Epidemiology of RSV in Adults and Children with Medically-Attended Acute Respiratory Illness over Three Seasons.

BACKGROUND: Data on the true prevalence of RSV among medically-attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over three seasons, which is informative in light of the recommendations for shared decision-making for vaccination in older adults. METHODS: Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated Multimorbidity-Weighted Index (MWI) were collected by in-person survey and electronic medical record review. RESULTS: Over three surveillance seasons (fall 2017 to spring 2020), 9.9% (n=441) of 4,442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months-4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). CONCLUSIONS: RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision-making for vaccination.

Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023.

As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.

K-medoids clustering of hospital admission characteristics to classify severity of influenza virus infection.

Background: Patients are admitted to the hospital for respiratory illness at different stages of their disease course. It is important to appropriately analyse this heterogeneity in surveillance data to accurately measure disease severity among those hospitalized. The purpose of this study was to determine if unique baseline clusters of influenza patients exist and to examine the association between cluster membership and in-hospital outcomes. Methods: Patients hospitalized with influenza at two hospitals in Southeast Michigan during the 2017/2018 (n = 242) and 2018/2019 (n = 115) influenza seasons were included. Physiologic and laboratory variables were collected for the first 24 h of the hospital stay. K-medoids clustering was used to determine groups of individuals based on these values. Multivariable linear regression or Firth's logistic regression were used to examine the association between cluster membership and clinical outcomes. Results: Three clusters were selected for 2017/2018, mainly differentiated by blood glucose level. After adjustment, those in C171 had 5.6 times the odds of mechanical ventilator use than those in C172 (95% CI: 1.49, 21.1) and a significantly longer mean hospital length of stay than those in both C172 (mean 1.5 days longer, 95% CI: 0.2, 2.7) and C173 (mean 1.4 days longer, 95% CI: 0.3, 2.5). Similar results were seen between the two clusters selected for 2018/2019. Conclusion: In this study of hospitalized influenza patients, we show that distinct clusters with higher disease acuity can be identified and could be targeted for evaluations of vaccine and influenza antiviral effectiveness against disease attenuation. The association of higher disease acuity with glucose level merits evaluation.

Prevalence and Clinical Outcomes of Respiratory Syncytial Virus vs Influenza in Adults Hospitalized With Acute Respiratory Illness From a Prospective Multicenter Study.

BACKGROUND: Current understanding of severe respiratory syncytial virus (RSV) infections in adults is limited by clinical underrecognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses (ARIs) in a prospective national surveillance network. METHODS: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across 3 respiratory seasons from hospitals participating across all sites of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (2016-2019). All participants were tested for RSV and influenza using real-time reverse-transcription polymerase chain reaction assay. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. RESULTS: Among 10 311 hospitalized adults, 6% tested positive for RSV (n = 622), 18.8% for influenza (n = 1940), and 75.1% negative for RSV and influenza (n = 7749). Congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) was more frequent with RSV than influenza (CHF: 37.3% vs 28.8%, P < .0001; COPD: 47.6% vs 35.8%, P < .0001). Patients with RSV more frequently had longer admissions (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.06-1.80) for stays >1 week) and mechanical ventilation (OR, 1.45; 95% CI, 1.09-1.93) compared with influenza but not compared with the influenza-negative group (OR, 1.03; 95% CI, .82-1.28 and OR, 1.17; 95% CI, .91-1.49, respectively). CONCLUSIONS: The prevalence of RSV across 3 seasons was considerable. Our findings suggest that those with RSV have worse outcomes compared with influenza and frequently have cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults with severe ARI.

Incidence and economic burden of respiratory syncytial virus among adults in the United States: A retrospective analysis using 2 insurance claims databases.

BACKGROUND: Respiratory syncytial virus (RSV) is a common, contagious, and seasonal pathogen causing 64 million acute respiratory infections annually in adults and children worldwide. High-risk adults, including older adults and those with cardiopulmonary conditions or weakened immune systems, are more likely to be infected. However, limited information exists on RSV incidence and associated costs among adults, including high-risk patients. OBJECTIVE: To evaluate the annual incidence of medically attended, International Classification of Diseases (ICD)-coded RSV among commercially insured adults and assess health care costs among adults with ICD-coded RSV in the United States. METHODS: Optum's deidentified Clinformatics Data Mart Database (January 01, 2007, to June 30, 2020) and IBM's MarketScan Databases (January 01, 2000, to July 31, 2020) were used. Medically attended, ICD-coded RSV incidence among adults was assessed from July 1 of a given year to June 30 of the next year and reported per 100,000 population. Trends in all-cause mean weekly costs pre-RSV and post-RSV diagnosis were reported. Results were reported overall and among patients aged 60-64 years, 65 years or older, 85 years or older, and 18-59 years at high risk of severe RSV (defined as having cardiopulmonary conditions or a weakened immune system). RESULTS: Annual incidence of medically attended, ICD-coded RSV in adults overall was 22.0-52.9 in Optum and 23.4-63.6 in MarketScan. Incidence rates were higher among patients aged 60-64 years (Optum: 25.2-66.1; MarketScan: 31.9-82.1), 65 years or older (Optum: 37.3-75.5; MarketScan: 54.1-97.3), 85 years or older (Optum: 92.4-140.6; MarketScan: 79.4-234.7), and 18-59 years at high risk of severe RSV (Optum: 41.3-135.9; MarketScan: 46.3-112.4). Mean weekly costs increased during the week before (Optum: $2,325; MarketScan: $2,080) and post-RSV diagnosis (Optum: $9,523; MarketScan: $3,551), compared with those in weeks 2-8 pre-RSV diagnosis (Optum: $1,350; MarketScan: $872). The increases in mean weekly costs during the week before and the week following RSV diagnosis were higher among patients aged 60-64 years (mean weekly costs in weeks 2-8 pre-RSV, week 1 pre-RSV, week 1 post-RSV; Optum: $1,623, $2,690, $10,823; MarketScan: $1,259, $2,992, $5,069), 65 years or older (Optum: $1,731, $3,067, $12,866; MarketScan: $1,517, $3,571, $5,268), 85 years or older (Optum: $1,563, $2,430, $18,134; MarketScan: $1,613, $4,113, $6,231), and 18-59 years at high risk of severe RSV (only for MarketScan: $1,237, $3,294, $5,531; costs were similar for Optum). CONCLUSIONS: Incidence of medically attended, ICD-coded RSV in adults was 22.0-63.6 per 100,000 population, a likely underestimation since RSV was not systematically tested and only RSV-coded cases were observed. Incremental costs associated with RSV were substantial. Incidence rates and costs were higher among patients aged 60 years or older and patients at high risk of severe RSV. DISCLOSURES: This study was sponsored by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design, interpretation of results, manuscript preparation, and publication decisions. B. Brookhart and D. Anderson are employees of Janssen Scientific Affairs, LLC, and are stockholders of Johnson & Johnson. C. Rossi, B. Emond, J. Wang, P. Lefebvre, and M.-H. Lafeuille are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study and manuscript. M. Mesa-Frias. and S. Drummond are former employees of Janssen Scientific Affairs, LLC. L. Lamerato is an employee of Henry Ford Health System and received research funding from Janssen Scientific Affairs, LLC.

Prescription Patterns of Novel Antihyperglycemic Medications.

BACKGROUND: Glucagon-like peptide-1 agonists (GLP-1a) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are recommended in carefully selected patients with type 2 diabetes. This study will assess prescription of these medications and investigate predictors of prescription. METHODS: This retrospective cross-sectional study included 31,354 patients. Data including sociodemographic descriptors, clinical histories, medications, and health insurance providers were extracted from a health system's administrative databases. Variables to be associated with prescription of a GLP-1a or SGLT-2i were assessed using a multivariable logistic regression model. RESULTS: Mean age was 62.58 years and 40.8% identified as African American. Only 3.4% were prescribed a GLP-1a and 2.1% received a SGLT-2i. Logistic regression demonstrated lower odds of receiving either medication in the highest age-group (70 to 79 years) (GLP-1a: odds ratio [OR] 0.44, P < .01, SGLT-2i: OR 0.39, P < .01) and in African Americans (GLP-1a: OR 0.64, P < .01, SGLT-2i: OR 0.28, P < .01). Atherosclerotic cardiovascular disease was not associated with GLP-1a prescription (P = .54) and conferred lower odds of being prescribed SGLT-2i (OR 0.68, P < .01). History of chronic kidney disease conferred lower odds of receiving GLP-1a and was not associated with the odds of receiving SGLT-2i. CONCLUSIONS: Prescription of GLP-1a and SGLT-2i medications was low as compared with existing literature. Advanced age and African American race were negatively associated with prescription of these medications. Contrary to guideline recommendations; atherosclerotic cardiovascular disease and chronic kidney disease were not positively associated with prescription.

Vaccine effectiveness against COVID-19 among symptomatic persons aged ≥12 years with reported contact with COVID-19 cases, February-September 2021.

BACKGROUND: Individuals in contact with persons with COVID-19 are at high risk of developing COVID-19; protection offered by COVID-19 vaccines in the context of known exposure is poorly understood. METHODS: Symptomatic outpatients aged ≥12 years reporting acute onset of COVID-19-like illness and tested for SARS-CoV-2 between February 1 and September 30, 2021 were enrolled. Participants were stratified by self-report of having known contact with a COVID-19 case in the 14 days prior to illness onset. Vaccine effectiveness was evaluated using the test-negative study design and multivariable logistic regression. RESULTS: Among 2229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2-positive. Adjusted vaccine effectiveness was 71% (95% confidence interval [CI], 49%-83%) among fully vaccinated participants reporting a known contact versus 80% (95% CI, 72%-86%) among those with no known contact (p-value for interaction = 0.2). CONCLUSIONS: This study contributes to growing evidence of the benefits of vaccinations in preventing COVID-19 and support vaccination recommendations and the importance of efforts to increase vaccination coverage.

Management of hepatocellular carcinoma from diagnosis in routine clinical practice.

Aim: To assess real-world management of patients diagnosed with hepatocellular carcinoma (HCC) within an integrated delivery network. Materials & methods: A retrospective cohort analysis of adults newly diagnosed with HCC from January 2014 to March 2019. Overall survival and treatment journey were assessed over the entire available follow-up period per patient. Results: Of the 462 patients, 85% had ≥1 treatment. The 24-month overall survival rate (95% CI) from first treatment was 77% (72-82%). Majority of Child-Pugh class A (71%) and B (60%) patients received locoregional therapy first. Half (53.6%) of the patients with liver transplantation first were Child-Pugh class C patients. Sorafenib was the predominant systemic therapy. Conclusion: This integrated delivery network data analysis offers a comprehensive insight into the real-world management of HCC.

Messenger RNA Vaccine Effectiveness Against Coronavirus Disease 2019 Among Symptomatic Outpatients Aged ≥16 Years in the United States, February-May 2021.

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care.

Fitness and prostate cancer screening, incidence, and mortality: Results from the Henry Ford Exercise Testing (FIT) Project.

BACKGROUND: The relation between cardiorespiratory fitness (CRF) and prostate cancer is not well established. The objective of this study was to determine whether CRF is associated with prostate cancer screening, incidence, or mortality. METHODS: The Henry Ford Exercise Testing Project is a retrospective cohort study of men aged 40 to 70 years without cancer who underwent physician-referred exercise stress testing from 1995 to 2009. CRF was quantified in metabolic equivalents of task (METs) (<6 [reference], 6-9, 10-11, and ≥12 METs), estimated from the peak workload achieved during a symptom-limited, maximal exercise stress test. Prostate-specific antigen (PSA) testing, incident prostate cancer, and all-cause mortality were analyzed with multivariable adjusted Poisson regression and Cox proportional hazard models. RESULTS: In total, 22,827 men were included, of whom 739 developed prostate cancer, with a median follow-up of 7.5 years. Men who had high fitness (≥12 METs) had an 28% higher risk of PSA screening (95% CI, 1.2-1.3) compared with those who had low fitness (<6 METs. After adjusting for PSA screening, fitness was associated with higher prostate cancer incidence (men aged <55 years, P = .02; men aged >55 years, P ≤ .01), but not with advanced prostate cancer. Among the men who were diagnosed with prostate cancer, high fitness was associated with a 60% lower risk of all-cause mortality (95% CI, 0.2-0.9). CONCLUSIONS: Although men with high fitness are more likely to undergo PSA screening, this does not fully account for the increased incidence of prostate cancer seen among these individuals. However, men with high fitness have a lower risk of death after a prostate cancer diagnosis, suggesting that the cancers identified may be low-risk with little impact on long-term outcomes.

A retrospective analysis of the relationship between race/ethnicity, age at delivery and the risk of gestational diabetes mellitus.

Objectives: To investigate the relationship between maternal race/ethnicity, maternal age at delivery, and the risk of gestational diabetes mellitus (GDM).Research design: Patients of Henry Ford Health System who delivered a live singleton child and were diagnosed with or without GDM in 2010-2015 were included. Maternal race/ethnicity, age, body mass index (BMI), parity, GDM in previous pregnancy, smoking status, and insurance membership were collected from the electronic health records. Neighborhood median family income data were obtained from US Census Bureau. Logistic regression analysis was performed to explore the effects of maternal race/ethnicity and age at delivery on the GDM outcome after adjusting for covariates including maternal BMI, parity, previous GDM, smoking status, and neighborhood family income.Results: There were 16,258 women included in the study. Of those, 1801 women (12.5%) were diagnosed with GDM. Delivery at older ages (≥23 years) was associated with a significantly higher risk of a GDM diagnosis than younger ages [<23 years, OR (95% CI) = 2.24 (1.84, 2.73)-5.02 (4.18, 6.03)], however, the risk was not as profound in African American women (OR = 1.65) compared to non-African American women (OR = 2.07). In a multivariable model controlling for age, BMI, parity, previous GDM, smoking status, and the neighborhood family income, the risks of a GDM diagnosis were significantly higher in Asians [OR (95% CI) = 2.81 (2.28, 3.48)], Hispanics [OR (95% CI) = 1.27 (1.05, 1.55)], and Arab Americans [OR (95% CI) = 1.46 (1.20, 1.78)] and lower in African Americans [OR (95% CI) = 0.64 (0.56, 0.74)] as compared to whites.Conclusions: Asians, Hispanics, and Arab Americans have higher risk and African Americans have lower risk of a GDM diagnosis compared to whites. Delivery at an older maternal age increases the risk of GDM diagnosis. Race/ethnicity moderates the association between older maternal age and risk of GDM diagnosis. This study provides information for public health professionals, health practitioners, and pregnant women to be aware of and better understand the risk of GDM as related to race/ethnicity and maternal age.

Influenza Vaccine Effectiveness in the Inpatient Setting: Evaluation of Potential Bias in the Test-Negative Design by Use of Alternate Control Groups.

The test-negative design is validated in outpatient, but not inpatient, studies of influenza vaccine effectiveness. The prevalence of chronic pulmonary disease among inpatients can lead to nonrepresentative controls. Test-negative design estimates are biased if vaccine administration is associated with incidence of noninfluenza viruses. We evaluated whether control group selection and effects of vaccination on noninfluenza viruses biased vaccine effectiveness in our study. Subjects were enrolled at the University of Michigan and Henry Ford hospitals during the 2014-2015 and 2015-2016 influenza seasons. Patients presenting with acute respiratory infection were enrolled and tested for respiratory viruses. Vaccine effectiveness was estimated using 3 control groups: negative for influenza, positive for other respiratory virus, and pan-negative individuals; it was also estimated for other common respiratory viruses. In 2014-2015, vaccine effectiveness was 41.1% (95% CI: 1.7, 64.7) using influenza-negative controls, 24.5% (95% CI: -42.6, 60.1) using controls positive for other virus, and 45.8% (95% CI: 5.7, 68.9) using pan-negative controls. In 2015-2016, vaccine effectiveness was 68.7% (95% CI: 44.6, 82.5) using influenza-negative controls, 63.1% (95% CI: 25.0, 82.2) using controls positive for other virus, and 71.1% (95% CI: 46.2, 84.8) using pan-negative controls. Vaccination did not alter odds of other respiratory viruses. Results support use of the test-negative design among inpatients.

Cardiorespiratory fitness and incident lung and colorectal cancer in men and women: Results from the Henry Ford Exercise Testing (FIT) cohort.

BACKGROUND: To the authors' knowledge, the relationship between cardiorespiratory fitness (CRF) and lung and colorectal cancer outcomes is not well established. METHODS: A retrospective cohort study was performed of 49,143 consecutive patients who underwent clinician-referred exercise stress testing from 1991 through 2009. The patients ranged in age from 40 to 70 years, were without cancer, and were treated within the Henry Ford Health System in Detroit, Michigan. CRF, measured in metabolic equivalents of task (METs), was categorized as <6 (reference), 6 to 9, 10 to 11, and ≥12. Incident cancer was obtained through linkage to the cancer registry and all-cause mortality from the National Death Index. RESULTS: Participants had a mean age of 54 ± 8 years. Approximately 46% were female, 64% were white, 29% were black, and 1% were Hispanic. The median follow-up was 7.7 years. Cox proportional hazard models, adjusted for age, race, sex, body mass index, smoking history, and diabetes, found that those in the highest fitness category (METs ≥12) had a 77% decreased risk of lung cancer (hazard ratio [HR], 0.23; 95% CI, 0.14-0.36) and a 61% decreased risk of incident colorectal cancer (HR, 0.39; 95% CI, 0.23-0.66; with additional adjustment for aspirin and statin use). Among those diagnosed with lung and colorectal cancer, those with high fitness had a decreased risk of subsequent death of 44% and 89%, respectively (HR, 0.56 [95% CI, 0.32-1.00] and HR, 0.11 [95% CI, 0.03-0.37], respectively). CONCLUSIONS: In what to the authors' knowledge is the largest study performed to date, higher CRF was associated with a lower risk of incident lung and colorectal cancer in men and women and a lower risk of all-cause mortality among those diagnosed with lung or colorectal cancer.

Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population.

BACKGROUND: Influenza vaccines are important for prevention of influenza-associated hospitalization. However, the effectiveness of influenza vaccines can vary by year and influenza type and subtype and mechanisms underlying this variation are incompletely understood. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness in hospitalized populations. METHODS: We enrolled adults hospitalized for treatment of acute respiratory illnesses during the 2014-2015 and 2015-2016 influenza seasons whose symptoms began <10 days prior to enrollment. Influenza infection status was determined by RT-PCR. Influenza vaccination status was defined by self-report and medical record/registry documentation. Serum specimens collected at hospital admission were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated how well antibody measured in these specimens represented pre-infection immune status, and measured associations between antibody and influenza vaccination and infection. RESULTS: Serum specimens were retrieved for 315 participants enrolled during the 2014-2015 season and 339 participants during the 2015-2016 season. Specimens were collected within 3 days of illness onset from 65% of participants. Geometric mean titers (GMTs) did not vary by the number of days from illness onset to specimen collection among influenza positive participants suggesting that measured antibody was representative of pre-infection immune status rather than a de novo response to infection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated. HAI titers against the 2014-2015 A(H3N2) vaccine strain did not correlate with protection from infection with antigenically-drifted A(H3N2) viruses that circulated that season. In contrast, higher HAI titers against the A(H1N1)pdm09 vaccine strain were associated with reduced odds of A(H1N1)pdm09 infection in 2015-2016. CONCLUSIONS: Serum collected shortly after illness onset at hospital admission can be used to assess correlates of protection against influenza infection. Broader implementation of similar studies would provide an opportunity to understand the successes and shortcomings of current influenza vaccines.

Assessing the Protective Potential of H1N1 Influenza Virus Hemagglutinin Head and Stalk Antibodies in Humans.

Seasonal influenza viruses are a major cause of human disease worldwide. Most neutralizing antibodies (Abs) elicited by influenza viruses target the head domain of the hemagglutinin (HA) protein. Anti-HA head Abs can be highly potent, but they have limited breadth since the HA head is variable. There is great interest in developing new universal immunization strategies that elicit broadly neutralizing Abs against conserved regions of HA, such as the stalk domain. Although HA stalk Abs can provide protection in animal models, it is unknown if they are present at sufficient levels in humans to provide protection against naturally acquired influenza virus infections. Here, we quantified H1N1 HA head- and stalk-specific Abs in 179 adults hospitalized during the 2015-2016 influenza virus season. We found that HA head Abs, as measured by hemagglutinin inhibition (HAI) assays, were associated with protection against naturally acquired H1N1 infection. HA stalk-specific serum total IgG titers were also associated with protection, but this association was attenuated and not statistically significant after adjustment for HA head-specific Ab titers. We found slightly higher titers of HA stalk-specific IgG1 and IgA Abs in sera from uninfected participants than in sera from infected participants; however, we found no difference in serum in vitro antibody-dependent cellular cytotoxicity activity. In passive transfer experiments, sera from participants with high HAI activity efficiently protected mice, while sera with low HAI activity protected mice to a lower extent. Our data suggest that HA head Abs are more efficient at protecting against H1N1 infection than HA stalk Abs.IMPORTANCE Abs targeting the HA head of influenza viruses are often associated with protection from influenza virus infections. These Abs typically have limited breadth, since mutations frequently arise in HA head epitopes. New vaccines targeting the more conserved HA stalk domain are being developed. Abs that target the HA stalk are protective in animal models, but it is unknown if these Abs exist at protective levels in humans. Here, we completed experiments to determine if Abs against the HA head and stalk were associated with protection from naturally acquired human influenza virus infections during the 2015-2016 influenza season.

Multimorbidity is associated with uptake of influenza vaccination.

OBJECTIVE: Patients with chronic conditions have higher rates of severe influenza-related illness and mortality. However, influenza vaccination coverage in high-risk populations continues to be suboptimal. We describe the association between cumulative disease morbidity, measured by a previously validated multimorbidity index, and influenza vaccination among community-dwelling adults. METHODS: We obtained interview and medical record data for participants  ≥18 years who sought outpatient care for influenza-like illness between 2011 and 2016 as part of an outpatient-based study of influenza vaccine effectiveness. We defined cumulative disease morbidity by using medical diagnosis codes to calculate a multimorbidity-weighted index (MWI) for each participant. MWI and influenza vaccination status was evaluated by logistic regression. Akaike information criterion was calculated for all models. RESULTS: Overall, 1458 (48%) of participants out of a total of 3033 received influenza vaccination. The median MWI was 0.9 (IQR 0.00-3.5) and was higher among vaccinated participants (median 1.6 versus 0.0; p < 0.001). We found a positive linear association between MWI and vaccination, and vaccination percentages were compared between categories of MWI. Compared to patients with no multimorbidity (MWI = 0), odds of vaccination were 17% higher in the second category (MWI 0.01-1.50; [OR: 1.17, 95% CI: 0.92-1.50]), 58% higher in the third category (MWI 1.51-3.00; [OR: 1.58, 95% CI: 1.26-1.99]), 130% higher in the fourth category (MWI 3.01-6.00; [OR: 2.30, 95% CI: 1.78-2.98]) and 214% higher in the fifth category (MWI 6.01-45.00;[OR: 3.14, 95% CI: 2.41-4.10]). Participants defined as high-risk had 86% greater odds of being vaccinated than non-high-risk individuals (OR: 1.86, 95% CI: 1.56-2.21). The AIC was lowest for MWI compared with high-risk conditions. CONCLUSIONS: Our results suggest a dose response relationship between level of multimorbidity and likelihood of influenza vaccination. Compared with high-risk condition designations, MWI provided improved precision and a better model fit for the measurement of chronic disease and influenza vaccination.

USE OF ELECTRONIC HEALTH RECORDS TO CHARACTERIZE A RARE DISEASE IN THE U.S.: TREATMENT, COMORBIDITIES, AND FOLLOW-UP TRENDS AMONG PATIENTS WITH A CONFIRMED DIAGNOSIS OF ACROMEGALY.

OBJECTIVE: Understanding of acromegaly disease management is hampered in the U.S. by the lack of a national registry. We describe medical management in a population with confirmed acromegaly. METHODS: Inpatient and outpatient electronic health records (EHRs) were used to create a database of de-identified patients assigned the Acromegaly and Gigantism International Classification of Diseases, 9th revision (ICD-9) code and/or an appropriate pituitary procedure code at 1 of 4 regional hospital systems over a 6- to 11-year period. Information regarding demographics, medical history, labs, procedures, and medications was collected and supplemented with a chart review to validate the diagnosis of acromegaly. RESULTS: Of 367 patients with validated acromegaly, available records showed that during the years studied, pituitary surgery was performed on 31%, 4% received radiosurgery, and 22% were prescribed a drug indicated for acromegaly. Insulin-like growth factor-1 (IGF-1) levels were measured in 62% of patients, 83% of whom had at least 1 normal value. Coded comorbidities reflect those reported previously in patients with acromegaly, with the exception of esophageal reflux in 20% of patient records. Fewer data regarding acromegaly-specific medications and testing were available for patients aged 65 and older. CONCLUSION: AcroMEDIC is a U.S. multisite retrospective study of acromegaly that captured medical management in the majority of patients included in the cohort. Chart review highlighted the importance of verification of coded diagnoses. Most of the acromegaly-related comorbidities identified here are known to increase with age and obesity. Patients ≥65 appeared to have less active management/monitoring of their disease. Medical attention should be directed to this population to address evolving needs over time. ABBREVIATIONS: AcroMEDIC = Acromegaly Multisite Electronic Data Innovative Consortium; BMI = body mass index; CCI = Charlson Comorbidity Index; EHR = electronic health record; GH = growth hormone; GHRA = growth hormone receptor antagonist; ICD-9 = International Classification of Diseases, 9th revision; IGF-1 = insulin-like growth factor-1; SSA = somatostatin analogue.

Development and Validation of Algorithms to Identify Statin Intolerance in a US Administrative Database.

OBJECTIVES: To develop and validate algorithms to define statin intolerance (SI) in an administrative database using electronic medical records (EMRs) as the reference comparison. METHODS: One thousand adults with one or more qualifying changes in statin therapy and one or more previous diagnoses of hyperlipidemia, hypercholesterolemia, or mixed dyslipidemia were identified from the Henry Ford Health System administrative database. Data regarding statin utilization, comorbidities, and adverse effects were extracted from the administrative database and corresponding EMR. Patients were stratified by cardiovascular (CV) risk. SI was classified as absolute intolerance or titration intolerance on the basis of changes in statin utilization and/or the occurrence of adverse effects and laboratory testing for creatine kinase. Measures of concordance (Cohen's kappa [κ]) and accuracy (sensitivity, specificity, positive predictive value [PPV], and negative predictive value) were calculated for the administrative database algorithms. RESULTS: Half of the sample population was white, 52.9% were women, mean age was 60.6 years, and 35.7% were at high CV risk. SI was identified in 11.5% and 14.0%, absolute intolerance in 2.2% and 3.1%, and titration intolerance in 9.7% and 11.8% of the patients in the EMR and the administrative database, respectively. The algorithm identifying any SI had substantial concordance (κ = 0.66) and good sensitivity (78.1%), but modest PPV (64.0%). The titration intolerance algorithm performed better (κ = 0.74; sensitivity 85.4%; PPV 70.1%) than the absolute intolerance algorithm (κ = 0.40; sensitivity 50%; PPV 35.5%) and performed best in the high CV-risk group (n = 353), with robust concordance (κ = 0.73) and good sensitivity (80.9%) and PPV (75.3%). CONCLUSIONS: Conservative but comprehensive algorithms are available to identify SI in administrative databases for application in real-world research. These are the first validated algorithms for use in administrative databases available to decision makers.

Influenza Vaccine Effectiveness Against Antigenically Drifted Influenza Higher Than Expected in Hospitalized Adults: 2014-2015.

BACKGROUND: The 2014-2015 influenza season was severe, with circulating influenza A (H3N2) viruses that were antigenically drifted from the vaccine virus. Reported vaccine effectiveness (VE) estimates from ambulatory care settings were markedly decreased. METHODS: Adults, hospitalized at 2 hospitals in southeast Michigan for acute respiratory illnesses, defined by admission diagnoses, of ≤10 days duration were prospectively enrolled. Throat and nasal swab specimens were collected, combined, and tested for influenza by real-time reverse transcription polymerase chain reaction. VE was estimated by comparing the vaccination status of those testing positive for influenza with those testing negative in logistic regression models adjusted for age, sex, hospital, calendar time, time from illness onset to specimen collection, frailty score, and Charlson comorbidity index (CCI). RESULTS: Among 624 patients included in the analysis, 421 (68%) were vaccinated, 337 (54%) were female, 220 (35%) were age ≥65 years, and 92% had CCI > 0, indicating ≥1 comorbid conditions. Ninety-eight (16%) patients tested positive for influenza A (H3N2); among 60 (61%) A (H3N2) viruses tested by pyrosequencing, 53 (88%) belonged to the drifted 3C.2a genetic group. Adjusted VE was 43% (95% confidence interval [CI], 4-67) against influenza A (H3N2); 40% (95% CI, -13 to 68) for those <65 years, and 48% (95% CI, -33 to 80) for those ≥65 years. Sensitivity analyses largely supported these estimates. CONCLUSIONS: VE estimates appeared higher than reports from similar studies in ambulatory care settings, suggesting that the 2014-2015 vaccine may have been more effective in preventing severe illness requiring hospitalization.

The occurrence of hyponatremia and its importance as a prognostic factor in a cross-section of cancer patients.

BACKGROUND: Hyponatremia is prognostic of higher mortality in some cancers but has not been well studied in others. We used a longitudinal design to determine the incidence and prognostic importance of euvolemic and hypervolemic hyponatremia in patients following diagnosis with lymphoma, breast (BC), colorectal (CRC), small cell lung (SCLC), or non-small cell lung cancer (NSCLC). METHODS: Medical record and tumor registry data from two large integrated delivery networks were combined for patients diagnosed with lymphoma, BC, CRC, or lung cancers (2002-2010) who had ≥1 administration of radiation/chemotherapy within 6 months of diagnosis and no evidence of hypovolemic hyponatremia. Hyponatremia incidence was measured per 1000 person-years (PY). Cox proportional hazard models assessed the prognostic value of hyponatremia as a time-varying covariate on overall survival (OS) and progression-free survival (PFS). RESULTS: Hyponatremia incidence (%, rate) was 76 % each, 1193 and 2311 per 1000 PY, among NSCLC and SCLC patients, respectively; 37 %, 169 in BC; 64 %, 637 in CRC, and 60 %, 395 in lymphoma. Hyponatremia was negatively associated with OS in BC (HR 3.7; P = <.01), CRC (HR 2.4; P < .01), lung cancer (HR 2.4; P < .01), and lymphoma (HR 4.5; P < .01). Hyponatremia was marginally associated with shorter PFS (HR 1.3, P = .07) across cancer types. CONCLUSIONS: The incidence of hyponatremia is higher than previously reported in lung cancer, is high in lymphoma, BC, and CRC and is a negative prognostic indicator for survival. Hyponatremia incidence in malignancy may be underestimated. The effects of hyponatremia correction on survival in cancer patients require further study.