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.

Healthcare Resource Utilization and Costs in Celiac Disease: A US Claims Analysis.

INTRODUCTION: Celiac disease (CeD) is a lifelong immune-mediated enteropathy in which dietary gluten triggers an inflammatory reaction in the small intestine. This retrospective cohort study examines healthcare resource utilization (HRU) and costs between patients with CeD and matched controls. METHODS: Patients with CeD (cases) with an endoscopic biopsy and ≥2 medical encounters with a CeD diagnosis between January 1, 2010, and October 1, 2015, were identified in the MarketScan databases. The date of the first claim with a CeD diagnosis on or after the endoscopic biopsy was the index date. Cases were matched 1:1 to patients without CeD (controls) on demographic characteristics and Deyo-Charlson Comorbidity Index score. Clinical characteristics, all-cause, and CeD-related HRU and costs (adjusted to 2017 US dollars) were compared between cases and controls during the 12 months before (baseline) and 24 months after (follow-up) the index date. RESULTS: A total of 11,008 cases (mean age 40.6 years, 71.3% women) were matched to 11,008 controls. During the follow-up, a higher proportion of cases had all-cause and CeD-related HRU including inpatient admissions, emergency department visits, gastroenterologist visits, dietician visits, endoscopic biopsies, and gastroenterology imaging (all P ≤ 0.002). Incremental all-cause and CeD-related costs were in the first ($7,921 and $2,894) and second ($3,777 and $935) year of follow-up, driven by outpatient services costs. DISCUSSION: In this US national claims database analysis, there was evidence of an increase in both all-cause and CeD-related HRU and related costs in patients with CeD compared with matched patients without CeD, suggesting a significant economic burden associated with CeD.

Direct and Indirect Healthcare Resource Utilization and Costs Among Migraine Patients in the United States.

OBJECTIVE: The goal of this analysis was to provide a contemporary estimate of the burden of migraine, incorporating both direct and indirect costs, by comparing the costs of migraine patients to a matched group of patients without migraine in a large, nationally representative sample of commercially insured patients in the United States. BACKGROUND: Previous studies have shown that the economic burden of migraine in the United States is substantial for payers, patients, and employers. Despite the availability of multiple acute and preventive pharmacological treatment options and a relatively stable migraine prevalence in the United States, there has been a documented increase in migraine-related healthcare resource and pharmacy use. Given the frequently disabling nature of migraine and its high prevalence, especially during peak productive years, and the lack of recent estimates of the burden of migraine, there is a need to update the existing literature with more current data. METHODS: This retrospective, observational cohort study identified migraine patients in the Truven Health Market Scan Research Databases between January 2008 and June 2013. Adult patients had 12 months of continuous enrollment before (baseline period) and after (follow-up period) the day they received migraine diagnoses and/or medications (index) and no diagnosis of HIV or malignancy during the study period. The patients with migraine were matched 1:1 to a group of patients without migraine on demographic variables and index date. Direct healthcare utilization and costs and indirect (absenteeism, short-term disability, and long-term disability) costs were assessed during the 12-month follow-up period and differences between patients with vs without migraine were assessed. Two additional multivariable logistic regression analyses were conducted. First, an analysis was conducted comparing the odds of having a short-term disability claim between patients with and without migraine after controlling for patient demographic and clinical characteristics. A second analysis, conducted among the migraine patients only, compared the odds of having a short-term disability claim between (1) patients treated with acute or preventive migraine medications only during the baseline period and patients with no migraine treatment during baseline and (2) patients treated with both acute and preventive migraine medications during the baseline period and patients with no migraine treatment during baseline, after controlling for patient demographic and clinical characteristics. RESULTS: Migraine patients had total annual direct plus indirect costs that were $8924 (in 2014 United States dollars) higher than those of demographically similar individuals without evidence of migraine. Migraine patients' mean annual direct all-cause healthcare costs were $6575 higher than those of matched patients without migraine ($11,010 [standard deviation = $19,663] vs $4436 [standard deviation=$13,081]; P < .01). Total mean annual indirect costs were $2350 higher in the migraine cohort than in the matched no migraine patients ($11,294 vs $8945. Migraine patients were 2.0 times more likely as their nonmigraine counterparts to use opioids (45.5% vs 21.9%; P < .01) and among patients with opioid prescriptions, migraine patients had 1.8 times the number of opioid prescriptions per patient than did those without migraine (4.9 [standard deviation = 6.9] vs 2.7 [standard deviation = 4.0]; P < .01). After adjusting for baseline demographic and clinical characteristics, migraine patients treated with either acute or preventive migraine medications (odds ratio = 0.81 [95% confidence interval = 0.72-0.91]; P < .01) or both acute and preventive migraine medications during the baseline period (odds ratio = 0.93 [95% confidence interval = 0.89-0.98]; P < .01) were significantly less likely to have short-term disability claims than untreated patients during the follow-up period (Migraine patients with either acute or preventive medications only: 7290/45,632 [16.0%]; with both acute and preventive medications: 3085/14,941 [20.6%]; untreated patients: 1604/11,169 [14.4%] had a short-term disability claim.) However, overall, migraine patients had 1.94 times the odds of having a short-term disability claim than their matched counterparts (95% confidence interval = 1.83-2.05; P < .01; migraine patients: 11,979/71,742 [16.7%]; nonmigraine patients: 4801/71,742 [6.7%] had a short-term disability claim). CONCLUSIONS: Results from this real-world assessment of the economic burden of migraine suggest that migraine imposes a substantial direct and indirect cost burden in the United States. Compared to matched nonmigraine patients, migraine patients were more likely to have work loss and longer periods of work loss, leading to significantly higher indirect costs. Migraine patients also had higher levels of healthcare utilization, despite the relatively stable prevalence of migraine and the available acute and preventive treatment options for migraine management.

Productivity loss and indirect costs associated with cardiovascular events and related clinical procedures.

BACKGROUND: The high acute costs of cardiovascular disease and acute cardiovascular events are well established, particularly in terms of direct medical costs. The costs associated with lost work productivity have been described in a broad sense, but little is known about workplace absenteeism or short term disability costs among high cardiovascular risk patients. The objective of this study was to quantify workplace absenteeism (WA) and short-term disability (STD) hours and costs associated with cardiovascular events and related clinical procedures (CVERP) in United States employees with high cardiovascular risk. METHODS: Medical, WA and/or STD data from the Truven Health MarketScan® Research Databases were used to select full-time employees aged 18-64 with hyperlipidemia during 2002-2011. Two cohorts (with and without CVERP) were created and screened for medical, drug, WA, and STD eligibility. The CVERP cohort was matched with a non-CVERP cohort using propensity score matching. Work loss hours and indirect costs were calculated for patients with and without CVERP and by CVERP type. Wages were based on the 2013 age-, gender-, and geographic region-adjusted wage rate from the United States Bureau of Labor Statistics. RESULTS: A total of 5,808 WA-eligible, 21,006 STD-eligible, and 3,362 combined WA and STD eligible patients with CVERP were well matched to patients without CVERP, creating three cohorts of patients with CVERP and three cohorts of patients without CVERP. Demographics were similar across cohorts (mean age 52.2-53.1 years, male 81.3-86.8%). During the first month of follow-up, patients with CVERP had more WA/STD-related hours lost compared with patients without CVERP (WA-eligible: 23.4 more hours, STD-eligible: 51.7 more hours, WA and STD-eligible: 56.3 more hours) (p < 0.001). Corresponding costs were $683, $895, and $1,119 higher, respectively (p < 0.001). Differences narrowed with longer follow-up. In the first month and year of follow-up, patients with coronary artery bypass graft experienced the highest WA/STD-related hours lost and costs compared with patients with other CVERP. CONCLUSIONS: CVERP were associated with substantial work loss and indirect costs. Prevention or reduction of CVERP could result in WA and STD-related cost savings for employers.

Red blood cell (RBC) transfusion rates among US chronic dialysis patients during changes to Medicare end-stage renal disease (ESRD) reimbursement systems and erythropoiesis stimulating agent (ESA) labels.

BACKGROUND: Several major ESRD-related regulatory and reimbursement changes were introduced in the United States in 2011. In several large, national datasets, these changes have been associated with decreases in erythropoiesis stimulating agent (ESA) utilization and hemoglobin concentrations in the ESRD population, as well as an increase in the use of red blood cell (RBC) transfusions in this population. Our objective was to examine the use of RBC transfusion before and after the regulatory and reimbursement changes implemented in 2011 in a prevalent population of chronic dialysis patients in a large national claims database. METHODS: Patients in the Truven Health MarketScan Commercial and Medicare Databases with evidence of chronic dialysis were selected for the study. The proportion of chronic dialysis patients who received any RBC transfusion and RBC transfusion event rates per 100 patient-months were calculated in each month from January 1, 2007 to March 31, 2012. The results were analyzed overall and stratified by primary health insurance payer (commercial payer or Medicare). RESULTS: Overall, the percent of chronic dialysis patients with RBC transfusion and RBC transfusion event rates per 100 patient-months increased between January 2007 and March 2012. When stratified by primary health insurance payer, it appears that the increase was driven by the primary Medicare insurance population. While the percent of patients with RBC transfusion and RBC transfusion event rates did not increase in the commercially insured population between 2007 and 2012 they did increase in the primary Medicare insurance population; the majority of the increase occurred in 2011 during the same time frame as the ESRD-related regulatory and reimbursement changes. CONCLUSIONS: The regulatory and reimbursement changes implemented in 2011 may have contributed to an increase in the use of RBC transfusions in chronic dialysis patients in the MarketScan dataset who were covered by Medicare plus Medicare supplemental insurance.

Number of Influenza Risk Factors Informs an Adult's Increased Potential of Severe Influenza Outcomes: A Multiseason Cohort Study From 2015 to 2020.

Background: While studies have evaluated factors influencing the risk of severe influenza outcomes, there is limited evidence on the additive impact of having multiple influenza risk factors and how this varies by age. Methods: Patients ≥18 years of age in the United States were evaluated retrospectively in 5 seasonal cohorts during the 2015-2020 influenza seasons. Patient-level electronic medical records linked to pharmacy and medical claims were used to ascertain covariates and outcomes. Multivariable logistic regression models were fitted for the overall population and by age subgroups to evaluate the association of demographic and clinical characteristics with odds of influenza-related medical encounters (ICD-10 codes J09*-J11*). The logistic regression models included sex, race/ethnicity, geographic region, baseline health care resource use, vaccination status, specific high-risk comorbidities, number of influenza risk factors, body mass index, and smoking status. Odds ratios from each of the 5 seasons were summarized via fixed effect meta-analysis. Results: Season cohort sizes ranged from 887 260 to 3 628 168 adults. Of all patient characteristics evaluated, an individual's cumulative number of high-risk influenza conditions, as defined per the Centers for Disease Control and Prevention, was the most predictive of an increased probability of having an influenza-related medical encounter overall and across age groups. For adults of any age, odds ratios for influenza hospitalization ranged from 1.8 (95% CI, 1.7-2.0) for 1 risk factor to 6.4 (95% CI, 5.8-7.0) for ≥4 risk factors. Conclusions: These results show that a simple measure such as the number of influenza risk factors can be highly informative of an adult's potential for severe influenza outcomes.

Diagnosis and treatment patterns among patients with newly diagnosed Helicobacter pylori infection in the United States 2016-2019.

Approximately 36% of the United States (US) population is infected with Helicobacter pylori (HP), a known major risk factor for peptic ulcer disease and gastric cancer. HP eradication reduces the rate of complications; however, the benefits are undermined by rising rates of HP eradication treatment failure. This real-world observational cohort analysis aims to describe HP diagnostic and treatment patterns among insured patients in the US. Using diagnoses, lab results, and treatment patterns, we identified adults (18+) with new diagnoses of HP in the Veradigm Health Insights EHR Database linked to Komodo claims data (1/1/2016-12/31/2019). Patients were required to have ≥ 12 months of data pre-/post-index. We captured patient characteristics, HP-related diagnostic testing, and the use of US guideline-recommended HP eradication regimens. HP eradication rates following first-line eradication treatment were measured among patients with available lab results. Overall, 31.8% of the 60,593 included patients did not receive guideline-recommended treatment. Among the 68.2% (41,340) with first-line treatment, 80.2% received clarithromycin-based triple therapy, and 6.6% received bismuth quadruple therapy. Of the 4569 patients with a repeated course of eradication therapy, 53.4% received the same regimen as their first-line, the majority (90.7%) of whom received two rounds of clarithromycin-based triple therapy. Among the 2455 patients with results of HP non-serology testing following first-line treatment, the 180-day eradication rate was 80.2% overall, with differences based on treatments and demographics. This study highlights gaps between guideline-recommended HP management and real-world patterns, underscoring the need to improve HP testing, treatment, and follow-up practices.

A Linked Electronic Medical Record-Claims Analysis of the Clinical and Economic Outcomes of Patients Coded for Erosive Esophagitis in the United States.

INTRODUCTION: Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective, observational cohort study was to describe the characteristics and healthcare burden of patients with EE. METHODS: We identified adults in the USA with an EE diagnosis between January  1, 2016 and February 28, 2019 in a linked dataset containing electronic health records (EHR) from the Veradigm Network EHR and claims data from Komodo Health. Patients were required to have 1 year of baseline data and 3 years of follow-up data. Patients were stratified by the number of PPI lines of therapy (LOT) during the 4-year study period. We descriptively captured patient characteristics and treatment patterns, along with all-cause and EE-related healthcare utilization and costs. RESULTS: Among the 158,347 qualifying adults with EE, 71,958 (45.4%) had 1 PPI LOT, 14,985 (9.5%) had 2 LOTs, 15,129 (9.6%) had 3+ LOTs, and 56,275 (35.5%) did not fill a PPI prescription. Omeprazole and pantoprazole comprised more than 70% of any LOT, with patients commonly switching between the two. Mean (standard deviation) annualized all-cause and EE-related healthcare costs in the follow-up period were $16,853 ($70,507) and $523 ($3659), respectively. Both all-cause and EE-related healthcare costs increased with LOTs. CONCLUSIONS: Patients with EE are commonly treated with prescription PPIs; however, 19.0% of patients cycled through multiple PPIs. Higher PPI use was associated with a higher comorbidity burden and higher healthcare costs compared to 0 PPI use.

Healthcare costs among patients with newly diagnosed helicobacter pylori infection in the United States: a linked claims-EHR study.

AIMS: The study objectives were to 1) characterize the cost drivers of patients with Helicobacter pylori (HP) and 2) estimate HP-related cost savings following lab-confirmed HP eradication with US guideline-recommended treatment compared to failed eradication. METHODS: We identified adults newly diagnosed with HP between 1/1/2016-12/31/2019 in the Veradigm Electronic Health Record Database linked to claims data (earliest HP diagnosis = index date). For the overall costs analysis, we required patients to have data available for ≥12 months before and after the index date. Then, we used multivariable modeling to assess the marginal effects of comorbidities on all cause-healthcare costs in the 12 months following HP diagnosis. For the eradication savings analysis, we identified patients with ≥1 HP eradication regimen, a subsequent HP lab test result, and ≥1 year of data after the test result. Then we used multivariable modeling to estimate HP-related cost while adjusting for eradication status, demographics, post-testing HP-related clinical variables, and the interactions between eradication status and each HP-related clinical variable. RESULTS: The overall cost analysis included 60,593 patients with HP (mean age 54.2 years, 65.5% female). Mean (SD) 12-month unadjusted all-cause costs were $23,693 ($78,089). Rare comorbidities demonstrated the highest marginal effect. The marginal effects of gastric cancer and PUD were $15,705 and $7,323, respectively. In the eradication savings analysis, 1,835 (80.0%) of the 2295 patients had lab test-confirmed HP eradication. Compared to failed eradication, there were significant one-year cost savings among patients with successful HP eradication and select conditions: $1,770 for PUD, $518 for atrophic gastritis, $494 for functional dyspepsia, and $352 for gastritis. CONCLUSIONS: The healthcare costs of patients with HP are partially confounded by their burden of high-cost comorbidities. In the subset of patients with available results, confirmed vs. failed eradication of HP was associated with short-term cost offsets among those with specific to HP-related sequelae.

Helicobacter pylori (HP) is a common infection. We aimed to better understand healthcare costs for people infected with HP. Specifically, we were interested in 1) investigating whether complications from HP were causing high costs. 2) whether successful eradication of HP would lead to lower healthcare costs. We captured data on adults diagnosed with HP between 2016 and 2019. The data used in this study came from medical records and insurance bills. In the first part of the study, we found that patients with HP often have other health issues, and these other health issues were driving high healthcare costs. The majority of cost savings associated with HP eradication accrue from the prevention of potential complications of long-term infection, such as peptic ulcer disease and, rarely, gastric cancer.

Outpatient red blood cell transfusion payments among patients on chronic dialysis.

BACKGROUND: Payments for red blood cell (RBC) transfusions are separate from US Medicare bundled payments for dialysis-related services and medications. Our objective was to examine the economic burden for payers when chronic dialysis patients receive outpatient RBC transfusions. METHODS: Using Truven Health MarketScan® data (1/1/02-10/31/10) in this retrospective micro-costing economic analysis, we analyzed data from chronic dialysis patients who underwent at least 1 outpatient RBC transfusion who had at least 6 months of continuous enrollment prior to initial dialysis claim and at least 30 days post-transfusion follow-up. A conceptual model of transfusion-associated resource use based on current literature was employed to estimate outpatient RBC transfusion payments. Total payments per RBC transfusion episode included screening/monitoring (within 3 days), blood acquisition/administration (within 2 days), and associated complications (within 3 days for acute events; up to 45 days for chronic events). RESULTS: A total of 3283 patient transfusion episodes were included; 56.4% were men and 40.9% had Medicare supplemental insurance. Mean (standard deviation [SD]) age was 60.9 (15.0) years, and mean Charlson comorbidity index was 4.3 (2.5). During a mean (SD) follow-up of 495 (474) days, patients had a mean of 2.2 (3.8) outpatient RBC transfusion episodes. Mean/median (SD) total payment per RBC transfusion episode was $854/$427 ($2,060) with 72.1% attributable to blood acquisition and administration payments. Complication payments ranged from mean (SD) $213 ($168) for delayed hemolytic transfusion reaction to $19,466 ($15,424) for congestive heart failure. CONCLUSIONS: Payments for outpatient RBC transfusion episodes were driven by blood acquisition and administration payments. While infrequent, transfusion complications increased payments substantially when they occurred.

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.

Impact of cytomegalovirus complications on resource utilization and costs following hematopoietic stem cell transplant.

Objective: The impact of cytomegalovirus (CMV) infection on healthcare resource utilization (HCRU) and costs post-allogeneic hematopoietic stem cell transplant (allo-HSCT) has not been well studied in the US. This retrospective, observational cohort study examined such outcomes in the first year following allo-HSCT.Methods: The IBM MarketScan administrative claims database was used to identify adults who underwent a first allo-HSCT between 1 January 2010 and 30 April 2015. Patients were required to have continuous medical and pharmacy enrollment for ≥12 months before and after the allo-HSCT. HCRU and medical costs (2016 US$) were compared by the presence or absence of CMV infection over 1-year follow-up.Results: A total of 1825 adults met the inclusion criteria (57.5% male; mean age 50.8 years). During the follow-up period, 410 (22.5%) patients had a CMV-related claim. Patients with CMV infection were significantly more likely to have a 60-day-(31.2 vs. 19.4%), 100-day-(50.0 vs. 30.5%) or 365-day readmission (78.0 vs. 57.8%) compared to those without a CMV-related event (all p < .001). During follow-up, patients with CMV infection had significantly greater mean total costs, reflecting higher inpatient costs ($677,240 vs. $462,562), outpatient costs ($141,366 vs. $94,312) and prescription drug costs ($27,391 vs. $22,082) (all p < .001). Valganciclovir (59.8%) and ganciclovir (33.7%) were the most commonly utilized anti-viral agents in patients with CMV.Conclusions: CMV infection was associated with significantly higher healthcare resource utilization and costs during the first year post-allo-HSCT. Additional research is warranted to further evaluate the consequences of post-HSCT CMV infection, as well as cost-effective measures to minimize its occurrence.

Treatment Patterns and Economic Burden by Lines of Therapy Among Patients with Advanced Hepatocellular Carcinoma Treated with Systemic Cancer Therapy.

PURPOSE: This study examined clinical and economic outcomes among patients with advanced hepatocellular carcinoma (HCC) treated with systemic agents by line of therapy. METHODS: Adults with ≥ 2 medical claims for primary diagnosed HCC (from January 1, 2008, through September 30, 2015) and ≥ 1 claim for systemic HCC-related therapy were identified in the IBM MarketScan® Research Databases. Continuous enrollment was required 6 months before and 1 month after diagnosis. Patients were categorized into first- (1L) and second-line (2L) treatment cohorts; those receiving sorafenib as 1L were evaluated. Treatment patterns, healthcare resource utilization, costs, and survival during 1L and 2L therapy were measured. Survival was assessed for patients linked to the Social Security Administration Master Death File. RESULTS: 1459 patients, 758 with death data, met the 1L cohort criteria; 163 patients, 87 with death data, later received 2L therapy. 77.1% had 1L sorafenib, alone or in combination. Median 1L treatment duration was 3.0 months; median survival time from start of 1L to death or censor was 6.8 months. There was no predominant 2L agent. Median 2L treatment duration was 3.0 months; median survival time from start of 2L was 9.3 months. Median total healthcare costs per patient per month were $13,297 for 1L (all), $13,471 for 1L (sorafenib), and $11,786 for 2L. CONCLUSIONS: Findings confirm high 1-year mortality for advanced HCC, suggesting a high cost burden. While no 2L therapy was available during this analysis, recently approved 2L agents have the potential to improve survival after sorafenib failure or intolerance.

Neural changes following remediation in adult developmental dyslexia.

Brain imaging studies have explored the neural mechanisms of recovery in adults following acquired disorders and, more recently, childhood developmental disorders. However, the neural systems underlying adult rehabilitation of neurobiologically based learning disabilities remain unexplored, despite their high incidence. Here we characterize the differences in brain activity during a phonological manipulation task before and after a behavioral intervention in adults with developmental dyslexia. Phonologically targeted training resulted in performance improvements in tutored compared to nontutored dyslexics, and these gains were associated with signal increases in bilateral parietal and right perisylvian cortices. Our findings demonstrate that behavioral changes in tutored dyslexic adults are associated with (1) increased activity in those left-hemisphere regions engaged by normal readers and (2) compensatory activity in the right perisylvian cortex. Hence, behavioral plasticity in adult developmental dyslexia involves two distinct neural mechanisms, each of which has previously been observed either for remediation of developmental or acquired reading disorders.

Comparing Medication Adherence and Persistence Among Patients with Type 2 Diabetes Using Sodium-Glucose Cotransporter 2 Inhibitors or Sulfonylureas.

BACKGROUND: Patients with type 2 diabetes treated with pharmacotherapy should be adherent to and persistent with their medications to experience glycemic control and prevent associated complications. OBJECTIVE: To compare medication adherence and persistence among patients with type 2 diabetes who are newly initiating a sodium-glucose cotransporter 2 (SGLT-2) inhibitor or a sulfonylurea. METHODS: This was a retrospective, observational cohort study using the MarketScan claims databases. The patients who were selected for the study had newly initiated treatment with an SGLT-2 inhibitor or a sulfonylurea between January 1, 2015, and December 31, 2015 (index date; class of earliest medication is defined as the index class); were aged ≥18 years on the index date; were continuously enrolled with health insurance for 12 months before and 6 months after (ie, follow-up) the index date; and had ≥1 baseline diagnoses of type 2 diabetes. Study exclusions were type 1 diabetes, pregnancy, and gestational diabetes. Medication adherence was measured by the proportion of days covered (PDC) with the index class during the follow-up period and dichotomized as adherent (PDC ≥80%) or nonadherent. Persistence was defined as the number of days from the index date until a >60-day continuous gap in days without the index drug class (ie, discontinuation) or the end of follow-up. A propensity score model was used to match patients receiving an SGLT-2 inhibitor to patients receiving a sulfonylurea in a 1:1 ratio based on patient characteristics. Logistic (ie, adherence) and Cox (ie, persistence) regression models were fit to the matched samples. RESULTS: Initially, the study included 17,724 patients who received an SGLT-2 inhibitor and 25,490 patients who received a sulfonylurea. After propensity score matching, 13,657 patients remained in each cohort. Compared with patients receiving a sulfonylurea, a statistically significantly greater percentage of patients receiving an SGLT-2 inhibitor were adherent to therapy (61.4% vs 53.9%, respectively; odds ratio of adherence, 1.364; 95% confidence interval [CI], 1.30-1.43; P <.001) and persistent (76.1% vs 68.9%, respectively; hazard ratio of discontinuation, 0.746; 95% CI, 0.71-0.78; P <.001). CONCLUSION: Maintaining adherence to and persistence with antidiabetes medication is vital to glycemic control among patients with type 2 diabetes. In this real-world study, patients who newly initiated treatment with SGLT-2 inhibitors were more likely to adhere to treatment and persist with the initiated therapy than similar patients who newly initiated treatment with sulfonylureas.

Healthcare utilization and costs in patients with tuberous sclerosiscomplex-related renal angiomyolipoma.

OBJECTIVE: To quantify healthcare utilization and costs in patients with tuberous sclerosis complex (TSC) and renal angiomyolipoma (AML) in a matched cohort of patients without TSC or AML. METHODS: Administrative data from the MarketScan Research Databases were used to select patients with TSC and renal AML during January 1, 2000-March 31, 2013 from the Commercial database and January 1, 2000-June 30, 2012 from the Medicaid database. Patients were required to have at least 30 days of follow-up from initiation into the study, and were followed until inpatient death, end of insurance coverage, or the end of study. Age, calendar year, and payer-matched controls that had no TSC and no AML were selected. All-cause annualized healthcare utilization and costs were calculated by service category. RESULTS: A total of 218 patients under 18 years and 377 patients 18 years and older with TSC-renal AML were selected from the Commercial database, and matched to 654 and 1,131 controls, respectively. Thirty-eight patients under 18 years and 110 patients 18 years or older with TSC-renal AML were selected from the Medicaid database, and matched to 54 and 212 controls, respectively. Within the Commercial cohort, and across both age groups, TSC-renal AML patients utilized more healthcare services than their matched controls. Within the Medicaid cohort, in both age groups, utilization was higher in TSC-renal AML patients vs control patients for inpatient admissions, emergency room visits, physician office visits, and hospital-based outpatient visits. Across age groups and in both the Commercial and Medicaid cohorts, the annual average total costs were significantly higher in TSC-renal AML patients compared to control patients (p < 0.05 for all). Healthcare costs ranged from $29,240-$48,499 for TSC-renal AML patients and from $2,082-$10,864 for control patients. CONCLUSIONS: Compared to controls, TSC-renal AML patients incurred substantially higher annual healthcare utilization and costs.

Natural history of patients with tuberous sclerosis complex related renal angiomyolipoma.

OBJECTIVE: To examine temporal relationships between tuberous sclerosis complex (TSC) and renal angiomyolipoma diagnosis and outcomes, treatment, and healthcare utilization. METHODS: Administrative data from the MarketScan Commercial Database was used to select TSC-related renal angiomyolipoma patients during 1 January 2000-31 March 2013. Patients were followed until the earliest of inpatient death or end of enrollment or study. Occurrence of kidney-related outcomes, kidney-related procedures, and all-cause healthcare utilization and time to occurrence were reported. Kaplan-Meier curves were used to display the unadjusted distribution of time to outcome. RESULTS: A total of 605 patients were selected (<18 years N = 225; ≥18 years N = 380). Mean time from TSC to renal angiomyolipoma diagnosis was 25.7 months in younger and 16.9 months in older patients. Patients ≥18 years had higher rates of chronic kidney disease (CKD), hematuria, kidney failure, embolization (EMB), and partial and complete nephrectomy compared to patients <18 years (all p < .05). Mean time from TSC-related renal angiomyolipoma diagnosis to CKD, hematuria, kidney failure, EMB, first emergency room and inpatient visits was shorter in older compared to younger patients (all p < .05). Probability of developing CKD was approximately 0.8 and 0.95 within 3 years in younger and older patients, respectively. CONCLUSIONS: Patients with TSC-related renal angiomyolipoma had high rates of kidney-related outcomes and procedures. These events sometimes preceded the angiomyolipoma diagnosis. A key study limitation was that due to the small sample size, results may have been biased by outliers. Research is needed to determine whether earlier angiomyolipoma diagnosis can impact occurrence of events and reduce healthcare utilization.

Factors Associated with Direct Health Care Costs Among Patients with Migraine.

BACKGROUND: Migraine imposes substantial economic burden on patients and the health care system. Approximately 18% of women and 6% of men suffer from migraine in the United States. This is a heterogeneous group, and little data are available to evaluate factors associated with migraine costs. OBJECTIVE: To evaluate characteristics associated with high costs among commercially insured patients with migraine. METHODS: This retrospective analysis identified patients with migraine in the Truven Health MarketScan Research Databases between January 2008 and June 2013. Patients were required to have 12 months continuous enrollment before and after migraine diagnoses and/or migraine-specific medications (index date). Patients with costs greater than the top 25th percentile of all-cause costs during the 12-month post-index period were classified into the upper quartile (UQ) cohort. Multiple logistic regression was used to evaluate demographic and clinical factors associated with being in the UQ cohort, and generalized linear models were used to estimate the incremental costs by select factors after controlling for other covariates. RESULTS: In the total population, 857,073 patients (mean [SD] age: 43.2 [12.5] years), were included, with 83.2% females. Average post-index annual all-cause costs were $13,045 (SD = $25,328) with the top 25th percentile of costs at $14,120. Overall, 44.4% and 54.8% of patients had ≥ 1 pre-index claim for opioids and triptans, respectively. Patients with ≥ 2 migraine-related emergency room visits were twice as likely to be in the UQ cohort (OR = 2.13, 95% CI = 2.02-2.25; P < 0.05) and incurred $3,125 incremental all-cause costs compared with those with < 2 visits. Patients who visited a neurologist were 33.0% more likely to be in the UQ cohort and had significantly higher adjusted all-cause costs ($11,794 vs. $9,868, P < 0.05). Opioid users had a 1.5-3 times increased likelihood of being in the UQ cohort (P < 0.05); adjusted all-cause annual costs ranged from $8,888 (95% CI = $8,862-$8,914) for nonusers to $15,210 (95% CI = $15,113-$15,307) for high users (7+ claims). Patients having 7+ triptan claims were 1.2 times as likely to be in the UQ cohort compared with nonusers, with estimated costs of $11,517 (95% CI = $11,438-$11,596) for high users and $10,753 (95% CI = $10,717-$10,790) for nonusers. CONCLUSIONS: Results suggest that certain modifiable factors, such as increased acute medication use (opioids and triptans) and more migraine-related emergency room visits are associated with higher all-cause health care costs for patients with migraine. These findings could be used to identify patients who require early intervention, enhanced symptoms monitoring, and appropriate disease management. Future studies could examine the effect of disease severity on health resource utilization and costs using survey or medical record data. DISCLOSURES: This study was funded by Amgen and conducted by Truven Health Analytics. Bonafede, Cappell, and Kim are employees of Truven Health Analytics, which received compensation from Amgen for the overall conduct of the study and preparation of the manuscript. Cai was an employee of Truven Health Analytics at the time of this study. Sapra, Shah, and Desai are employees of Amgen. Katherine Widnell was an employee of Amgen when the manuscript draft was developed. Winner reports receiving research support from Allergan, Amgen, A-Z, Teva, Pfizer, Novartis, and Lilly. Study concept and design were contributed by Bonafede, Sapra, Shah, and Desai, along with Widnell and Winner. Kim and Cai took the lead in data collection, assisted by Bonafede and Cappell. Data interpretation was performed by Widnell and Winter, along with the other authors. All authors contributed to the writing and revision of the manuscript.

The effect of DPP-4 inhibitors on asthma control: an administrative database study to evaluate a potential pathophysiological relationship.

RATIONALE: DPP-4 may regulate immunological pathways implicated in asthma. Assessing whether DPP-4 inhibitor (DPP-4i) use might affect asthma control is clinically important because DPP-4i use in type 2 diabetes mellitus management (T2DM) is increasing. This study evaluated associations between DPP-4i use and asthma control. METHODS: This was a retrospective, observational, matched cohort study using administrative claims in the MarketScan® Commercial Claims and Encounters (Commercial) and Medicare Supplemental and Coordination of Benefits (Medicare Supplemental) databases. Adult asthma patients initiating an oral DPP-4i or a non-DPP-4i between November 1, 2006 and March 31, 2014 were included. Patients were followed for asthma-related outcomes for 12 months after initiation of the antidiabetes medication. Outcomes included risk-domain asthma control (RDAC), defined as no asthma hospitalizations, no lower respiratory tract infections, and no oral corticosteroid (OCS) prescriptions; overall asthma control (RDAC criteria plus limited short-acting beta agonist use); treatment stability (RDAC criteria plus no increase of ≥50% in inhaled corticosteroid dose or addition of other asthma therapy); and severe asthma exacerbation rates (asthma-related hospitalizations, emergency room visits, or acute treatments with OCS). Comparisons were made between two matched cohorts (DPP-4i vs. non-DPP-4i initiators) using multivariable logistic regression and generalized linear modeling. Covariates included baseline demographic and clinical characteristics related to asthma and T2DM. RESULTS: The adjusted odds of achieving RDAC (odds ratio [OR]: 1.05; 95% CI: 0.964 to 1.147), overall asthma control (OR: 1.04; 95% CI: 0.956 to 1.135), and treatment stability (OR: 1.04; 95% CI: 0.949 to 1.115) did not differ between the DPP-4i and non-DPP-4i cohorts. A difference was not found between cohorts in severe asthma exacerbation rates during the 12 months following initiation of antidiabetes treatment (mean = 0.32 vs. 0.34 exacerbations per subject-year, respectively; p=0.064). CONCLUSION: Asthma control was similar between patients initiating DPP-4i and non-DPP-4i antidiabetes medications, suggesting no association between DPP-4i use and asthma control.

Long-term Clinical Morbidity in Patients With Renal Angiomyolipoma Associated With Tuberous Sclerosis Complex.

OBJECTIVE: To estimate the incidence rates of kidney-related clinical outcomes among patients with tuberous sclerosis complex (TSC)-related angiomyolipoma (AML) compared to an age-matched control cohort in the United States. MATERIALS AND METHODS: This was a retrospective, observational study. Administrative data from the MarketScan Research Databases were used to select patients with TSC and renal AML. An age-matched group with no TSC or renal AML was identified for comparison. Outcomes were incidence rates per 100 patient-years and number of months to development of hematuria, chronic kidney disease, renal hemorrhage, kidney failure, and inpatient death. RESULTS: Among the commercially insured TSC-renal AML patients (N = 605) and matched controls (N = 1815), 37.2% were <18 years old. Among Medicaid TSC-renal AML patients (N = 246) and matched controls (N = 738), 38.6% were aged <18. In the commercial sample, in both age groups (<18 and ≥18), the incidence rate of each clinical outcome measured was higher in the TSC-renal AML cohort than in the control cohort, with several differences reaching statistical significance. Compared with younger patients, older TSC-renal AML patients had higher incidence rates of clinical outcomes (hematuria: 20.4 vs 8.7; chronic kidney disease: 9.6 vs 3.5; renal hemorrhage 2.7 vs 0.7; kidney failure: 1.9 vs 0.4) and took less time on average to develop each clinical outcome. A similar pattern of results was observed among patients with Medicaid insurance. CONCLUSION: TSC-renal AML patients are at significantly higher risk for renal morbidity relative to the general population.