Bion's Transformations and Clinical Practice.

Wilfred Bion's contributions to psychoanalysis are numerous: his early work on the psychology of groups that grew out of his experiences in the first World War; theories and work on the treatment of psychosis with Melanie Klein and later psychoanalysis with her; and the beginning of his own theoretical and clinical ideas, which nurtured analytic thinking and treatment approaches beginning in the mid-1960's followed by his relocation to the United States (1967). Bion's thinking can be deceptively simple, such as his statement that his third book, Transformations (1965), considered by many as exceptionally dense, is about "the communication of both patient and analyst about an emotional experience" (p. 29).

Perceptions of metabolic syndrome management utilization in relation to patient experience and health-related quality of life.

Background: One factor for the poor health outcomes among adult people with metabolic syndrome (MetS) is poor utilization of disease management resources, which may be attributable to prior experience with pharmacists (PEwP) and perceptions of disease management resource utilization (PMU). Therefore, understanding patients' experience could be critical to improving their perceptions and promoting health outcomes. Objectives: The study explored the influence of PEwP and PMU on the health-related quality of life (HRQoL) of people with MetS. Methods: Data on perceptions of healthcare, medication, and pharmacy services utilization, PEwP, and HRQoL were collected using validated tools via an electronic survey. Chi-square and ordinal regression tests were used to predict the association between PMU, PEwP, and HRQoL. Also, mediation analysis through Haye's model 4 explored the direct and indirect relationship of PMU and PEwP on HRQoL. Results: A total of 706 completed surveys were collected and used for analyses. On average, respondents reported three comorbidities. Of the respondents, 72.0% had good PEwP, while 32.6% had good PMU. Comparatively, 38.4% of those with good PEwP had good PMU, compared to 17.3% of those with poor PEwP. Also, 47.0% of those with good PMU had good HRQoL compared to 35.3% with poor PMU. The odds of having fair or good PMU were nearly triple (OR = 2.97, p < 0.001) among those with good PEwP compared to those with poor PEwP. Also, respondents with good PMU had 58% (OR = 1.58, p = 0.008) higher odds of having fair or good HRQoL. Analysis through bootstrap indicated a significant relationship (BootCI = -0.072, -0.022) between PEwP and HRQoL via respondents' PMU. Conclusions: MetS individuals with good experience and PMU were more likely to have good HRQoL. Prior experience with pharmacists influenced PMU and indirectly impacted HRQoL. Therefore, pharmacists must consider patients' experience and management utilization perceptions to promote health outcome among people with MetS, while implementing interventions.

Structural Racism, Residential Segregation, and Exposure to Trauma: The Persistent Impact of Redlining.

INTRODUCTION: As part of New Deal era federal housing policy, the Home Owners Loan Corporation (HOLC) developed maps grading US neighborhoods by perceived financial security. Neighborhoods with high concentrations of racial and ethnic minorities were deemed financially unstable and denied federal investment, a practice colloquially known as redlining. The aim of this study was to assess the association of historical redlining within Austin, Texas to spatial patterns of penetrating traumatic injury. METHODS: Retrospective cross sectional study utilizing data from violent penetrating trauma admissions between January 1, 2014 - December 31, 2021, at the single Level 1 trauma center in Austin, Texas. Using ArcGIS, addresses where the injury took place were geocoded and spatial joining was used to match them to their corresponding census tract, for which 1935 HOLC financial designations are classified as: "Hazardous", "Definitely Declining", "Still Desirable", "Best", or "Non HOLC Graded". Tracts with designations of "Hazardous" and "Definitely Declining" were categorized as Redlined. The adjusted incidence rate ratio comparing rates of penetrating trauma among historically Redlined vs. Not Redlined and Not Graded census tracts was calculated. RESULTS: 1,404 violent penetrating trauma admissions were identified for the study period, of which 920 occurred within the county of interest. Among these, 5% occurred in census tracts that were Not Redlined, 13% occurred in Redlined tracts, and 82% occurred in non HOLC graded tracts. When adjusting for differences in current census tract demographics and social vulnerability, historically Redlined areas experienced a higher rate of penetrating traumatic injury (Not Redlined IRR = 0.42, 95% CI 0.19-0.94, p = 0.03; Not Graded IRR = 0.15, 95% CI 0.07-0.29, p < 0.001). CONCLUSIONS: Neighborhoods unfavorably classified by HOLC in 1935 continue to experience a higher incidence rate of violent penetrating trauma today. These results underscore the persistent impacts of structural racism and of historical residential segregation policies on exposure to trauma. LEVEL OF EVIDENCE: Level IV, Prognostic and Epidemiological.

Time Savings and Safety of EMS Administration of Antibiotics for Open Fractures.

INTRODUCTION: Early administration of antibiotics for open fractures reduces serious bone and soft tissue infections. The effectiveness of antibiotics in reducing these infections is time-dependent, with various surgical associations recommending administration within one hour of injury, or within one hour of patient arrival to the emergency department (ED). The extent to which prehospital antibiotic administration in these situations might reduce the time to treatment has not been previously reported. The purpose of this study was to describe current prehospital use of antibiotics for traumatic injury, to assess the safety of prehospital antibiotic administration, and to estimate the potential time-savings associated with antibiotic administration by EMS clinicians. METHODS: This was a retrospective analysis of the 2019 through 2022 ESO Data Collaborative research data set. Included subjects were patients that had a linked ICD-10 code indicating an open extremity fracture and who received prehospital antibiotics. Time to antibiotic administration was calculated as the elapsed time from EMS dispatch until antibiotic administration. The minimum potential time saved by EMS antibiotic administration was calculated as the elapsed time from administration until ED arrival. To assess safety, epinephrine and diphenhydramine administration were used as proxies for the adverse events of anaphylaxis and minor allergic reactions. RESULTS: There were 523 patients meeting the inclusion criteria. The median (and interquartile range [IQR]) elapsed time from EMS dispatch until antibiotic administration was 31 (IQR: 24-41) minutes. The median potential time savings associated with prehospital antibiotic administration was 15 (IQR: 8-22) minutes. Notably, 144 (27.5%) of the patients who received prehospital antibiotics had total prehospital times exceeding one hour. None of the patients who received antibiotics also received epinephrine for presumed anaphylaxis. CONCLUSIONS: EMS clinicians were able to safely administer antibiotics to patients with open fractures a median of 15 minutes before arrival at the hospital, and 99 percent of the patients receiving antibiotics had them administered within one hour of EMS dispatch. EMS administration of antibiotics may be a safe way to increase compliance with recommendations for early antibiotic administration for open fractures.

Integrated Hepatitis C-Opioid Use Disorder Care Through Facilitated Telemedicine: A Randomized Trial.

Importance: Facilitated telemedicine may promote hepatitis C virus elimination by mitigating geographic and temporal barriers. Objective: To compare sustained virologic responses for hepatitis C virus among persons with opioid use disorder treated through facilitated telemedicine integrated into opioid treatment programs compared with off-site hepatitis specialist referral. Design, Setting, and Participants: Prospective, cluster randomized clinical trial using a stepped wedge design. Twelve programs throughout New York State included hepatitis C-infected participants (n = 602) enrolled between March 1, 2017, and February 29, 2020. Data were analyzed from December 1, 2022, through September 1, 2023. Intervention: Hepatitis C treatment with direct-acting antivirals through comanagement with a hepatitis specialist either through facilitated telemedicine integrated into opioid treatment programs (n = 290) or standard-of-care off-site referral (n = 312). Main Outcomes and Measures: The primary outcome was hepatitis C virus cure. Twelve programs began with off-site referral, and every 9 months, 4 randomly selected sites transitioned to facilitated telemedicine during 3 steps without participant crossover. Participants completed 2-year follow-up for reinfection assessment. Inclusion criteria required 6-month enrollment in opioid treatment and insurance coverage of hepatitis C medications. Generalized linear mixed-effects models were used to test for the intervention effect, adjusted for time, clustering, and effect modification in individual-based intention-to-treat analysis. Results: Among 602 participants, 369 were male (61.3%); 296 (49.2%) were American Indian or Alaska Native, Asian, Black or African American, multiracial, or other (ie, no race category was selected, with race data collected according to the 5 standard National Institutes of Health categories); and 306 (50.8%) were White. The mean (SD) age of the enrolled participants in the telemedicine group was 47.1 (13.1) years; that of the referral group was 48.9 (12.8) years. In telemedicine, 268 of 290 participants (92.4%) initiated treatment compared with 126 of 312 participants (40.4%) in referral. Intention-to-treat cure percentages were 90.3% (262 of 290) in telemedicine and 39.4% (123 of 312) in referral, with an estimated logarithmic odds ratio of the study group effect of 2.9 (95% CI, 2.0-3.5; P < .001) with no effect modification. Observed cure percentages were 246 of 290 participants (84.8%) in telemedicine vs 106 of 312 participants (34.0%) in referral. Subgroup effects were not significant, including fibrosis stage, urban or rural participant residence location, or mental health (anxiety or depression) comorbid conditions. Illicit drug use decreased significantly (referral: 95% CI, 1.2-4.8; P = .001; telemedicine: 95% CI, 0.3-1.0; P < .001) among cured participants. Minimal reinfections (n = 13) occurred, with hepatitis C virus reinfection incidence of 2.5 per 100 person-years. Participants in both groups rated health care delivery satisfaction as high or very high. Conclusions and Relevance: Opioid treatment program-integrated facilitated telemedicine resulted in significantly higher hepatitis C virus cure rates compared with off-site referral, with high participant satisfaction. Illicit drug use declined significantly among cured participants with minimal reinfections. Trial Registration: ClinicalTrials.gov Identifier: NCT02933970.

Utilizing Nurse Practitioners and Physician Assistants in Academic Emergency Departments Does Not Reduce Residents' Exposure to More Complex Patients.

BACKGROUND: Whether integration of nurse practitioners (NPs) and physician assistants (PAs) into academic emergency departments (EDs) affects emergency medicine (EM) resident clinical learning opportunities is unclear. OBJECTIVE: We sought to compare EM resident exposure to more-complex patients, as well as patients undergoing Accreditation Council for Graduate Medical Education (ACGME)-required procedures, at nonpediatric academic EDs with lower, moderate, and higher levels of NP/PA utilization. METHODS: In this cross-sectional study of National Hospital Ambulatory Medical Care Survey (NHAMCS) data for 2016-2020, nonpediatric academic EDs were classified into the following three groups based on the percentage of patients seen by an NP or PA: lower (≤ 10%), moderate (10.1-30%), and higher (> 30%) NP/PA utilization. The proportion of EM resident-seen patients meeting previously established complex patient criteria was then determined for EDs at each level of NP/PA utilization. The proportion of EM resident-seen patients receiving certain ACGME-required procedures was also determined. Survey analytic procedures and weighting as recommended by NHAMCS were used to calculate and compare proportions using 95% CIs. RESULTS: The weighted 2016-2020 NHAMCS data sets represent 44,130,996 adult resident-seen patients presenting to nonpediatric academic EDs. The proportion of resident-seen patients meeting complex patient criteria did not significantly differ for lower (43.2%; 95% CI 30.6-56.8%), moderate (41.7%; 95% CI 33.0-50.9%), or higher (38.9%; 95% CI 29.3-49.4%) NP/PA utilization EDs. The proportion of patients undergoing an ACGME-required procedure also did not significantly differ across level of NP/PA utilization. CONCLUSIONS: Higher levels of NP/PA utilization in nonpediatric academic EDs do not appear to reduce EM resident exposure to more-complex patients or ACGME-required procedures.

Antiviral and Anti-Inflammatory Therapeutic Effect of RAGE-Ig Protein against Multiple SARS-CoV-2 Variants of Concern Demonstrated in K18-hACE2 Mouse and Syrian Golden Hamster Models.

SARS-CoV-2 variants of concern (VOCs) continue to evolve and reemerge with chronic inflammatory long COVID sequelae, necessitating the development of anti-inflammatory therapeutic molecules. Therapeutic effects of the receptor for advanced glycation end products (RAGE) were reported in many inflammatory diseases. However, a therapeutic effect of RAGE in COVID-19 has not been reported. In the present study, we investigated whether and how the RAGE-Ig fusion protein would have an antiviral and anti-inflammatory therapeutic effect in the COVID-19 system. The protective therapeutic effect of RAGE-Ig was determined in vivo in K18-hACE2 transgenic mice and Syrian golden hamsters infected with six VOCs of SARS-CoV-2. The underlying antiviral mechanism of RAGE-Ig was determined in vitro in SARS-CoV-2-infected human lung epithelial cells (BEAS-2B). Following treatment of K18-hACE2 mice and hamsters infected with various SARS-CoV-2 VOCs with RAGE-Ig, we demonstrated (1) significant dose-dependent protection (i.e., greater survival, less weight loss, lower virus replication in the lungs); (2) a reduction of inflammatory macrophages (F4/80+/Ly6C+) and neutrophils (CD11b+/Ly6G+) infiltrating the infected lungs; (3) a RAGE-Ig dose-dependent increase in the expression of type I IFNs (IFN-α and IFN-ß) and type III IFN (IFNλ2) and a decrease in the inflammatory cytokines (IL-6 and IL-8) in SARS-CoV-2-infected human lung epithelial cells; and (4) a dose-dependent decrease in the expression of CD64 (FcgR1) on monocytes and lung epithelial cells from symptomatic COVID-19 patients. Our preclinical findings revealed type I and III IFN-mediated antiviral and anti-inflammatory therapeutic effects of RAGE-Ig protein against COVID-19 caused by multiple SARS-CoV-2 VOCs.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.

Temporal changes in the prehospital management of trauma patients: 2014-2021.

INTRODUCTION: Aggressive prehospital interventions (PHI) in trauma may not improve outcomes compared to prioritizing rapid transport. The aim of this study was to quantify temporal changes in the frequency of PHI performed by EMS. METHODS: Retrospective chart review of adult patients transported by EMS to our trauma center from January 1, 2014 to 12/31/2021. PHI were recorded and annual changes in their frequency were assessed via year-by-year trend analysis and multivariate regression. RESULTS: Between the first and last year of the study period, the frequency of thoracostomy (6% vs. 9%, p â€‹= â€‹0.001), TXA administration (0.3% vs. 33%, p â€‹< â€‹0.001), and whole blood administration (0% vs. 20%, p â€‹< â€‹0.001) increased. Advanced airway procedures (21% vs. 12%, p â€‹< â€‹0.001) and IV fluid administration (57% vs. 36%, p â€‹< â€‹0.001) decreased. ED mortality decreased from 8% to 5% (p â€‹= â€‹0.001) over the study period. On multivariate regression, no PHI were independently associated with increased or decreased ED mortality. CONCLUSION: PHI have changed significantly over the past eight years. However, no PHI were independently associated with increased or decreased ED mortality.

Short-Stay Left Colectomy for Colon Cancer: Is It Safe?

BACKGROUND: Advances in surgical practices have decreased hospital length of stay (LOS) after surgery. This study aimed to determine the safety of short-stay (≤24-hour) left colectomy for colon cancer patients in the US. STUDY DESIGN: Adult colon cancer patients who underwent elective left colectomies were identified using the American College of Surgeons NSQIP database (2012 to 2021). Patients were categorized into 4 LOS groups: LOS 1 day or less (≤24-hour short stay), 2 to 4, 5 to 6, and 7 or more. Primary outcomes were 30-day postoperative overall and serious morbidity. Secondary outcomes were 30-day mortality and readmission. Multivariable logistic regression was performed to explore the association between LOS and overall and serious morbidity. RESULTS: A total of 15,745 patients who underwent left colectomies for colon cancer were identified with 294 (1.87%) patients undergoing short stay. Short-stay patients were generally younger and healthier with lower 30-day overall morbidity rates (LOS ≤1 day: 3.74%, 2 to 4: 7.38%, 5 to 6: 16.12%, and ≥7: 37.64%, p < 0.001). Compared with patients with LOS 2 to 4 days, no differences in mortality and readmission rates were observed. On adjusted analysis, there was no statistical difference in the odds of overall (LOS 2 to 4 days: odds ratio 1.90, 95% CI 1.01 to 3.60, p = 0.049) and serious morbidity (LOS 2 to 4 days: odds ratio 0.86, 95% CI 1.42 to 1.76, p = 0.672) between the short-stay and LOS 2 to 4 days groups. CONCLUSIONS: Although currently performed at low rates in the US, short-stay left colectomy is safe for a select group of patients. Attention to patient selection, refinement of clinical pathways, and close follow-up may enable short-stay colectomies to become a more feasible reality.

Prehospital Intervention Improves Outcomes for Patients Presenting in Atrial Fibrillation with Rapid Ventricular Response.

OBJECTIVE: To compare outcomes of patients presenting to emergency medical services (EMS) with atrial fibrillation with rapid ventricular response (AF-RVR) who did and did not receive prehospital advanced life support (ALS) rate or rhythm control intervention(s). METHODS: This retrospective cohort study used the 2021 ESO Data Collaborative (Austin, TX) dataset. We identified 9-1-1 scene responses for patients aged 16 to 100 years old presenting with AF and an initial heart rate ≥ 110 beats per minute (bpm). Prehospital ALS interventions for AF-RVR included medications (e.g., calcium channel blockers, beta blockers, etc.) or electrical cardioversion. Outcome measures included prehospital rate control (i.e., final prehospital heart rate < 110 bpm), emergency department (ED) discharge to home, ED and hospital length of stay, and mortality. We also evaluated prehospital adverse events-specifically bradycardia, hypotension, and cardiac arrest. We used propensity score matching to compare outcomes among treated and untreated patients with similar demographic and clinical characteristics. We determined the average treatment effect on the treated (ATET) with 95% confidence intervals (CI) and the number needed to treat (NNT). RESULTS: After propensity score matching, prehospital outcomes were available for 4,859 treated patients matched with 4,859 similar untreated patients. Prehospital rate control was more frequent for treated than for untreated patients (41.0% vs. 18.2%, ATET +22.8%, CI: +21.1%; +24.6%, NNT = 5). Hospital outcomes were available for 1,347 treated patients matched with 1,347 similar untreated patients. Treated patients were more likely to be discharged from the ED (37.9% vs. 34.0%, ATET +3.9%, CI: +0.2%; +7.5%, NNT = 26) and less likely to die (4.3% vs. 6.7%, ATET -2.5%, CI: -4.2%; -0.8%, NNT = 40) compared to untreated patients. Hypotension occurred more often in treated patients (ATET +2.6%, CI: +1.5%; +3.7%), but resolved before ED arrival in 73% of affected patients. Otherwise, adverse event rates did not significantly differ for the two groups. CONCLUSIONS: In this propensity score matched study of patients presenting to EMS with AF-RVR, prehospital ALS interventions were associated with more frequent prehospital rate control, more frequent discharge to home from the ED, and lower mortality.

Recommitting to AACP Engaged Governance for the Common Good: Report of the 50th Anniversary Commission to Reimagine the AACP House of Delegates.

The 50th Anniversary Commission to Reimagine the American Association of Colleges of Pharmacy (AACP) House of Delegates (HOD Commission) was charged to consider and recommend changes to the AACP Board of Directors and AACP HOD regarding a broad range of issues related to the HOD. The 2021-2022 HOD Commission met virtually many times throughout the year as 2 sub-groups and a full commission, using Basecamp for shared documents and timelines, and it provided interim reports to the Board of Directors in November and February. A survey of 2022 delegates was developed and administered; responses from 163 delegates informed final recommendations as described in the report. The HOD Commission affirms the need for and purpose of AACP's HOD and urges that all schools/colleges of pharmacy recommit to engaged governance for the common good.

What quantifies good primary care in the United States? A review of algorithms and metrics using real-world data.

Primary care physicians (PCPs) play an indispensable role in providing comprehensive care and referring patients for specialty care and other medical services. As the COVID-19 outbreak disrupts patient access to care, understanding the quality of primary care is critical at this unprecedented moment to support patients with complex medical needs in the primary care setting and inform policymakers to redesign our primary care system. The traditional way of collecting information from patient surveys is time-consuming and costly, and novel data collection and analysis methods are needed. In this review paper, we describe the existing algorithms and metrics that use the real-world data to qualify and quantify primary care, including the identification of an individual's likely PCP (identification of plurality provider and major provider), assessment of process quality (for example, appropriate-care-model composite measures), and continuity and regularity of care index (including the interval index, variance index and relative variance index), and highlight the strength and limitation of real world data from electronic health records (EHRs) and claims data in determining the quality of PCP care. The EHR audits facilitate assessing the quality of the workflow process and clinical appropriateness of primary care practices. With extensive and diverse records, administrative claims data can provide reliable information as it assesses primary care quality through coded information from different providers or networks. The use of EHRs and administrative claims data may be a cost-effective analytic strategy for evaluating the quality of primary care.

Politics and the Public Health Workforce: Lessons Suggested from a Five-State Study.

Policy Points The United States public health system relies on an inadequate and inefficient mix of federal, state, and local funding. Various state-based initiatives suggest that a promising path to bipartisan support for increased public health funding is to gain the support of local elected officials by providing state (and federal) funding directly to local health departments, albeit with performance strings attached. Even with more funding, we will not solve the nation's public health workforce crisis until we make public health a more attractive career path with fewer bureaucratic barriers to entry. CONTEXT: The COVID-19 pandemic exposed the shortcomings of the United States public health system. High on the list is a public health workforce that is understaffed, underpaid, and undervalued. To rebuild that workforce, the American Rescue Plan (ARP) appropriated $7.66 billion to help create 100,000 new public health jobs. As part of this initiative, the Centers for Disease Control and Prevention (CDC) distributed roughly $2 billion to state, local, tribal, and territorial health agencies for use between July 1, 2021, and June 30, 2023. At the same time, several states have enacted (or are considering enacting) initiatives to increase state funding for their local health departments with the goal of ensuring that these departments can deliver a core set of services to all residents. The differences in approach between this first round of ARP funding and theseparate state initiatives offer an opportunity to compare, contrast, and suggest lessons learned. METHODS: After interviewing leaders at the CDC and other experts on the nation's public health workforce, we visited five states (Kentucky, Indiana, Mississippi, New York, and Washington) to examine, by means of interviews and documents, the implementation and impact of both the ARP workforce funds as well as the state-based initiatives. FINDINGS: Three themes emerged. First, states are not spending the CDC workforce funding in a timely fashion; although the specifics vary, there are several organizational, political, and bureaucratic obstacles. Second, the state-based initiatives follow different political paths but rely on the same overarching strategy: gain the support of local elected officials by providing funding directly to local health departments, albeit with performance strings attached. These state initiatives offer their federal counterparts a political roadmap toward a more robust model of public health funding. Third, even with increased funding, we will not meet the nation's public health workforce challenges until we make public health a more attractive career path (with higher pay, improved working conditions, and more training and promotion opportunities) with fewer bureaucratic barriers to entry (most importantly, with less reliance on outdated civil service rules). CONCLUSION: The politics of public health requires a closer look at the role played by county commissioners, mayors, and other local elected officials. We need a political strategy to persuade these officials that their constituents will benefit from a better public health system.

Analysis of the Gene Therapies Authorized by the United States Food and Drug Administration and the European Medicines Agency.

BACKGROUND: Gene therapy, altering the genes inside human cells, has recently emerged as an alternative for preventing and treating disease. Concerns have been expressed about the clinical value and the high cost of gene therapies. OBJECTIVE: This study assessed the characteristics of the clinical trials, authorizations, and prices of gene therapies in the United States and the European Union. RESEARCH DESIGN: We collected regulatory information from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and manufacturer-listed prices from the United States, UK, and Germany. Descriptive statistics and t tests were conducted in the study. RESULTS: As of January 1, 2022, the FDA and EMA authorized 8 and 10 gene therapies, respectively. The FDA and EMA granted orphan designation to all gene therapies except talimogene laherparepvec. Pivotal clinical trials were nonrandomized, open level, uncontrolled, phase I-III, and included a limited number of patients. Study primary outcomes were mainly surrogate endpoints without demonstration of direct patient benefit. The price of gene therapies at market entry ranged from $200,064 to $2,125,000 million. CONCLUSIONS: Gene therapy is used to treat incurable diseases that affect only a small number of patients (orphan diseases). Based on this, they are approved by the EMA and FDA with insufficient clinical evidence to ensure safety and efficacy, in addition to the high cost.

Disentangling the Cost of Orphan Drugs Marketed in the United States.

The increasing number and high prices of orphan drugs have triggered concern among patients, payers, and policymakers about the affordability of new drugs approved using the incentives set by the Orphan Drug Act (ODA) of 1983. This study evaluated the factors associated to the differences in the treatment cost of new orphan and non-orphan drugs approved by the FDA from 2017 to 2021. A generalized linear model (GLM) with the Gamma log-link analysis was used to ascertain the association of drug characteristics with the treatment costs of orphan and non-orphan drugs. The results of the study showed that the median and interquartile range (IQR) drug cost was USD 218,872 (IQR = USD 23,105) for orphan drugs and USD 12,798 (IQR = USD 57,940) for non-orphan drugs (p < 0.001). Higher market entry prices were associated with biologics (108%; p < 0.001), orphan status (177%; p < 0.001), US sponsor companies (48%; p = 0.035), chronic use (1083%; p < 0.001), treatment intent (163%; p = 0.004), and indications for oncology (624%; p < 0.001) or genetic disorders (624%; p < 0.001). Higher market entry treatment cost for newly approved drugs were associated with biologics, orphan status, US sponsor companies, chronic use, therapeutic intent, and indications for oncology or genetic disorders.

Ambulance Transport Destinations In The US Differ By Patient Race And Ethnicity.

Patients in the US belonging to racial or ethnic minority groups often receive medical care in different hospitals than White patients, which contributes to health care disparities. We explored whether ambulance transport destinations contribute to this phenomenon. Using a national emergency medical services research data set for calendar year 2020, we made within-ZIP code comparisons of the transport destinations for White patients and non-White patients transported by ambulance from emergency scenes. We used the dissimilarity index to measure transport destination discordances and decided a priori that a more than 5 percent difference in transport destinations (that is, dissimilarity index >0.05) would be practically meaningful. We found meaningful differences in the destination hospitals for White and non-White patients transported by ambulance from locations in the same ZIP code. The median ZIP code dissimilarity index was 0.08, 64 percent of ZIP codes had a dissimilarity index above 0.05, and 61 percent of patients were transported from ZIP codes with a dissimilarity index above 0.05. Forty-one percent of ZIP codes had a dissimilarity index above 0.10, and one-third of the patients were transported from those ZIP codes. These data indicate that ambulance transport destinations contribute to discordances in where White and non-White patients receive medical care.