Diversity's Pandemic Distractions.

Pandemic diseases have a nasty history of racialization. COVID-19 is no exception. Beyond the obvious racist invocations of the "China virus" or the "Wuhan Flu" are subtler racializing dynamics that are often veiled in more benign motives but are nonetheless deeply problematic. The racialization of COVID-19 proceeded along two distinct trajectories each of which threatened to reinforce inaccurate biologized conceptions of race while diverting attention from the social, legal, and political forces historically structuring race-based health disparities. First, early on as significant racial disparities in disease incidence and mortality became evident, a frame of race-based genetic difference came to the fore as a possible explanation. Second, as vaccine development ramped up there came widespread calls for racially "diversifying" clinical trials for the vaccines being tested. The rationales for such diversification were varied but tended to reinforce genetic frames of racial difference. Most common was the assertion (without substantial evidence) that vaccines might work differently in Black or Brown bodies and so racial diversity in trials was imperative for reasons of safety and efficacy. Derrick Bell cautioned 20 years ago that "the concept of diversity … is a serious distraction in the ongoing efforts to achieve racial justice." (Derrick Bell, Diversity's Distractions, 103 Colum. L. Rev. 1622, 1622 (2003).) This article explores the dynamics of how the concept of "diversity" racialized responses to COVID-19 and considers their broader implications for understanding and responding to racial disparities in the face of pandemic emergencies and beyond. In the short term, vaccine developers did a decent job of enrolling minorities in their clinical trials and the vaccines have proven to have the same safety and efficacy across races. In the long term, diversity in the biomedical context of pandemic response not only distracts attention from important structural causes of health injustice, but it also focuses attention on the genetics of disparities in a manner that has the potential to reinforce pernicious and false ideas of essential biological difference among racial groups. This article argues that an uncritical embrace of the idea of diversity in analyzing and responding to emergent health crises has the potential to distract us from considering deeper historical and structural formations contributing to racial health disparities. It proceeds first by exploring the dynamics through which initial responses to racial disparities in COVID-19 became geneticized. It will then move on to unpack the rationales for such racialization, examine their merits (or lack thereof), and consider their implications for developing an equitable response to pandemic emergencies. The next section will examine the subsequent racialization of clinical trials for COVID-19 vaccines through the concept of "diversity." It then moves on to explore how the geneticization of COVID-19 racial disparities laid the foundations for a similar geneticization of race in vaccine development. It will argue that in failing to clearly distinguish social and biological rationales for diversity, such framings, while generally well-intentioned, are poorly supported and work in tandem with the geneticization of racial disparities in COVID-19 morbidity and mortality to locate the causes of disparities in the minds and bodies of minoritized populations; again this distracts attention from the historical and structural forces contributing to such disparities. The article concludes by recognizing a certain intractability to the problems of using race in biomedical research and practice, particularly in the context of public health emergencies. It offers modest suggestions for improvement that could have significant practical effects if taken to heart by researchers, clinicians, and policy makers.

Infarcted Tarsal Pyogenic Granuloma Simulating Malignant Melanoma.

The authors describe a rapidly enlarging, pedunculated brown tarsal lesion in a 34-year-old man with a history of chalazia. Following excision, histopathologic analysis showed the features of a necrotic pyogenic granuloma. This unique case expands the differential diagnosis of conjunctival malignant melanoma.

Spontaneous Reattachment of a Detached Sutured Descemet-Stripping Automated Endothelial Keratoplasty Graft.

Introduction: This is a case report of a spontaneous reattachment of Descemet-stripping automated endothelial keratoplasty (DSAEK). This graft was primarily sutured, and 20% sulfur hexafluoride (SF6) was injected into the anterior chamber, followed by graft detachment and spontaneous reattachment, 3 months later. Case Presentation: A 78-year-old male presented with DSAEK graft detachment, which was the patient's second DSAEK (the first also did not adhere). During the second surgery, the DSAEK graft was sutured and 20% SF6 was injected intraoperatively. Graft reattachment occurred without any intervention or repositioning 3 months after the 2nd DSAEK surgery. Conclusion: Spontaneous DSEAK late graft reattachment is possible, particularly in the setting of an anchoring suture. In some patients, waiting can be an option that can spare the patient the possible risks of graft repositioning, rebubbling, or repeating the DSAEK. Suturing the DSAEK graft primarily may have served as an anchor to keep the graft approximate and aid in attachment. A graft suture can be considered in the setting of a previously failed DSAEK due to DSAEK graft detachment.

Topography-guided hyperopic LASIK with and without high irradiance collagen cross-linking: initial comparative clinical findings in a contralateral eye study of 34 consecutive patients.

PURPOSE: To evaluate the safety and efficacy of intrastromally applied collagen cross-linking (CXL) in a comparative contralateral eye study of topography-guided femtosecond laser-assisted hyperopic LASIK. METHODS: Thirty-four consecutive patients with hyperopia and hyperopic astigmatism elected to have bilateral topography-guided LASIK and were randomized to receive a single drop of 0.1% sodium phosphate riboflavin solution under the flap followed by 3-minute exposure of 10 mW/cm2 ultraviolet A (UVA) light with the flap realigned in one eye (CXL group) and no intrastromal CXL in the contralateral eye (no CXL group). All eyes were treated with the WaveLight FS200 femtosecond laser and WaveLight EX500 excimer laser (Alcon Laboratories Inc). Refractive error and keratometric, topographic, and tomographic measurements were evaluated over mean follow-up of 23 months. RESULTS: Preoperatively, mean spherical equivalent refraction was +3.15 +/- 1.46 diopters (D) and +3.40 +/- 1.78 D with a mean cylinder of 1.20 +/- 1.18 D and 1.40 +/- 1.80 D and mean uncorrected distance visual acuity (UDVA) (decimal) of 0.1 +/- 0.26 and 0.1 +/-0.25 in the CXL and no CXL groups, respectively. At 2 years postoperatively, mean spherical equivalent refraction was -0.20 +/- 0.56 D and +0.20 +/- 0.40 D with mean cylinder of 0.65 +/- 0.56 D and 0.76 +/- 0.72 D and mean UDVA of 0.95 +/- 0.15 and 0.85 +/- 0.23 in the CXL and no CXL groups, respectively. Eyes with CXL demonstrated a mean regression from treatment of +0.22 +/- 0.31 D, whereas eyes without CXL showed a statistically significant greater regression of +0.72 +/- 0.19 D (P = .0001). CONCLUSIONS: Topography-guided hyperopic LASIK with or without intrastromal CXL is safe and effective, with greater long-term efficacy (less regression) in eyes with CXL. Our data suggest that the regression seen with hyperopic LASIK may be related to biomechanical changes in corneal shape over time.

The two (institutional) cultures: a consideration of structural barriers to interdisciplinarity.

C. P. Snow's famous Two Cultures essay has become a foil for decades of discussions over the relation between science and the humanities. The problem of the "two cultures" is often framed in terms of how the particular epistemological claims or general intellectual orientations of particular individuals on either side of this purported divide obstruct interdisciplinary dialogue or cooperation. This formulation, however, fails to consider the institutional frameworks within which such debates occur. This article examines the broader structural constraints that provide incentives, erect barriers, or otherwise shape the potential for interdisciplinary research and practice, with particular attention to work involving the life sciences. It argues that in order to understand the nature and scope of the problems facing interdisciplinary work, we must focus on the institutional constraints that shape how individuals frame questions, pursue investigations, develop careers, and collaborate.

Orbital dissemination of Lemierre syndrome from gram-positive septic emboli.

A 45-year-old patient presented with bilateral orbital abscesses. He was found to have Lemierre syndrome, a condition involving septic thrombophlebitis of the internal jugular vein. The patient developed severe proptosis, sepsis, and cavernous sinus thrombosis. Despite aggressive antibiotic and anticoagulation therapy, visual loss was rapid, and the patient ultimately died. Lemierre syndrome, previously thought to be rare, is now becoming more commonly reported. Its prompt diagnosis and treatment are essential for patient survival.

SMRT Regulates Metabolic Homeostasis and Adipose Tissue Macrophage Phenotypes in Tandem.

The Silencing Mediator of Retinoid and Thyroid Hormone Receptors (SMRT) is a nuclear corepressor, regulating the transcriptional activity of many transcription factors critical for metabolic processes. While the importance of the role of SMRT in the adipocyte has been well-established, our comprehensive understanding of its in vivo function in the context of homeostatic maintenance is limited due to contradictory phenotypes yielded by prior generalized knockout mouse models. Multiple such models agree that SMRT deficiency leads to increased adiposity, although the effects of SMRT loss on glucose tolerance and insulin sensitivity have been variable. We therefore generated an adipocyte-specific SMRT knockout (adSMRT-/-) mouse to more clearly define the metabolic contributions of SMRT. In doing so, we found that SMRT deletion in the adipocyte does not cause obesity-even when mice are challenged with a high-fat diet. This suggests that adiposity phenotypes of previously described models were due to effects of SMRT loss beyond the adipocyte. However, an adipocyte-specific SMRT deficiency still led to dramatic effects on systemic glucose tolerance and adipocyte insulin sensitivity, impairing both. This metabolically deleterious outcome was coupled with a surprising immune phenotype, wherein most genes differentially expressed in the adipose tissue of adSMRT-/- mice were upregulated in pro-inflammatory pathways. Flow cytometry and conditioned media experiments demonstrated that secreted factors from knockout adipose tissue strongly informed resident macrophages to develop a pro-inflammatory, MMe (metabolically activated) phenotype. Together, these studies suggest a novel role for SMRT as an integrator of metabolic and inflammatory signals to maintain physiological homeostasis.

Patenting race.

As genetic databases continue to yield new insights and inventions, the commercial incentive to conflate race and genetics may be hard to resist.

Quantification of the Cost and Potential Environmental Effects of Unused Pharmaceutical Products in Cataract Surgery.

IMPORTANCE: Pharmaceutical products, including unused portions, may contribute to financial and environmental costs in the United States. Because cataract surgery is performed millions of times each year in the United States and throughout the rest of the world, understanding these financial and environmental costs associated with cataract surgery is warranted. OBJECTIVE: To investigate the financial and environmental costs of unused pharmaceutical products after phacoemulsification surgery. DESIGN, SETTING, AND PARTICIPANTS: This descriptive qualitative study included 4 surgical sites in the northeastern United States (a private ambulatory care center, private tertiary care center, private outpatient center, and federally run medical center for veterans). Prices and data for use of services and pharmaceuticals were obtained for the tertiary care and outpatient centers from January 1 through April 30, 2016; for the ambulatory care center from June 1, 2017, through March 31, 2018; and the federal medical center from November 1, 2017, through February 28, 2018. Data were collected from routine phacoemulsification surgical procedures without vitreous loss or other complications. Volume or weight of medications remaining after surgery was measured. Total and mean costs of medications per case and month were calculated. Environmental effects were estimated using economic input-output life cycle assessment methods. Data were analyzed from December 1, 2017, through June 30, 2018. MAIN OUTCOMES AND MEASURES: Cost of unused pharmaceutical products (in US dollars) and kilogram equivalents of carbon emissions (carbon dioxide [CO2-e]), air pollution (fine particulate matter emissions of ≤10 µm in diameter [PM10-e]), and eutrophication potential (nitrogen [N-e]). RESULTS: A total of 116 unique drugs were surveyed among the 4 centers. Assuming unmeasured medications had no materials left unused, a cumulative mean 83 070 of 183 304 mL per month (45.3%) of pharmaceuticals were unused by weight or volume across all sites. Annual unused product cost estimates reached approximately $195 200 per site. A larger percentage of eyedrops (65.7% by volume) were unused compared with injections (24.8%) or systemic medications (59.9%). Monthly unused quantities at the ambulatory care center (65.9% by volume [54 971 of 83 440 mL]), tertiary care center (21.3% [17 143 of 80 344 mL]), federal medical center (38.5% [265 of 689 mL]), and outpatient center (56.8% [10 691 of 18 832 mL]) resulted in unnecessary potential emissions at each center of 2135, 2498, 418, and 711 kg CO2-e/mo, respectively. Unnecessary potential air pollution between sites varied from 0.8 to 4.5 kg PM10-e/mo, and unnecessary eutrophication potential between sites varied from 0.07 to 0.42 kg N-e/mo. CONCLUSIONS AND RELEVANCE: This study suggests that unused pharmaceutical products during phacoemulsification result in relatively high financial and environmental costs. If these findings can be substantiated and shown to be generalizable in the United States or elsewhere, reducing these costs may be of value.

Flaws in the U.S. Food and Drug Administration's rationale for supporting the development and approval of BiDil as a treatment for heart failure only in black patients.

The U.S. Food and Drug Administration's (FDA) rationale for supporting the development and approval of BiDil (a combination of hydralazine hydrochloride and isosorbide dinitrate; H-I) for heart failure specifically in black patients was based on under-powered, post hoc subgroup analyses of two relatively old trials (V-HeFT I and II), which were further complicated by substantial covariate imbalances between racial groups. Indeed, the only statistically significant difference observed between black and white patients was found without any adjustment for potential confounders in samples that were unlikely to have been adequately randomized. Meanwhile, because the accepted baseline therapy for heart failure has substantially improved since these trials took place, their results cannot be combined with data from the more recent trial (A-HeFT) amongst black patients alone. There is therefore little scientific evidence to support the approval of BiDil only for use in black patients, and the FDA's rationale fails to consider the ethical consequences of recognizing racial categories as valid markers of innate biological difference, and permitting the development of group-specific therapies that are subject to commercial incentives rather than scientific evidence or therapeutic imperatives. This paper reviews the limitations in the scientific evidence used to support the approval of BiDil only for use in black patients; calls for further analysis of the V-HeFT I and II data which might clarify whether responses to H-I vary by race; and evaluates the consequences of commercial incentives to develop racialized medicines. We recommend that the FDA revise the procedures they use to examine applications for race-based therapies to ensure that these are based on robust scientific claims and do not undermine the aims of the 1992 Revitalization Act.

Exploiting race in drug development: BiDil's interim model of pharmacogenomics.

This paper explores events surrounding the US Food and Drug Administration's formal approval of the heart failure drug BiDil in 2005. BiDil is the first drug ever to be approved with a race-specific indication, in this case to treat heart failure in 'self-identified black patients'. BiDil has been cast by many as a step toward the promised land of individualized pharmacogenomic therapies. This paper argues, however, that when examined in context, the approval of BiDil emerges as a new model of how a pharmaceutical company may exploit race in the marketplace by literally capitalizing on the racial identity of minority populations and leveraging the disproportionate risk of adverse health outcomes they suffer into a cheaper, more efficient way to gain the US Food and Drug Administration's approval for drugs. Discussions of BiDil in both popular media and professional journals have repeatedly elided the difference between pharmacogenomic and race-based medicine. In fact, broad-based true pharmacogenomic therapies remain years-perhaps decades-in the future. The story of BiDil's development elucidates an alternative model to developing tailored therapies that promises to fill in the gap between the promise and reality of pharmacogenomic medicine. It is a model that exploits race to gain regulatory and commercial advantage, while ignoring its power to promote a regeneticization of racial categories in society at large.

Pharmacokinetic and behavioral characterization of a long-term antipsychotic delivery system in rodents and rabbits.

RATIONALE: Non-adherence with medication remains the major correctable cause of poor outcome in schizophrenia. However, few treatments have addressed this major determinant of outcome with novel long-term delivery systems. OBJECTIVES: The aim of this study was to provide biological proof of concept for a long-term implantable antipsychotic delivery system in rodents and rabbits. MATERIALS AND METHODS: Implantable formulations of haloperidol were created using biodegradable polymers. Implants were characterized for in vitro release and in vivo behavior using prepulse inhibition of startle in rats and mice, as well as pharmacokinetics in rabbits. RESULTS: Behavioral measures demonstrate the effectiveness of haloperidol implants delivering 1 mg/kg in mice and 0.6 mg/kg in rats to block amphetamine (10 mg/kg) in mice or apomorphine (0.5 mg/kg) in rats. Additionally, we demonstrate the pattern of release from single polymer implants for 1 year in rabbits. CONCLUSIONS: The current study suggests that implantable formulations are a viable approach to providing long-term delivery of antipsychotic medications in vivo using animal models of behavior and pharmacokinetics. In contrast to depot formulations, implantable formulations could last 6 months or longer. Additionally, implants can be removed throughout the delivery interval, offering a degree of reversibility not available with depot formulations.

Genes, race, and population: avoiding a collision of categories.

A wide array of federal mandates have a profound impact on the use of racial and ethnic categories in biomedical research, clinical practice, product development, and health policy. Current discussions over the appropriate use of racial and ethnic categories in biomedical contexts have largely focused on the practices of individual researchers. By contrast, our discussion focuses on relations between the daily practices of biomedical professionals and federal regulatory mandates. It draws upon the legal doctrine of equal protection to move beyond such debates and to propose guidelines to address the structural forces imposed by federal regulations that mandate how data about race and ethnicity are used in biomedical research. It offers a framework to manage the tension involved in using existing federally mandated categories of race and ethnicity alongside new scientific findings about human genetic variation.

Effect of drug type on the degradation rate of PLGA matrices.

We compare the rate of drug release through the degradation of 50:50 polylactic-co-glycolic acid polymer pellets, for six different drugs: Thiothixene, Haloperidol, Hydrochlorothiozide, Corticosterone, Ibuprofen, and Aspirin. Despite using the same polymer matrix and drug loading (20% by weight), we find that the rate of polymer degradation and the drug release profile differ significantly between the drugs. We conclude that the design of biodegradable polymeric drug carriers with high drug loadings must account for the effect of the drug on the polymer degradation and drug release rate.

Race, pharmacogenomics, and marketing: putting BiDil in context.

This article endeavors to place into context recent developments surrounding the United States Food and Drug Administration recent approval of BiDil (isosorbide dinitrate/hydralazine hydrochloride) (NitroMed, Inc., Lexington, MA) as the first ever race-specific drug--in this case to treat heart failure in African Americans. It focuses in particular on both commercial incentives and statistical manipulation of medical data as framing the drive to bring BiDil to market as a race-specific drug. In current discourse about pharmacogenomics, targeting a racial audience is perceived as necessary because at this point the technology and resources do not exist to scan efficiently every individual's genetic profile. The article argues that medical researchers may say they are using race as a surrogate to target biology in drug development, but corporations are using biology as a surrogate to target race in drug marketing. Pharmacogenomics may hold great promise, but on our way to that Promised Land, it is imperative to review such short cuts with a critical eye.