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.

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Development and validation of algorithms for identifying lines of therapy in multiple myeloma using real-world data.

Aim: To validate algorithms based on electronic health data to identify composition of lines of therapy (LOT) in multiple myeloma (MM). Materials & methods: This study used available electronic health data for selected adults within Henry Ford Health (Michigan, USA) newly diagnosed with MM in 2006-2017. Algorithm performance in this population was verified via chart review. As with prior oncology studies, good performance was defined as positive predictive value (PPV) ≥75%. Results: Accuracy for identifying LOT1 (N = 133) was 85.0%. For the most frequent regimens, accuracy was 92.5-97.7%, PPV 80.6-93.8%, sensitivity 88.2-89.3% and specificity 94.3-99.1%. Algorithm performance decreased in subsequent LOTs, with decreasing sample sizes. Only 19.5% of patients received maintenance therapy during LOT1. Accuracy for identifying maintenance therapy was 85.7%; PPV for the most common maintenance therapy was 73.3%. Conclusion: Algorithms performed well in identifying LOT1 - especially more commonly used regimens - and slightly less well in identifying maintenance therapy therein.

Electronic health data helps us understand treatment in the 'real world'. The data has great value in cancer if we can identify the drugs patients get. Yet this is hard in multiple myeloma (MM), where treatment is complex. Algorithms (set of decision rules) to identify drugs can help here. We tested an existing algorithm for identifying 'lines of therapy' (LOT) given to patients with MM. Each LOT included one or more drugs for MM. We also developed and tested a new algorithm for 'maintenance therapy'. This is a treatment given to help maintain the response to the main MM treatment. We tested how well the algorithms identified MM treatments in electronic health data. This data came from Henry Ford Health, a healthcare system in Michigan, USA. Treatments were confirmed by cancer specialists who reviewed medical charts. The LOT algorithm was good at finding the first LOT patients. The maintenance algorithm did a fair job of identifying the most used therapy. Our algorithms could help researchers study the real-world treatment of MM.

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.

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.

Epidemiology and outcomes in patients with anemia of CKD not on dialysis from a large US healthcare system database: a retrospective observational study.

BACKGROUND: Optimal management of anemia of chronic kidney disease (CKD) remains controversial. This retrospective study aimed to describe the epidemiology and selected clinical outcomes of anemia in patients with CKD in the US. METHODS: Data were extracted from Henry Ford Health System databases. Adults with stages 3a-5 CKD not on dialysis (estimated glomerular filtration rate < 60 mL/min/1.73m2) between January 1, 2013 and December 31, 2017 were identified. Patients on renal replacement therapy or with active cancer or bleeding were excluded. Patients were followed for ≥12 months until December 31, 2018. Outcomes included incidence rates per 100 person-years (PY) of anemia (hemoglobin < 10 g/dL), renal and major adverse cardiovascular events, and of bleeding and hospitalization outcomes. Adjusted Cox proportional hazards models identified factors associated with outcomes after 1 and 5 years. RESULTS: Among the study cohort (N = 50,701), prevalence of anemia at baseline was 23.0%. Treatments used by these patients included erythropoiesis-stimulating agents (4.1%), iron replacement (24.2%), and red blood cell transfusions (11.0%). Anemia incidence rates per 100 PY in patients without baseline anemia were 7.4 and 9.7 after 1 and 5 years, respectively. Baseline anemia was associated with increased risk of renal and major cardiovascular events, hospitalizations (all-cause and for bleeding), and transfusion requirements. Increasing CKD stage was associated with increased risk of incident anemia, renal and major adverse cardiovascular events, and hospitalizations. CONCLUSIONS: Anemia was a prevalent condition associated with adverse renal, cardiovascular, and bleeding/hospitalization outcomes in US patients with CKD. Anemia treatment was infrequent.

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.

Risk of chemotherapy-induced febrile neutropenia in patients with metastatic cancer not receiving granulocyte colony-stimulating factor prophylaxis in US clinical practice.

OBJECTIVES: To evaluate the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis in US patients with selected metastatic cancers and chemotherapy-induced febrile neutropenia (FN) incidence and associated outcomes among the subgroup who did not receive prophylaxis. METHODS: This retrospective cohort study was conducted at four US health systems and included adults with metastatic cancer (breast, colorectal, lung, non-Hodgkin lymphoma [NHL]) who received myelosuppressive chemotherapy (2009-2017). Patients were stratified by FN risk level based on risk factors and chemotherapy (low/unclassified risk, intermediate risk without any risk factors, intermediate risk with ≥ 1 risk factor [IR + 1], high risk [HR]). G-CSF use was evaluated among all patients stratified by FN risk, and FN/FN-related outcomes were evaluated among patients who did not receive first-cycle G-CSF prophylaxis. RESULTS: Among 1457 metastatic cancer patients, 20.5% and 28.1% were classified as HR and IR + 1, respectively. First-cycle G-CSF prophylaxis use was 48.5% among HR patients and 13.9% among IR + 1 patients. In the subgroup not receiving first-cycle G-CSF prophylaxis, FN incidence in cycle 1 was 7.8% for HR patients and 4.8% for IR + 1 patients; during the course, corresponding values were 16.9% and 15.9%. Most (> 90%) FN episodes required hospitalization, and mortality risk ranged from 7.1 to 26.9% across subgroups. CONCLUSION: In this retrospective study, the majority of metastatic cancer chemotherapy patients for whom G-CSF prophylaxis is recommended did not receive it; FN incidence in this subgroup was notably high. Patients with elevated FN risk should be carefully identified and managed to ensure appropriate use of supportive care.

Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States.

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation. METHODS: Data were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing > 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation. RESULTS: Overall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P < 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P < 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232). CONCLUSIONS: Significant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting.

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.

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.

Effect of clinically significant thresholds of eosinophil elevation on health care resource use in asthma.

BACKGROUND: Blood eosinophil counts correlate with exacerbations, but there is a lack of consensus on a clinically relevant definition of eosinophil count elevation. OBJECTIVE: To analyze health care resource use among patients with elevated blood eosinophil counts defined at 150 cells/µL or greater and 300 cells/µL or greater. METHODS: Data on patients who received a diagnosis of asthma between 2007 and 2016 were extracted from EMRClaims + database. Patients were defined as having elevated eosinophil counts if any test result during 3 months before follow-up found blood eosinophil count of 150 cells/µL or more or 300 cells/µL or more. Hospitalizations, emergency department visits, outpatient visits, and associated costs were compared. With logistic regression, likelihood of hospitalization was assessed in the presence of eosinophil elevation. RESULTS: Among 3687 patients who met the study criteria, 1152 received a test within 3 months before the follow-up period, of whom 644 (56%) had elevated eosinophil counts of 150 cells/µL or greater and 322 (29%) had eosinophil counts of 300 cells/µL or greater. Overall, the mean (SD) number of hospitalizations for patients with elevated eosinophil counts vs the comparator was significantly greater (0.29 [0.92] vs 0.17 [0.57], P < .001 at ≥150 cells/µL and 0.30 [0.95] vs 0.18 [0.61] at ≥300 cells/µL, P = .001). The total mean cost was significantly greater for patients with elevated eosinophil counts (at ≥150 cells/µL: $10,262 vs $7149, P < .001 and at ≥300 cells/µL: $9966 vs $7468, P = .003). CONCLUSION: Patients with asthma incurred greater health care resource use when their blood eosinophil counts were elevated at 150 cells/µL or greater and 300 cells/µL or greater as measured within 3 months of follow-up.

Prenatal airshed pollutants and preterm birth in an observational birth cohort study in Detroit, Michigan, USA.

Detroit, Michigan, currently has the highest preterm birth (PTB) rate of large cities in the United States. Disproportionate exposure to ambient air pollutants, including particulate matter ≤2.5 µm (PM2.5), PM ≤ 10 µm (PM10), nitrogen dioxide (NO2) and benzene, toluene, ethylbenzene, and xylenes (BTEX) may contribute to PTB. Our objective was to examine the association of airshed pollutants with PTB in Detroit, MI. The Geospatial Determinants of Health Outcomes Consortium (GeoDHOC) study collected air pollution measurements at 68 sites in Detroit in September 2008 and June 2009. GeoDHOC data were coupled with 2008-2010 Michigan Air Sampling Network measurements in Detroit to develop monthly ambient air pollution estimates at a spatial density of 300 m2. Using delivery records from two urban hospitals, we established a retrospective birth cohort of births by Detroit women occurring from June 2008 to May 2010. Estimates of air pollutant exposure throughout pregnancy were assigned to maternal address at delivery. Our analytic sample size included 7961 births; 891 (11.2%) were PTB. After covariate adjustment, PM10 (P = 0.003) and BTEX (P < 0.001), but not PM2.5 (P = 0.376) or NO2 (P = 0.582), were statistically significantly associated with PTB. In adjusted models, for every 5-unit increase in PM10 there was a 1.21 times higher odds of PTB (95% CI 1.07, 1.38) and for every 5-unit increase in BTEX there was a 1.54 times higher odds of PTB (95% CI 1.25, 1.89). Consistent with previous studies, higher PM10 was associated with PTB. We also found novel evidence that higher airshed BTEX is associated with PTB. Future studies confirming these associations and examining direct measures of exposure are needed.

Add-on tiotropium versus step-up inhaled corticosteroid plus long-acting beta-2-agonist in real-world patients with asthma.

Background: A step-up approach (increasing inhaled corticosteroid [ICS] dose and/or add-on treatment) is recommended for asthma that is uncontrolled despite ICS plus long-acting beta-2-agonist (LABA) combination treatment. Understanding the impact of different treatment options on health outcomes can help guide treatment decision-making. Objective: To compare the effectiveness of add-on tiotropium 1.25 µg (two puffs once daily) versus an increased ICS plus LABA dose in a real-world cohort of patients with asthma initiated on ICS plus LABA. Methods: De-identified data from patients ages ≥12 years and with asthma who were initiated on ICS plus LABA, and then had tiotropium added (Tio group; index date) or an ICS plus LABA dose increased (inc-ICS group; index date) were collected from two medical and pharmacy claims data bases (2014-2018). To account for population/group differences, propensity score matching was performed. The primary end point was the exacerbation risk after the index date. Secondary end points included exacerbation rates 6 and 12 months postindex, health-care resource utilization, costs, and short-acting beta-2-agonist (SABA) refills 12 months postindex. Results: Overall, 7857 patients (Tio group, 2619; inc-ICS group, 5238) were included. The exacerbation risk was 35% lower in the Tio group than in the inc-ICS group (hazard ratio 0.65 [95% confidence interval, 0.43-0.99]; p = 0.044). Exacerbation rates in the Tio group also were significantly lower within 6 and 12 months postindex (64% and 73%, respectively). All-cause and asthma-related emergency department (ED) visits were 47% and 74% lower, respectively (p < 0.0001 for both), and all-cause and asthma-related hospitalizations were 48% (p < 0.01) and 76% (p < 0.001) lower, respectively, in the Tio group. Also, significantly fewer patients in the Tio group versus the inc-ICS group required SABA refills (56% versus 67%, p < 0.0001). Conclusion: Add-on tiotropium significantly decreased the risk and rate of exacerbations, decreased all-cause and asthma-related ED visits and hospitalizations, and reduced SABA refills compared with increasing the ICS plus LABA dose. The findings supported the use of add-on tiotropium for patients with uncontrolled asthma taking ICS plus LABA.

Tight versus standard blood pressure control on the incidence of myocardial infarction and stroke: an observational retrospective cohort study in the general ambulatory setting.

BACKGROUND: The 2017 American College of Cardiology and American Heart Association guideline defined hypertension as blood pressure (BP) ≥ 130/80 mmHg compared to the traditional definition of ≥140/90 mmHg. This change raised much controversy. We conducted this study to compare the impact of tight (TBPC) versus standard BP control (SBPC) on the incidence of myocardial infarction (MI) and stroke. METHODS: We retrospectively identified all hypertensive patients in an ambulatory setting based on the diagnostic code for 1 year at our institution who were classified by the range of BP across 3 years into 2 groups of TBPC (< 130 mmHg) and SBPC (130-139 mmHg). We compared the incidence of new MI and stroke between the 2 groups across a 2-year follow-up. Multivariate analysis was done to identify independent predictors for the incidence of new MI and stroke. RESULTS: Of 5640 study patients, the TBPC group showed significantly less incidence of stroke compared to the SBPC group (1.5% vs. 2.7%, P < 0.010). No differences were found in MI incidence between the 2 groups (0.6% vs. 0.8%, P = 0.476). Multivariate analysis showed that increased age independently increased the incidence of both MI (OR 1.518, 95% CI 1.038-2.219) and stroke (OR 1.876, 95% CI 1.474-2.387), and TBPC independently decreased the incidence of stroke (OR 0.583, 95% CI 0.374-0.910) but not of MI. CONCLUSIONS: Our observational study suggests that TBPC may be beneficial in less stroke incidence compared to SBPC but it didn't seem to affect the incidence of MI. Our study is limited by its retrospective design with potential confounders.

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.

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.

Diabetes mellitus and hyperglycemia control on the risk of colorectal adenomatous polyps: a retrospective cohort study.

BACKGROUND: Colorectal cancer (CRC) develops from colorectal adenomatous polyps. This study is to determine if diabetes mellitus (DM), its treatment, and hemoglobin A1c (HbA1c) level are associated with increased risk of colorectal adenomatous polyps. METHODS: This was a retrospective cohort study that included patients who had at least one colonoscopy and were continuously enrolled in a single managed care organization during a 10-year period (2002-2012). Of these patients (N = 11,933), 1800 were randomly selected for chart review to examine the details of colonoscopy and pathology findings and to confirm the diagnosis of DM. Multivariable logistic regression analyses were performed to assess the associations between DM, its treatment, HbA1c level and adenomatous polyps (our main outcome). RESULTS: Among the total of 11,933 patients with a mean (standard deviation) age of 56 (± 8.8) years, 2306 (19.3%) had DM and 75 (0.6%) had CRC. Among the 1800 under chart review, 445 (24.7%) had DM, 11 (0.6%) had CRC and 537 (29.8%) had adenomatous polyps. In bivariate analysis, patients with DM had 1.45 odds of developing adenomatous polyps compared to those without DM. This effect was attenuated (odds ratio = 1.25, 95% CI: 0.96-1.62, p = 0.09) after adjusting for confounders such as age, gender, race/ethnicity, and body mass index. There was no significant association between type or duration of DM treatment or HbA1c level and adenomatous polyps. CONCLUSIONS: Our study confirmed the known increased risk of adenomatous polyps with advancing age, male gender, Hispanic race/ethnicity and higher body mass index. Although it suggested an association between DM and adenomatous polyps, a statistically significant association was not observed after controlling for other potential confounders. Further studies with a larger sample size are needed to further elucidate this relationship.

Clinical and Economic Burden of Peristomal Skin Complications in Patients With Recent Ostomies.

PURPOSE: The purpose of this study was to estimate the risk and economic burden of peristomal skin complications (PSCs) in a large integrated healthcare system in the Midwestern United States. DESIGN: Retrospective cohort study. SUBJECTS AND SETTING: The sample comprised 128 patients; 40% (n = 51) underwent colostomy, 50% (n = 64) underwent ileostomy, and 10% (n = 13) underwent urostomy. Their average age was 60.6 ± 15.6 years at the time of ostomy surgery. METHODS: Using administrative data, we retrospectively identified all patients who underwent colostomy, ileostomy, or urostomy between January 1, 2008, and November 30, 2012. Trained medical abstractors then reviewed the clinical records of these persons to identify those with evidence of PSC within 90 days of ostomy surgery. We then examined levels of healthcare utilization and costs over a 120-day period, beginning with date of surgery, for patients with and without PSC, respectively. Our analyses were principally descriptive in nature. RESULTS: The study cohort comprised 128 patients who underwent ostomy surgery (colostomy, n = 51 [40%]; ileostomy, n = 64 [50%]; urostomy, n = 13 [10%]). Approximately one-third (36.7%) had evidence of a PSC in the 90-day period following surgery (urinary diversion, 7.7%; colostomy, 35.3%; ileostomy, 43.8%). The average time from surgery to PSC was 23.7 ± 20.5 days (mean ± SD). Patients with PSC had index admissions that averaged 21.5 days versus 13.9 days for those without these complications. Corresponding rates of hospital readmission within the 120-day period following surgery were 47% versus 33%, respectively. Total healthcare costs over 120 days were almost $80,000 higher for patients with PSCs. CONCLUSIONS: Approximately one-third of ostomy patients over a 5-year study period had evidence of PSCs within 90 days of surgery. Costs of care were substantially higher for patients with these complications.