Understanding COVID-19 Health Disparities With Birth Country and Language Data.

INTRODUCTION: Understanding of COVID-19-related disparities in the U.S. is largely informed by traditional race/ethnicity categories that mask important social group differences. This analysis utilizes granular information on patients' country of birth and preferred language from a large health system to provide more nuanced insights into health disparities. METHODS: Data from patients seeking care from a large Midwestern health system between January 1, 2019 and July 31, 2021 and COVID-19-related events occurring from March 18, 2020 to July 31, 2021 were used to describe COVID-19 disparities. Statistics were performed between January 1, 2022 and March 15, 2023. Age-adjusted generalized linear models estimated RR across race/ethnicity, country of birth grouping, preferred language, and multiple stratified groups. RESULTS: The majority of the 1,114,895 patients were born in western advanced economies (58.6%). Those who were Hispanic/Latino, were born in Latin America and the Caribbean, and preferred Spanish language had highest RRs of infection and hospitalization. Black-identifying patients born in sub-Saharan African countries had a higher risk of infection than their western advanced economies counterparts. Subanalyses revealed elevated hospitalization and death risk for White-identifying patients from Eastern Europe and Central Asia and Asian-identifying patients from Southeast Asia and the Pacific. All non-English languages had a higher risk of all COVID-19 outcomes, most notably Hmong and languages from Burma/Myanmar. CONCLUSIONS: Stratifications by country of birth grouping and preferred language identified culturally distinct groups whose vulnerability to COVID-19 would have otherwise been masked by traditional racial/ethnic labels. Routine collection of these data is critical for identifying social groups at high risk and for informing linguistically and culturally relevant interventions.

Factors Associated With Adherence to First-line Antiviral Therapy Among Commercially Insured Patients With Chronic Hepatitis B.

Background: Nonadherence to antiviral therapy can lead to poor clinical outcomes among patients with chronic hepatitis B (CHB). We used a claims database to evaluate risk factors for nonadherence to antiviral therapy among commercially insured patients with CHB in the United States. Methods: We obtained data for commercially insured adult patients with CHB prescribed entecavir or tenofovir disoproxil fumarate (TDF) in 2019. Primary outcomes were adherence to entecavir and adherence to TDF. Enrollees with a proportion of days covered (PDC) ≥80% were considered adherent. We presented adjusted odds ratios (AORs) from multivariate logistic regressions. Results: Eighty-three percent (n = 640) of entecavir patients were adherent, and 81% (n = 687) of TDF patients were adherent. Ninety-day supply (vs 30-day supply; AOR, 2.21; P < .01), mixed supply (vs 30-day supply; AOR, 2.19; P = .04), and ever using a mail order pharmacy (AOR, 1.92, P = .03) were associated with adherence to entecavir. Ninety-day supply (vs 30-day supply; AOR, 2.51; P < .01), mixed supply (vs 30-day supply; AOR, 1.82; P = .04), and use of a high-deductible health plan (vs no high-deductible health plan; AOR, 2.29; P = .01) were associated with adherence to TDF. Out-of-pocket spending of >$25 per 30-day supply of TDF was associated with reduced odds of adherence to TDF (vs <$5 per 30-day supply of TDF; AOR, 0.34; P < .01). Conclusions: Ninety-day and mixed-duration supplies of entecavir and TDF were associated with higher fill rates as compared with 30-day supplies among commercially insured patients with CHB.

Conflicts of Interest Among Infectious Diseases Clinical Practice Guideline Authors and the Pharmaceutical Industry.

This cross-sectional study assesses the prevalence of conflicts of interest (COI) associated with guideline-recommended drugs among Infectious Diseases Society of America clinical practice guideline authors and compliance with the Council on Medical Specialty Societies and Institute of Medicine guidelines.

Cost-effectiveness of treatment strategies for populations from strongyloidiasis high-risk areas globally who will initiate corticosteroid treatment in the United States.

BACKGROUND: The risk of developing strongyloidiasis hyperinfection syndrome appears to be elevated among individuals who initiate corticosteroid treatment. Presumptive treatment or treatment after screening for populations from Strongyloides stercoralis-endemic areas has been suggested before initiating corticosteroids. However, potential clinical and economic impacts of preventative strategies have not been evaluated. METHODS: Using a decision tree model for a hypothetical cohort of 1000 individuals from S. stercoralis-endemic areas globally initiating corticosteroid treatment, we evaluated clinical and economic impacts of two interventions, 'Screen and Treat' (i.e. screening and ivermectin treatment after a positive test), and 'Presumptively Treat,' compared to current practice (i.e. 'No Intervention'). We evaluated the cost-effectiveness (net cost per death averted) of each strategy using broad ranges of pre-intervention prevalence and hospitalization rates for chronic strongyloidiasis patients initiating corticosteroid treatment. RESULTS: For the baseline parameter estimates, 'Presumptively Treat' was cost-effective (i.e. clinically superior with cost per death averted less than a threshold of $10.6 million per life) compared to 'No Intervention' ($532 000 per death averted) or 'Screen and Treat' ($39 000 per death averted). The two parameters contributing the most uncertainty to the analysis were the hospitalization rate for individuals with chronic strongyloidiasis who initiate corticosteroids (baseline 0.166%) and prevalence of chronic strongyloidiasis (baseline 17.3%) according to a series of one-way sensitivity analyses. For hospitalization rates greater than 0.022%, 'Presumptively Treat' would remain cost-effective. Similarly, 'Presumptively Treat' remained preferred at prevalence rates of 4% or above; 'Screen and Treat' was preferred for prevalence between 2% and 4%, and 'No Intervention' was preferred for prevalence less than 2%. CONCLUSIONS: The findings support decision-making for interventions for populations from S. stercoralis endemic areas before initiating corticosteroid treatment. Although some input parameters are highly uncertain and prevalence varies across endemic countries, 'Presumptively Treat' would likely be preferred across a range for many populations given plausible parameters.

Evaluation of Preferred Language and Timing of COVID-19 Vaccine Uptake and Disease Outcomes.

Importance: Beyond traditional race and ethnicity demographic characteristics, additional discrete data variables are needed for informed health interventions in the US. Objective: To examine whether COVID-19 vaccine uptake patterns and associated disease outcomes differ among language preference groups. Design, Setting, and Participants: A cohort study of 851 410 individuals aged 18 years or older in a large multispecialty health system in Minnesota and western Wisconsin was conducted between December 15, 2020, and March 31, 2022. Exposure: Self-identified language preference and limited English proficiency (LEP) as measured by interpreter need were used to create subgroups using US census categories and attention to capture languages known to represent refugee groups. Main Outcomes and Measures: The primary outcome was COVID-19 vaccination uptake rates and time to first vaccine. Secondary outcomes were rates of COVID-19-associated hospitalization and death. Results: Most of the 851 410 participants (women, 493 910 [58.0%]; median age, 29 [IQR, 35-64] years) were US-born English speakers; 7.5% were born in other countries, 4.0% had a language preference other than English (LPOE), and 3.0% indicated LEP as measured by interpreter need. Marked temporal clusters were observed for COVID-19 vaccination uptake, hospitalizations, and deaths associated with primary series vaccine eligibility, booster availability, and COVID-19 variants. Delayed first-dose vaccine was observed with LPOE (hazard ratio [HR], 0.83; 95% CI, 0.82-0.84) and interpreter need (HR, 0.81; 95% CI, 0.80-0.82) compared with those with English language preference and proficiency. Patients with LPOE were approximately twice as likely to be hospitalized (rate ratio [RR], 1.85; 95% CI, 1.63-2.08) or die (RR, 2.13; 95% CI, 1.65-2.69). Patients with LEP experienced even higher rates of hospitalization (RR, 1.98; 95% CI, 1.73-2.25) and COVID-19-associated death (RR, 2.32; 95% CI, 1.79-2.95). Outcomes varied for individual language preference groups. Conclusions and Relevance: In this study, delayed time to first-dose vaccine was associated with increased COVID-19 hospitalization and death rates for specific LPOE and LEP groups. The findings suggest that data collection of language preference and interpreter need provides actionable health intervention information. Standardized system-level data collection, including at a national level, may improve efficient identification of social groups with disproportionate health disparities and provide key information on improving health equity in the US.

Costs of malaria treatment in the United States.

We estimated inpatient and outpatient payments for malaria treatment in the USA. The mean cost per hospitalized patient was significantly higher than for non-hospitalized patients (e.g. $27 642 vs $1177 among patients with private insurance). Patients with severe malaria payed two to four times more than those hospitalized with uncomplicated malaria.

Food and Drug Administration Approval of Artesunate for Severe Malaria: Enough to Achieve Best Practice?

Intravenous artesunate has been the global standard of care for severe malaria for over 2 decades. Yet, until recently, artesunate has only been available to patients through an expanded-access protocol from the Centers for Disease Control and Prevention. In May 2020, the Food and Drug Administration approved artesunate, allowing US hospitals to stock the drug and ensuring prompt treatment for this life-threatening infection. However, because of artesunate's high cost and the infrequency of severe malaria in the United States, hospitals may be reluctant to stock the drug. As US health systems weigh the decision to stock artesunate, we propose a hospital tier framework to inform this decision and support clinicians caring for patients who present with severe malaria.

Hospital pharmacy acquisition of nonstocked antimicrobials-current processes and areas for improvement.

BACKGROUND: The delivery of prompt and appropriate antimicrobial therapy for life-threatening infections is an important antimicrobial stewardship measure and a priority for hospitals. OBJECTIVES: To better understand U.S. hospital pharmacy stocking processes and acquisition of nonstocked antimicrobials and to identify strategies for improving this process. METHODS: This mixed-methods study recruited infectious diseases and antimicrobial stewardship pharmacists. Semistructured interviews with pharmacists in Minnesota were conducted via video conferencing software from January 21, 2021, to March 17, 2021. Audio recordings of the interviews guided survey development and were also transcribed, coded, and qualitatively analyzed. Surveys were distributed throughout the United States via an e-mail listserv, and responses were collected between August 5, 2021, and September 15, 2021. RESULTS: Ten interviews and 78 surveys were included in the analysis. Formulary and stocking practices varied based on institution. Stocking decisions were most frequently based on the frequency of use, clinical utility, and cost of antimicrobials. Nonstocked antimicrobials were often ordered from the wholesale distributor but, if needed urgently, acquired from another local institution. Antibacterial agents were the most frequently needed nonstocked antimicrobials, especially those targeting multidrug-resistant gram-negative bacteria. When acquiring nonstocked antimicrobials, barriers include process inefficiencies, cost, availability, and safety concerns. Improved information sharing between local institutions may help improve this process. CONCLUSION: In this exploratory study, antimicrobial stocking practices varied within U.S. hospitals. Acquisition of nonstocked, urgently needed antimicrobials from neighboring hospitals may be common; however, this process lacks guidance and is often inefficient. Establishing better mechanisms for information sharing may improve this process and should be explored.

Health Care Utilization in the 6 Months Following SARS-CoV-2 Infection.

Importance: After SARS-CoV-2 infection, many patients present with persistent symptoms for at least 6 months, collectively termed post-COVID conditions (PCC). However, the impact of PCC on health care utilization has not been well described. Objectives: To estimate COVID-19-associated excess health care utilization following acute SARS-CoV-2 infection and describe utilization for select PCCs among patients who had positive SARS-CoV-2 test results (including reverse transcription-polymerase chain reaction and antigen tests) compared with control patients whose results were negative. Design, Setting, and Participants: This matched retrospective cohort study included patients of all ages from 8 large integrated health care systems across the United States who completed a SARS-CoV-2 diagnostic test during March 1 to November 1, 2020. Patients were matched on age, sex, race and ethnicity, site, and date of SARS-CoV-2 test and were followed-up for 6 months. Data were analyzed from March 18, 2021, to June 8, 2022. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Ratios of rate ratios (RRRs) for COVID-19-associated health care utilization were calculated with a difference-in-difference analysis using Poisson regression models. RRRs were estimated overall, by health care setting, by select population characteristics, and by 44 PCCs. COVID-19-associated excess health care utilization was estimated by health care setting. Results: The final matched cohort included 127 859 patients with test results positive for SARS-CoV-2 and 127 859 patients with test results negative for SARS-CoV-2. The mean (SD) age of the study population was 41.2 (18.6) years, 68 696 patients in each group (53.7%) were female, and each group included 66 211 Hispanic patients (51.8%), 9122 non-Hispanic Asian patients (7.1%), 7983 non-Hispanic Black patients (6.2%), and 34 326 non-Hispanic White patients (26.9%). Overall, SARS-CoV-2 infection was associated with a 4% increase in health care utilization over 6 months (RRR, 1.04 [95% CI, 1.03-1.05]), predominantly for virtual encounters (RRR, 1.14 [95% CI, 1.12-1.16]), followed by emergency department visits (RRR, 1.08 [95% CI, 1.04-1.12]). COVID-19-associated utilization for 18 PCCs remained elevated 6 months from the acute stage of infection, with the largest increase in COVID-19-associated utilization observed for infectious disease sequelae (RRR, 86.00 [95% CI, 5.07-1458.33]), COVID-19 (RRR, 19.47 [95% CI, 10.47-36.22]), alopecia (RRR, 2.52 [95% CI, 2.17-2.92]), bronchitis (RRR, 1.85 [95% CI, 1.62-2.12]), pulmonary embolism or deep vein thrombosis (RRR, 1.74 [95% CI, 1.36-2.23]), and dyspnea (RRR, 1.73 [95% CI, 1.61-1.86]). In total, COVID-19-associated excess health care utilization amounted to an estimated 27 217 additional medical encounters over 6 months (212.9 [95% CI, 146.5-278.4] visits per 1000 patients). Conclusions and Relevance: This cohort study documented an excess health care burden of PCC in the 6 months after the acute stage of infection. As health care systems evolve during a highly dynamic and ongoing global pandemic, these data provide valuable evidence to inform long-term strategic resource allocation for patients previously infected with SARS-CoV-2.

Blastomycosis-Some Progress but Still Much to Learn.

Blastomycosis, caused by Blastomyces spp., is an endemic mycosis capable of causing significant disease throughout the body. Higher rates of infection are seen in the Mississippi and Ohio River valleys, the Great Lakes region of the United States and Canada, much of Africa, and, to a lesser extent, in India and the Middle East. Limited reporting inhibits our true understanding of the geographic distribution of blastomycosis. An estimated 50% of those infected remain asymptomatic. Of those who present with symptomatic disease, pulmonary involvement is most common, while the most common extrapulmonary sites are the skin, bones, genitourinary system, and central nervous system. Itraconazole is the standard therapy for mild-moderate disease. Data for other azoles are limited. Amphotericin is used for severe disease, and corticosteroids are occasionally used in severe disease, but evidence for this practice is limited. Despite increasing incidence and geographic reach in recent years, there are still significant knowledge gaps in our understanding of blastomycosis. Here, we provide an updated review of the epidemiology, clinical presentations, and diagnostic and therapeutic approaches for this infection. We also discuss areas needing further research.

Low Treatment Rates of Parasitic Diseases with Standard-of-Care Prescription Drugs in the United States, 2013-2019.

To assess appropriate drug treatment of parasitic diseases in the United States, we examined the treatment rates of 11 selected parasitic infections with standard-of-care prescription drugs and compared them to the treatment rates of two more common bacterial infections (Clostridioides difficile and streptococcal pharyngitis). We used the 2013 to 2019 IBM® MarketScan® Commercial Claims and Encounters and MarketScan® Multi-State Medicaid databases, which included up to 7 years of data for approximately 88 million and 17 million individuals, respectively, to estimate treatment rates of each infection. The number of patients diagnosed with each parasitic infection varied from 57 to 5,266, and from 12 to 2,018, respectively, across the two databases. Treatment rates of 10 of 11 selected parasitic infections (range, 0-56%) were significantly less than those for streptococcal pharyngitis and Clostridioides difficile (range, 65-85%); giardiasis treatment (64%) was comparable to Clostridioides difficile (65%) in patients using Medicaid. Treatment rates for patients with opisthorchiasis, clonorchiasis, and taeniasis were less than 10%. Although we could not verify that patients had active infections because of limitations inherent to claims data, including coding errors and the inability to review patients' charts, these data suggest a need for improved treatment of parasitic infections. Further research is needed to verify the results and identify potential clinical and public health consequences.

Low Use of Standard-of-Care Antiparasitic Drugs and Increased Estimated Outpatient Payments for Treating Schistosomiasis in the United States, 2013-19.

Drug utilization and payment estimates for standard-of-care treatment of schistosomiasis have not been reported previously in the United States. This study estimates the utilization of praziquantel (standard-of-care drug) among patients with schistosomiasis and outpatient payments among those who were treated with praziquantel, and investigates the factors associated with praziquantel use from 2013-19 using IBM's MarketScan® Commercial Claims and Encounters database. Claims data showed that only 21% of patients with schistosomiasis diagnoses were treated with praziquantel. The mean total drug payments per patient treated with praziquantel increased from $110 in 2013-14 to $612 in 2015-18 (P < 0.01), and use decreased. These factors, including residing in a rural area, having a documented Schistosoma haematobium infection, or having a first schistosomiasis diagnosis in 2015-16, were associated with a decreased likelihood of patients receiving standard-of-care treatment. Policy solutions to exorbitant drug pricing, and better awareness and education among healthcare providers about schistosomiasis-especially those practicing in rural areas with high immigrant populations-are needed.

Antifungal drug price increases in the United States, 2000-2019.

BACKGROUND: Antifungal drugs treat a variety of conditions, ranging from localised dermatologic disease to life-threatening systemic infections. Some common antifungal drugs experienced large price increases in recent years, however, factors contributing to these price increases are poorly understood. We sought to examine trends in antifungal drug prices and determine underlying drivers of price changes. METHODS: Antifungal drug products in the United States were identified using the Food and Drug Administration (FDA) Label database. For each product, we determined the wholesale acquisition cost per unit over time between 2000 and 2019, adjusting for inflation, and examined variables that could impact price: route of administration, number of FDA indications, the quantity of professional guideline recommendations, use for prophylaxis, number of FDA-approved manufacturers, and whether it was compounded. Price trajectories were clustered into four groups: (1) stable, 2) moderate, (3) high, and (4) extreme price increases. RESULTS: Of 139 identified drug products, one outlier was removed due to exorbitant price increases. Cluster 1 (n = 31) demonstrated the most stable prices with a 25% mean price increase. Clusters 2 (n = 97), 3 (n = 7), and 4 (n = 3) demonstrated moderate, high, and extreme price increases with 52%, 318%, and 900% mean price increases, respectively. Atypical routes of administration and compounding were over-represented in clusters 3 and 4. There was no correlation between the number of manufacturers and price changes. CONCLUSIONS: Antifungal drugs exhibited large, inflation-adjusted price increases. Atypical routes of administration and compounding were over-represented within clusters exhibiting extraordinary price increases. Our data support policies aiming to curb large price increases for medically important drugs.

Incidence of Guillain-Barré Syndrome After COVID-19 Vaccination in the Vaccine Safety Datalink.

Importance: Postauthorization monitoring of vaccines in a large population may detect rare adverse events not identified in clinical trials such as Guillain-Barré syndrome (GBS), which has a background rate of 1 to 2 per 100 000 person-years. Objective: To describe cases and incidence of GBS following COVID-19 vaccination and assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines. Design, Setting, and Participants: This cohort study used surveillance data from the Vaccine Safety Datalink at 8 participating integrated health care systems in the United States. There were 10 158 003 participants aged at least 12 years. Data analysis was performed from November 2021 to February 2022. Exposures: Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine, including mRNA vaccine doses 1 and 2, December 13, 2020, to November 13, 2021. Main Outcomes and Measures: GBS with symptom onset in the 1 to 84 days after vaccination, confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared with the background rate, rate ratios (RRs) comparing GBS incidence in the 1 to 21 vs 22 to 42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs mRNA vaccination, using Poisson regression adjusted for age, sex, race and ethnicity, site, and calendar day. Results: From December 13, 2020, through November 13, 2021, 15 120 073 doses of COVID-19 vaccines were administered to 7 894 989 individuals (mean [SE] age, 46.5 [0.02] years; 8 138 318 doses received [53.8%] by female individuals; 3 671 199 doses received [24.3%] by Hispanic or Latino individuals, 2 215 064 doses received [14.7%] by Asian individuals, 6 266 424 doses received [41.4%] by White individuals), including 483 053 Ad.26.COV2.S doses, 8 806 595 BNT162b2 doses, and 5 830 425 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of GBS per 100 000 person-years in the 1 to 21 days after Ad.26.COV2.S was 32.4 (95% CI, 14.8-61.5), significantly higher than the background rate, and the adjusted RR in the 1 to 21 vs 22 to 42 days following Ad.26.COV2.S was 6.03 (95% CI, 0.79-147.79). Thirty-six cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate per 100 000 person-years in the 1 to 21 days after mRNA vaccines was 1.3 (95% CI, 0.7-2.4) and the adjusted RR in the 1 to 21 vs 22 to 42 days following mRNA vaccines was 0.56 (95% CI, 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs mRNA vaccines, the adjusted RR was 20.56 (95% CI, 6.94-64.66). Conclusions and Relevance: In this cohort study of COVID-19 vaccines, the incidence of GBS was elevated after receiving the Ad.26.COV2.S vaccine. Surveillance is ongoing.

Drug-dispensing limits within Medicaid during the COVID-19 pandemic.

SUMMARY The 1-month drug-dispensing limit is a common drug utilization tool used by state Medicaid agencies to control spending. Since the beginning of the COVID-19 pandemic, many states relaxed the 1-month dispensing limit restriction in order to align with social distancing recommendations. Yet, some states have not relaxed this limit and have differed substantially regarding the policies that have been implemented. Among states that relaxed the 1-month supply limit, determining which chronic disease drugs qualified for this extension can be challenging for patients and clinicians. As more commercial and Medicare insurance beneficiaries are offered 90-day drug supplies, the 30-day drug supply limit with Medicaid has become a health equity issue, since many individuals insured by Medicaid have already experienced a disproportionate impact from and remain at high risk for severe COVID-19 disease. Thus, we propose policy solutions to ensure that Medicaid beneficiaries have safe and uninterrupted access to chronic disease medications during and beyond the COVID-19 pandemic. DISCLOSURES: No funding was received for this work. Alpern has received funding from Arnold Ventures for research related to the use and spending of off-patent drugs, unrelated to this work, and is a member of the Pharmacy and Therapeutics Committee at Regions Hospital, St. Paul, MN. DeSilva has received CDC support for work on Vaccine Safety Datalink, VISION network, and Center of Excellence for Newcomer Health, unrelated to this work. Chomilo is Medicaid Medical Director for the State of Minnesota's Department of Human Services.

The Erosion of Public Trust and SARS-CoV-2 Vaccines- More Action Is Needed.

As states and health systems prepare to deliver severe acute respiratory syndrome coronavirus 2 vaccines to the American public, a confluence of factors has the potential to interfere with these efforts: misinformation about coronavirus disease 2019, vaccine hesitancy, and the erosion of the American public's trust in the vaccine regulatory process due to recent and ongoing events. Broad action is needed to address these issues, including improved and consistent communication by the Food and Drug Administration, restoration of the Centers for Disease Control as an independent and science-driven institution, and more aggressive policies to counteract misinformation, particularly on social media platforms.