Relative Vaccine Effectiveness of Cell- vs Egg-Based Quadrivalent Influenza Vaccine Against Test-Confirmed Influenza Over 3 Seasons Between 2017 and 2020 in the United States.

Background: Influenza vaccine viruses grown in eggs may acquire egg-adaptive mutations that may reduce antigenic similarity between vaccine and circulating influenza viruses and decrease vaccine effectiveness. We compared cell- and egg-based quadrivalent influenza vaccines (QIVc and QIVe, respectively) for preventing test-confirmed influenza over 3 US influenza seasons (2017-2020). Methods: Using a retrospective test-negative design, we estimated the relative vaccine effectiveness (rVE) of QIVc vs QIVe among individuals aged 4 to 64 years who had an acute respiratory or febrile illness and were tested for influenza in routine outpatient care. Exposure, outcome, and covariate data were obtained from electronic health records linked to pharmacy and medical claims. Season-specific rVE was estimated by comparing the odds of testing positive for influenza among QIVc vs QIVe recipients. Models were adjusted for age, sex, geographic region, influenza test date, and additional unbalanced covariates. A doubly robust approach was used combining inverse probability of treatment weights with multivariable regression. Results: The study included 31 824, 33 388, and 34 398 patients in the 2017-2018, 2018-2019, and 2019-2020 seasons, respectively; ∼10% received QIVc and ∼90% received QIVe. QIVc demonstrated superior effectiveness vs QIVe in prevention of test-confirmed influenza: rVEs were 14.8% (95% CI, 7.0%-22.0%) in 2017-2018, 12.5% (95% CI, 4.7%-19.6%) in 2018-2019, and 10.0% (95% CI, 2.7%-16.7%) in 2019-2020. Conclusions: This study demonstrated consistently superior effectiveness of QIVc vs QIVe in preventing test-confirmed influenza over 3 seasons characterized by different circulating viruses and degrees of egg adaptation.

Incidence of Influenza-Related Medical Encounters and the Associated Healthcare Resource Use and Complications Across Adult Age Groups in The United States During the 2015-2020 Influenza Seasons.

BACKGROUND: Research on influenza burden in adults has focused on crude subgroups with cut-points at 65-years, limiting insight into how burden varies with increasing age. This study describes the incidence of influenza-related outpatient visits, emergency room (ER) visits, and hospitalizations, along with healthcare resource use and complications in the aging adult population. METHODS: Individuals ≥18 years of age in the United States were evaluated retrospectively in five seasonal cohorts (2015-2020 seasons) in strata of age with 5-year increments. Person-level electronic medical records linked to pharmacy and medical claims were used to ascertain patient characteristics and outcomes. Influenza-related medical encounters were identified based on diagnostic codes (ICD-10 codes J09*-J11*). RESULTS: Incidence of influenza-related outpatient visits was highest among people aged 18-34 years and declined with increasing age. For ER visits, incidence tended to be elevated for people aged 18-34 years, relatively stable from 35 through 60, and increased rapidly after 60. Hospitalization incidence remained relatively stable until about 50 years of age and then increased with age. One in three patients was diagnosed with pneumonia after hospitalization, regardless of age. Across seasons, age groups, and clinical settings, on average, 40.8% of individuals were prescribed antivirals and 17.2% antibiotics. CONCLUSIONS: Incidence of influenza-related hospitalizations begins to increase around age 50 rather than the more common cut-point of 65, whereas incidence of outpatient visits was highest among younger adults. Influenza infections frequently led to antiviral and antibiotic prescriptions, underscoring the role influenza vaccination can play in combating antimicrobial resistance.

Comparison of COVID-19 and Influenza-Related Outcomes in the United States during Fall-Winter 2022-2023: A Cross-Sectional Retrospective Study.

Influenza and COVID-19 contribute significantly to the infectious disease burden during the respiratory season, but their relative burden remains unknown. This study characterizes the frequency and severity of medically attended COVID-19 and influenza during the peak of the 2022-2023 influenza season in the pediatric, adult, and older adult populations and characterizes the prevalence of underlying conditions among patients hospitalized with COVID-19. This cross-sectional analysis included individuals in the Veradigm EHR Database linked to Komodo claims data with a medical encounter between 1 October 2022 and 31 March 2023 (study period). Patients with medical encounters were identified with a diagnosis of COVID-19 or influenza during the study period and stratified based on the highest level of care received with that diagnosis. Among 23,526,196 individuals, there were more COVID-19-related medical encounters than influenza-related encounters, overall and by outcome. Hospitalizations with COVID-19 were more common than hospitalizations with influenza overall (incidence ratio = 4.6) and in all age groups. Nearly all adults hospitalized with COVID-19 had at least one underlying medical condition, but 37.1% of 0-5-year-olds and 25.0% of 6-17-year-olds had no underlying medical conditions. COVID-19 was associated greater burden than influenza during the peak of the 2022-2023 influenza season.

Comparative Effectiveness of Bivalent (Original/Omicron BA.4/BA.5) COVID-19 Vaccines in Adults.

The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech), were developed to provide greater protection against the predominate circulating variants by including mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US using a nationwide dataset linking primary care electronic health records and pharmacy/medical claims data. The study population (aged ≥18 years) received either vaccine between 31 August 2022 and 28 February 2023. We used propensity score weighting to adjust for baseline differences between groups. We estimated the rVE against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary) for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients, with an adjusted rVE of 9.8% (95% confidence interval: 2.6-16.4%) and 5.1% (95% CI: 3.2-6.9%), respectively, for mRNA-1273.222 versus BNT162b2 Bivalent. The incremental relative effectiveness was greater among adults ≥ 65; the rVE against COVID-19-related hospitalizations and outpatient visits in these patients was 13.5% (95% CI: 5.5-20.8%) and 10.7% (8.2-13.1%), respectively. Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults.

The incremental cost of non-alcoholic steatohepatitis and type 2 diabetes in the United States using real-world data.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) and type 2 diabetes (T2D) are both linked to substantial healthcare costs and are often co-occurring. We aim to quantify the incremental cost of NASH and T2D using real-world data. METHODS: Adults (≥18 years old) with ≥2 diagnosis codes for NASH and/or ≥2 diagnosis codes for T2D between 1/1/2016 and 12/31/2021 and ≥24 months of continuous claims enrollment (study period) were identified in electronic health records or claims in the Veradigm Integrated Dataset. Patients were stratified into 3 cohorts: NASH-only, T2D-only, and NASH + T2D. We calculated annualized costs for the 24-month study period and fit a generalized linear model (excluding the most expensive 1%) that controlled for disease cohort, age, sex, and modified Charlson comorbidity index to estimate the per year all-cause healthcare costs and incremental cost of adding T2D to a NASH diagnosis (or vice versa). RESULTS: We identified 23,111 patients diagnosed with NASH-only, 3,548,786 patients with T2D-only, and 30,339 patients with NASH + T2D. The model-predicted mean costs per year were $7,668 for patients with NASH-only, $11,226 for patients with T2D-only, and $16,812 for patients with NASH + T2D. The incremental increase in costs per year of adding T2D to NASH was 63% (+$4,846), and the incremental increase in costs per year of adding NASH to T2D was 42% (+$4,692). CONCLUSIONS: Both NASH and T2D contribute to the high healthcare costs among patients with a dual diagnosis. Results from our analysis indicate that NASH comprises a high portion of total healthcare costs among patients with NASH and T2D.

Relative Effectiveness of BNT162b2, mRNA-1273, and Ad26.COV2.S Vaccines and Homologous Boosting in Preventing COVID-19 in Adults in the US.

Background: Few head-to-head comparisons have been performed on the real-world effectiveness of coronavirus disease 2019 (COVID-19) booster vaccines. We evaluated the relative effectiveness (rVE) of a primary series of mRNA-1273 vs BNT162b2 and Ad26.COV2.S and a homologous mRNA booster against any medically attended, outpatient, and hospitalized COVID-19. Methods: A data set linking primary care electronic medical records with medical claims data was used for this retrospective cohort study of US patients age ≥18 years vaccinated with a primary series between February and October 2021 (Part 1) and a homologous mRNA booster between October 2021 and January 2022 (Part 2). Adjusted hazard ratios (HRs) were derived from 1:1 matching adjusted across potential covariates. rVE was (1 - HRadjusted) × 100. Additional analysis was performed across regions and age groups. Results: Following adjustment, Part 1 rVE for mRNA-1273 vs BNT162b2 was 23% (95% CI, 22%-25%), 23% (95% CI, 22%-25%), and 19% (95% CI, 14%-24%), while the rVE for mRNA-1273 vs Ad26.COV2.S was 50% (95% CI, 48%-51%), 50% (95% CI, 48%-52%), and 57% (95% CI, 53%-61%) against any medically attended, outpatient, and hospitalized COVID-19, respectively. The adjusted rVE in Part 2 for mRNA-1273 vs BNT162b2 was 14% (95% CI, 10%-18%), 13% (95% CI, 8%-17%), and 19% (95% CI, 1%-34%) against any medically attended, outpatient, and hospitalized COVID-19, respectively. rVE against medically attended COVID-19 was higher in adults age ≥65 years (35%; 95% CI, 24%-47%) than in those age 18-64 years (13%; 95% CI, 9%-17%) after the booster. Conclusions: In this study, mRNA-1273 was more effective than BNT162b2 or Ad26.COV2.S following a primary series during the Delta-dominant period and more effective than BNT162b2 as a booster during the Omicron-dominant period.

Healthcare resource utilization and costs of care in the United States for patients with non-alcoholic steatohepatitis.

AIMS: This retrospective, observational cohort study aimed to determine the burden of comorbidities, hospitalization, and healthcare costs among patients with non-alcoholic steatohepatitis (NASH) in the United States stratified by fibrosis-4 (FIB-4) or body mass index (BMI). METHODS: Adults with NASH were identified in the Veradigm Health Insights Electronic Health Record Database and linked Komodo claims data. The index date was the earliest coded NASH diagnosis between 1 January 2016 and 31 December 2020 with valid FIB-4 and ≥6 months of database activity and continuous enrollment pre- and post-index. We excluded patients with viral hepatitis, alcohol-use disorder, or alcoholic liver disease. Patients were stratified by FIB-4: FIB-4 ≤ 0.95, 0.95 < FIB-4 ≤ 2.67, 2.67 < FIB-4 ≤ 4.12, FIB-4 > 4.12) or BMI (BMI <25, 25 ≤ BMI ≤30, BMI > 30). Multivariate analysis was used to assess the relationship of FIB-4 with costs and hospitalizations. RESULTS: Among 6,743 qualifying patients, index FIB-4 was ≤0.95 for 2,345 patents, 0.95-2.67 for 3,289 patients, 2.67-4.12 for 571 patients, and >4.12 for 538 patients (mean age 55.8 years; 62.9% female). Mean age, comorbidity burden, cardiovascular disease risk, and healthcare utilization increased with increasing FIB-4. Mean ± SD annual costs increased from $16,744±$53,810 to $34,667±$67,691 between the lowest and highest FIB-4 cohorts and were higher among patients with BMI <25 ($24,568±$81,250) than BMI >30 ($21,542±$61,490). A one-unit increase in FIB-4 at index was associated with a 3.4% (95%CI: 1.7%-5.2%) increase in mean total annual cost and an 11.6% (95%CI: 8.0%-15.3%) increased likelihood of hospitalization. CONCLUSIONS: A higher FIB-4 was associated with increased healthcare costs and risk of hospitalization in adults with NASH; however, even patients with FIB-4 ≤ 0.95 presented a significant burden.

Influenza Vaccine Uptake in the United States before and during the COVID-19 Pandemic.

The COVID-19 pandemic, along with disruptions to routine medical care, brought renewed urgency to public health messaging about the importance of influenza vaccination. This retrospective cohort study used a database of linked claims and electronic medical record data to evaluate clinical and demographic characteristics and influenza vaccination history associated with changes in influenza vaccine uptake following the start of the COVID-19 pandemic. Influenza vaccine uptake was examined in six seasons (2015−2016 through 2020−2021). Individuals were grouped by vaccination history in the five seasons before 2020−2021. Characteristics of 2020−2021 vaccinated vs. unvaccinated individuals were compared, stratified by vaccination history. Overall influenza vaccination uptake was highest in 2020−2021 (35.4%), following a trend of increasing uptake since 2016−2017 (31.4%). Uptake in 2020−2021 was observed in all age groups except ≥65 years, and the increase was particularly notable in individuals <18 years. In the previous five seasons, individuals ≤17 and >65 years, White, and Asian individuals were most likely, while 18-to-49-year-olds and those with fewer comorbidities were least likely, to be consistently vaccinated. Influenza vaccination status in 2020−2021 aligned with vaccination history; few differences in patient characteristics (age, comorbidities, state of residence) were observed when stratified by vaccination history.

A Qualitative Analysis of Provider Notes of Atopic Dermatitis-Related Visits Using Natural Language Processing Methods.

INTRODUCTION: Real-world disease management of atopic dermatitis (AD) is hampered by a lack of consistency between providers that treat AD regarding assessment of severity, disease activity, and quality of life. Variability and inconsistency in documentation makes it difficult to understand the impact of AD. This study summarizes AD-related symptoms and concerns captured in unstructured qualitative provider notes by healthcare providers during visits with patients with AD. METHODS: Provider notes were obtained for patients with AD (n = 133,025) from a USA-based ambulatory electronic health records system. The sample included both children (n = 69,551) and adults at least 18 years of age (n = 63,474) receiving treatment from a variety of specialties including primary care, dermatology, and allergy/immunology. Key skin-related words were identified from a review of a sample of notes and natural language processing (NLP) was applied to determine the frequency of the keywords and bigram patterns. RESULTS: Provider notes largely focused on symptoms (primarily itch) and symptom relief rather than the impact of AD on work or lifestyle. Despite the known relationship between itch and skin pain, neuralgia was not widely documented. Compared to primary care providers, dermatologists' and allergist/immunologists' notes had more documentation of symptom-related issues. Personal and work/life burden issues were not widely documented regardless of specialty. CONCLUSION: The topics documented in case notes by healthcare providers about their patients with AD focus largely on symptoms and, to a lesser extent, treatment, but do not reflect the burden of AD on patients' lives. This finding highlights a potential care gap that warrants further investigation.

Glycemic Control Among Patients Newly Prescribed IDegLira Across Prior Therapy Group in US Real-World Practice.

INTRODUCTION: IDegLira is a fixed-ratio combination of insulin degludec and liraglutide indicated for the treatment of type 2 diabetes (T2D). We report the first real-world study describing change in glycated hemoglobin (HbA1c) among US patients who initiated IDegLira. The aim of the study was to observe and describe changes in glycemic control and weight in patients initiating IDegLira in real-world clinical practice. METHODS: Patients in the Practice Fusion electronic medical record database who initiated treatment with IDegLira between March 2017 and June 2018 were identified (n = 1384). To be included in the analyses, the study population needed to meet age, time in database pre- and post-initiation, and availability of HbA1c data at baseline and follow-up requirements. Data were analyzed according to baseline therapy subgroups and whether patients were intensifying (primary analysis group) or simplifying (secondary analysis group) their diabetes treatment. Changes in clinical outcomes from baseline were evaluated by paired t tests and linear regression. RESULTS: The overall study population comprised 296 patients, of whom 206 were included in the primary analysis group and 90 were included in the secondary analysis group. In the adjusted analyses, there was a reduction in HbA1c of - 1.1% in the primary analysis group, with the HbA1c reduction in all prior therapy groups ranging from - 0.8% for those previously on basal insulin to - 1.0% for those previously on non-injectable therapy (p < 0.0001 for all). In a similar adjusted analysis, there was a statistically significant but small (1.0 lb/0.45 kg) change in weight in the primary analysis group. In the secondary analysis, patients previously on more than one injection daily switched to a more simplified therapy without compromising on glycemic control (HbA1c change of - 0.16%). CONCLUSION: Consistent with previous real-world studies, IDegLira lowered HbA1c across different background prior glucose-lowering therapies, with minimal impact on weight.

How well can familial hypercholesterolemia be identified in an electronic health record database?

BACKGROUND: Familial hypercholesterolemia (FH) is a condition characterized by high cholesterol levels and increased risk for coronary heart disease (CHD) that often goes undiagnosed. The Dutch Lipid Network Criteria (DLNC) are used to identify FH in clinical settings via physical examination, personal and family history of CHD, in addition to the presence of deleterious mutations of the LDLR, ApoB, and PCSK9 genes. Agreement between clinical and genetic diagnosis of FH varies. While an ICD diagnosis code was not available for coding FH until 2016, Systematized Nomenclature of Medicine (SNOMED) clinical concept codes, including genetic diagnoses, for FH have been utilized in electronic health records (EHRs). OBJECTIVE: To evaluate the concordance of identifying FH via SNOMED and ICD-10 CM codes vs the DLNC in an EHR database. METHODS: Using the Practice Fusion EHR database, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated comparing an FH cohort identified via SNOMED and ICD-10 CM codes to one identified via the DLNC. RESULTS: Among 907,616 patients with hypercholesterolemia, 2,180 were identified as FH via SNOMED code (zero were identified via ICD-10 CM), 259 had a DLNC score 6-8 (probable FH), and 45 had a DLNC score >8 (definite FH). Compared to DLNC score >8, the sensitivity, specificity, and PPV of the FH SNOMED code were 84.4%, 99.4%, and 6.4%, respectively. Compared to DLNC score ≥6, the sensitivity was 36.8% and the specificity was 99.5% with a PPV of 18.7%. CONCLUSION: Compared to the clinical criteria for FH, identification of FH patients via SNOMED diagnosis codes had high sensitivity and specificity, but low PPV. The discordance of these two techniques in identifying FH patients speaks to the challenges in identifying FH patients in large electronic databases such as administrative claims and EHR.

Effectiveness of a Cloud-Based EHR Clinical Decision Support Program for Body Mass Index (BMI) Screening and Follow-up.

The effectiveness of a clinical decision support (CDS) program encouraging clinicians to record patient's Body Mass Index (BMI) and document appropriate follow-up plans is evaluated. Test (4,987 practices, 33,445 clinicians) and control groups (881 practices, 6,316 clinicians) were selected using stratified random sampling. Three CDS alerts for BMI screening and follow-up based on evidence based clinical quality guidelines were displayed at the point of care in a cloud-based EHR. The effectiveness of the CDS program was measured over 4 months by tracking recorded BMI and documented follow-up plans. Over the program, BMI recording increased minimally and documentation of follow-up plans increased 5-fold (p=0.05) compared to the control group. The overweight test group patients (18- 64yo) gained less weight (p=0.06) than the control group and underweight patients gained more weight (p<0.01) during the program period. Outcome studies with longer follow-up periods are needed to further confirm positive outcomes.

Dialysis care and death following Hurricane Sandy.

BACKGROUND: Hurricane Sandy affected access to critical health care infrastructure. Patients with end-stage renal disease (ESRD) historically have experienced problems accessing care and adverse outcomes during disasters. STUDY DESIGN: Retrospective cohort study with 2 comparison groups. SETTING & PARTICIPANTS: Using Centers for Medicare & Medicaid Services claims data, we assessed the frequency of early dialysis, emergency department (ED) visits, hospitalizations, and 30-day mortality for patients with ESRD in Sandy-affected areas (study group) and 2 comparison groups: (1) patients with ESRD living in states unaffected by Sandy during the same period and (2) patients with ESRD living in the Sandy-affected region a year prior to the hurricane (October 1, 2011, through October 30, 2011). FACTOR: Regional variation in dialysis care patterns and mortality for patients with ESRD in New York City and the State of New Jersey. MEASUREMENTS: Frequency of early dialysis, ED visits, hospitalizations, and 30-day mortality. RESULTS: Of 13,264 study patients, 59% received early dialysis in 70% of the New York City and New Jersey dialysis facilities. The ED visit rate was 4.1% for the study group compared with 2.6% and 1.7%, respectively, for comparison groups 1 and 2 (both P<0.001). The hospitalization rate for the study group also was significantly higher than that in either comparison group (4.5% vs 3.2% and 3.8%, respectively; P<0.001 and P<0.003). 23% of study group patients who visited the ED received dialysis in the ED compared with 9.3% and 6.3% in comparison groups 1 and 2, respectively (both P<0.001). The 30-day mortality rate for the study group was slightly higher than that for either comparison group (1.83% vs 1.47% and 1.60%, respectively; P<0.001 and P=0.1). LIMITATIONS: Lack of facility level damage and disaster-induced power outage severity data. CONCLUSIONS: Nearly half the study group patients received early dialysis prior to Sandy's landfall. Poststorm increases in ED visits, hospitalizations, and 30-day mortality were found in the study group, but not in the comparison groups.

Using Medicare data to identify individuals who are electricity dependent to improve disaster preparedness and response.

During a disaster or prolonged power outage, individuals who use electricity-dependent medical equipment are often unable to operate it and seek care in acute care settings or local shelters. Public health officials often report that they do not have proactive and systematic ways to rapidly identify and assist these individuals. In June 2013, we piloted a first-in-the-nation emergency preparedness drill in which we used Medicare claims data to identify individuals with electricity-dependent durable medical equipment during a disaster and securely disclosed it to a local health department. We found that Medicare claims data were 93% accurate in identifying individuals using a home oxygen concentrator or ventilator. The drill findings suggest that claims data can be useful in improving preparedness and response for electricity-dependent populations.