Estimated prevalence of moderate to severely elevated total homocysteine levels in the United States: A missed opportunity for diagnosis of homocystinuria?

Classical homocystinuria (HCU) is a genetic disorder caused by mutations in the cystathionine beta synthase gene, which results in impaired metabolism of the sulfur-bearing amino acid homocysteine and its accumulation in blood and tissues. Classical HCU can be detected via newborn screening in the United States, but the test is widely acknowledged to miss many patients. While severely elevated homocysteine levels (>100 µmol /L) frequently lead to a classical HCU diagnosis, intermediate levels (>30 to 100 µmol /L), though linked to many of the known complications of HCU, are not always recognized as associated with HCU. We aimed to identify and describe potentially undiagnosed classical HCU patients using a nationally-representative database of administrative claims and laboratory results. We estimated the national prevalence of patients with homocysteine >30 µmol /L, and compared their demographic and clinical characteristics to those of patients with homocysteine levels ≤30 µmol/L. Among 57,580 patients with a homocysteine test result, 1.8% had a value >30 µmol /L. Patients with homocysteine >30 µmol /L were more frequently diagnosed with hypothyroidism (39.2% vs. 20.7%, p < .001) and renal disease (9.7% vs. 5.5%, p < .001), and were more likely to have a prescription for an anxiolytic/antidepressant (44.5% vs. 38.9%), opioid (58.4% vs. 53.1%), steroid (46.4% vs. 42.5%), or thyroid hormone (38.8% vs. 18.8%), compared to patients with homocysteine ≤30 µmol /L (all p < .05). Both groups were equally likely to have a diagnosis of homocystinuria or another disorder of sulfur-bearing amino acid metabolism (3.8% vs. 4.0%, p = .752). The age-adjusted national prevalence of homocysteine >30 µmol /L was estimated at 33,068 (95% CI: 1033 - 35,104). These findings suggest that thousands of people in the US may be living with intermediate to severely elevated homocysteine levels and may require further evaluation for the presence of classical HCU.

Associations between ambient wood smoke and other particulate pollutants and biomarkers of systemic inflammation, coagulation and thrombosis in cardiac patients.

BACKGROUND: Increased particulate air pollution has been associated with both an increased risk of myocardial infarction (MI) and adverse changes in cardiac biomarkers. Up to 30% of ambient wintertime fine particles (PM2.5) in Rochester, NY are from wood burning. Our study examined associations between ambient levels of a marker of wood smoke (Delta-C) and other particulate air pollutants and biomarkers of inflammation, coagulation and thrombosis. METHODS: We measured blood concentrations of C-reactive protein (CRP), D-dimer, fibrinogen, P-selectin, platelet factor 4 (PF-4), von Willebrand factor (vWF), and myeloperoxidase (MPO) of 135 patients undergoing cardiac catheterization during the winters of 2011-2013. We coupled these data with hourly ambient concentrations of Delta-C, black carbon (BC; marker of traffic pollution), and ultrafine (10-100nm; UFP), accumulation mode (100-500nm; AMP), and fine particles (<2.5µm; PM2.5). Using linear regression models, we estimated the change in each biomarker associated with increased pollutant concentrations at intervals between 1 and 96h preceding blood collection. RESULTS: Each 0.13µg/m3 increase in Delta-C concentration in the prior 12h was associated with a 0.91% increase in fibrinogen levels (95% CI=0.23%, 1.59%), but unexpectedly in the prior 48h, each 0.17µg/m3 increase in Delta-C concentration was associated with a 2.75% decrease in MPO levels (95% CI=-5.13%,-0.37%). We did not see associations between Delta-C concentrations and any other biomarkers. Interquartile range (IQR) increases in PM2.5, BC, UFP, and AMP concentrations were generally associated with increased CRP and fibrinogen, but not PF4, D-dimer, vWF, or P-selectin. CONCLUSIONS: In a population of cardiac patients, we noted adverse changes in fibrinogen associated with increased concentrations of a marker of wood smoke. Increases in PM2.5, BC, AMP, and UFP concentrations in the previous 96h were also associated with adverse changes in markers of systemic inflammation and coagulation, but not with markers of endothelial cell dysfunction or platelet activation.

Fine Particulates, Preterm Birth, and Membrane Rupture in Rochester, NY.

BACKGROUND: It remains unclear whether fine particulate (PM2.5) exposure affects risk of preterm birth and prelabor rupture of membranes. Unmeasured, poorly measured, and undiscovered individual-level confounders might have introduced bias into past studies that relied on between-women comparisons. METHODS: This was a longitudinal study of preterm birth and prelabor rupture of membranes in Rochester, NY, 2004-2012 (N = 3,264 women, N = 7,121 singleton births). We used conditional logistic regression to match pregnancies to the same woman and estimate the odds of each outcome associated with average PM2.5 concentrations during each trimester and whole pregnancy. RESULTS: For preterm birth, adjusted odds ratios (95% confidence interval) for 1 µg/m increase in PM2.5 in the first trimester, second trimester, third trimester, and whole pregnancy were 1.11 (1.04, 1.18), 1.09 (1.02, 1.16), 1.06 (1.00, 1.13), and 1.17 (1.07, 1.28), respectively. For prelabor rupture of membranes, corresponding odds ratios were 1.00 (0.97, 1.04), 0.99 (0.96, 1.02), 0.99 (0.96, 1.03), and 0.99 (0.94, 1.04), respectively. CONCLUSION: Risk of preterm birth was greater for pregnancies with elevated PM2.5 exposure than other pregnancies to the same women at lower exposure. We did not observe an association between PM2.5 concentrations and prelabor rupture of membranes.

Increased ultrafine particles and carbon monoxide concentrations are associated with asthma exacerbation among urban children.

OBJECTIVES: Increased air pollutant concentrations have been linked to several asthma-related outcomes in children, including respiratory symptoms, medication use, and hospital visits. However, few studies have examined effects of ultrafine particles in a pediatric population. Our primary objective was to examine the effects of ambient concentrations of ultrafine particles on asthma exacerbation among urban children and determine whether consistent treatment with inhaled corticosteroids could attenuate these effects. We also explored the relationship between asthma exacerbation and ambient concentrations of accumulation mode particles, fine particles (≤2.5 micrograms [µm]; PM2.5), carbon monoxide, sulfur dioxide, and ozone. We hypothesized that increased 1-7 day concentrations of ultrafine particles and other pollutants would be associated with increases in the relative odds of an asthma exacerbation, but that this increase in risk would be attenuated among children receiving school-based corticosteroid therapy. METHODS: We conducted a pilot study using data from 3 to 10 year-old children participating in the School-Based Asthma Therapy trial. Using a time-stratified case-crossover design and conditional logistic regression, we estimated the relative odds of a pediatric asthma visit treated with prednisone (n=96 visits among 74 children) associated with increased pollutant concentrations in the previous 7 days. We re-ran these analyses separately for children receiving medications through the school-based intervention and children in a usual care control group. RESULTS: Interquartile range increases in ultrafine particles and carbon monoxide concentrations in the previous 7 days were associated with increases in the relative odds of a pediatric asthma visit, with the largest increases observed for 4-day mean ultrafine particles (interquartile range=2088p/cm(3); OR=1.27; 95% CI=0.90-1.79) and 7-day mean carbon monoxide (interquartile range=0.17ppm; OR=1.63; 95% CI=1.03-2.59). Relative odds estimates were larger among children receiving school-based inhaled corticosteroid treatment. We observed no such associations with accumulation mode particles, black carbon, fine particles (≤2.5µm), or sulfur dioxide. Ozone concentrations were inversely associated with the relative odds of a pediatric asthma visit. CONCLUSIONS: These findings suggest a response to markers of traffic pollution among urban asthmatic children. Effects were strongest among children receiving preventive medications through school, suggesting that this group of children was particularly sensitive to environmental triggers. Medication adherence alone may be insufficient to protect the most vulnerable from environmental asthma triggers. However, further research is necessary to confirm this finding.

Real-world changes in costs over time among patients in the United States with hereditary angioedema on long-term prophylaxis with lanadelumab.

AIMS: Investigate trends in paid lanadelumab costs over time in a population of patients persistent for 18 months, and to understand overall hereditary angioedema (HAE) treatment cost trends, including costs of acute medication/short-term prophylaxis and supportive care. Lastly, we sought to describe the proportion of lanadelumab patients with evidence of down titration via changes in total paid amounts for lanadelumab in a fixed time period. METHODS: Patients were identified in the Merative MarketScan Databases who had ≥1 claim for lanadelumab during 1/1/2018-6/30/2022 (index), a ≤ 60-d gap in days of supply over 18 months, and were enrolled for ≥6 months pre-index and 18 months post-index. Lanadelumab and HAE-specific costs were assessed during follow-up months 0-6, 7-12, and 13-18. Down titration was defined as a ≥ 25% decrease in lanadelumab costs from months 0-6 to months 7-12 or 13-18. Outcomes were compared between time periods using paired t-tests and McNemar's test. RESULTS: Fifty-four lanadelumab users were included; 25 (46%) had evidence of down titration. Lanadelumab costs decreased from $316,724 to $269,861 to $246,919 in months 0-6, 7-12, and 13-18, respectively (p < .01); total HAE treatment costs decreased from $377,076 to $329,855 to $286,074 in months 0-6, 7-12, and 13-18, respectively (p < .01). LIMITATIONS: Persistence was determined via days of supply on medication claims; use of the medication was not confirmed. Down titration was based on costs; the lanadelumab regimen could not be assessed. Results may not be generalizable to uninsured patients or those without commercial or Medicare insurance. CONCLUSIONS: Patients on long-term prophylaxis with lanadelumab experienced a significant reduction (24%) in HAE treatment costs over 18 months, driven by lower costs of acute medications and lanadelumab down titration. Down titration among appropriate patients with controlled HAE may lead to substantial savings in healthcare costs.

Risk factors for severe COVID-19 among patients with systemic lupus erythematosus: a real-world analysis of a large representative US administrative claims database, 2020-2021.

OBJECTIVES: To identify risk factors for progression to severe COVID-19 and estimate the odds of severe COVID-19 associated with vaccination among patients with systemic lupus erythematosus (SLE). METHODS: This retrospective cohort study identified adults with SLE in the Merative™ MarketScan® Databases. Patients were continuously enrolled the year before 1 April 2020 (baseline) and had a COVID-19 diagnosis between 1 April 2020 and the earliest of death, enrolment end or 31 December 2021. Severe COVID-19 was defined as hospitalisation with a COVID-19 diagnosis. Demographics on 1 April 2020, baseline comorbidities, corticosteroid use ≤30 days before COVID-19 diagnosis and other SLE medication use ≤6 months before COVID-19 diagnosis were assessed. Vaccination was identified by claims for a COVID-19 vaccine or vaccine administration. Backward stepwise logistic regression estimated odds of progression to severe COVID-19 associated with patient characteristics and vaccination. RESULTS: Among 2890 patients with SLE with COVID-19, 500 (16.4%) had a COVID-19-related hospitalisation. Significant risk factors for progression to severe COVID-19 included rituximab (OR (95% CI) 2.92 (1.67 to 5.12)), renal failure (2.15 (95% CI 1.56 to 2.97)), Medicaid (vs Commercial; 2.01 (95% CI 1.58 to 2.57)), complicated hypertension (1.96 (95% CI 1.38 to 2.77)) and time of infection, among others. Vaccination had a significant protective effect (0.68(95% CI 0.54 to 0.87)) among all patients with SLE with COVID-19, but the effect was not significant among those with prior use of belimumab, rituximab or corticosteroids. CONCLUSIONS: Certain chronic comorbidities and SLE medications increase the odds of progression to severe COVID-19 among patients with SLE, but vaccination confers significant protection. Vaccine effectiveness may be attenuated by SLE treatments. Protective measures such as pre-exposure prophylaxis and booster vaccines should be encouraged among patients with SLE.

Economic and clinical burden of managing transfusion-dependent ß-thalassemia in the United States.

AIMS: To describe clinical complications, treatment use, healthcare resource utilization (HCRU), and costs among patients with transfusion-dependent ß-thalassemia (TDT) in the United States. MATERIALS AND METHODS: Merative MarketScan Databases were used to identify patients with ß-thalassemia between 1 March 2010, and 1 March 2019. Patients were eligible for inclusion with ≥1 inpatient claim or ≥2 outpatient claims for ß-thalassemia and ≥8 red blood cell transfusions (RBCTs) during any 12-month period after and including the date of the first qualifying ß-thalassemia diagnosis code. Matched controls consisted of individuals without ß-thalassemia. Clinical and economic outcomes of patients were assessed during ≥12 months of follow-up, defined as the period from the index date (i.e. the first RBCT) to either the end of continuous enrollment in benefits, inpatient death, or 1 March 2020. RESULTS: Overall, 207 patients with TDT and 1035 matched controls were identified. Most patients received iron chelation therapy (ICT) (91.3%), with a mean of 12.1 (standard deviation [SD] = 10.3) ICT claims per-patient-per-year (PPPY). Many also received RBCTs, with a mean of 14.2 (SD = 4.7) RBCTs PPPY. TDT was associated with higher annual ($137,125) and lifetime ($7.1 million) healthcare costs vs. matched controls ($4183 and $235,000, respectively). Annual costs were driven by ICT (52.1%) and RBCT use (23.6%). Patients with TDT had 7-times more total outpatient visits/encounters, 3-times more prescriptions, and 33-times higher total annual costs than matched controls. LIMITATIONS: This analysis may underestimate the burden of TDT, as indirect healthcare costs (e.g. absenteeism, presenteeism, etc.) were not included. Results may not be generalizable to patients excluded from this analysis, including those with other types of insurance or without insurance. CONCLUSIONS: Patients with TDT have high HCRU and direct healthcare costs. Treatments that eliminate the need for RBCTs could reduce the clinical and economic burden of managing TDT.

Economic and Clinical Burden of Managing Sickle Cell Disease with Recurrent Vaso-Occlusive Crises in the United States.

INTRODUCTION: The aim of this study was to describe the clinical complications, treatment use, healthcare resource utilization (HCRU), and costs among patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in the US. METHODS: Merative MarketScan Databases were used to identify patients with SCD with recurrent VOCs from March 1, 2010, to March 1, 2019. Inclusion criteria were ≥ 1 inpatient or ≥ 2 outpatient claims for SCD and ≥ 2 VOCs per year in any 2 consecutive years after the first qualifying SCD diagnosis. Individuals without SCD in these databases were used as matched controls. Patients were followed for ≥ 12 months, from their second VOC in the 2nd year (index date) to the earliest of inpatient death, end of continuous enrollment in medical/pharmacy benefits, or March 1, 2020. Outcomes were assessed during follow-up. RESULTS: In total, 3420 patients with SCD with recurrent VOCs and 16,722 matched controls were identified. Patients with SCD with recurrent VOCs had a mean of 5.0 VOCs (standard deviation [SD] = 6.0), 2.7 inpatient admissions (SD 2.9), and 5.0 emergency department visits (SD 8.0) per patient per year during follow-up. Compared to matched controls, patients with SCD with recurrent VOCs incurred higher annual ($67,282 vs. $4134) and lifetime ($3.8 million vs. $229,000 over 50 years) healthcare costs. CONCLUSION: Patients with SCD with recurrent VOCs experience substantial clinical and economic burden driven by inpatient costs and frequent VOCs. There is a major unmet need for treatments that alleviate or eliminate clinical complications, including VOCs, and reduce healthcare costs in this patient population.

PRIMUS - Prompt Initiation of Maintenance Therapy in the US: A Real-World Analysis of Clinical and Economic Outcomes Among Patients Initiating Triple Therapy Following a COPD Exacerbation.

PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) may experience moderate (requiring outpatient care) or severe (requiring hospitalization) disease exacerbations. Guidelines recommend escalation from dual to triple therapy (inhaled corticosteroid + long-acting beta agonist + long-acting muscarinic antagonist) after two moderate or one severe exacerbation in a year. This study examined whether prompt initiation of triple therapy lowers risk of future exacerbations and reduces healthcare costs, compared to delayed/very delayed triple therapy after an exacerbation. PATIENTS AND METHODS: This retrospective observational study of US healthcare claims included patients ≥40 years old with COPD who initiated triple therapy (1/1/2011-3/31/2020) after ≥2 moderate or ≥1 severe exacerbation in the prior year. The earliest of the second moderate or first severe exacerbation was the index date. Patients were stratified by triple therapy timing: prompt (≤30 days post-index), delayed (31-180 days), very delayed (181-365 days). COPD exacerbations, all-cause and COPD-related healthcare utilization and costs were assessed during 12 months post-index (follow-up). Multivariable regression estimated the effect of each 30-day delay in triple therapy on the odds of exacerbations, number of exacerbations, and costs during follow-up, controlling for patient characteristics. RESULTS: A total of 24,770 patients were included: 7577 prompt, 9676 delayed, 7517 very delayed. Each 30-day delay of triple therapy was associated with 11% and 7% increases in the odds of any exacerbation and a severe exacerbation, respectively (odds ratio [95% CI]: 1.11 [1.10-1.13] and 1.07 [1.05-1.08]), a 4.3% (95% CI: 3.9-4.6%) increase in the number of exacerbations, a 1.8% (95% CI: 1.3-2.3%) increase in all-cause costs, and a 2.1% (95% CI: 1.6-2.6%) increase in COPD-related costs during follow-up. CONCLUSION: Promptly initiating triple therapy after two moderate or one severe exacerbation is associated with decreased morbidity and economic burden in COPD. Proactive disease management may be warranted to prevent future exacerbations and lower costs among patients with COPD.

Prompt initiation of triple therapy following hospitalization for a chronic obstructive pulmonary disease exacerbation in the United States: An analysis of the PRIMUS study.

BACKGROUND: Severe exacerbations requiring hospitalization contribute a substantial portion of the morbidity and costs of chronic obstructive pulmonary disease (COPD). Triple therapy (inhaled corticosteroid + long-acting ß-agonist + long-acting muscarinic antagonist) is a recommended option for patients who experience recurrent COPD exacerbations or persistent symptoms. Few real-world studies have specifically examined the effect of prompt initiation of triple therapy, specifically among patients hospitalized for a COPD exacerbation. OBJECTIVE: To assess whether prompt initiation of triple therapy following a severe COPD exacerbation was associated with lower risk of subsequent exacerbations and lower health care use and costs and the effects of each 30-day delay of initiation. METHODS: Adults aged 40 years or older with COPD were identified in the Merative MarketScan Databases between January 1, 2010, and December 31, 2019, and were required to meet the following criteria: open or closed triple therapy (date of first closed prescription or last component of open=index treatment date), more than 1 inpatient admission with a primary COPD diagnosis (ie, severe exacerbation) in the prior 12 months (index exacerbation), 12 months of continuous enrollment before (baseline) and after (follow-up) index exacerbation, and absence of select respiratory diseases and cancer. Patients were stratified based on timing of open or closed triple therapy after the index exacerbation: prompt (≤30 days), delayed (31-180 days), or very delayed (181-365 days). Multivariable regression controlled for baseline characteristics (age, sex, insurance type, index year, comorbidities, prior treatment, and prior exacerbations) and estimated the odds of subsequent exacerbations, change in the number of exacerbations, and change in health care costs during 12-month follow-up associated with each 30-day delay of triple therapy initiation. RESULTS: A total of 6,772 patients met inclusion criteria (2,968 [43.8%] prompt, 1,998 [29.5%] delayed, and 1,806 [26.7%] very delayed). The adjusted odds of any exacerbation and a severe exacerbation during 12-month follow-up increased by 13% (odds ratio [95% CI]: 1.13 [1.11-1.15]) and 10% (1.10 [1.08-1.12]), respectively, for each 30-day delay in triple therapy initiation, and the mean number of exacerbations increased by 5.4% (95% CI = 4.7%-6.1%). There was a 3.0% increase (95% CI = 2.2%-3.8%) in mean all-cause costs and a 3.7% increase (95% CI = 2.9%-4.6%) in total COPD-related costs for each 30-day delay of triple therapy initiation. CONCLUSIONS: Longer delays in triple therapy initiation after a COPD hospitalization result in greater risk of subsequent exacerbations and higher health care resource use and costs. Adequate post-discharge follow-up care and earlier consideration of triple therapy may improve clinical and economic outcomes among patients with COPD. DISCLOSURES: This study was funded by AstraZeneca. Dr Evans is employed by Merative, formerly IBM Watson Health, and Mr Tkacz was employed by IBM Watson Health at the time of this study; Merative/IBM Watson Health received funding from AstraZeneca to conduct this study. Mr Pollack, Dr Staresinic, Dr Feigler, and Dr Patel are employed by AstraZeneca. Dr Touchette, Dr Portillo, and Dr Strange are paid consultants to AstraZeneca. Dr Strange also participates in research grants paid to the Medical University of South Carolina by AstraZeneca, CSA Medical, and Nuvaira, and is a consultant to GlaxoSmithKline, Morair, and PulManage regarding COPD.

Systemic Corticosteroid-related Adverse Outcomes and Health Care Resource Utilization and Costs Among Patients with Chronic Rhinosinusitis with Nasal Polyposis.

PURPOSE: Nasal polyps (NPs) develop in 20% to 30% of patients with chronic rhinosinusitis. Severe forms of chronic rhinosinusitis with nasal polyposis (CRSwNP) may be treated with systemic corticosteroids (SCSs), which increase the risk for adverse clinical outcomes. This study compared the incidence of SCS-related adverse outcomes and health care resource utilization and costs between patients with CRSwNP who had SCS exposure and those who did not have SCS exposure. METHODS: This retrospective cohort study used health care claims data from adult patients with CRSwNP identified in the IBMⓇ MarketScanⓇ Databases between January 2003 and June 2019. The first SCS prescription date in SCS users or a matched date in SCS nonusers (controls) represented the index date. Enrollment for ≥1 year before and after the index date was required. SCS-related adverse outcomes and costs were compared between all SCS users and controls, and among subgroups of patients who had claims for 1-3 and ≥4 SCS prescriptions in the 12-month postindex period. Comparisons were also made among SCS users and controls who previously had and did not have NP surgery, and those with and without comorbid asthma. Inverse probability of treatment weights was applied to all comparisons, which were evaluated for a variable-length follow-up period. FINDINGS: SCS users (n = 37,740) had a greater risk for any adverse outcome than controls (n = 7032) (incidence rate ratio [IRR] = 1.10; 95% CI, 1.05-1.16). The risk for adverse outcomes was highest in the subgroups that did not have NP surgery and that had ≥4 SCS claims (n = 2993) versus controls who did not have NP surgery (n = 5078) (IRR = 1.30; 95% CI, 1.18-1.44). Similarly, patients with asthma and ≥4 SCS claims (n = 4195) had a greater risk for SCS-related outcomes versus controls with asthma (n = 1226) (IRR = 1.36; 95% CI, 1.19-1.55). SCS users incurred 60% higher all-cause costs versus non-SCS users (P < 0.001). IMPLICATIONS: In patients with CRSwNP, SCS use was associated with a higher risk for adverse outcomes and with increased health care costs compared with controls without SCS exposure. Alternative treatment strategies that avoid and/or reduce SCS use may decrease health care costs and the risk for adverse outcomes among patients with CRSwNP.

Impact of Plan-Level Access Restrictions on Effectiveness of Biologics Among Patients with Rheumatoid or Psoriatic Arthritis.

BACKGROUND: Novel disease-modifying antirheumatic drugs (DMARDs) can slow disease progression among patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA); however, some health plans require prior authorization (PA) or step therapy for access to treatments. OBJECTIVES: This retrospective study compared treatment effectiveness among RA and PsA patients with and without plan-level access restrictions to biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs). Medication adherence, a component of effectiveness, was also examined as a secondary outcome. METHODS: RA and PsA patients aged 18-64 years with one or more claims for subcutaneous bDMARDs between January 1, 2014 and December 31, 2015, with plan-level access data available, were identified within the IBM MarketScan claims database. The primary outcome was treatment effectiveness assessed during the 12 months following the first qualifying DMARD claim. Multivariate modeling examined the correlation between access restrictions and treatment effectiveness. Medication adherence during the 12-month follow-up period was also compared between patients with and without access restrictions. RESULTS: Among 3993 RA and 1713 PsA patients, 34.2 and 35.1%, respectively, had access restrictions, of whom 70.5 and 78.9%, respectively, had plans with step therapy. Compared with patients whose plans did not require step therapy, odds of treatment effectiveness were 19% lower (odds ratio [OR] 0.81, 95% CI: 0.67-0.98; p  = 0.033) for RA patients and 27% lower (OR 0.73, 95% CI: 0.55-0.98; p = 0.037) for PsA patients in plans with step therapy. Differences in effectiveness were driven by differences in medication adherence, the odds of which were 19% lower (OR 0.81, 95% CI 0.68-0.96; p = 0.014) among RA patients and 29% lower (OR 0.71, 95% CI: 0.54-0.94; p = 0.017) among PsA patients in plans with versus without step therapy. CONCLUSIONS: Compared with patients in plans without access restrictions or with PA only, RA and PsA patients in insurance plans with step therapy had lower odds of treatment effectiveness, mainly due to lower odds of adhering to treatment, during the 12 months following subcutaneous bDMARD initiation.

Benchmarking HIV Quality Measures Across US Payer Types.

Despite advances in antiretroviral therapy (ART), human immunodeficiency virus (HIV) remains a significant issue in the United States. Early diagnosis, continuous treatment access/adherence, and long-term care engagement help patients benefit fully from ART; however, a shortfall in care engagement remains, potentially leading to poorer health outcomes. This analysis benchmarks rates of health care quality and process measures to identify areas for improvement. This retrospective, claims-based, real-world cohort study assessed the percentage of prevalent (existing) and incident (newly diagnosed) patients with HIV with commercial or public health insurance meeting 4 National Quality Forum (NQF)-endorsed, 1 Pharmacy Quality Alliance (PQA), and 3 Centers for Disease Control and Prevention (CDC) measures over a 4-year period. Most prevalent patients consistently met the NQF-endorsed prescribed ART and gaps in visits measures. Longer-term visit frequency measure rates were well below the 90% Joint United Nations Programme on HIV/AIDS target. Proportion of prevalent patients meeting each NQF-endorsed measure was maintained/increased with increasing age in 2015-2016. Substantially fewer incident patients than prevalent patients met NQF-endorsed measures across all measurement periods, particularly for visit frequency (32%-51%). PQA ART adherence was low (36%-73%). CDC receipt of care rates were high (83%-92%), whereas retention in care rates were low (67%-72%) among prevalent patients. For incident patients, linkage to care rates were consistently low (21%-44%). This study benchmarks current US HIV care engagement and highlights the need for improvement in early care engagement, ART adherence and long-term retention of care among patients with HIV.

Differences in health care outcomes between postdischarge COPD patients treated with inhaled corticosteroid/long-acting ß2-agonist via dry-powder inhalers and pressurized metered-dose inhalers.

PURPOSE: The aim of this study was to examine real-world differences in health care resource use (HRU) and costs among COPD patients in the USA treated with a dry powder inhaler (DPI) or pressurized metered-dose inhaler (pMDI) following a COPD-related hospitalization. METHODS: This retrospective analysis used the Truven MarketScan® databases. Eligibility criteria included 1) age ≥40 years, 2) COPD diagnosis, 3) inpatient admission with a diagnosis of COPD exacerbation, 4) inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) prescription within 10 days of hospital discharge (index date), and 5) continuous enrollment for 12 months preindex and 90 days postindex. Outcomes included pre- and postindex HRU and costs. DPI and pMDI groups were compared on postindex outcomes via multivariate models controlling for demographic and baseline characteristics. RESULTS: The sample included 1,960 DPI and 1,086 pMDI ICS/LABA patients. During the preindex period, pMDI patients were significantly more likely to be prescribed a short-acting ß-agonist, experienced more COPD exacerbation-related hospital days, and had a greater number of pulmonologist visits compared to DPI patients (P<0.05), all suggestive of greater disease severity. However, multivariate models revealed that pMDI patients incurred 10% lower all-cause postindex costs (predicted mean costs [2016 US dollars]: $2,673 vs $2,956) and 19% lower COPD-related costs (predicted mean costs: $138 vs $169; P<0.05). Additionally, pMDI patients were 28% less likely to experience a COPD exacerbation-related hospital readmission within 60 days postdischarge compared to the DPI patients (OR: 0.72, 95% CI: 0.52-0.99, P<0.05). CONCLUSION: Despite greater COPD-related HRU and costs preceding index hospitalization, US patients using a pMDI after hospital discharge incurred significantly lower all-cause and COPD-related health care costs compared with those using a DPI, in addition to a decreased likelihood of a COPD exacerbation-related hospital readmission. Results suggest that inhaler device type may influence COPD outcomes and that COPD patients may derive greater clinical benefit from treatment delivered via pMDI vs DPI.

Are patients with high-risk polycythemia vera receiving cytoreductive medications? A retrospective analysis of real-world data.

BACKGROUND: Patients with polycythemia vera (PV) have a higher mortality risk compared with the general population, primarily driven by cardiovascular disease, thrombotic events (TEs), and hematologic transformations. The goal of risk-adapted therapy in PV is prevention of TEs. Current treatment recommendations indicate that high-risk patients (aged ≥ 60 years and/or with history of TEs) should be managed with cytoreductive medications, phlebotomy, and low-dose aspirin. This noninterventional study was conducted to describe real-world cytoreductive medication treatment in adult patients with PV, stratified by risk, in the United States. METHODS: This retrospective analysis used claims data from the Truven Health MarketScan® database. Inclusion criteria were ≥ 2 nondiagnostic claims for PV ≥ 30 days apart, age ≥ 18 years, continuous enrollment during the preindex period (January 1 to December 31, 2012), and continuous enrollment or death during the postindex period (January 1, 2013, to December 31, 2014). Assessments included patient demographics, clinical characteristics, and treatment with cytoreductive medications. RESULTS: A total of 2856 patients were identified for this analysis, including 1823 with high-risk PV and 1033 with low-risk PV. Mean (SD) age was 62.5 (13.5) years, and 65.9% of patients were male. Preindex comorbid conditions of interest were more common in high-risk than low-risk patients, including hypertension (65.0% vs 43.1%), type 2 diabetes (21.7% vs 10.1%), and congestive heart failure (6.6% vs 0.6%). Among patients who received preindex cytoreductive therapy, the most commonly used medications in high-risk (n = 666) and low-risk (n = 160) patients were hydroxyurea (94.7 and 87.5%, respectively), anagrelide (7.4 and 11.9%), and interferon (1.7 and 4.4%). Among patients who initiated cytoreductive therapy postindex, the most commonly used medications in high-risk (n = 100) and low-risk (n = 35) patients were hydroxyurea (97.0 and 91.4%, respectively), anagrelide (4.0 and 2.9%), and interferon (2.0 and 8.6%). Overall, 42.0% of high-risk and 18.9% of low-risk patients received cytoreductive medication during the preindex or postindex periods. CONCLUSIONS: Despite consistent guideline recommendations for cytoreductive therapy in patients with high-risk PV, this analysis revealed that only a minority of these patients received cytoreductive medication. A notable proportion of high-risk patients with PV would likely benefit from a revised treatment plan that aligns with current guidelines.

Temporal Trends in Survival and Healthcare Costs in Patients with Multiple Myeloma in the United States.

BACKGROUND: In recent years, the development of new therapies for multiple myeloma has improved the survival of patients, but newer treatments may also affect healthcare costs. To date, no real-world study has examined the concurrent changes in survival and total healthcare costs over time in patients with multiple myeloma. OBJECTIVE: To examine the temporal changes in survival and healthcare costs among patients with multiple myeloma in the United States. METHOD: This retrospective claims-based cohort study is based on death files in the Truven Health MarketScan Research Commercial and Medicare Supplemental databases. The study included adults who had at least 1 inpatient or 2 outpatient claims with a diagnosis of multiple myeloma between January 1, 2006, and December 31, 2014; continuous insurance enrollment for at least 12 months before and at least 30 days after the first diagnosis (ie, index date); and no previous malignancy. Patients were followed from the index date through the earliest among (1) the date of death recorded in the death files, (2) the end of enrollment in the MarketScan database, or (3) end of the study (September 30, 2015). The mortality rates and the total all-cause and multiple myeloma-specific healthcare costs per patient per month were compared between patients diagnosed in 2006-2010 and those diagnosed in 2011-2014. RESULTS: A total of 5199 patients were included in the study (2597 diagnosed between 2006 and 2010 and 2602 diagnosed between 2011 and 2014). We found a 35% decrease in the risk for death (hazard ratio, 0.65; 95% confidence interval, 0.57-0.74) among patients diagnosed in 2011-2014 compared with those diagnosed in 2006-2010. In addition, 18% and 26% increases were found in all-cause and multiple myeloma-specific healthcare costs, respectively, over the same time period (adjusted mean all-cause costs, $13,960 vs $16,449, respectively; adjusted mean multiple myeloma-specific costs, $7476 vs $9422, respectively). CONCLUSION: The percent decrease in mortality in patients with multiple myeloma has been greater than the percent increase in healthcare costs in recent years, which may be attributable to improved treatments for multiple myeloma and changes in disease management. With the mortality rate having decreased more than the increase in healthcare costs over the same time period, the results of this study suggest that although healthcare spending has increased over time, there is a survival benefit.

LDL cholesterol levels after switch from atorvastatin to rosuvastatin.

OBJECTIVE: Initial statin therapy may not always adequately reduce elevated low-density lipoprotein cholesterol (LDL-C) levels. Although alternative therapies are available, switching to another statin may be beneficial, especially for those at highest risk of cardiovascular disease and events. This study examined changes in LDL-C levels following a switch from 40/80 mg of atorvastatin (ATV) to 20/40 mg of rosuvastatin (RSV). METHODS: This retrospective cohort study used data from the MarketScan administrative claims databases linked to laboratory values. Patients with or at risk for atherosclerotic cardiovascular disease (ASCVD) who switched from ATV 40/80 mg to RSV 20/40 mg and had LDL-C values measured within 90 days before and 30-180 days after the switch were included. The change in LDL-C was quantified for each patient and summarized across all patients and within each switch pattern (e.g. ATV40 to RSV20). RESULTS: There was a significant mean (SD) decrease in LDL-C of 21% (30%) across the whole sample (N = 136) after switching from ATV to RSV. The greatest decrease occurred in patients who switched from ATV40 to RSV40 (N = 20; -29% [19%]; p < .001). Similar changes were observed overall and within each switch pattern when the analysis was limited to patients who were persistent on RSV in the post-switch period (N = 112; -24% [24%]; p < .001). CONCLUSIONS: Switching from ATV to RSV was associated with a significant decrease in LDL-C among high-risk patients. Switching between these two high-intensity statins may offer a viable alternative to other treatment modifications aimed at lowering LDL-C in this population.

The Relative Costs of High- vs. Low-Energy-Density Foods and More vs. Less Healthful Beverages Consumed by Children.

OBJECTIVE: To compare grocery costs between relatively high energy density foods and sugar-sweetened/high-fat beverages and lower energy density foods and more healthful beverages in children's diets. METHODS: Sixty foods were divided into high and low energy density baskets. Fourteen beverages were designated to either basket based on fat and added-sugar content. Prices were collected at 60 grocery stores and composite costs compared between baskets using Wilcoxon tests. RESULTS: The cost per kilogram of high energy density foods was greater, but the cost per quart of sugar-sweetened/high-fat beverages was lower than more healthful beverages. The cost per 1000 calories and the cost per serving of the high energy density basket were lower. CONCLUSIONS: The relative cost of high and low energy density foods in children's diets depends on how cost is quantified. "Pound-for-pound," lower energy density foods and more healthful beverages are generally less expensive, but high energy density foods and less healthful beverages are cheaper per serving. Cost metrics including other factors (e.g. time cost) may further clarify the role of grocery prices in children's diets.

Daily land use regression estimated woodsmoke and traffic pollution concentrations and the triggering of ST-elevation myocardial infarction: a case-crossover study.

Prior work has reported acute associations between ST-elevation myocardial infarction (STEMI) and short-term increases in airborne particulate matter. Subsequently, the association between STEMI and hourly measures of Delta-C (marker of woodsmoke) and black carbon (marker of traffic pollution) measured at a central site in Rochester, NY, were examined, but no association was found. Therefore, land use regression estimates of Delta-C and black carbon concentrations at each patient's residence were developed for 246 STEMI patients treated at the University of Rochester Medical Center during the winters of 2008-2012. Using case-crossover methods, the rate of STEMI associated with increased Delta-C and BC concentration on the same and previous 3 days was estimated after adjusting for 3-day mean temperature and relative humidity. Non-statistically significant increased rates of STEMI associated with interquartile range increases in concentrations of BC in the previous 2 days (1.10 µg/m3; OR = 1.12; 95% CI 0.93, 1.35) and Delta-C in the previous 3 days (0.43 µg/m3; OR = 1.16; 95% CI 0.96, 1.40) were found. Significantly increased rates of STEMI associated with interquartile range increases in concentrations of BC (1.23 µg/m3; OR = 1.04; 95% CI = 0.87, 1.24) or Delta-C (0.40 µg/m3; OR = 0.94; 95% CI = 0.85, 1.09) on the same day were not observed likely due, in part, to temporal misalignment. Therefore, sophisticated spatial-temporal models will be needed to minimize exposure error and bias by better predicting concentrations at individual locations for individual hours, especially for outcomes with short-term responses to air pollution (< 24 h).