Real-World Treatment Patterns and Clinical Outcomes Among Patients With Advanced Renal Cell Carcinoma.

BACKGROUND: Nearly 30% of new renal cell carcinoma (RCC) cases are diagnosed at an advanced or metastatic stage. Recent approvals of immunotherapies (IO) have significantly impacted patient care, but real-world outcomes of these treatments have not been widely evaluated. METHODS: Eligible physicians abstracted demographic and clinical data from patient medical records for patients with advanced clear and non-clear cell RCC (aRCC) who initiated treatment between January 1, 2018, and December 31, 2020. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. A multivariate Cox regression model was developed to assess the impact of treatment category on clinical outcomes while controlling for International Metastatic RCC Database Consortium (IMDC) risk category, histology, and other patient characteristics. RESULTS: A total of 498 patients were included (201 from US, 62 from Canada, 58 from UK, 59 from France, 58 from Germany, 60 from Spain). Of these, 250 received tyrosine kinase inhibitor (TKI) monotherapy, 197 received immunotherapy (IO) combination (119 IO+TKI, 78 IO+IO), and 32 received IO monotherapy as first-line treatment for aRCC; 19 patients received various other regimens. 16% of patients had a favorable IMDC risk score. Based on results of multivariable Cox regression, PFS (hazard ratio [HR] [95% confidence interval (CI)]: 0.50 [0.36-0.72]) (P < .001) and time to next treatment (TTNT) were significantly longer (HR [95% CI]: 0.54 [0.39-0.73]) (P < .001) for patients treated with IO combination versus TKI monotherapy. IO combination had a numerically reduced, but statistically insignificant, risk of death versus TKI monotherapy (HR: 0.66; P = .114). IO+TKI combination was associated with significantly longer PFS and reduced risk of progression (HR: 0.52; P = .04) versus IO+IO combination; similar results were observed for TTNT (HR: 0.57; P = .03). CONCLUSION: Our evaluation of real-world treatment outcomes in aRCC revealed that IO + TKI combination is associated with improved PFS and prolonged TTNT compared with TKI monotherapy and IO+IO combination.

Recent Trends in Hypoparathyroidism-Related Inpatient and Emergency Department Admissions and Costs in the United States.

Hypoparathyroidism (HypoPT) is a rare disease associated with high morbidity. Its economic impact is not well understood. This retrospective, cross-sectional study used data from the United States-based National Inpatient Sample and the Nationwide Emergency Department Sample from 2010 to 2018 to quantify overall trends in number, cost, charges, and length of stay (LOS) for inpatient hospitalizations and number and charges for emergency department (ED) visits for HypoPT-related and for non-HypoPT-related causes. Additionally, the study estimated the marginal effect of HypoPT on total inpatient hospitalization costs and LOS as well as ED visit charges. Over the observed period, a mean of 56.8-66.6 HypoPT-related hospitalizations and 14.6-19.5 HypoPT-related ED visits were recorded per 100 000 visits per year. Over this period, the rate of HypoPT-related inpatient hospitalizations and ED visits increased by 13.5% and 33.6%, respectively. The mean LOS for HypoPT-related hospitalizations was consistently higher than for non-HypoPT-related causes. Total annual HypoPT-related inpatient hospitalization costs increased by 33.6%, and ED visit charges increased by 96.3%. During the same period, the annual costs for non-HypoPT-related hospitalizations and charges for ED visits increased by 5.2% and 80.3%, respectively. In all years, HypoPT-related hospital encounters resulted in higher charges and costs per individual visit than non-HypoPT-related encounters. The marginal effect of HypoPT on inpatient hospitalization costs and LOS, and on ED charges, increased over the period of observation. This study demonstrated that HypoPT was associated with substantial and increasing healthcare utilization in the United States between 2010 and 2018.

Evaluating Real-World Characteristics of Patients With Advanced Urothelial Carcinoma Eligible for Avelumab Maintenance Therapy: A Multicountry Retrospective Medical Chart Review.

INTRODUCTION: Urothelial carcinoma (UC) is a malignancy of the urothelium that encompasses the renal pelvis, bladder, and urethra. Current treatment guidelines for advanced (ie, locally advanced or metastatic) UC recommend using avelumab maintenance therapy in patients with nonprogressive disease following first-line platinum-based chemotherapy. This study aimed to assess the representativeness of the patient population in the JAVELIN Bladder 100 (JB-100) trial, which examined the efficacy and safety of avelumab first-line maintenance, vs. real-world patients with advanced UC that had not progressed with first-line platinum-based chemotherapy treated between 2015 and 2018 by reviewing demographic and clinical characteristics. PATIENTS AND METHODS: A medical chart review (MCR) study collected demographics and treatment characteristics for patients with advanced UC in the United States, the United Kingdom, and France. Data were analyzed descriptively for review with data collected from patients enrolled in JB-100. RESULTS: Clinical characteristics were consistent between JB-100 and the MCR. Most patients were male, received 4 to 6 cycles of platinum-based chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients in the MCR had either stable disease or a response with platinum-based chemotherapy (∼75% achieved a complete or partial response). Fewer than half (42.5%) of all patients in the MCR received subsequent therapy. CONCLUSION: Patient demographics, clinical characteristics, and treatment patterns from a MCR of patients with advanced UC that had not progressed following first-line platinum-based chemotherapy appeared similar to data from patients enrolled in JB-100. Future studies should examine whether real-world outcomes are consistent with findings from JB-100. GOV IDENTIFIER: NCT02603432.

Treatment and resource utilization for menopausal symptoms in the United States: a retrospective review of real-world evidence from US electronic health records.

OBJECTIVE: The aim of this study was to generate real-world evidence documenting use of prescription and nonprescription therapies recorded by health care providers for women experiencing vasomotor symptoms (VMS) associated with menopause. METHODS: This noninterventional, retrospective, observational cohort study used data from US patient medical records. Participating health care providers were gynecologists, internal medicine/family physicians, or advanced practice providers who typically saw three or more women per week presenting with menopausal symptoms and could identify eligible medical records; providers were recruited from local medical association directories and from listings from previously conducted research. Eligible women presented January 2016 through December 2019, were 40 to 60 years of age, and reported experiencing bothersome hot flashes at least twice within 24 hours. RESULTS: A total of 283 health care providers provided data for 1,016 women. The most common symptoms at initial presentation were hot flashes (91.2%), sleep problems (49.9%), and vaginal dryness (47.0%). At least one therapy for menopausal symptoms was recorded for 883 women (86.9%), and 611 (60.1%) had documentation of prescription medication, most commonly hormone therapy (70.4%). Nearly 40% of women had no prescription medication documented, and approximately 13% had no therapy documented. Despite experiencing bothersome menopausal symptoms, approximately 50% delayed seeking care for more than 6 months. Women had a mean of 2.1 (SD, 2.0) office visits related to menopause from initial presentation to completion of review, and health care resource utilization did not vary by treatment status. Subgroup analyses indicated nominal differences in treatment use across ethnic groups and varying prescribing patterns for menopausal symptoms by practitioner type and US region. CONCLUSIONS: A high proportion of women with VMS remain untreated even when experiencing bothersome symptoms of menopause. Improved management of VMS is required to provide relief from the symptoms effectively and safely.

Diagnostic characteristics, treatment patterns, and clinical outcomes for patients with advanced/metastatic medullary thyroid cancer.

BACKGROUND: Medullary thyroid cancer (MTC) accounts for approximately 1.6% of new cases of thyroid cancer. The objective of this study was to describe patient characteristics, biomarker testing, treatment patterns, and clinical outcomes among patients with advanced/metastatic MTC in a real-world setting in the United States and to identify potential gaps in the care of these patients. METHODS: Selected oncologists retrospectively reviewed medical records of patients aged ≥ 12 years diagnosed with advanced MTC. Patients must have initiated ≥ 1 line of systemic treatment for advanced/metastatic MTC between January 2013-December 2018 to be eligible. Patient characteristics, biomarker testing, and treatment patterns were summarized descriptively; progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: The 203 patients included in this study had a mean (SD) age of 52.2 (10.4) years; mean (SD) duration of follow-up from start of first-line treatment was 24.5 (16.0) months. Most patients (82.8%) were initially diagnosed with stage IVA, IVB, or IVC disease. Among all patients, 121 (59.6%) had testing for RET mutations, of whom 37.2% had RET-mutant MTC. The RET-mutation type was reported for 28 patients; the most common mutations reported were M918T (64.3%) and C634R (32.1%). Of the 203 patients, 75.9% received only one line of systemic treatment for advanced disease, and 36% were still undergoing first-line therapy at the time of data extraction. Cabozantinib (30.0%), vandetanib (30.0%), sorafenib (17.2%), and lenvatinib (4.9%) were the most common first-line treatments. Among 49 patients who received second-line treatment, most received cabozantinib (22.4%), vandetanib (20.4%), lenvatinib (12.2%), or sunitinib (12.2%). Median PFS (95% confidence interval [CI]) from start of first- and second-line treatments was 26.6 months (20.8-60.8) and 15.3 months (6.6-not estimable [NE]), respectively. Median OS from initiation of first- and second-line treatment was 63.8 months (46.3-NE) and 22.4 months (12.4-NE), respectively. CONCLUSIONS: For the treatment of advanced/metastatic MTC, no specific preference of sequencing systemic agents was observed in the first- and second-line settings. Considering the recent approval of selective RET inhibitors for patients with RET-mutant MTC, future research should investigate how treatment patterns evolve for these patients.

Referral and adjuvant treatment patterns after nephrectomy in high-risk locoregional renal cell carcinoma.

BACKGROUND: It is unclear whether patients with renal cell carcinoma (RCC) are routinely assessed for recurrence risk post-nephrectomy and whether patients at high recurrence risk are seen by providers who can evaluate candidacy for adjuvant systemic therapy (AST) and clinical trials. MATERIALS AND METHODS: We identified all patients with locoregional RCC who underwent nephrectomy via an institutional database within Duke University Health System between 1 April 2015 and 31 December 2019. Medical records were reviewed to identify patient characteristics, post-nephrectomy referrals, treatment, and follow-up. Patients with tumor stage ≥3 and grade ≥2, regional lymph node metastasis, or both, were classified as high recurrence risk. RESULTS: Of 618 patients with locoregional RCC who underwent nephrectomy, 136 (22%) had high recurrence risk. Of those, 25 patients with high-risk disease (18%) were referred to medical oncology for discussion of AST; 23 (92%) of these referrals took place in 2018-2019. One patient received adjuvant sunitinib and two patients participated in adjuvant immunotherapy trials. The decision not to receive AST was primarily made by the oncologist in 10 (46%), the patient in 8 (36%), and unrecorded in 4 (18%) of 22 cases, for multiple reasons. Individual surgeons referred high-risk patients for discussion of AST with varying frequency, ranging from 0% to 100% in 2019. CONCLUSIONS: Despite increasing number of patients with locoregional RCC at high recurrence risk referred to medical oncologists after nephrectomy, few patients received AST, including participation in clinical trials. With increasing AST options and ongoing clinical trials in this space, these findings highlight the need for continued efforts at identifying effective AST and referring patients most likely to benefit to medical oncologists. ClinicalTrials.gov, NCT04309617.

Treatment practices and costs among patients with psoriatic arthritis: A Japanese hospital claims database analysis.

OBJECTIVE: Assess patient characteristics, real-world treatment patterns, and health care resource utilization (HCRU) among patients with psoriatic arthritis (PsA) in Japan. METHODS: Patients diagnosed with PsA from April 2009 through July 2017 were identified from the Medical Data Vision database. Patient characteristics, treatment patterns, and HCRU were evaluated for these patients. RESULTS: A total of 639 patients met inclusion criteria and were included in the analysis for patients with a PsA diagnosis. Over 12 months following diagnosis, patients received oral NSAIDs (61.7%), conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (55.1%), corticosteroids (35.1%), topical NSAIDs (34.0%), adalimumab (14.7%), infliximab (9.7%), secukinumab (5.0%), ustekinumab (4.5%), ixekizumab (1.6%), and golimumab (1.6%). A total of 227 (35.5%) patients initiated biologic DMARDs (bDMARDs) over the median 25.2 months of study follow-up. Compared with the overall group of patients diagnosed with PsA, patients who initiated bDMARDs had higher median total per-patient health care costs ($27,772 vs. $11,316), lower median per-patient hospitalization costs ($31,164 vs. $39,359), and fewer median hospital days per admission (8.0 vs. 12.0 days). CONCLUSION: This study presents knowledge of the current state of patient characteristics, treatment patterns, HCRU, and costs among patients with PsA in Japan. Considering the relatively recent guideline recommendations, the preliminary treatment patterns suggest physicians may be following treatment guidelines.

Treatment patterns and health care resource utilization among Japanese patients with ankylosing spondylitis: A hospital claims database analysis.

OBJECTIVES: To understand the current state of treatment patterns and health care resource utilization among patients in Japan with ankylosing spondylitis (AS) managed in the real-world setting. METHODS: Patient records from the Medical Data Vision database were analyzed to identify patients with ICD-10 AS from April 2009 through July 2017. Measures evaluated included demographic, clinical, and other characteristics at diagnosis; treatment patterns; health care resource utilization; and costs. RESULTS: Four hundred and seventeen patients met the study's inclusion criteria. Treatments observed during the first year after the initial AS diagnosis included nonsteroidal anti-inflammatory drugs (79.6%), corticosteroids (39.3%), methotrexate (22.3%), sulfasalazine (16.8%), adalimumab (14.2%), and infliximab (12.2%). At any time during the mean 33 months of study follow-up, biologic disease-modifying antirheumatic drugs (bDMARDs) were initiated by 115 patients. During the study follow-up, patients who initiated bDMARDs had higher median total per-patient annual health care costs ($26,937 vs $15,323), lower median per-patient hospitalization costs ($29,817 vs. $39,509), and fewer median hospital days per admission (7.0 vs. 11.0 days) compared with the overall group of patients diagnosed with AS. CONCLUSION: This database study provides knowledge of patient characteristics, treatment patterns, HCRU, and costs for patients with AS in Japan. The study outcomes demonstrate a need for increased awareness of proper AS management.

The adult vaccination landscape in the United States during the Affordable Care Act era: Results from a large retrospective database analysis.

BACKGROUND: Early provisions of the Affordable Care Act (ACA) reduced financial barriers to preventive care, including routinely recommended vaccines; however, vaccination coverage remains suboptimal. This study examined characteristics of routine adult vaccinations and potential missed opportunities for vaccinations through the lens of healthcare resource utilization among adults in the ACA era. METHODS: This was a retrospective analysis of healthcare claims from the Truven Health MarketScan Commercial Claims and Encounters (CCAE), Medicare Supplemental (MS), and Multi-State Medicaid databases among adults aged 19 years or older. Influenza, Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis), herpes zoster (HZ), and pneumococcal vaccinations were identified between 2011 and 2016. Potential missed opportunities were defined as well-visits at which individuals were age-eligible for vaccination but did not receive it, assessed during recommended windows for each vaccine. Missed encounters were defined as having no well-visits. Multivariable logistic regression was used to identify factors associated with vaccination and potential missed opportunities. RESULTS: Family/internal medicine and unknown/other providers administered most influenza, Tdap, and pneumococcal vaccinations, for the CCAE/MS and Medicaid cohorts, respectively. HZ vaccinations were primarily administered through pharmacies. The proportion of vaccination events increased in the pharmacy setting between 2011 and 2016. Having preventive care visits, non-well-visits, and receiving most care from a family/internal medicine practitioner were associated with increased odds of vaccination. Missed encounters were common in Medicaid enrollees. Potential missed opportunities were more prevalent in the CCAE/MS cohort than among Medicaid enrollees. Having non-well-visits was associated with a reduced likelihood of having a missed opportunity. CONCLUSION: Since the ACA implementation, preventive care among adults was sporadic. Many adults had limited opportunities for vaccination. The large prevalence of missed opportunities suggests vaccination uptake could be improved. Better support for vaccination or referrals for providers who may not traditionally vaccinate could improve vaccine uptake.

Corrigendum to: Longitudinal, Nationwide, Cohort Study to Assess Incidence, Outcomes, and Costs Associated With Complicated Urinary Tract Infection.

[This corrects the article DOI: 10.1093/ofid/ofz446.].

Use of Antifungals and Outcomes Among Inpatients at Risk of Invasive Aspergillosis or Mucormycosis in the USA: A Retrospective Cohort Study.

INTRODUCTION: Prophylaxis and treatment of invasive aspergillosis (IA) and mucormycosis (IM) within a real-world US inpatient setting is undocumented since the introduction of isavuconazole. This retrospective medical record review aimed to describe characteristics, triazole use, and outcomes among inpatients across the USA who initiated antifungal monotherapy (AFMT) as prophylaxis or treatment of IA/IM. METHODS: A convenience sample of US physicians abstracted data from randomly selected records of hospitalized patients aged ≥ 18 years initiating AFMT (amphotericin B, isavuconazole, voriconazole, or posaconazole) as prophylaxis or treatment of IA/IM between 2013 and 2017. Retrieved data included background characteristics, dosage and duration of AFMT, healthcare resource use, and survival. Characteristics and outcomes were compared (prophylaxis vs treatment) using Fisher's exact and one-way analysis of variance tests where applicable. Exploratory Kaplan-Meier analyses described overall and inpatient survival. RESULTS: Physicians (n = 23) retrieved 124 patient records (43 prophylaxis; 81 treatment). Median duration of first-line AFMT was 14 days (range 1-603 days) and 19 days (range 3-351 days) in the prophylaxis and treatment groups, respectively. One patient received second-line therapy. Median duration of hospitalization was 29 days (range 4-259 days) and 31 days (range 6-980 days) in the prophylaxis and treatment groups, respectively. Admission to intensive care occurred in 14% and 52% of patients in the prophylaxis and treatment groups, respectively. At the time of data retrieval, overall and inpatient survival rates in the prophylaxis group were 88% and 87%, respectively, and in the treatment group were 66% and 76%, respectively. CONCLUSIONS: This study documented real-world prophylactic and therapeutic AFMT use for IA/IM and associated outcomes among hospitalized patients in the USA since approval of isavuconazole. IA/IM were associated with lengthy hospital stays commonly requiring intensive care. Prophylactic and therapeutic AFMT dosages and duration generally followed recommendations and switching between agents was rare. FUNDING: Astellas Pharma Global Development, Inc., Northbrook, IL, USA.

Meningococcal Vaccination Among Adolescents in the United States: A Tale of Two Age Platforms.

PURPOSE: Despite recommended routine vaccination with meningococcal conjugate vaccine (MenACWY) at ages 11-12 years with a booster at age 16 years, national estimates indicate MenACWY uptake is lower in older adolescents than younger adolescents. This study aimed to identify factors associated with MenACWY uptake among adolescents. METHODS: Commercial Claims and Encounters (CCAE) and Medicaid MarketScan Databases from 2011 to 2016 were retrospectively analyzed (2017) to determine receipt of ≥1 dose of MenACWY during early (10.5 through 13 years) and late (15.5 through 18 years) adolescence. Multivariable logistic regression and nonlinear decomposition analyses were used to identify factors associated with MenACWY vaccination, potential missed opportunities, and differences between age groups. RESULTS: A larger proportion of younger adolescents than older adolescents received MenACWY: CCAE, 71.7% versus 48.9% (p < .001); Medicaid, 59.3% versus 31.8% (p < .001), respectively. In multivariable models (CCAE), older adolescents were less likely than younger ones to receive MenACWY (adjusted odds ratios [95% confidence intervals]: .68 [.67, .69]) and more likely to have a potential missed opportunity (1.27 [1.25, 1.28]). Decomposition results showed lower MenACWY uptake in older adolescents is largely attributed to fewer non-MenACWY vaccines received, fewer preventive care visits, and interaction with nonpediatric healthcare providers. DISCUSSION: Missed opportunities and infrequent preventive care encounters contribute to lack of vaccination in younger and older adolescents. However, the disparity in uptake between the two age groups was largely attributable to differences in healthcare utilization, suggesting a need for unique strategies to increase uptake among older adolescents, such as solidifying a vaccination platform for ages 16-18 years through encouragement of annual preventive care visits.

Universal screening for Lynch syndrome among patients with colorectal cancer: patient perspectives on screening and sharing results with at-risk relatives.

Universal screening for Lynch syndrome (LS) among all cases of colorectal cancer (CRC) could increase the diagnosis of LS and reduce morbidity and mortality of LS-associated cancers. Given universal screening includes all patients, irrespective of high risk factors such early age at onset or family history of CRC, it is important to understand perspectives of all patients and not just those at high risk. As part of a study to assess the feasibility and implementation of universal screening, 189 patients newly diagnosed with CRC were surveyed about their interest in screening for LS and communication of results with at-risk family members. Overall, participants responded positively regarding screening for LS, with most wanting to know their genetic risks in general (86%) and risk of hereditary CRC (93%). Prior to receiving screening results, most participants stated they intended to share their screening results with parents (89%), siblings (96%), and children (96%). Of the 28 participants who received a positive LS screening result, 26 (93%) reported sharing their result with at least one first-degree family member. Interest in screening for LS and communication of screening results with family members was not associated with high risk factors. This study indicates that patients are interested in being screened for LS and that sharing information on the risk of LS with at-risk family members is not a significant barrier. These findings provide novel insight into patient perspectives about screening for LS and can guide successful implementation of universal screening programs.

Low Back Imaging When Not Indicated: A Descriptive Cross-System Analysis.

CONTEXT: Guideline-discordant imaging to evaluate incident low back pain is common. OBJECTIVE: We compared rates of guideline-discordant imaging in patients with low back pain in two care delivery systems with differing abilities to track care through an electronic health record (EHR), and in their patients' insurance status, to measure the association between these factors and rates of ordered low back imaging. DESIGN: We used data from two Kaiser Permanente (KP) Regions and from OCHIN, a community health center network. We extracted data on imaging performed after index visits for low back pain from June 1, 2011, to May 31, 2012, in these systems. Adjusted logistic regression measured associations between system-level factors and imaging rates. MAIN OUTCOME MEASURES: Imaging rates for incident low back pain using 2 national quality metrics: Clinical Quality Measure 0052, a measure for assessing Meaningful Use of EHRs, and the Healthcare Effectiveness Data and Information Set measure "Use of Imaging Studies for Low Back Pain." RESULTS: Among 19,503 KP patients and 2694 OCHIN patients with incident low back pain, ordered imaging was higher among men and whites but did not differ across health care systems. OCHIN's publicly insured patients had higher rates of imaging compared with those with private or no insurance. CONCLUSION: Rates of ordered imaging to evaluate incident low back pain among uninsured OCHIN patients were lower than in KP overall; among insured OCHIN patients, rates were higher than in KP overall. Research is needed to establish causality and develop interventions.

Universal tumor screening for Lynch syndrome: Assessment of the perspectives of patients with colorectal cancer regarding benefits and barriers.

BACKGROUND: Universal tumor screening for Lynch syndrome, the most common form of hereditary colorectal cancer (CRC), has been recommended among all patients newly diagnosed with CRC. However, there is limited literature regarding patient perspectives of tumor screening for Lynch syndrome among patients with CRC who are not selected for screening based on family history criteria. METHODS: A total of 145 patients aged 39 to 87 years were administered surveys assessing perceived risk, patient perspectives, and potential benefits of and barriers to tumor screening for Lynch syndrome. Associations between patient-specific and cancer-specific factors and survey responses were analyzed. RESULTS: The majority of participants perceived their risk of developing Lynch syndrome as being low, with 9 participants (6.2%) anticipating an abnormal screening result. However, most participants endorsed the potential benefits of screening for themselves and their families, with 84.8% endorsing ≥6 benefits and 50.3% endorsing all 8 benefits. Participants also endorsed few potential barriers to screening, with 89.4% endorsing ≤4 of 9 potential barriers. A common barrier was worry about the cost of additional testing and surveillance, which was endorsed by 54.5% of participants. The level of distress associated with tumor screening for Lynch syndrome, which was very low, was not associated with age or CRC stage. CONCLUSIONS: The results of the current study indicate that patients with CRC overall have a positive attitude toward tumor screening for Lynch syndrome, endorse the benefits of screening, and experience low levels of distress. These findings provide insight into patient attitudes toward tumor screening for Lynch syndrome among unselected patients with CRC to inform educational approaches that assist in patient decision-making and guide the successful implementation of screening programs.

A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

OBJECTIVE: To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Multicenter, block-randomized, observer-masked clinical trial. PARTICIPANTS: Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. INTERVENTION: Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. MAIN OUTCOME MEASURES: Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. RESULTS: Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). CONCLUSIONS: There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

Recurrence of uveitis after discontinuation of infliximab.

PURPOSE: To evaluate the recurrence of uveitis after discontinuation of infliximab once control of inflammation is achieved. METHODS: A retrospective cohort study was conducted of patients seen at the Proctor Foundation between 1998 and 2010 who discontinued infliximab after achieving corticosteroid-sparing control by Standardization of Uveitis Nomenclature criteria. The main outcome was the proportion of patients who had a relapse of uveitis. RESULTS: Eighteen patients attempted to discontinue infliximab after achieving control of inflammation, and 11 patients had a relapse. Median time to relapse was 603 days (95% CI: 85-1461 days). Patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 4) relapsed faster (median time to relapse: 76 days, p = 0.002) compared with patients who did not have JIA-associated uveitis (median = 1169 days). CONCLUSIONS: The majority of patients who achieved control of inflammation on infliximab had a recurrence after discontinuing therapy. Patients with JIA experienced recurrence faster compared to other patients.

Acanthamoeba, fungal, and bacterial keratitis: a comparison of risk factors and clinical features.

PURPOSE: To determine risk factors and clinical signs that may differentiate between bacterial, fungal, and acanthamoeba keratitis among patients presenting with presumed infectious keratitis. DESIGN: Hospital-based cross-sectional study. METHODS: We examined the medical records of 115 patients with laboratory-proven bacterial keratitis, 115 patients with laboratory-proven fungal keratitis, and 115 patients with laboratory-proven acanthamoeba keratitis seen at Aravind Eye Hospital, Madurai, India, from 2006-2011. Risk factors and clinical features of the 3 organisms were compared using multinomial logistic regression. RESULTS: Of 95 patients with bacterial keratitis, 103 patients with fungal keratitis, and 93 patients with acanthamoeba keratitis who had medical records available for review, 287 (99%) did not wear contact lenses. Differentiating features were more common for acanthamoeba keratitis than for bacterial or fungal keratitis. Compared to patients with bacterial or fungal keratitis, patients with acanthamoeba keratitis were more likely to be younger and to have a longer duration of symptoms, and to have a ring infiltrate or disease confined to the epithelium. CONCLUSIONS: Risk factors and clinical examination findings can be useful for differentiating acanthamoeba keratitis from bacterial and fungal keratitis.

Association between atopy and herpetic eye disease: results from the pacific ocular inflammation study.

IMPORTANCE: Immune dysregulation in patients with atopy has been hypothesized to increase susceptibility to viral infections. Herpetic eye disease (due to herpes simplex and herpes zoster) is a significant cause of visual impairment, and data on an association between this sight-threatening disease and atopy are limited. OBJECTIVE: To assess the association between atopy and herpetic eye disease, including herpes simplex virus (HSV) ocular disease and herpes zoster ophthalmicus (HZO). DESIGN, SETTING, AND PARTICIPANTS: Retrospective, population-based case-control study from January 1, 2006, through December 31, 2007, at Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population. Participants were 217,061 patients enrolled in the Kaiser Permanente Hawaii health plan during the study period. MAIN OUTCOMES AND MEASURES: Clinical diagnosis of HSV ocular disease or HZO during the study period determined by an initial search of the electronic medical record of Kaiser Permanente Hawaii and then confirmed through individual medical record review by a uveitis and cornea fellowship-trained ophthalmologist. Atopic disease status was determined based on International Classification of Diseases, Ninth Revision codes for patients with HSV ocular disease or HZO and 2 control groups, each randomly selected at a 4:1 ratio of controls to cases. RESULTS: One hundred fourteen patients with HSV ocular disease and 137 patients with HZO were identified. Using the age- and sex-matched controls, patients who had atopy had a 2.6-fold (95% CI, 1.6-4.2; P < .001) higher odds of having HSV ocular disease compared with patients who did not have atopy. Similarly, patients with atopy had a 1.8-fold (95% CI, 1.2-2.8; P = .01) increased odds of having HZO. Patients with 2 or more atopic conditions had an 8.9-fold (95% CI, 3.5-22.6; P < .001) higher odds of having HSV ocular disease and a 2.9-fold (95% CI, 1.1-7.7; P = .04) higher odds of having HZO. CONCLUSIONS: AND RELEVANCE The association between atopy and herpetic eye disease may be explained by various factors, including immunologic dysfunction in patients with atopy. Clinically, these results could help support the diagnosis of herpetic eye disease in these patients.

Incidence and prevalence of uveitis: results from the Pacific Ocular Inflammation Study.

IMPORTANCE: Uveitis is responsible for a significant proportion of legal blindness in the United States. Currently, there are few population-based reports characterizing the epidemiology of uveitis. OBJECTIVE: To ascertain the incidence and prevalence of uveitis in a Hawaiian population and compare these estimates with those from prior population-based studies. DESIGN: Retrospective, population-based cohort study conducted from January 1, 2006, to December 31, 2007. SETTING: Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population with locations throughout the Hawaiian islands. PARTICIPANTS: All patients enrolled in the Kaiser Permanente Hawaii health plan during the study (N = 217,061). MAIN OUTCOMES AND MEASURES: Clinical diagnosis of uveitis, either incident or prevalent, during the study determined by an initial search of the electronic medical record database of Kaiser Permanente Hawaii for uveitis-associated International Classification of Diseases, Ninth Revision diagnosis codes and subsequently confirmed through individual record review by a uveitis specialist. RESULTS: Of 217,061 eligible patients, 872 were identified using International Classification of Diseases, Ninth Revision codes and 224 cases of uveitis were confirmed. The overall uveitis incidence rate was 24.9 cases per 100,000 person-years. The annual prevalence rates for 2006 and 2007 were 57.5 and 58.0 per 100,000 persons, respectively. No difference in incidence rate was found by sex (P = .63), but female patients had a higher prevalence (P = .008). Incidence and prevalence increased with older age (P < .001 for incidence and prevalence). Pacific Islanders had a lower prevalence rate than non-Pacific Islanders (2006: P = .09, 2007: P = .04), while white individuals had a higher prevalence rate than nonwhite individuals (2006: P = .07, 2007: P = .01). CONCLUSIONS AND RELEVANCE: The incidence and prevalence of uveitis in this population were much lower than in the Northern California Epidemiology of Uveitis Study, but similar to the Northwest Veterans Affairs Study. The results of this study highlight incidence and prevalence estimates in a new population and provide novel comparisons by race. These differences by race raise questions regarding the effects of genetic and environmental influences on the pathophysiology of uveitis.