Ethan Cowan

The OHRP and SUPPORT - Another view

A group of physicians, bioethicists, and scholars in allied fields agrees with the Office for Human Research Protections about the informed-consent documents in SUPPORT.

Given Financial Constraints, It Would Be Unethical To Divert Antiretroviral Drugs From Treatment To Prevention

Striking advances in HIV prevention have set the stage for renewed debate on setting priorities in the fight against HIV/AIDS. Two new prevention strategies--preexposure prophylaxis and treatment as prevention--use antiretroviral drugs for prevention of HIV/AIDS in addition to treating patients. The potential for success of these new prevention strategies sets up an ethical dilemma: where resources are limited and supplies of lifesaving antiretroviral medications are insufficient to treat those currently living with HIV, how should these resources be divided between treatment and prevention? This article explores several ethical principles used in formulating public health policy. Assuming that limited resources are available for spending on drugs, we conclude that it would be unethical to watch patients with treatable AIDS worsen and die, even with supportive care, so that medications for treatment can be diverted for prevention.

Counselor-Based Rapid HIV Testing in Community Pharmacies

The purpose of this study was to examine the results of implementing a rapid counselor-based HIV testing program in community pharmacies. A prospective cross-sectional study was conducted on a convenience sample of clients at five community pharmacies in New York City (NYC). In 294 days of pharmacy testing, 2805 clients were eligible to receive testing, and 2030 individuals agreed to test. The average age was 33±15 years, 41% were male, 59% were Hispanic, 77% had been previously tested for HIV, and 34% were uninsured. HIV incidence was 0.3%, median CD4 cell count was 622.0, and the average age of the newly diagnosed positives was 36.0±13.9 years. Participants were satisfied with a counselor-based rapid HIV testing program in community-based pharmacies.

Adherence to Highly Active Antiretroviral Treatment in HIV-Infected Rwandan Women

Background Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women. Methods The Rwanda Womens Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART. Results Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm3 at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit. Conclusion Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population.

HIV pre-exposure prophylaxis (PrEP)- knowledge and attitudes among a New York City emergency department patient population

Background HIV Pre-exposure Prophylaxis (PrEP), in which HIV-negative individuals receive antiretroviral medications to prevent HIV acquisition, has shown potential as a means to reduce HIV incidence among high-risk persons. The acceptability of PrEP among at-risk persons will strongly impact the effectiveness of PrEP. This study aimed to assess knowledge and attitudes towards PrEP within a demographically-mixed community with high HIV prevalence. Materials and methods A cross-sectional study was conducted with a convenience sample of Emergency Department (ED) patients at two New York City municipal hospitals. Eligible participants completed an anonymous written survey about knowledge and acceptability of PrEP. Means and standard deviations were calculated for continuous variables and proportions for categorical variables. Standard bivariate methods were used to compare acceptability and knowledge by race, ethnicity and gender. Results 474 ED patients agreed to participate. The study population was 40.9% male, 40.7% Latino and 38.2% non-Hispanic Black. 7 participants (1.5%) self-identified as MSM. Mean age was 35.3, SD +/- 13.1 years. 66.4% reported inconsistent condom use and 78.4% had previously had an HIV test. 13.3% reported knowledge of either the term “PrEP” or the use of antiretroviral medications to prevent HIV acquisition. More people indicated they were unlikely or extremely unlikely to use PrEP (40.1%) than indicated they would likely take PrEP if available (32.2%). Many (27.7%) were unsure if they would or would not take PrEP. 44.4% thought that individuals would stop using condoms if on PrEP, while 27.0% thought that individuals would continue using them. Some participants (28.4%) incorrectly thought that PrEP needed to be taken only prior to sex. There were no differences in knowledge or acceptability of PrEP by gender. Latinos were more likely (17.6%) than blacks (8.8%) and others (12.4%) to report knowledge of PrEP. Conclusions Potential providers of PrEP must consider limitations in acceptability to this HIV prevention strategy. Future administration of PrEP must incorporate patient education to ensure user understanding of the technology and its potential limitations.

Orbital Fracture Clinical Decision Rule Development: Burden of Disease and Use of a Mandatory Electronic Survey Instrument

OBJECTIVES In preparation for development of a clinical decision rule (CDR) to promote more efficient use of computed tomography (CT) for diagnosing orbital fractures, the authors sought to estimate the annual incidence of orbital fractures in emergency departments (EDs) and the usage of CT to make these diagnoses. The authors also sought to evaluate a mandatory electronic data collection instrument (EDCI) administered to providers to facilitate CDR data collection. METHODS National estimates were made by analyzing the 2007 National Hospital Ambulatory Medical Care Survey (NHAMCS) database, while hospital billing system and coding data were used to make local estimates. An EDCI was integrated into the CT ordering system such that providers had to complete the form to perform a CT. Because the EDCI had to be filled out for every CT ordered, data collection efficiency was measured by compliance (counting the number of unrealistic data collection instrument answers) and by timing a convenience sample of providers completing the EDCI. RESULTS Out of 116.8 million ED visits in the United States in 2007, 4.1 million patients were treated for injuries of the eye and face. Of those, 820,252 patients underwent CT imaging, with 102,999 patients (12.5%) diagnosed with an orbital fracture. In our local hospital system with 122,500 annual ED visits, 752 CTs of orbits were performed, with 172 (23%) orbital fractures. The EDCI compliance rate was 94.9% and took less than 5 minutes to complete. CONCLUSIONS National and local data demonstrate a low yield for CT imaging in identifying orbital fractures. Data collection using a mandatory EDCI linked to computerized provider order entry can provide prospective, consecutive patient data that are needed to develop a CDR for the selective use of CT imaging in orbital trauma. Such a decision rule could increase the efficiency in diagnosing orbital fractures, thereby improving patient care, reducing radiation exposure, and decreasing costs.

Derivation of a clinical risk score for traumatic orbital fracture.

BACKGROUND Given that orbital fractures are found in only one of every eight patients receiving computed tomography for acute orbital trauma, we sought to prospectively identify clinical predictors of orbital fracture that may obviate the need for exposing low-risk patients to ionizing radiation. METHODS Prospective cohort study conducted from July 2007 through October 2009 at two urban emergency departments. Consecutive patients undergoing computed tomography for acute blunt orbital trauma were evaluated on 15 clinical findings before imaging. The primary outcome of interest was presence of any acute orbital fracture. The secondary outcome was a fracture requiring emergent operative intervention. Multivariable logistic regression analysis with multiple imputation was used to derive a predictive risk score. RESULTS A total of 2,262 patients with acute orbital trauma were enrolled. Median age was 38 years with male predominance (68.3%). Acute orbital fractures were found in 360 patients (15.9%). The derived risk score included orbital rim tenderness, periorbital emphysema, subconjunctival hemorrhage, pain with extraocular movement, impaired extraocular movement, and epistaxis. Across 10 multiply imputed data sets, a mean of 660 patients (29.2%) lacked all six equally weighted predictors, of which 6.3% (95% confidence interval, 4.3–8.2) experienced an acute orbital fracture and only 0.5% (95% confidence interval, 0.0–1.0) required emergent operative intervention. CONCLUSION Six clinical predictors identify patients with blunt orbital trauma at increased risk for acute orbital fracture. A risk score of 0 identifies patients at very low risk for emergent operative intervention. Multicenter studies are needed to validate these findings and derive a clinical decision instrument to reduce orbital imaging without compromising patient safety. LEVEL OF EVIDENCE Diagnostic study, level II.

Conducting research in disease outbreaks.

Conducting research in an emergency situation, such as an outbreak of disease, poses ethical challenges. These challenges differ according to the type of research: epidemiologic or clinical, and for the latter, whether the disease outbreak can be anticipated in advance. We address these three situations, proposing different potential solutions for each. In an outbreak situation, public health authorities undertake a rapid response in an effort to document the existence and magnitude of a public health problem in the community and to implement appropriate measures to address the problem [1]. This rapid response will in some cases preclude the possibility of clearance by a research ethics committee since the time required to develop and submit a detailed research protocol and respond to any requested modifications by the committee, followed by re-review, would thwart the very purpose of the response. According to one prominent view, to require a full written protocol and submission to an ethics review board would not be in the interests of the individuals or the community because the resulting delays would frequently cause excess disease and death [2]. These authors suggest, however, that emergency response consent forms could be developed and used in these situations. Other individuals engaged in public health practice have voiced concern that subjecting their work to the routinely required “regulatory constraints imposed on research” would prevent flexible and timely approaches to situations such as disease outbreaks [3]. They argue that timeliness is a major requirement that would have to be counterbalanced with other ethical concerns. An example is that of pandemic influenza outbreaks, in which it is alleged that the review process would impair the ability of public health agencies to react in a timely manner. For researchers and public health agencies, therefore, the question is how to comply with the ethical requirement that research be approved by a properly constituted, independent ethical review committee (ERC) but still enable a prompt response when an outbreak occurs. If we concede that existing methods of ethical review are too protracted to be useful in outbreak situations, can alternative mechanisms be employed to ensure that such investigations undergo some type of ethical review? How can the rights and welfare of individuals be protected during investigations of disease outbreaks, and at the same time enable such investigations to be carried out expeditiously? In addition to review by a research ethics committee, a fundamental ethical requirement in research is to obtain informed consent from participants. Although not all research requires the informed consent of individual subjects, the vast majority of clinical research, most social and behavioral research, and some epidemiologic research must be carried out with the voluntary, informed consent of participants or their legally authorized representatives. In contrast, in many instances of public health practice, collection and use of information or human biological specimens can be conducted without a written informed consent document and without obtaining permission to store the samples for future use. However, a problem could arise if an investigator wants to use these samples, collected initially for public health purposes, for research. Current research practice calls for obtaining consent for the use of specimens in future research that may not be known at the time they are collected. Samples obtained in a non-research context without such provisions may require going back to get consent from sampled individuals, which could be logistically difficult, if not impossible. For example, samples with no identifying information could not be traced back to the individuals from whom they were obtained. Additionally, if a considerable time has elapsed between the collection of identifiable samples and the plan to use them in research, it could be difficult to locate the individuals. If researchers intend to use previously collected samples without going back to get consent, they must provide a justification in the protocol submitted to the research ethics committee. It is hard to see, even in non-research contexts, how human biological specimens could be obtained or even how individuals could be surveyed without first obtaining their permission to draw blood or to ask questions that may intrude on their privacy. Nevertheless, procedures for obtaining consent from individuals in an outbreak situation could depart from those typically used in other investigations and still be ethically acceptable. It is surely not necessary to include all 26 items listed as “essential information for prospective research subjects” in the CIOMS International Ethical Guidelines for Biomedical Research [4]. It is important, however, for investigators to ensure that individuals understand that what they are consenting to is research, and not routine activities carried out by public health practitioners during a disease outbreak. Nevertheless, ensuring a participants understanding of the difference between public health practice and research may be complicated by the emotional distress that potential participants can experience during an outbreak situation. Although appropriate steps are needed when participants become vulnerable in such situations, that would not change the level of risk from minimal to more than minimal risk. The level of risk is determined by the procedures in the research proposal and not by the characteristics of the population. When populations are vulnerable for whatever reason, the approach to participants in research requires establishing safeguards or added protections. Such safeguards can range from specifying exclusion criteria for potential subjects in great distress to taking steps to work sensitively to protect the rights and interests of marginalized populations. An institutional review board (IRB) chair or designated reviewer can always request additional reviewers to ensure that vulnerable individuals are adequately protected.

Nonoccupational Post-Exposure Prophylaxis for HIV in New York State Emergency Departments:

New York State (NYS) established guidelines for nonoccupational post-exposure prophylaxis (nPEP) to HIV in 1997. To assess current nPEP practices in NYS Emergency Departments (EDs), we electronically surveyed all ED directors in NYS, excluding Veterans’ Affairs hospitals, about nPEP and linkage-to-care protocols in the EDs. Basic descriptive statistics were used for analysis. The response rate was 96% (184/191). Of respondents, 88% reported evaluating any patient with a possible nonoccupational exposure to HIV, in accordance with NYS guidelines. Of these, 83% provided the patient with a starter pack of medications, while 4% neither supplied nor prescribed antiretroviral drugs in the ED. Sexually transmitted infection screening, risk reduction counseling, and education about symptoms of acute HIV seroconversion were performed inconsistently, despite NYS guidelines recommendations. Only 22% of EDs confirmed whether linkage to follow-up care was successful. Most NYS EDs prescribe nPEP to appropriate patients but full implementation of guidelines remains incomplete.

Analysis of HIV testing acceptance and risk factors of an adolescent cohort using emergency department-based multimedia HIV testing and counseling.

Background The social environment in the Bronx, NY, has led to HIV infection rates among young people that are much higher than the national average. Methods A prospective observational study on a convenience sample of medically stable emergency department (ED) patients was conducted from October 1, 2005, to August 31, 2012. Acceptability of the tested model was determined by assessing the number of patients tested and identified HIV infections. Data were compared with data from the rest of the ED that tested for HIV. Results A total of 10,149 adolescents were approached during this period, of which 9.5% refused or were ineligible to test. Of those approached, 38.9% of patients were male, 59.7% were Hispanic, and 33.6% were black. The mean age was 19.4 ± 1.4 years, and 8.2% of patients were men who have sex with men. For risk behavior profiles, 24.3% never used condoms in the past 3 months. Incidence of HIV was less than 1%, and 92.6% of HIV-positive patients were linked to care. Of the patients who completed a postsatisfaction survey, 82.4% felt influenced to change their sexual practices. A smaller percentage of adolescent had tested previously for HIV compared with nonadolescents (67.7% vs. 80.6%). There was a slightly larger percentage of adolescents that accepted HIV testing compared with nonadolescents (95.4% vs. 90.8%). Adolescents who were positive for HIV were tested earlier in the progression of the disease, with higher median CD4 cell counts and lower viral loads compared with nonadolescents. Conclusions Adolescents were highly receptive to a multimedia-integrated ED-based HIV testing program, as indicated by their high uptake of testing.