Social, political, and economic determinants of access to biologics: A scoping review of structural determinants in the clinical disparities literature.

BACKGROUND: The number of biologics among new medication approvals is increasing. Social, political, and economic factors influence access to these expensive medications. Disparities in access to new medications can exacerbate health disparities. The notion of "structural determinants" provides a theoretical framework for broadly evaluating the integration of upstream social, political, and economic determinants in the clinical study of access. OBJECTIVE: To review the literature on access to FDA approved biologic medications with particular focus on the integration of social, political, and economic determinants into study design and interpretation. METHODS: We used PRISMA guidelines to review studies on racial and socioeconomic disparities in biologic access through August 2020. We assessed whether the design or interpretation of studies considered key economic determinants of access: the biologics supply chain, trade agreements, patents, drug research and development, insurance reimbursement, and non-insurance drug policies. RESULTS: 100 studies met our inclusion criteria. Sixty-six studies considered insurance reimbursement, but trade law, patents, and other key economic determinants were rarely considered. The literature focuses on a small number of older biologics. CONCLUSIONS: A small number of studies model the integration of structural determinants into clinical research on access to biologics, but overall this literature has many limitations and lacks integration of structural determinants. Increased interdisciplinary collaboration, availability of manufacturer data, and use of disease registries can help create structurally grounded understandings of the relationship between the political economy of expensive medications and clinical disparities.

Indeterminate serotonin release assays are associated with a high mortality rate.

Background: The serotonin release assay (SRA) is considered the gold standard for diagnosis of heparin-induced thrombocytopenia (HIT). Although the SRA holds high sensitivity and specificity when results are definitive, up to 10% of samples from patients with suspected HIT yield "indeterminate" results. Objectives: We aimed to study the clinical course of patients with indeterminate results. Methods: We conducted a cohort analysis of 2056 patients that underwent SRA testing. Results: Of 2056 total patients, 152 (7.4%) had indeterminate assays. The prevalence of thrombocytopenia <50,000 × 106 was higher in patients with an indeterminate or positive SRA, compared with a negative SRA (39.5% and 40.0% vs. 27.5%, p < 4.0 × 10-4). Patients with an indeterminate SRA were more likely to have been treated in the intensive care unit than patients with a positive SRA (93.3% vs. 73.7%, p = 0.03). The mean thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, and other causes for thrombocytopenia score in patients with indeterminate SRA was 2.9, corresponding to a HIT probability of <5%. Of 152 patients, 128 (78.9%) had heparin-PF4 optical densities (ODs) below 0.60 OD, whereas four patients (2.6%) had ODs above 2.00 OD. Inpatient mortality was significant in patients with indeterminate SRAs compared with positive or negative SRA (49.3% vs. 21.1% and 27.2%, p < 2.4 × 10-10). Conclusions: Our data suggest that an indeterminate SRA may signal an in vivo platelet activation process that is not related to heparin but is associated with increased mortality.

Evaluation of the Effects of the COVID-19 Pandemic on Electronic Consultation Use in Primary Care.

Background: Little is known about electronic consultation (e-consult) utilization during the COVID-19 pandemic when health systems rapidly implemented and scaled telehealth alternatives to in-person care. It is also unknown if e-consult utilization during the pandemic replaced or merely deferred the need for a specialty appointment. We evaluated if primary care providers' (PCPs) e-consult utilization and specialists' recommendations for specialty appointments changed after the transition to telemedicine during the COVID-19 pandemic. Methods: This cohort study used an interrupted time series analysis of e-consult utilization in a large, urban academic health care system between December 1, 2019, and June 27, 2020; the post-telemedicine time period began March 15, 2020. The primary outcome measure was the odds of an e-consult ordered during a PCP appointment; the secondary outcome measure was the odds of a specialist recommending a specialty appointment in an e-consult. Results: During 193,263 PCP appointments, 1,318 e-consults were placed to internal medicine subspecialties. Compared to the pre-telemedicine time period, the odds of a PCP ordering an e-consult increased (OR 1.04, 95% CI [1.02-1.07]) and the odds of specialists recommending specialty appointments increased (OR 1.11, 95% CI [1.06-1.15]). Conclusions: E-consult use increased following the transition to telemedicine in the context of the COVID-19 pandemic, suggesting that PCPs consider the e-consult a valuable tool for patient care when there is limited availability of specialty appointments. However, recommendations for specialty appointments following an e-consult also increased, suggesting that the e-consult may not replace the need for a specialty appointment.

A History of Heart Failure Is an Independent Risk Factor for Death in Patients Admitted with Coronavirus 19 Disease.

AIMS: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. METHODS AND RESULTS: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. CONCLUSIONS: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19.

Systematic Review of Evidence-Based Guidelines for Prehospital Care.

Introduction: Multiple national organizations have identified a need to incorporate more evidence-based medicine in emergency medical services (EMS) through the creation of evidence-based guidelines (EBGs). Tools like the Appraisal of Guidelines for Research and Evaluation (AGREE) II and criteria outlined by the National Academy of Medicine (NAM) have established concrete recommendations for the development of high-quality guidelines. While many guidelines have been created that address topics within EMS medicine, neither the quantity nor quality of prehospital EBGs have been previously reported. Objectives: To perform a systematic review to identify existing EBGs related to prehospital care and evaluate the quality of these guidelines using the AGREE II tool and criteria for clinical guidelines described by the NAM. Methods: We performed a systematic search of the literature in MEDLINE, EMBASE, PubMED, Trip, and guidelines.gov, through September 2018. Guideline topics were categorized based on the 2019 Core Content of EMS Medicine. Two independent reviewers screened titles for relevance and then abstracts for essential guideline features. Included guidelines were appraised with the AGREE II tool across 6 domains by 3 independent reviewers and scores averaged. Two additional reviewers determined if each guideline reported the key elements of clinical practice guidelines recommended by the NAM via consensus. Results: We identified 71 guidelines, of which 89% addressed clinical aspects of EMS medicine. Only 9 guidelines scored >75% across AGREE II domains and most (63%) scored between 50 and 75%. Domain 4 (Clarity of Presentation) had the highest (79.7%) and domain 5 (Applicability) had the lowest average score across EMS guidelines. Only 38% of EMS guidelines included a reporting of all criteria identified by the NAM for clinical practice guidelines, with elements of a systematic review of the literature most commonly missing. Conclusions: EBGs exist addressing a variety of topics in EMS medicine. This systematic review and appraisal of EMS guidelines identified a wide range in the quality of these guidelines and variable reporting of key elements of clinical guidelines. Future guideline developers should consider established methodological and reporting recommendations to improve the quality of EMS guidelines.