described. RESULTS: Initially, 1691 patients were identified: 190 and 1501 in the probable and suspected HAE cohorts, respectively. After physician note review, the confirmed HAE cohort comprised 254 patients and the suspected HAE cohort decreased to 1299 patients; 138 patients were determined not to have HAE and were excluded. The overall false-positive rate for the initial algorithms was 8.2%. Across final cohorts, the median age was 50 years and > 60% of patients were female. HAE-specific prescriptions were identified for 31% and 2% of the confirmed and suspected HAE cohorts, respectively. CONCLUSIONS: Unstructured EMR data can provide valuable information for identifying patients with HAE-1/2. Further research is needed to develop algorithms for more representative HAE cohorts in retrospective studies.

Use of Low-Density Lipoprotein-Lowering Therapies Before and After PCSK9 Inhibitor Initiation.

Background Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are used to reduce low-density lipoprotein (LDL) cholesterol. PCSK9i use after initiation, as well as persistence with or alterations to other LDL-lowering therapy after PCSK9i initiation, is not well understood. Methods and Results We conducted a retrospective study of alirocumab or evolocumab (PCSK9i) new users from July 2015 to December 2017 in the MarketScan Early View database of US commercial insurance beneficiaries. We determined the prevalence of PCSK9i interruption (≥30-day gap in supply) and LDL-lowering therapy use in the year after PCSK9i initiation. The average age of 6151 patients initiating PCSK9i therapy was 63 years, 44.4% were women, and 76.8% had atherosclerotic cardiovascular disease. Overall, 52.2% (95% CI, 50.8%-53.7%) of patients had an interruption in PCSK9i therapy in the first year after treatment initiation and 62.5% remained on PCSK9i therapy at 1-year postinitiation. Also, 27.7% of patients were taking a statin at the time of PCSK9i initiation, with only 22.4% on statin therapy at 1 year after PCSK9i initiation. Ezetimibe use decreased from 20.9% at the time of PCSK9i initiation to 12.0% a year later. By 1 year after PCSK9i initiation, 44.0% of patients had experienced an interruption in all LDL-lowering therapies, and 26.6% were no longer on any LDL-lowering therapies. Conclusions After PCSK9i initiation, statins were often discontinued, whereas more than half of patients experienced an interruption in PCSK9i therapy. These results suggest that many new PCSK9i users may remain at high risk for cardiovascular events because of interruptions in LDL-lowering therapy.

Ophthalmic Manifestations of Facial Dog Bites in Children.

PURPOSE: To characterize ophthalmic manifestations and periocular injuries of pediatric facial dog bites. METHODS: A retrospective review of all children younger than 18 years who sought medical attention after a dog bite to the face between January 1, 2003 and May 22, 2014 was performed at a large tertiary pediatric hospital. Data on type and location of injury, surgical intervention, and complications were collected. RESULTS: A total of 1,989 children aged 0.19 to 17 years were identified with dog bites. Dog bites to the face occurred in most patients (n = 1, 414 [71%]). Of those children with facial dog bite injuries, 230 (16%) suffered ophthalmic manifestations. The average age was 4.3 years. Eyelid injuries occurred in 227 (99%) of children, 47 (20%) sustained canalicular system injuries, 3 (1.3%) suffered corneal abrasions, and 2 patients sustained facial nerve injury resulting in lagophthalmos. No patients suffered vision loss. Complications occurred in 32 patients (14%), with the most common being epiphora in 9 patients (28%), upper eyelid ptosis in 8 (25%), and prominent scar formation in 4 patients (13%). Thirteen children (5.7%) needed one or more secondary procedure to correct complications. CONCLUSIONS: The authors report the clinical features and management on the largest series of ophthalmic and periocular injuries associated with pediatric facial dog bites. These injuries occur in about 1 in 6 dog bites to the face and primarily involve the ocular adnexa. Despite early and appropriate surgical management, complications and the need for revision surgery are relatively common.

Prevalence of and risk for gastrointestinal bleeding and peptic ulcerative disorders in a cohort of HIV patients from a U.S. healthcare claims database.

The primary study objectives were to estimate the frequencies and rates of gastrointestinal bleeding and peptic ulcerative disorder in HIV-positive patients compared with age- and sex-matched HIV-negative subjects. Data from a US insurance claims database was used for this analysis. Among 89,207 patients with HIV, 9.0% had a GI bleed, 1.0% had an upper gastrointestinal bleed, 5.6% had a lower gastrointestinal bleed, 1.9% had a peptic ulcerative disorder diagnosis, and 0.6% had both gastrointestinal/peptic ulcerative disorder. Among 267,615 HIV-negative subjects, the respective frequencies were 6.9%, 0.6%, 4.3%, 1.4%, and 0.4% (p<0.0001 for each diagnosis subcategory). After combining effect measure modifiers into comedication and comorbidity strata, gastrointestinal bleeding hazard ratios (HRs) were higher for HIV-positive patients without comedication/comorbidity, and those with comedication alone (HR, 2.73; 95% confidence interval [CI], 2.62-2.84; HR, 1.59; 95% CI, 1.47-1.71). The rate of peptic ulcerative disorder among those without a history of ulcers and no comorbidity/comedication was also elevated (HR, 2.72; 95% CI, 2.48-2.99). Hazard ratios of gastrointestinal bleeding, and peptic ulcerative disorder without a history of ulcers were lower among patients infected with HIV with comedication/comorbidity (HR, 0.64; 95% CI, 0.56-0.73; HR, 0.46; 95% CI, 0.33-0.65). Rates of gastrointestinal bleeding plus peptic ulcerative disorder followed a similar pattern. In summary, the rates of gastrointestinal/peptic ulcerative disorder events comparing HIV-infected subjects to non-HIV-infected subjects were differential based on comorbidity and comedication status.

Sphenoid Wing Meningioma With Extraocular Muscle Involvement Mimicking Idiopathic Orbital Inflammation.

Meningiomas are slow growing, typically benign, tumors originating from arachnoid cap cells. Specifically, sphenoid wing or spheno-orbital meningiomas infiltrate the lesser wing of the sphenoid, lateral orbital wall, and orbital roof with occasional extension to the superior orbital fissure, optic canal, anterior clinoid process, and middle cranial fossa where neurologic and ophthalmologic functions are impaired by compressive injury. The extraocular muscles are rarely involved. The authors present a rare case of an spheno-orbital meningioma causing extraocular muscle enlargement mimicking idiopathic orbital inflammation and highlight important diagnostic clues to meningioma.

Orbital Metastasis Is Associated With Decreased Survival in Stage M Neuroblastoma.

BACKGROUND: Approximately 30% of patients with metastatic (stage M) neuroblastoma present with periorbital ecchymosis from orbital osseous disease. Though locoregional disease is staged by imaging, the prognostic significance of metastatic site in stage M disease is unknown. We hypothesize that, compared to nonorbital metastasis, orbital metastasis is associated with decreased survival in patients with stage M neuroblastoma, and that periorbital ecchymosis reflects location and extent of orbital disease. PROCEDURE: Medical records and imaging from 222 patients with stage M neuroblastoma seen at St. Jude Children's Research Hospital between January 1995 and May 2009 were reviewed. Thirty-seven patients were <18 months of age at diagnosis and 185 were ≥18 months of age. Overall survival (OS) and 5-year survival (5YS) were compared for patients with and without orbital, calvarial and nonorbital osseous metastasis, and with and without periorbital ecchymosis (log-rank test). Associations of periorbital ecchymosis with orbital metastasis location/extent were explored (Fisher's exact test, t-test). RESULTS: In patients ≥18 months of age, only orbital metastasis was associated with decreased 5YS (P = 0.0323) and OS (P = 0.0288). In patients <18 months of age, neither orbital, calvarial, or nonorbital bone metastasis was associated with OS or 5YS. Periorbital ecchymosis was associated with higher number of involved orbital bones (P = 0.0135), but not location or survival. CONCLUSIONS: In patients ≥ 18 months of age with stage M neuroblastoma, orbital metastatic disease is associated with decreased 5YS and OS. In future clinical trials, orbital disease may be useful as an imaging-based risk factor for substratification of stage M neuroblastoma.

Postoperative shift in ocular alignment following single vertical rectus recession on adjustable suture in adults without thyroid eye disease.

PURPOSE: To determine whether overcorrection shifts occur after vertical rectus recession on adjustable suture in the absence of thyroid eye disease. METHODS: The medical records of patients without thyroid eye disease who underwent vertical rectus recession surgery from 2001 to 2008 were retrospectively reviewed for shifts in alignment between suture adjustment at postoperative day 1 and 2 months' follow-up. Superior rectus and inferior rectus recessions were compared. In addition, we compared the use of a nonabsorbable polyester suture to an absorbable polyglactin 910 suture in nonthyroid patients undergoing inferior rectus recessions. RESULTS: A total of 59 patients were included (superior rectus, 30; inferior rectus, 29). We found a mean undercorrection shift of 1.1 (range, 17.5(Δ) undercorrection to 16(Δ) overcorrection) and 1.0(Δ) (range, 12(Δ) undercorrection shift to 6(Δ) overcorrection shift) for superior and inferior rectus recessions, respectively, between 1 day and 2 months postoperatively. CONCLUSIONS: There was no trend toward overcorrection following unilateral vertical rectus adjustable suture recessions in patients without thyroid eye disease, suggesting that thyroid myopathy may account for overcorrection shifts seen with this surgery.

Combination topical therapy for conjunctival primary acquired melanosis with atypia and periocular lentigo maligna.

PURPOSE: To report the case of a patient who initially presented with primary acquired melanosis (PAM) without atypia of the conjunctiva and later developed lentigo maligna of the eyelids and PAM with atypia of the conjunctiva. We illustrate the utility of combination topical therapy with adjunctive cryotherapy to treat extensive eyelid and conjunctival lesions. METHODS: Case report with a review of the current literature. RESULTS: Combination of imiquimod 5% cream (Aldara, 3M Pharmaceuticals) and cryotherapy for periorbital lentigo maligna with topical interferon-α2b for conjunctival PAM with atypia led to clinical resolution of pigmented lesions for 21 months. CONCLUSIONS: In our experience, combination topical therapy provides an effective alternative to surgery with superior cosmetic and functional outcomes.

Predicting the need for surgical intervention in pediatric orbital cellulitis.

PURPOSE: To investigate the predictive value of the complete ophthalmic examination at first presentation in foreseeing the need for surgery in patients with pediatric orbital cellulitis. DESIGN: Retrospective observational case series. METHODS: We reviewed 136 cases of radiographically confirmed orbital cellulitis between 2004 and 2012 at Children's Hospital Colorado. The presenting ophthalmic examinations, imaging results, medical and surgical interventions, and clinical complications were recorded. The main outcome measures were ophthalmic examinations on presentation, medical or surgical interventions, and complications. RESULTS: The median age was 6.5 years. Of the patients, 56 (41%) underwent surgical intervention, and 80 patients (59%) were managed medically. Patients requiring surgery had higher rates of extraocular motility (EOM) restriction (78.6% vs 38.8% P<0.01), proptosis (64.3% vs 21.2%, P<0.01), elevated intraocular pressure (IOP) (35.7% vs 12.5%, P<0.01), and age over 9 years (58.9% vs 20.0%, P<0.01). Using any combination of the above risk factors at presentation, the probability of surgical intervention increases from 7% (95% confidence interval [CI] 1%-13%) with zero risk factors to 95% (95% CI 89%-100%) with 4 risk factors. CONCLUSIONS: In pediatric orbital cellulitis, the likelihood of surgical intervention can be estimated accurately based on the ophthalmic examination on initial presentation to the hospital. Risk factors for surgery include age older than 9 years, proptosis, EOM restriction, and elevated IOP. These factors may be used to identify patients at high risk for failure of medical management early in the clinical course.

Outcomes of endonasal dacryocystorhinostomy without mucosal flap preservation.

PURPOSE: Dacryocystorhinostomy (DCR) is the standard procedure for the treatment of acquired nasolacrimal duct obstruction (NLDO) that can be performed through an external or endonasal approach. Both techniques create a fistula from the lacrimal sac into the nasal cavity via a bony osteotomy. Historically, external DCR has been considered the gold standard; however, recent reports suggest endonasal DCR is an effective alternative. There are numerous variations of endonasal DCR described in the literature that report variable success rates. The purpose of this study is to describe the approach and success rate with endonasal DCR in which nasal mucosa, bone, and lacrimal sac mucosa are sequentially removed. METHODS: The authors retrospectively reviewed cases of endonasal DCR from 2004 to 2011 from 2 institutions (the University of California, San Diego, California, and the Fante Eye and Face Center in Denver, Colorado, U.S.A.). Patients with a history of epiphora and NLDO confirmed with punctal irrigation were included. Exclusion criteria were the presence of canalicular obstruction, history of orbital trauma, and prior DCR surgery. Success was defined as subjective relief of epiphora and confirmation of ostium patency with irrigation. RESULTS: A total of 324 patients (74 men, 250 women; mean age 59.3) encompassing 407 endonasal DCR cases were included in the study. The total case success rate was 92.2% with an average follow-up time of 91.5 days. Revision surgery was performed in 7 of the failed cases and resulted in success in 6 of these cases. CONCLUSIONS: Endonasal DCR is a simple and effective approach to surgically treat NLDO and offers success rates comparable with external DCR.

Approaches to antifungal therapies and their effectiveness among patients with cryptococcosis.

The goal of this study was to determine the degree to which the persistence of cryptococcosis, overall 1-year mortality, and 1-year mortality due to cryptococcosis were influenced by initial antifungal treatment regimen in a cohort of adults with cryptococcosis treated at a tertiary care medical center. Risk factors, underlying conditions, treatment, and mortality information were obtained for 204 adults with cryptococcosis from Duke University Medical Center (DUMC) from 1996 to 2009. Adjusted risk ratios (RR) for persistence and hazard ratios (HR) for mortality were estimated for each exposure. The all-cause mortality rate among patients with nonsevere disease (20%) was similar to that in the group with disease (26%). However, the rate of cryptococcosis-attributable mortality with nonsevere disease (5%) was much lower than with severe disease (20%). Flucytosine exposure was associated with a lower overall mortality rate (HR, 0.4; 95% confidence interval [CI], 0.2 to 0.9) and attributable mortality rate (HR, 0.5; 95% CI, 0.2 to 1.2). Receiving a nonrecommended antifungal regimen was associated with a higher relative risk of persistent infection at 4 weeks (RR, 1.9; 95% CI, 0.9 to 4.3), and the rate of attributable mortality among those not receiving the recommended dose of initial therapy was higher than that of those receiving recommended dosing (HR, 2.3; 95% CI, 1.0 to 5.0). Thus, the 2010 Infectious Diseases Society of America (IDSA) guidelines are supported by this retrospective review as a best-practice protocol for cryptococcal management. Future investigations should consider highlighting the distinction between all-cause mortality and attributable mortality so as not to overestimate the true effect of cryptococcosis on patient death.

Bilateral Candida and atypical mycobacterial infection after frontalis sling suspension with silicone rod to correct congenital ptosis.

In this case report, the authors describe an unusual complication of a frontalis sling suspension with silicone rods. A 5-year-old girl with blepharophimosis syndrome underwent frontalis sling suspension using an open sky technique. Four weeks after surgery, she was noted to have pustules over both upper eyelids and eyebrows. Cultures from the surgical sites grew Mycobacterium chelonae and Candida parapsilosis. Intravenous antibiotics and antifungals and sling explantation were curative. One month after sling explantation, the patient maintained an adequate marginal reflex distance 1. Atypical mycobacterial and Candida infection should be considered in the differential diagnoses of postoperative infection after frontalis sling suspension with silicone rods.

Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative/non-transplant.

BACKGROUND: The Infectious Disease Society of America (IDSA) 2010 Clinical Practice Guidelines for the management of cryptococcosis outlined three key populations at risk of disease: (1) HIV-infected, (2) transplant recipient, and (3) HIV-negative/non-transplant. However, direct comparisons of management, severity and outcomes of these groups have not been conducted. METHODOLOGY/PRINCIPAL FINDINGS: Annual changes in frequency of cryptococcosis diagnoses, cryptococcosis-attributable mortality and mortality were captured. Differences examined between severe and non-severe disease within the context of the three groups included: demographics, symptoms, microbiology, clinical management and treatment. An average of nearly 15 patients per year presented at Duke University Medical Center (DUMC) with cryptococcosis. Out of 207 study patients, 86 (42%) were HIV-positive, 42 (20%) were transplant recipients, and 79 (38%) were HIV-negative/non-transplant. HIV-infected individuals had profound CD4 lymphocytopenia and a majority had elevated intracranial pressure. Transplant recipients commonly (38%) had renal dysfunction. Nearly one-quarter (24%) had their immunosuppressive regimens stopped or changed. The HIV-negative/non-transplant population reported longer duration of symptoms than HIV-positive or transplant recipients and 28% (22/79) had liver insufficiency or underlying hematological malignancies. HIV-positive and HIV-negative/non-transplant patients accounted for 89% of severe disease cryptococcosis-attributable deaths and 86% of all-cause mortality. CONCLUSIONS/SIGNIFICANCE: In this single-center study, the frequency of cryptococcosis did not change in the last two decades, although the underlying case mix shifted (fewer HIV-positive cases, stable transplant cases, more cases with neither). Cryptococcosis had a relatively uniform and informed treatment strategy, but disease-attributable mortality was still common.

Orbital implants for fracture repair.

PURPOSE OF REVIEW: To review the latest advancements in implant materials for orbital fracture repair, including analysis of the last year in research. RECENT FINDINGS: Advances in the manufacture of highly biocompatible alloplastic materials offer an alternative to traditional autologous implants for orbital fracture repair. The emergence of the composite implant offers the stability and strength of traditional titanium mesh, while the porous polyethylene shell allows for greater fibrovascular integration and a potential for decreased risk of postoperative complications. Development of copolymers and biomechanical constructs for the delivery of bone stimulating proteins and stem cells serve to restore orbital volume after fracture repair through stimulation of the patient's own tissue. These recent developments are promising; however, their safety and efficacy have not been verified in humans. SUMMARY: The appropriate choice of orbital implant for fracture repair ensures appropriate orbital reconstruction in an effort to alleviate diplopia, enophthalmos, orbital dystopia, and extraocular muscle restriction.