Catherine E. Oldenburg

Corticosteroids for Bacterial Keratitis: The Steroids for Corneal Ulcers Trial (SCUT)

OBJECTIVE To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers. METHODS Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization. MAIN OUTCOME MEASURES The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation. RESULTS Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (-0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, -0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, -0.31 to -0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (-0.37 to -0.04; P = .02). CONCLUSIONS We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers. APPLICATION TO CLINICAL PRACTICE Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00324168.

Individual- and Structural-Level Risk Factors for Suicide Attempts Among Transgender Adults

This study assessed individual (ie, internalized transphobia) and structural forms of stigma as risk factors for suicide attempts among transgender adults. Internalized transphobia was assessed through a 26-item scale including four dimensions: pride, passing, alienation, and shame. State-level structural stigma was operationalized as a composite index, including density of same-sex couples; proportion of Gay–Straight Alliances per public high school; 5 policies related to sexual orientation discrimination; and aggregated public opinion toward homosexuality. Multivariable logistic generalized estimating equation models assessed associations of interest among an online sample of transgender adults (N = 1,229) representing 48 states and the District of Columbia. Lower levels of structural stigma were associated with fewer lifetime suicide attempts (AOR 0.96, 95% CI 0.92–0.997), and a higher score on the internalized transphobia scale was associated with greater lifetime suicide attempts (AOR 1.18, 95% CI 1.04–1.33). Addressing stigma at multiple levels is necessary to reduce the vulnerability of suicide attempts among transgender adults.

State-level structural sexual stigma and Hiv prevention in a national online sample of Hiv-uninfected Msm in the United States

Background:Stigmatizing social environments (of which ‘structural stigma’ is one component) negatively affect health-related outcomes. However, few studies have examined structural stigma related to sexual minority status as a risk factor for HIV outcomes among MSM. Methods:In August 2013, members of a large MSM social and sexual networking site in the United States completed a survey about HIV-prevention practices. A previously validated composite index provided values for state-level structural stigma, including density of same-sex couples, proportion of public high schools with Gay-Straight Alliances, state laws protecting sexual minorities, and public opinion toward homosexuality. Multivariable logistic generalized estimating equations assessed the relationship between structural stigma and condomless anal intercourse, use and awareness of antiretroviral-based HIV-prevention strategies (i.e. pre and postexposure prophylaxis, or PEP and PrEP), and comfort discussing male–male sex with primary care providers. Results:Among the 4098 HIV-uninfected MSM, lower state-level structural stigma was associated with decreased odds of condomless anal intercourse [adjusted odds ratio (aOR) 0.97 per one unit increase in structural stigma score, 95% confidence interval (CI) 0.94–0.99], increased odds of awareness of PEP (aOR 1.06, 95% CI 1.02–1.09), and PrEP (aOR 1.06, 95% CI 1.02–1.10), having taken PEP (aOR 1.15, 95% CI 1.05–1.26) and PrEP (aOR 1.21, 95% CI 1.01–1.44), and comfort discussing male–male sex with providers (aOR 1.08, 95% CI 1.05–1.11), after adjusting for social and state-level confounders. Conclusion:MSM living in more stigmatizing environments had decreased use of antiretroviral-based HIV-prevention strategies compared to those in less stigmatizing environments. Legal reforms protecting sexual minorities should be evaluated as structural interventions that could reduce HIV risk among MSM.

Pseudomonas aeruginosa Keratitis: Outcomes and Response to Corticosteroid Treatment

PURPOSE To compare the clinical course and effect of adjunctive corticosteroid therapy in Pseudomonas aeruginosa with those of all other strains of bacterial keratitis. METHODS Subanalyses were performed on data collected in the Steroids for Corneal Ulcers Trial (SCUT), a large randomized controlled trial in which patients were treated with moxifloxacin and were randomly assigned to 1 of 2 adjunctive treatment arms: corticosteroid or placebo (4 times a day with subsequent reduction). Multivariate analysis was used to determine the effect of predictors, organism, and treatment on outcomes, 3-month best-spectacle-corrected visual acuity (BSCVA), and infiltrate/scar size. The incidence of adverse events over a 3-month follow-up period was compared using Fishers exact test. RESULTS SCUT enrolled 500 patients. One hundred ten patients had P. aeruginosa ulcers; 99 of 110 (90%) enrolled patients returned for follow-up at 3 months. Patients with P. aeruginosa ulcers had significantly worse visual acuities than patients with other bacterial ulcers (P = 0.001) but showed significantly more improvement in 3-month BSCVA than those with other bacterial ulcers, adjusting for baseline characteristics (-0.14 logMAR; 95% confidence interval, -0.23 to -0.04; P = 0.004). There was no significant difference in adverse events between P. aeruginosa and other bacterial ulcers. There were no significant differences in BSCVA (P = 0.69), infiltrate/scar size (P = 0.17), and incidence of adverse events between patients with P. aeruginosa ulcers treated with adjunctive corticosteroids and patients given placebo. CONCLUSIONS Although P. aeruginosa corneal ulcers have a more severe presentation, they appear to respond better to treatment than other bacterial ulcers. The authors did not find a significant benefit with corticosteroid treatment, but they also did not find any increase in adverse events. (ClinicalTrials.gov number, NCT00324168.).

Knowledge, beliefs and practices regarding antiretroviral medications for HIV prevention: Results from a survey of healthcare providers in New England

Background Antiretroviral treatment for HIV-infection before immunologic decline (early ART) and pre-exposure chemoprophylaxis (PrEP) can prevent HIV transmission, but routine adoption of these practices by clinicians has been limited. Methods Between September and December 2013, healthcare practitioners affiliated with a regional AIDS Education and Training Center in New England were invited to complete online surveys assessing knowledge, beliefs and practices regarding early ART and PrEP. Multivariable models were utilized to determine characteristics associated with prescribing intentions and practices. Results Surveys were completed by 184 practitioners. Respondent median age was 44 years, 58% were female, and 82% were white. Among ART-prescribing clinicians (61% of the entire sample), 64% were aware that HIV treatment guidelines from the Department of Health and Human Services recommended early ART, and 69% indicated they would prescribe ART to all HIV-infected patients irrespective of immunologic status. However, 77% of ART-prescribing clinicians would defer ART for patients not ready to initiate treatment. Three-fourths of all respondents were aware of guidance from the U.S. Centers for Disease Control and Prevention recommending PrEP provision, 19% had prescribed PrEP, and 58% of clinicians who had not prescribed PrEP anticipated future prescribing. Practitioners expressed theoretical concerns and perceived practical barriers to prescribing early ART and PrEP. Clinicians with higher percentages of HIV-infected patients (aOR 1.16 per 10% increase in proportion of patients with HIV-infection, 95% CI 1.01–1.34) and infectious diseases specialists (versus primary care physicians; aOR 3.32, 95% CI 0.98–11.2) were more likely to report intentions to prescribe early ART. Higher percentage of HIV-infected patients was also associated with having prescribed PrEP (aOR 1.19, 95% CI 1.06–1.34), whereas female gender (aOR 0.26, 95% CI 0.10–0.71) was associated with having not prescribed PrEP. Conclusions These findings suggest many clinicians have shifted towards routinely recommending early ART, but not PrEP, so interventions to facilitate PrEP provision are needed.

Organism, minimum inhibitory concentration, and outcome in a fungal corneal ulcer clinical trial.

Purpose: To analyze the minimum inhibitory concentration (MIC) of isolates from fungal keratitis to natamycin and voriconazole and to assess the relationship between organism, MIC, and clinical outcome. Methods: Data were collected as part of a randomized, controlled, double-masked clinical trial. Main outcome measures included best spectacle-corrected visual acuity, infiltrate/scar size, time to reepithelialization, and perforation. Speciation and analysis of MIC to natamycin and voriconazole were done according to Clinical and Laboratory Standards Institute standards. The relationship between MIC and organism, organism and outcome measure, and each outcome measure and MIC were assessed. Results: Of the 120 samples obtained in the trial, 84 isolates had an identifiable organism and were available for further analyses. Fusarium spp and Aspergillus spp were the most commonly isolated organisms. MIC was significantly different across the groups of organisms (P = 0.0001). A higher MIC was significantly associated with an increased likelihood of perforation [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.02–4.04; P = 0.04]. There was no significant association between MIC and 3-week visual acuity (OR, 0.058; 95% CI, −0.01 to 0.13; P = 0.11), 3-month visual acuity (OR, 0.01; 95% CI,−0.08 to 1.04; P = 0.79), 3-week infiltrate/scar size (OR, 0.12, 95% CI, −0.02 to 0.27; P = 0.10), 3-month infiltrate/scar size (OR, 0.12; 95% CI, −0.02 to 0.25; P = 0.09), or time to reepithelialization (hazards ratio, 1.19; 95% CI, 0.98–1.45; P = 0.08). Conclusion: A higher MIC was associated with an increased odds of perforation. The results of this study suggest that resistance to antifungal medication may be associated with worse outcomes in fungal keratitis.

The Steroids for Corneal Ulcers Trial: Study Design and Baseline Characteristics

OBJECTIVES To provide comprehensive trial methods and baseline data for the Steroids for Corneal Ulcers Trial and to present epidemiological characteristics such as risk factors, causative organisms, and ulcer severity. METHODS Baseline data from a 1:1 randomized, placebo-controlled, double-masked clinical trial comparing prednisolone phosphate, 1%, with placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and had been taking moxifloxacin for 48 hours. The primary outcome for the trial is best spectacle-corrected visual acuity at 3 months from enrollment. This report provides comprehensive baseline data, including best spectacle-corrected visual acuity, infiltrate size, microbiological results, and patient demographics, for patients enrolled in the trial. RESULTS Of 500 patients enrolled, 97% were in India. Two hundred twenty patients (44%) were agricultural workers. Median baseline visual acuity was 0.84 logMAR (Snellen, 20/125) (interquartile range, 0.36-1.7; Snellen, 20/50 to counting fingers). Baseline visual acuity was not significantly different between the United States and India. Ulcers in India had larger infiltrate/scar sizes (P = .04) and deeper infiltrates (P = .04) and were more likely to be localized centrally (P = .002) than ulcers enrolled in the United States. Gram-positive bacteria were the most common organisms isolated from the ulcers (n = 366, 72%). CONCLUSIONS The Steroids for Corneal Ulcers Trial will compare the use of a topical corticosteroid with placebo as adjunctive therapy for bacterial corneal ulcers. Patients enrolled in this trial had diverse ulcer severity and on average significantly reduced visual acuity at presentation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00324168.

Practice patterns and opinions in the treatment of acanthamoeba keratitis

Purpose: Management of acanthamoeba keratitis remains challenging for ophthalmologists. We conducted a survey of members of The Cornea Society to elicit expert opinions on the diagnosis and treatment of acanthamoeba keratitis. Methods: An online survey was sent to all subscribers of The Cornea Society via the kera-net listserv. Descriptive statistics were performed. Results: Eighty-two participants completed the online survey. Of the 82 respondents, 76.8% included the combination of clinical examination and culture in their diagnostic strategy and 43.9% used confocal microscopy. Most respondents (97.6%) had used combination therapy with multiple agents to treat acanthamoeba keratitis at some point in the past, whereas a smaller proportion (47.6%) had ever used monotherapy. Respondents most commonly chose polyhexamethylene biguanide as the ideal choice for monotherapy (51.4%), and dual therapy with a biguanide and diamidine as the ideal choice for combination therapy (37.5%). The majority of respondents (62.2%) reported using topical corticosteroids at least some of the time for acanthamoeba keratitis. Keratoplasty was an option considered by most respondents (75.6%), although most (85.5%) would only perform surgery after medical treatment failure. Conclusions: There was a wide range of current practice patterns for the diagnosis and treatment of acanthamoeba keratitis. The lack of sufficiently powered comparative effectiveness studies and clinical trials makes evidence-based decision-making for this disease difficult.

Retention in care outcomes for HIV pre-exposure prophylaxis implementation programmes among men who have sex with men in three US cities.

Despite the efficacy of pre‐exposure prophylaxis (PrEP) in preventing HIV transmission, few studies have evaluated PrEP use and retention in care outcomes in real‐world settings outside of clinical trials.

Poverty matters: contextualizing the syndemic condition of psychological factors and newly diagnosed HIV infection in the United States.

Background:‘Syndemic factors’, defined as co-occurring psychological conditions including major depressive disorder, substance and alcohol use, and intimate partner violence, have been shown to increase HIV incidence among MSM in the United States. However, this relationship has not been well characterized in the general population, particularly in the context of poverty. Design:Prospective cohort study including a nationally-representative sample of 34 427 men and women in the National Epidemiologic Survey on Alcohol and Related Conditions wave 1 (2001–2002) and wave 2 (2004–2005). Methods:Weighted multivariable logistic regression models were used to assess the association between syndemic factors and newly diagnosed HIV infection, and to assess how living below the poverty line (based on 2001 US Poverty Guidelines) modified this relationship. Results:The proportion of participants reporting new HIV diagnosis in the past year was 0.22%, increasing from 0.19% among individuals with no syndemic factor to 5.1% among those with four syndemic factors. Adjusting for potentially confounding factors, each additional syndemic factor was associated with a 47% increase in odds of HIV infection [adjusted odds ratio (aOR) 1.47, 95% confidence interval (CI) 1.30–1.65]. The effect of syndemic factors was stronger among individuals living below federal poverty guidelines (aOR 1.96, 95% CI 1.57–2.44) compared to those living above poverty guidelines (aOR 1.21, 95% CI 1.07–1.36). Conclusions:Among the US general population, the association between co-occurring syndemic factors and incident HIV infection was stronger in the setting of poverty. Mental health interventions, particularly in socioeconomically disadvantaged areas, should be considered to reduce transmission of HIV.