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Background: Two classes of newer glucose-lowering drugs (GLDs), sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, improve cardiovascular and renal outcomes among patients with type 2 diabetes (T2D). However, racial and ethnic minority groups carry higher cardiovascular risks but have lower access to newer GLDs. Contextual-level social determinants of health (SDOH) may be the underlying factor associated with newer GLD adoption., Objective: To identify the association between contextual-level SDOH and real-world adoption of newer GLDs among Medicare beneficiaries and to examine the nonstationarity in the associations., Methods: Data were from 15% random samples of January 2017 to December 2018 nationwide Medicare beneficiaries. We identified patients with T2D who did not use newer GLDs in the year before the index date-January 1, 2018-and followed the cohort for 1 year to record their status of initiating a newer GLD. We used a geographically weighted multivariable Poisson regression model to determine to what extent the SDOH-newer GLD initiation association (β coefficient) varied geographically., Results: We identified 795,469 eligible Medicare beneficiaries with T2D during the study period from our dataset. Of the study cohort, mean age was 73.1 (SD = 10.5) years, 424,312 (53.3%) were female, 562,994 (70.8%) were non-Hispanic White, 96,891 (12.2%) were non-Hispanic Black, 84,744 (10.6%) were Hispanic, and 29,645 (3.7%) were Asian/Pacific Islander. Newer GLD initiation was negatively associated with the percentage of the population reporting non-Hispanic Black race, Hispanic ethnicity, and unemployment, as revealed by nonspatial regression analyses. The county-level median household income was also associated with higher newer GLD initiation. The spatial analysis presented distinct distributions of local parameter estimates for each contextual-level SDOH., Conclusions: We identified key contextual-level SDOH associated with real-world adoption of newer GLDs and explored their geographic variation through spatially explicit, data-driven analytical approaches. Identifying areas of strong association between SDOH and newer GLD initiation is crucial for policymakers to allocate resources and develop interventions that address structural inequities.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL), accounting for nearly one-third of all NHL. The therapeutic landscape for patients with FL has significantly expanded over the past decade, but the disease continues to be considered incurable. Hematopoietic cell transplantation (HCT) is potentially curative in some cases. Recently, the emergence of chimeric antigen receptor T-cell therapy (CAR-T) for patients with relapsed/refractory (R/R) FL has yielded impressive response rates and long-term remissions, but definitive statement on the curative potential of CAR-T is currently not possible due to limited patient numbers and relatively short follow up. A consensus on the contemporary role, optimal timing, and sequencing of HCT (autologous or allogeneic) and cellular therapies in FL is needed. As a result, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines endorsed this effort to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 15 consensus statements/recommendations. These clinical practice recommendations will help guide clinicians managing patients with FL. Of note, the use of bispecific antibodies in R/R FL was not in the scope of this project., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Despite their frequent concurrent use, little is known about the concomitant use of calcium channel blockers (CCBs) and selective serotonin reuptake inhibitors (SSRIs) on fracture risk. We compared risk of fractures in patients concomitantly treated with CCBs and SSRIs versus CCB-only users. We compared risk of fractures among concomitant CCB-SSRI users initiating cytochrome P450 3A4 (CYP3A4)-inhibiting SSRIs versus non-CYP3A4 inhibiting SSRIs., Methods: This retrospective cohort study used IBM MarketScan commercial claims and Medicare Supplemental database (2007-2019). We included adults diagnosed with hypertension and depression, newly initiating SSRIs while being treated with CCBs (ie, concomitant CCB-SSRI users) and those who did not (ie, CCB-only users). Primary outcome was the first occurrence of any fracture. We used stabilized inverse probability of treatment weighting (sIPTW) based on propensity scores to balance baseline risk between groups. Cox proportional hazard regression modeling was used to compare fracture risk., Results: We identified 191 352 concomitant CCB-SSRI and 956 760 CCB-only users (mean age = 56 years, 50.1% males). After sIPTW, compared with CCB-only users, CCBs-SSRIs users had a higher risk of fractures (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.22-1.66). No difference in the risk of fractures between concomitant users of CCB-CYP3A4-inhibiting SSRIs and those of CCB-non-CYP3A4 inhibiting SSRIs (HR: 1.10, 95% CI: 0.87-1.40) was observed., Conclusion and Relevance: Short-term concomitant CCB-SSRI use was associated with increased fracture risk. Concomitant CCBs and CYP3A4-inhibiting SSRIs compared with CCBs and non-CYP3A4 inhibiting SSRIs use was not associated with increased risk., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Park has received grant funding from Bristol Myers Squibb. None of these are relevant to this study. The remaining authors report no conflicts of interest.

Purpose: Sacubitril/valsartan (SAC/VAL) or angiotensin receptor blockers (ARBs) are recommended therapy for heart failure with preserved ejection fraction (HFpEF), but little is known about their real-world comparative effectiveness among patients with HFpEF. The objective of this study was to determine the comparative effectiveness of SAC/VAL vs ARBs in preventing HF-related hospitalization or all-cause hospitalization among patients with HFpEF., Methods: We conducted a cohort study using IBM MarketScan commercial and Medicare supplemental databases to identify patients aged 18 years or older with a diagnosis of HFpEF and initiation of SAC/VAL (2015-2020) or ARB (2009-2014) therapy. The index date was the date of the first SAC/VAL or ARB prescription fill. After propensity score (PS) matching with a ratio of 1 up to 3, Cox proportional hazards regression was used with robust variance estimators to compare the risks of HF-related hospitalization and all-cause hospitalization between the 2 therapies. Several subgroup and sensitivity analyses were conducted to check the robustness of the main analysis., Results: After PS matching, 2,520 patients (846 receiving SAC/VAL and 1,674 receiving an ARB) were included in the final analyses. After controlling for covariates, there was no difference in the risk of HF-related hospitalization between SAC/VAL and ARB recipients (adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 0.99-1.77). There was also no difference in the risk of all-cause hospitalization between SAC/VAL and ARB recipients (aHR, 1.06; 95% CI, 0.91-1.24)., Conclusion: Among individuals with private or Medicare Advantage insurance plans, there was no significant difference in the risk of HF-related hospitalization or all-cause hospitalization between adults with HFpEF who received SAC/VAL and those who received ARB therapy., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: There are no clear recommendations for the perioperative timing and initiation of venous thromboembolism pharmacologic prophylaxis (VTEp) among polytrauma patients undergoing high-risk bleeding orthopedic operative intervention, leading to variations in VTEp administration. Our study examined the association between the timing of VTEp and VTE complications in polytrauma patients undergoing high-risk operative orthopedic interventions nationwide., Methods: We performed a retrospective cohort study of trauma patients 18 years or older who underwent high-risk bleeding operative orthopedic interventions for pelvic, hip, and femur fractures within 24 hours of admission at American College of Surgeons-verified trauma centers using the 2019-2020 American College of Surgeons Trauma Quality Improvement Program databank. We excluded patients with a competing risk of nonorthopedic surgical bleeding. We assessed operative orthopedic polytrauma patients who received VTEp within 12 hours of orthopedic surgical intervention compared with VTEp received beyond 12 hours of intervention. The primary outcome assessed was overall VTE events. Secondary outcomes were orthopedic reinterventions within 72 hours after primary orthopedic surgery, deep venous thromboembolism, and pulmonary embolism rates., Results: The study included 2,229 patients who underwent high-risk orthopedic operative intervention. The median time to VTEp initiation was 30 hours (interquartile range, 18-44 hours). After adjustment for baseline patient, injury, and hospital characteristics, VTEp initiated more than 12 hours from primary orthopedic surgery was associated with increased odds of VTE (adjusted odds ratio, 2.02; 95% confidence interval, 1.08-3.77). Earlier initiation of prophylaxis was not associated with an increased risk for surgical reintervention (hazard ratio, 0.90; 95% confidence interval, 0.62-1.34)., Conclusion: Administering VTEp within 24 hours of admission and within 12 hours of major orthopedic surgery involving the femur, pelvis, or hip demonstrated an associated decreased risk of in-hospital VTE without an accompanying elevated risk of bleeding-related orthopedic reintervention. Clinicians should reconsider delays in initiating or withholding perioperative VTEp for stable polytrauma patients needing major orthopedic intervention., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all-cause mortality associated with receipt of short- vs. long-acting ESAs. This retrospective cohort analysis included Medicare hemodialysis beneficiaries aged ≥ 18 years in the United States Renal Data System from January 2015 to December 2017. We included adults who survived > 90 days after initiating hemodialysis and received either short- or long-acting ESAs. Outcomes were MACE (first occurrence of stroke, acute myocardial infarction, or cardiovascular-related mortality) and all-cause mortality. After stabilized inverse probability of treatment weighting, Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for each outcome. Of 68,607 patients (mean age: 65 years, 45% females), 33,658 (49%) received long-acting ESAs and 34,949 (51%) received short-acting ESAs. There was no difference in the risk of MACE associated with receipt of short- vs. long-acting ESAs (HR: 1.02 (95% CI: 0.98-1.08)). However, long-acting (vs. short-acting) ESA receipt was associated with a lower risk of all-cause mortality (HR: 0.91 (95% CI: 0.87-0.96)). Compared with short-acting ESAs, long-acting ESAs were associated with a lower risk of all-cause mortality, with no difference in the risk of MACE. Future studies with a longer follow-up are needed to confirm these findings., (© 2024 The Authors. Clinical Pharmacology & Therapeutics © 2024 American Society for Clinical Pharmacology and Therapeutics.)

Competing Interests: Disclosures None.

Background: Prior studies have shown disparities in the uptake of cardioprotective newer glucose-lowering drugs (GLDs), including sodium-glucose cotranwsporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a). This study aimed to characterize geographic variation in the initiation of newer GLDs and the geographic variation in the disparities in initiating these medications., Methods: Using 2017-2018 claims data from a 15% random nationwide sample of Medicare Part D beneficiaries, we identified individuals diagnosed with type 2 diabetes (T2D), who had ≥1 GLD prescriptions, and did not use SGLT2i or GLP1a in the year prior to the index date,1/1/2018. Patients were followed up for a year. The cohort was spatiotemporally linked to Dartmouth hospital-referral regions (HRRs), with each patient assigned to 1 of 306 HRRs. We performed multivariable Poisson regression to estimate adjusted initiation rates, and multivariable logistic regression to assess racial disparities in each HRR., Results: Among 795,469 individuals with T2D included in the analyses, the mean (SD) age was 73 (10) y, 53.3% were women, 12.2% were non-Hispanic Black, and 7.2% initiated a newer GLD in the follow-up year. In the adjusted model including clinical factors, compared to non-Hispanic White patients, non-Hispanic Black (initiation rate ratio, IRR [95% CI]: 0.66 [0.64-0.68]), American Indian/Alaska Native (0.74 [0.66-0.82]), Hispanic (0.85 [0.82-0.87]), and Asian/Pacific islander (0.94 [0.89-0.98]) patients were less likely to initiate newer GLDs. Significant geographic variation was observed across HRRs, with an initiation rate spanning 2.7%-13.6%., Conclusions: This study uncovered substantial geographic variation and the racial disparities in initiating newer GLDs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Study Objective: Clinicians may prescribe new medications (marker drug) to treat statin-related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence of statin-related adverse events., Design: A secondary analysis based on our previous work, a high-throughput sequence symmetry analysis screening for potential statin-related prescribing cascades., Data Source: MarketScan Commercial and Medicare Supplemental Insurance claims databases between 2005 and 2019., Patients: Adults who initiated a statin between 2007 and 2018, and who were continuously enrolled in the same healthcare plan for at least 720 days before and 360 days after statin initiation., Intervention: Among the previously identified 57 potential prescribing cascades, 42 statin-marker class dyad with a sample size of ≥ 500 were assessed in this study., Measurements: We measured patients' baseline characteristics within -360 days of statin initiation and reported by modifiable statin characteristics. We also performed logistic regression and reported the adjusted odds ratios (aOR) with 95% confidence intervals (CI) of modifiable statin characteristics after adjusting for baseline characteristics., Main Results: We identified 1,307,867 statin initiators who met the study criteria (21% elderly, 52% female). Compared with patients initiating low-intensity statins, those initiating moderate- or high-intensity statins had significantly greater odds to develop 29 (69%) prescribing cascades, including antidiabetic drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors (aOR 1.22; 95% CI, 1.11-1.35) and glucagon-like peptide-1 (GLP-1) analogs (aOR 1.31; 95% CI, 1.16-1.47), and opioids (aOR 1.18; 95% CI, 1.13-1.23). Individual statin agent selection also had a differential effect on 34 (81%) of the prescribing cascades. For example, compared with simvastatin initiators, the probability of initiating osmotically acting laxatives was significantly higher for lovastatin initiators (aOR 1.09; 95% CI, 1.03-1.15) and significantly lower in atorvastatin initiators (aOR 0.92; 95% CI, 0.89-0.94)., Conclusion: Compared with low-intensity statins, high-intensity statins are associated with increased risk in many potential prescribing cascades, while the choice of individual statin agents affects the risk of prescribing cascades bidirectionally., (© 2023 Pharmacotherapy Publications, Inc.)

Background: The pediatric literature describes reliance on community-based organizations for home-based palliative and hospice care for children. Objective: To quantify and describe the inclusion of children in services, staffing, and care scope offered by community-based hospice organizations in the United States. Design and Subjects: This study utilized an online survey distributed to organizational members of the National Hospice and Palliative Care Organization (NHPCO) in the United States. Results: A total of 481 hospice organizations from 50 states, Washington DC, and Puerto Rico responded. Twenty percent do not provide services for children. Nonmetro geographies are less likely to provide services for children. Pediatric services provided include home-based pediatric hospice (57%), home-based palliative care (31%), inpatient pediatric hospice (23%), and inpatient pediatric palliative care (14%). Hospice annual pediatric census is an average of 16.5 children, while palliative care annual census is an average of 36. Less than half (48%) of responding agencies have a team that is dedicated to only pediatric care. Medicaid and the Children's Health Insurance Program are the most common forms of reimbursement, with 13% depicting "no reimbursement" for provision of care for children and many relying on philanthropy coverage. Lack of trained personnel, discomfort, and competing priorities were depicted as the most common barriers. Conclusions: Children remain underrepresented in the extension of care offered through community-based hospice organizations in the United States particularly in nonmetro settings. Further research into strong training, staffing, and reimbursement models is warranted.

While opioid prescribing has significantly decreased from a peak in 2012, less is known about the national utilization of non-opioid analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (APAP) in the context of the opioid crisis. The objective of this study is to characterize the prescribing trends of NSAIDs and APAP in the US ambulatory care setting. We conducted repeated cross-sectional analyses using the 2006-2016 National Ambulatory Medical Care Survey. NSAID-involved visits were defined as patient visits among adults in which NSAIDs were ordered, supplied, administered, or continued. We used similarly-defined APAP visits as a referent group for context. After excluding aspirin and other NSAID/APAP combination products containing opioids, we calculated the annual proportion of NSAID-involved visits among all ambulatory visits. We conducted trend analyses using multivariable logistic regression adjusted for years, patient, and prescriber characteristics. From 2006 to 2016, there were 775.7 million NSAID-involved visits and 204.3 million APAP-involved visits. Most NSAIDs-involved visits were from patients aged 46-64 years (39.6%), female (60.4%), White (83.2%), and having commercial insurance (49.0%). There were significant increasing trends for the proportion of NSAID-involved visits (8.1-9.6%) and APAP-involved visits (1.7-2.9%) (both P < .0001). We observed an overall increase in NSAID and APAP-involved visits in US ambulatory care settings from 2006 to 2016. This trend may be attributed to decreasing opioid prescribing and raises safety concerns related to acute or chronic NSAID and APAP use. PERSPECTIVE: This study shows an overall increasing trend in NSAID use reported in nationally representative ambulatory care visits in the United States. This increase coincides with previously reported significant decreases in opioid analgesic use, particularly after 2012. Given the safety concerns related to chronic or acute NSAID use, there is a need to continue monitoring the use trends of this class of medication., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended by the American Heart Association for management of heart failure with preserved ejection fraction (HFpEF), but little is known about their in-class comparative effectiveness in real-world settings., Objectives: To assess the in-class comparative effectiveness of SGLT2i for preventing HF-related and all-cause hospitalizations among patients with HFpEF., Methods: Using MarketScan® Commercial and Medicare Supplemental research databases (2012-2020), this cohort study included adults with HFpEF treated with SGLT2i. Stabilized inverse probability treatment weighted Cox proportional hazards regression was used to compare HF-related and all-cause hospitalizations in three pairwise comparisons: dapagliflozin versus canagliflozin, empagliflozin versus canagliflozin, and dapagliflozin versus empagliflozin. Subgroup and sensitivity analyses were conducted to assess robustness of the main analysis., Results: In total, 3629 SGLT2i users (881 dapagliflozin, 1120 canagliflozin, and 1628 empagliflozin) were included. Compared with canagliflozin, dapagliflozin was associated with decreased risk of HF-related hospitalization (adjusted hazard ratio [aHR], 0.75; 95% confidence interval [CI], 0.56-1.01) and all-cause hospitalization (aHR, 0.84; 95% CI 0.73-0.97). Compared with canagliflozin, empagliflozin was associated with 55% decreased risk of HF-related hospitalization (aHR, 0.45; 95% CI 0.34-0.59) and 18% decreased risk of all-cause hospitalization (aHR, 0.82; 95% CI 0.73-0.93). Compared with empagliflozin, dapagliflozin was associated with 50% increased risk of HF-related hospitalization (aHR, 1.50; 95% CI 1.09-2.07) and a statistically nonsignificant increase in the risk of all-cause hospitalization (aHR, 1.05; 95% CI 0.92-1.20)., Conclusions: Compared with canagliflozin or dapagliflozin use, empagliflozin use was associated with decreased risk of HF-related and all-cause hospitalizations. Compared with canagliflozin, dapagliflozin was associated with a reduced risk of HF-related and all-cause hospitalizations., (© 2023 Pharmacotherapy Publications, Inc.)

Purpose: Statins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin-related prescribing cascades has been performed to our knowledge., Methods: We utilized sequence symmetry analysis to iteratively screen prescribing sequences of all therapeutic classes ("marker" classes) based on Level 4 Anatomical Therapeutic Chemical codes among adult statin initiators, using IBM Marketscan commercial and Medicare supplemental claims databases (2005-2019). Order of initiation and secular trend-adjusted sequence ratios were calculated for each statin-marker class dyad, among marker class initiators ±90 days of statin initiation. Among signals classified as prescribing cascades, we calculated naturalistic number needed to harm (NNTH) within 1 year as the inverse of the excess risk among exposed., Results: We identified 2 265 519 statin initiators (mean ± SD age, 56.4 ± 12.0 years; 48.7% women; 7.5% with cardiovascular disease). Simvastatin (34.4% of statin initiators) and atorvastatin (33.9%) were the most commonly initiated statins. We identified 160 significant statin-marker class dyad signals, of which 35.6% (n = 57) were classified as potential prescribing cascades. Of the top 25 strongest signals (lowest NNTH), 12 were classified as potential prescribing cascades, including osmotically acting laxatives (NNTH, 44, 95% CI 43-46), opioids + non-opioid combination analgesics (81, 95% CI 74-91), and first-generation cephalosporins (204, 95% CI 175-246)., Conclusions: Using high-throughput sequence symmetry analysis screening, we identified previously known prescribing cascades as well as potentially new prescribing cascades based on known and unknown statin-related adverse events., (© 2023 John Wiley & Sons Ltd.)

Background: The use of a new medication (e.g., potassium supplementation) for managing a drug-induced adverse event (e.g., loop diuretic-induced hypokalemia) constitutes a prescribing cascade. However, loop diuretics are often stopped while potassium may be unnecessarily continued (i.e., relic). We aimed to quantify the occurrence of relics using older adults previously experiencing a loop diuretic-potassium prescribing cascade as an example., Methods: We conducted a prescription sequence symmetry analysis using the population-based Medicare Fee-For-Service data (2011-2018) and partitioned the 150 days following potassium initiation by day to assess the daily treatment scenarios (i.e., loop diuretics alone, potassium alone, combination of loop diuretics and potassium, or neither). We calculated the proportion of patients developing the relic, proportion of person-days under potassium alone, the daily probability of the relic, and the proportion of patients filling potassium after loop diuretic discontinuation. We also identified the risk factors of the relic., Results: We identified 284,369 loop diuretic initiators who were 8 times more likely to receive potassium supplementation simultaneously or after (i.e., the prescribing cascade), rather than before, loop diuretic initiation (aSR 8.0, 95% CI 7.9-8.2). Among the 66,451 loop diuretic initiators who subsequently (≤30 days) initiated potassium, 20,445 (30.8%) patients remained on potassium after loop diuretic discontinuation, and 9365 (14.1%) patients subsequently filled another potassium supplementation. Following loop diuretic initiation, 4.0% of person-days were for potassium alone, and daily probability of the relic was the highest after day 90 of loop diuretic initiation (5.6%). Older age, female sex, higher diuretic daily dose, and greater baseline comorbidities were risk factors for the relic, while patients having the same prescriber or pharmacy involved in the use of both medications were less likely to experience the relic., Conclusions: Our findings suggest the need for clinicians to be aware of the potential of relic to avoid unnecessary drug use., (© 2022 The American Geriatrics Society.)

Background Knowledge of real-world antihypertensive use is limited to prevalent hypertension, limiting our understanding of how treatment evolves and its contribution to persistently poor blood pressure control. We sought to characterize antihypertensive initiation among new users. Methods and Results Using Medicaid and Medicare data from the OneFlorida+ Clinical Research Consortium, we identified new users of ≥1 first-line antihypertensives (angiotensin-converting enzyme inhibitor, calcium channel blocker, angiotensin receptor blocker, thiazide diuretic, or β-blocker) between 2013 and 2021 among adults with diagnosed hypertension, and no antihypertensive fill during the prior 12 months. We evaluated initial antihypertensive regimens by class and drug overall and across study years and examined variation in antihypertensive initiation across demographics (sex, race, and ethnicity) and comorbidity (chronic kidney disease, diabetes, and atherosclerotic cardiovascular disease). We identified 143 054 patients initiating 188 995 antihypertensives (75% monotherapy; 25% combination therapy), with mean age 59 years and 57% of whom were women. The most commonly initiated antihypertensive class overall was angiotensin-converting enzyme inhibitors (39%) followed by β-blockers (31%), calcium channel blockers (24%), thiazides (19%), and angiotensin receptor blockers (11%). With the exception of β-blockers, a single drug accounted for ≥75% of use of each class. β-blocker use decreased (35%-26%), and calcium channel blocker use increased (24%-28%) over the study period, while initiation of most other classes remained relatively stable. We also observed significant differences in antihypertensive selection across demographic and comorbidity strata. Conclusions These findings indicate that substantial variation exists in initial antihypertensive prescribing, and there remain significant gaps between current guideline recommendations and real-world implementation in early hypertension care.

Background: Limited evidence exists regarding long-term effectiveness and safety of aldosterone antagonists (AAs) versus beta blockers (BBs) as fourth-line antihypertensive agents in patients with resistant hypertension (RH). We evaluated the comparative effectiveness and safety of aldosterone AA versus BB., Methods: We conducted a real-world retrospective cohort study using IBM MarketScan commercial claims and Medicare Supplemental claims (2007-2019). Patients with RH entered the cohort (ie, index date) when they newly initiated either AA or BB. The effectiveness outcome was major adverse cardiovascular events. Safety outcomes were hyperkalemia, gynecomastia, and kidney function deterioration. Potential confounding was addressed by adjustment for baseline characteristics via stabilized inverse probability of treatment weighting (SIPTW) based on propensity scores. Cox proportional hazards regression with SIPTWs were used to estimate adjusted hazard ratio (aHR) and 95% CI comparing risk for outcomes between AA and BB groups., Results: We identified 80 598 patients with RH (mean age: 61 years, 51% males), of which 6626 initiated AA and 73 972 initiated BB as the fourth antihypertensive agent. Among patients with RH, initiation of AA as a fourth-line antihypertensive agent did not significantly reduce major adverse cardiovascular event risk relative to BB initiation (aHR, 0.77 [95% CI, 0.50-1.19]) but did substantially increase the risk of hyperkalemia (aHR, 3.86 [95% CI, 2.78-5.34]), gynecomastia (aHR, 9.51 [95% CI, 5.69-15.89]), and kidney function deterioration (aHR, 1.63 [95% CI, 1.34-1.99])., Conclusions: Long-term clinical trials powered to assess major adverse cardiovascular events are necessary to understand the risk-benefit trade-off of AA as fourth-line therapy for RH.

Objectives: The 2016 U.S. presidential election was a major source of stress among many adults. Psychosocial stress can manifest physiologically in elevated blood pressure (BP). Little is known regarding the association of macro-level sociopolitical events with BP changes at the population-level. This study sought to characterize population-level changes in BP following the 2016 U.S. presidential election., Methods: Using 2015-2018 National Health and Nutrition Examination Survey, we included participants aged ≥18 years during the same periods prior to (May to October 2015/2016) and after (May to October 2017/2018) the election. Survey-weighted data were analyzed to compare population-level systolic BP (SBP) and diastolic BP (DBP) pre- and post-election, stratified by race/ethnicity. Sex differences were also investigated., Results: We observed significant increases in SBP among non-Hispanic (NH) Asian participants (+3.4 mmHg; p = .046), but not among other racial/ethnic participants. DBP increased among NH Black participants (+2.3 mmHg; p = .049) and Mexican American participants (+2.9 mmHg; p = .007), but not among other racial/ethnic participants. These changes appeared attributable to differential BP changes by sex., Conclusions: At the population-level, variable changes in BP were observed by race/ethnicity following the 2016 U.S. presidential election, possibly driven by SBP elevations among women., (© 2022 Wiley Periodicals LLC.)

Background and Objectives: In 2011, the Centers for Medicare & Medicaid Services implemented bundling of all services for patients receiving dialysis, including erythropoietin-stimulating agents use, and the Food and Drug Administration recommended conservative erythropoietin-stimulating agent dosing., Design, Setting, Participants, & Measurements: This retrospective cohort study investigated anemia care and clinical outcomes before and after the Centers for Medicare & Medicaid Services bundled payment and the revised Food and Drug Administration-recommended erythropoietin-stimulating agent labeling for Medicare-insured adults receiving hemodialysis using data from the United States Renal Data System from January 1, 2006 to December 31, 2016. Clinical outcomes included major adverse cardiovascular event (stroke, acute myocardial infarction, and all-cause mortality), cardiovascular mortality, and heart failure. Measurements were compared between prepolicy (2006-2010) and postpolicy (2012-2016) implementation using interrupted time series and Cox proportional hazards regression models., Results: Of 481,564 patients, erythropoietin-stimulating agent use immediately decreased by 84.8 per 1000 persons ( P <0.001), with a significant decrease in the slope of the trend line (both P =0.001). Blood transfusion use rapidly increased by 8.34 per 1000 persons in April 2012 and then gradually decreased (both P =0.001). The percentage of patients with hemoglobin >11 g/dl decreased from 68% in January 2006 to 28% in December 2016, whereas those with hemoglobin <9 g/dl increased from 5% to 9%. Overall major adverse cardiovascular event (adjusted hazard ratio, 0.95; 95% confidence interval, 0.94 to 0.96), stroke (adjusted hazard ratio, 0.83; 95% confidence interval, 0.80 to 0.86), all-cause mortality (adjusted hazard ratio, 0.87; 95% confidence interval, 0.86 to 0.89), cardiovascular mortality (adjusted hazard ratio, 0.81; 95% confidence interval, 0.79 to 0.83), and heart failure (adjusted hazard ratio, 0.86; 95% confidence interval, 0.84 to 0.88) risks were lower. Acute myocardial infarction risk (adjusted hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.06) was higher after policies changed., Conclusions: The Medicare reimbursement policy and Food and Drug Administration-recommended erythropoietin-stimulating agent dosing changes were associated with lower erythropoietin-stimulating agent use and lower hemoglobin levels. These changes in anemia care were associated with lower risks of major adverse cardiovascular event, stroke, mortality, and heart failure but higher risk of acute myocardial infarction among adults receiving hemodialysis., (Copyright © 2022 by the American Society of Nephrology.)

Study Objective: To compare the risk of antihypertensive treatment intensification (TI) and major adverse cardiovascular events (MACE) with the initiation of serotonin norepinephrine reuptake inhibitors compared to selective serotonin reuptake inhibitors (SSRIs) in patients with stable hypertension and depression., Design: Retrospective cohort study., Data Source: IBM MarketScan® commercial claims database and Medicare Supplemental claims database from 2007 to 2019., Patients: Patients aged 18 years or older with stable treated hypertension and depression who newly initiate either serotonin norepinephrine reuptake inhibitors or SSRIs., Intervention: Serotonin norepinephrine reuptake inhibitors versus SSRIs., Measurements and Main Results: The primary outcomes were: (1) TI (first occurrence of antihypertensive regimen augmentation or dose escalation); (2) MACE (first occurrence of stroke or acute myocardial infarction). Baseline risk between the two groups was balanced via 1:1 propensity score (PS) matching. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (95% CI). After 1:1 PS matching, we included 19,160 patients in the study cohort (mean age: 52 years, 62% females) of which 9580 initiated serotonin norepinephrine reuptake inhibitors and 9580 initiated SSRIs. Patients who initiated serotonin norepinephrine reuptake inhibitors had 15 MACE events (incidence rate per 1000 person-years [IR], 3.9) and 1675 TI events (IR, 540.2), compared with 17 MACE events (IR, 4.0) and 1774 TI events (IR, 518.5) in the SSRI group. The risk of TI (aHR: 1.01, [95% CI: 0.94, 1.08]) and MACE (aHR: 0.98, [95% CI: 0.49, 1.96]) did not differ among patients initiated serotonin norepinephrine reuptake inhibitors versus SSRIs., Conclusions: Among patients with stable hypertension and depression, initiation of serotonin norepinephrine reuptake inhibitors had a similar risk of antihypertensive TI and MACE compared to initiation of SSRIs. Future study with a larger sample size is needed to confirm our findings., (© 2022 Pharmacotherapy Publications, Inc.)

In collaboration with the American College of Veterinary Pathologists.

Where an individual grows up has large implications for their long-term economic outcomes, including earnings and intergenerational mobility. Even within the United States, the "causal effect of place" varies greatly and cannot be fully explained by socioeconomic conditions. Across different nations, variation in growth and mobility have been linked to more individualistic cultures. We assess how variation of historically driven individualism within the United States affects mobility. Areas in the United States that were isolated on the frontier for longer periods of time during the 19th century have a stronger culture of "rugged individualism" [S. Bazzi, M. Fiszbein, M. Gebresilasse, Econometrica 88, 2329-2368 (2020)]. We combine county-level measures of frontier experience with modern measures of the causal effect of place on mobility-the predicted percentage change in an individual's earnings at age 26 y associated with "growing up" in a particular county [R. Chetty, N. Hendren, Q. J. Econ. 133, 1163-1228 (2018)]. Using commuting zone fixed effects and a suite of county-level controls to absorb regional variation in frontier experience and modern economic conditions, we find an additional decade of frontier experience results in 25% greater modern-day income mobility for children of parents in the 25th percentile of income and 14% for those born to parents in the 75th percentile. We use mediation analysis to present suggestive evidence that informal manifestations of "rugged individualism"-those embodied by the individuals themselves-are more strongly associated with upward mobility than formal policy or selective migration., Competing Interests: The authors declare no competing interest.

Autologous (auto-) and allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities in contemporary treatment algorithms for mantle cell lymphoma (MCL). Chimeric antigen receptor (CAR) T cell therapy recently received approval for MCL; however, its exact place and sequence in relation to HCT remain unclear. The American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and the European Society for Blood and Marrow Transplantation jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-HCT, allo-HCT, and CAR T cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated, with a few key statements as follows: in the first line setting, auto-HCT consolidation represents standard of care in eligible patients, whereas there is no clear role of allo-HCT or CAR T cell therapy outside of clinical trials. In the R/R setting, the preferential option is CAR T cell therapy, especially in patients with MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T cell therapy fails or is infeasible. Several recommendations were based on expert opinion, where the panel developed consensus statements for important real-world clinical scenarios to guide clinical practice. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL., (Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Large-scale digital flu vaccine campaigns have experienced difficulty increasing vaccination coverage among African Americans and Hispanics, and are routinely inundated by negative responses from vaccine opponents. A digital campaign employing user-generated content from social media 'micro' influencers who are predominantly followed by African Americans and Hispanics was implemented during the 2018-19 and 2019-20 flu seasons to disseminate positive information about the flu vaccine. At the time, this constituted the largest influencer-driven health campaign focused on these communities in the United States. Comments on posts were qualitatively coded to determine content perceptions among those exposed to posts. Digital metrics were also analyzed. During Year 1, posts reached 9 million+ social media users and generated 64 612 likes or shares, and 1512 responses. In Year 2, posts reached 8 million+ users and generated 155 600 likes or shares, and 3122 responses. Around 94% of public responses to posts were positive, suggesting this is a promising strategy to communicate health information and could shift social norms, particularly for heavily debated topics such as vaccination. This strategy represents a more community-led and participatory approach than most large-scale vaccination campaigns have attempted, with immediate applicability to communications about the COVID-19 vaccine., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This guideline for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by the American Radium Society was developed by a multidisciplinary expert panel of medical, pediatric, and radiation oncologists convened to formulate guidelines for evaluation and treatment. The guideline development was based on an in-depth literature review and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of the recommendations by the panel. Given the scarcity of compelling data for strong recommendations for a rare lymphoma that has been shown to be more indolent than classical Hodgkin lymphoma, in instances where evidence is not available or equivocal, expert opinion guided the recommendations. Four clinical variants exemplify common scenarios and represent the consensus recommendations for patients with nodular lymphocyte Hodgkin lymphoma. A summary of the available published literature is also presented.

Background: Nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased risk of adverse cardiovascular events prompting labeling revisions cautioning their use among patients with cardiovascular disease (CVD). However, little is known regarding long-term trends in real-world prescribing of NSAIDs within the CVD population. We aimed to characterize the use of prescription NSAIDs among U.S. adults with CVD from 1988 to 2016., Methods: We used the National Health and Nutrition Examination Survey cross-sectional data from 1988-1994 and 19992016 to identify participants aged greater than or equal to 18 years with hypertension (defined by self-report, mean blood pressure ≥ 140/90 mm Hg, or antihypertensive medication use), or aged greater than or equal to 20 years with self-reported congestive heart failure (CHF), coronary heart disease (CHD), angina, myocardial infarction (MI), or stroke. Prevalence of prescription NSAID use was analyzed in 6-year examination periods. Weighted logistic regression was performed to test time trends in prescription NSAID use., Results: Overall, prescription NSAID use declined among all CVD populations. The highest prevalence of overall prescription NSAID use was observed during the 1999-2004 examination years, thereafter declining through the 2005-2010 and 2011-2016 examination years: in patients with hypertension (13.9% [1999-2004] to 8.5% [2011-2016]), CHF (14.6%-8.5%), CHD (16.3%-7.4%), angina (17.6%-8.5%), MI (16.1%-9.0%), and stroke (15.7%-7.9%). Decreased use of COX-2-selective inhibitors was observed during the same period; whereas, nonselective NSAID use remained relatively stable. Trends in prescription NSAID use were reflective of the general adult population., Conclusions: Prescription NSAID use among patients with CVD appears to have declined from 1988 to 2016, primarily due to reduced COX-2-selective inhibitor use. Nonetheless, the prevalence of prescription NSAIDs has persisted among a subset of high-risk CVD populations., (© 2020 Pharmacotherapy Publications, Inc.)

Objective: Identifying biomarkers is a priority in translational chronic pain research. Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, are adrenocortical steroids in the blood with neuroprotective properties that also produce sex hormones. They may capture key sex-specific neuroendocrine mechanisms of chronic pain., Design: Cross-sectional study., Methods: Using data from 1,216 community-dwelling adults aged 34-84 from the Midlife in the United States (MIDUS) cohort, we examined blood DHEA and DHEA-S levels in association with chronic pain in men and women, adjusting for demographics, chronic diseases, medications including opioids, and psychosocial factors. If an association was found, we further explored dose-response relationships by the number of pain locations and the degree of pain interference., Results: In women, chronic pain was associated with 0.072 lower (95% confidence interval [CI], -0.127 to -0.017) log10 DHEA-S µg/dL, with pain in one to two locations associated with 0.068 lower (95% CI, -0.131 to -0.006) and in three or more locations 0.071 lower (95% CI, -0.148 to 0.007) log10 DHEA-S (P for trend = 0.074). Furthermore for women, low-interference pain was associated with 0.062 lower (95% CI, -0.125 to -0.000), whereas high-interference pain was associated with 0.138 lower (95% CI, -0.233 to -0.043) log10 DHEA-S (P for trend = 0.004). Chronic pain was not associated with DHEA or DHEA-S levels in men or DHEA levels in women., Conclusions: Chronic pain and its functional interference correspond to lower blood DHEA-S levels in women., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Clinical guidelines increasingly recommended ambulatory blood pressure monitoring (ABPM) for hypertension diagnosis and management. Yet, ABPM is used infrequently in the United States, possibly because of low insurance coverage and high patient costs. We sought to analyze out-of-pocket payments (OPPs) for ABPM among privately insured patients., Methods: We conducted a retrospective analysis using IBM® MarketScan® commercial claims of beneficiaries aged ≥18 years receiving ABPM from January 2012 to December 2018. The date of first ABPM claim (Healthcare Common Procedure Coding System codes 93784, 93786, 93788, or 93790) was considered the index date. Patients with 12 months of continuous enrollment preindex and 30-day postindex were included. Per beneficiary OPP was calculated by aggregating all ABPM-related OPPs within the 30-day postindex window (ABPM episode)., Results: Of 22,317 beneficiaries receiving ABPM, 62% had $0 OPP and 38% had OPP >$0. Among the latter, median OPP per beneficiary for an ABPM episode was $23 (interquartile range [IQR], $14, $32), driven primarily by full ABPM claims (median, $22; IQR, $14, $24). Among individual components, scan analysis and report claims (median, $25; IQR, $13, $49) had the greatest OPP. The median OPP per ABPM episode did not change substantively from 2012 through 2018., Conclusions: Among commercially insured in the United States, nearly 4-in-10 have an OPP for ABPM. Though most OPPs are relatively modest, some patients incur substantial OPP. Our findings highlight the need for policymakers to ensure adequate ABPM coverage in the commercial insurance marketplace., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)-directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity., Methods: Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy., Results: Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes., Conclusion: To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.

Purpose: There is limited evidence to support the use of direct-acting oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and active cancer. This study aimed to assess the effectiveness of DOACs versus warfarin for the prevention of recurrent VTE and major bleeding events in patients with VTE and active cancer., Methods: We identified patients with incident VTE and active cancer who newly initiated treatment with DOACs or warfarin from Truven Health MarketScan Commercial Claims and Medicare supplemental databases. Patients were followed up from treatment initiation (index date) until the occurrence of >7-day gap in treatment, the start of the study comparator, an outcome of interest (recurrent VTE or major bleeding), inpatient death, disenrollment, or end of the study period, whichever occurred first. We controlled for confounders via propensity score matching and estimated the hazard ratios (HRs) using Cox proportional hazards regression models., Findings: A total of 9952 patients were included in the matched cohort (4976 DOACs users and 4976 warfarin users). Patient characteristics were well balanced after matching. We observed a lower incidence of recurrent VTE (3 vs 5 per 100 person-years) and major bleeding events (2 vs 3 per 100 person-years) in the DOAC group compared to warfarin group, respectively. In Cox regression models, use of DOACs (vs warfarin) was associated with a lower risk of recurrent VTE (hazard ratio (HR), 0.59; 95% CI, 0.42-0.82) and major bleeding events (HR, 0.64; 95% CI, 0.44-0.94)., Implications: On the basis of our findings, among patients with VTE and active cancer, DOACs offer superior effectiveness with a lower risk of bleeding when compared with warfarin for the secondary prevention of VTE., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We conducted a cross-sectional analysis using a database from commercial health plans in the United States to describe trends in the use of antidiabetic medications among patients with type 2 diabetes and heart failure (HF) from 2006 through 2017. We used loop diuretic dose as a surrogate for HF severity (mild HF 0-40 mg/day, moderate-severe HF >40 mg/day). We assessed antidiabetic medication dispensing in the 90 days following HF diagnosis. Over the 12-year period, we identified an increase in the use of metformin (39.2% vs. 62.6%), dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.5% vs. 17.1%) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) (0.0% vs. 9.0%), but a decrease in the use of sulphonylureas (47.8% vs. 27.8%) and thiazolidinediones (TZDs) (31.7% vs. 5.3%). In 2017, patients with moderate-severe HF more commonly used insulin (43.1%); a majority of mild HF patients used metformin (62.8%). A proportion of patients with moderate-severe HF used TZDs (4.4%). Among patients with diabetes and HF, the use of metformin and DPP-4i rapidly increased, but a proportion of patients with moderate-severe HF continued to use TZDs. Despite their promising cardiovascular safety profile, SGLT-2i use remains limited., (© 2020 John Wiley & Sons Ltd.)

Polymorphous adenocarcinoma (PAC) shows histologic diversity with streaming and targetoid features whereas cribriform adenocarcinoma of salivary gland (CASG) demonstrates predominantly cribriform and solid patterns with glomeruloid structures and optically clear nuclei. Opinions diverge on whether CASG represents a separate entity or a variant of PAC. We aimed to assess the level of agreement among 25 expert Head and Neck pathologists in classifying these tumors. Digital slides of 48 cases were reviewed and classified as: PAC, CASG, tumors with ≥50% of papillary architecture (PAP), and tumors with indeterminate features (IND). The consensus diagnoses were correlated with a previously reported molecular alteration. The consensus diagnoses were PAC in 18/48, CASG in16/48, PAP in 3/48, and IND in 11/48. There was a fair interobserver agreement in classifying the tumors (κ=0.370). The full consensus was achieved in 3 (6%) cases, all of which were classified as PAC. A moderate agreement was reached for PAC (κ=0.504) and PAP (κ=0.561), and a fair agreement was reached for CASG (κ=0.390). IND had only slight diagnostic concordance (κ=0.091). PAC predominantly harbored PRKD1 hotspot mutation, whereas CASG was associated with fusion involving PRKD1, PRKD2, or PRKD3. However, such molecular events were not exclusive as 7% of PAC had fusion and 13% of CASG had mutation. In conclusion, a fair to moderate interobserver agreement can be achieved in classifying PAC and CASG. However, a subset (23%) showed indeterminate features and was difficult to place along the morphologic spectrum of PAC/CASG among expert pathologists. This may explain the controversy in classifying these tumors.

Ambulatory blood pressure monitoring (ABPM) is increasingly recommended for confirming hypertension diagnosis and ongoing hypertension monitoring. However, reimbursement in the United States is variable and low compared with other advanced health care systems. We examined the reimbursement of ABPM and factors associated with successful reimbursement. A retrospective analysis of IBM MarketScan ® commercial claims database was conducted for patients ≥18 years with ≥1 ABPM claim from January 2012 to December 2016. The date of first the ABPM claim was used as the index date. Per-beneficiary ABPM episode reimbursements were calculated by aggregating all ABPM-related reimbursements within a 30-day post-index window, considered as an ABPM episode. Multivariable logistic regression was used to identify predictors of successful reimbursement. Of 20 875 beneficiaries with ABPM claims, 16 920 (81.0%) were reimbursed. The median reimbursement per beneficiary for an ABPM episode was $89 (Inter Quartile Range [IQR], $62, $132), driven primarily by reimbursement for the full procedure (median, $86; IQR, $66, $110). Comparing benefit plan types, consumer-directed health plans provided the highest median reimbursement ($96; IQR, $61, $175). Successful reimbursement was associated with female patient sex (adjusted OR [aOR], 1.20; 95% CI, 1.11-1.28), having a health maintenance organization (aOR 2.11; 95% CI, 1.82-2.43) or point of service (aOR 2.08; 95% CI, 1.74-2.49) as benefit plan types, claim filing by a specialist (aOR 1.26; 95% CI, 1.14-1.40) and services provided at an outpatient hospital (aOR 1.17; 95% CI, 1.01-1.35). Among commercially insured Americans, our data suggest significant variability in successful reimbursement. Accordingly, more uniform criteria for ABPM reimbursement may facilitate greater use of guideline-recommended monitoring., (© 2019 Wiley Periodicals, Inc.)

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: Withdrawing medications that interfere with blood pressure (BP) is recommended in patients with uncontrolled BP, yet real-world use of such agents is not well characterized among individuals with hypertension. We aimed to evaluate the use of BP-interfering prescription medications among US patients with hypertension., Methods: This retrospective drug utilization study used medical and prescription claims (January 2008 to December 2014) in the MarketScan commercial claims database. We included adults, aged 18-65 years, with a hypertension diagnosis (International Classification of Diseases, Ninth Revision, code 401) and ≥1 antihypertensive medication fill. Two hypertension cohorts were examined-new antihypertensive drug users (incident hypertension) and patients requiring titration to a fourth antihypertensive (incident treatment-resistant hypertension [TRH]). Patient-level exposure to BP-interfering medications was assessed 6 months before and after the index date, defined as the first prescription fill of an antihypertensive drug or the first occurrence of overlapping use of ≥4 antihypertensive drugs., Results: We identified 521,028 patients with incident hypertension and 131,764 patients with incident TRH. The most prevalent BP-interfering prescription medications were nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophens, and hormones. Overall, 18.3% of the incident hypertension cohort and 17.6% of the incident TRH cohort initiated a BP-interfering medication following antihypertensive titration. Among patients previously taking a BP-interfering medication, 57.6% with incident hypertension and 64.9% with incident TRH refilled that medication after antihypertensive intensification., Conclusions: The use of prescription BP-interfering medications, especially NSAIDs, is prevalent among patients requiring intensification of their antihypertensive regimen. Greater efforts to limit the use of these medications, where feasible, may be required among patients with uncontrolled hypertension.

Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. The antihypertensive drugs should be administered at maximum or maximally tolerated daily doses. RH also includes patients whose BP achieves target values on ≥4 antihypertensive medications. The diagnosis of RH requires assurance of antihypertensive medication adherence and exclusion of the "white-coat effect" (office BP above goal but out-of-office BP at or below target). The importance of RH is underscored by the associated risk of adverse outcomes compared with non-RH. This article is an updated American Heart Association scientific statement on the detection, evaluation, and management of RH. Once antihypertensive medication adherence is confirmed and out-of-office BP recordings exclude a white-coat effect, evaluation includes identification of contributing lifestyle issues, detection of drugs interfering with antihypertensive medication effectiveness, screening for secondary hypertension, and assessment of target organ damage. Management of RH includes maximization of lifestyle interventions, use of long-acting thiazide-like diuretics (chlorthalidone or indapamide), addition of a mineralocorticoid receptor antagonist (spironolactone or eplerenone), and, if BP remains elevated, stepwise addition of antihypertensive drugs with complementary mechanisms of action to lower BP. If BP remains uncontrolled, referral to a hypertension specialist is advised.

The application of allogeneic hematopoietic cell transplantation (allo-HCT) in non-Hodgkin lymphoma (NHL) patients ≥65 years in the United States is limited by lack of Medicare coverage for this indication. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report allo-HCT outcomes of NHL patients aged ≥65 years (older cohort; n = 446) compared with a cohort of younger NHL patients aged 55-64 years (n = 1183). We identified 1629 NHL patients undergoing a first reduced-intensity conditioning (RIC) or nonmyeloablative conditioning allo-HCT from 2008 to 2015 in the United States. Cord blood or haploidentical transplants were excluded. The median age was 68 years (range 65-77) for the older cohort vs 60 years (range 55-64) in the younger cohort. The 4-year adjusted probabilities of nonrelapse mortality (NRM), relapse/progression (R/P), progression-free survival (PFS), and overall survival (OS) of the younger and older groups were 24% vs 30% ( P = .03), 41% vs 42% ( P = .82), 37% vs 31% ( P = .03), and 51% vs 46% ( P = .07), respectively. Using multivariate analysis, compared with the younger group, the older cohort was associated with increased NRM, but there was no difference between the 2 cohorts in terms of R/P, PFS, or OS. The most common cause of death was disease relapse in both groups. In NHL patients eligible for allo-HCT, there was no difference in OS between the 2 cohorts. Age alone should not determine allo-HCT eligibility in NHL, and Medicare should expand allo-HCT coverage to older adults.

Objectives: A goal SBP 120 mmHg or less reduced mortality in high-risk Systolic Blood Pressure Intervention Trial patients; however, mortality implications of concomitant DBP lowering in coronary artery disease (CAD) are uncertain. We examined the relationship between DBP lowering and all-cause mortality with lower achieved SBPs in a large cohort., Methods: We categorized 17 131 hypertensive patients from the INternational VErapamil-trandolapril STudy US cohort, aged at least 50 years with CAD, by mean achieved SBP (<120, 120 to <130, 130 to <140, and ≥140 mmHg) and DBP tertiles (low, middle, and high per SBP category) during active follow-up. Long-term mortality was determined via National Death Index. Multivariable Cox regression was performed to investigate the impact of DBP lowering among all SBP categories and within each SBP category., Results: There were 6031 deaths over mean follow-up of 11.6 years (198 352 patient-years). In unadjusted analyses, achieving DBP in the lowest tertile portended greatest mortality risk across all SBP categories. In multivariate analysis, using SBP 120 to less than 130 mmHg, DBP at least 79 mmHg as reference (mortality nadir), achieving DBP in the lowest tertile (DBP < 69 mmHg) was associated with excess mortality risk among those with SBP less than 120 mmHg (adjusted hazard ratio 1.60; 95% confidence interval, 1.33-1.91). However, among those with SBP 120 to less than 140 mmHg, adjusted mortality risk did not differ significantly with low DBPs. Among those with SBP at least 140 mmHg, mortality risk remained high regardless of DBP., Conclusion: In older CAD patients, the mortality risk related to excess DBP lowering is accentuated in those achieving intensive SBP control less than 120 mmHg, raising concerns about intensive SBP lowering in these patients.

This topic addresses the treatment of newly diagnosed patients with favorable prognosis stage I and II Hodgkin lymphoma. In most cases, combined modality therapy (chemotherapy followed by involved site radiation therapy) constitutes the current standard of care. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the appropriate use of combined modality therapy for favorable prognosis stage I and II Hodgkin lymphoma. Increasing information about the late effects of treatment has led to attempts to decrease toxicity by using less chemotherapy (decreased duration and/or intensity or different agents) and less radiation therapy (reduced volume and/or dose) while maintaining excellent efficacy.

Importance: Current information on the prevalence and sociodemographic and clinical profiles of individuals in the general population with DSM-5 drug use disorder (DUD) is limited. Given the present societal and economic context in the United States and the new diagnostic system, up-to-date national information is needed from a single uniform data source., Objective: To present nationally representative findings on the prevalence, correlates, psychiatric comorbidity, disability, and treatment of DSM-5 DUD diagnoses overall and by severity level., Design, Setting, and Participants: In-person interviews were conducted with 36,309 adults in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III, a cross-sectional representative survey of the United States. The household response rate was 72%; person-level response rate, 84%; and overall response rate, 60.1%. Data were collected April 2012 through June 2013 and analyzed from February through March 2015., Main Outcomes and Measures: Twelve-month and lifetime DUD, based on amphetamine, cannabis, club drug, cocaine, hallucinogen, heroin, nonheroin opioid, sedative/tranquilizer, and/or solvent/inhalant use disorders., Results: Prevalences of 12-month and lifetime DUD were 3.9% and 9.9%, respectively. Drug use disorder was generally greater among men, white and Native American individuals, younger and previously or never married adults, those with lower education and income, and those residing in the West. Significant associations were found between 12-month and lifetime DUD and other substance use disorders. Significant associations were also found between any 12-month DUD and major depressive disorder (odds ratio [OR], 1.3; 95% CI, 1.09-1.64), dysthymia (OR, 1.5; 95% CI, 1.09-2.02), bipolar I (OR, 1.5; 95% CI, 1.06-2.05), posttraumatic stress disorder (OR, 1.6; 95% CI, 1.27-2.10), and antisocial (OR, 1.4; 95% CI, 1.11-1.75), borderline (OR, 1.8; 95% CI, 1.41-2.24), and schizotypal (OR, 1.5; 95% CI, 1.18-1.87) personality disorders. Similar associations were found for any lifetime DUD with the exception that lifetime DUD was also associated with generalized anxiety disorder (OR, 1.3; 95% CI, 1.06-1.49), panic disorder (OR, 1.3; 95% CI, 1.06-1.59), and social phobia (OR, 1.3; 95% CI, 1.09-1.64). Twelve-month DUD was associated with significant disability, increasing with DUD severity. Among respondents with 12-month and lifetime DUD, only 13.5% and 24.6% received treatment, respectively., Conclusions and Relevance: DSM-5 DUD is a common, highly comorbid, and disabling disorder that largely goes untreated in the United States. These findings indicate the need for additional studies to understand the broad relationships in more detail; estimate present-day economic costs of DUDs; investigate hypotheses regarding etiology, chronicity, and treatment use; and provide information to policy makers about allocation of resources for service delivery and research. Findings also indicate an urgent need to destigmatize DUD and educate the public, clinicians, and policy makers about its treatment to encourage affected individuals to obtain help., Competing Interests: Disclosures: None reported.

Importance: Laws and attitudes toward marijuana in the United States are becoming more permissive but little is known about whether the prevalence rates of marijuana use and marijuana use disorders have changed in the 21st century., Objective: To present nationally representative information on the past-year prevalence rates of marijuana use, marijuana use disorder, and marijuana use disorder among marijuana users in the US adult general population and whether this has changed between 2001-2002 and 2012-2013., Design, Setting, and Participants: Face-to-face interviews conducted in surveys of 2 nationally representative samples of US adults: the National Epidemiologic Survey on Alcohol and Related Conditions (data collected April 2001-April 2002; N = 43,093) and the National Epidemiologic Survey on Alcohol and Related Conditions-III (data collected April 2012-June 2013; N = 36,309). Data were analyzed March through May 2015., Main Outcomes and Measures: Past-year marijuana use and DSM-IV marijuana use disorder (abuse or dependence)., Results: The past-year prevalence of marijuana use was 4.1% (SE, 0.15) in 2001-2002 and 9.5% (SE, 0.27) in 2012-2013, a significant increase (P < .05). Significant increases were also found across demographic subgroups (sex, age, race/ethnicity, education, marital status, income, urban/rural, and region). The past-year prevalence of DSM-IV marijuana use disorder was 1.5% (0.08) in 2001-2002 and 2.9% (SE, 0.13) in 2012-2013 (P < .05). With few exceptions, increases in the prevalence of marijuana use disorder between 2001-2002 and 2012-2013 were also statistically significant (P < .05) across demographic subgroups. However, the prevalence of marijuana use disorder among marijuana users decreased significantly from 2001-2002 (35.6%; SE, 1.37) to 2012-2013 (30.6%; SE, 1.04)., Conclusions and Relevance: The prevalence of marijuana use more than doubled between 2001-2002 and 2012-2013, and there was a large increase in marijuana use disorders during that time. While not all marijuana users experience problems, nearly 3 of 10 marijuana users manifested a marijuana use disorder in 2012-2013. Because the risk for marijuana use disorder did not increase among users, the increase in prevalence of marijuana use disorder is owing to an increase in prevalence of users in the US adult population. Given changing laws and attitudes toward marijuana, a balanced presentation of the likelihood of adverse consequences of marijuana use to policy makers, professionals, and the public is needed., Competing Interests: Disclosures: None reported.

Physician-pharmacist collaborative care (PPCC) is effective in improving blood pressure (BP) control, but primary care provider (PCP) engagement in such models has not been well-studied. The authors analyzed data from PPCC referrals to 108 PCPs, for patients with uncontrolled hypertension, assessing the proportion of referral requests approved, disapproved, and not responded to, and reasons for disapproval. Of 2232 persons with uncontrolled hypertension, PPCC referral requests were sent for 1516 (67.9%): 950 (62.7%) were approved, 406 (26.8%) were disapproved, and 160 (10.6%) received no response. Approval rates differed widely by PCP with a median approval rate of 75% (interquartile range, 41%-100%). The most common reasons for disapproval were: PCP prefers to manage hypertension (19%), and BP controlled per PCP (18%); 8% of cases were considered too complex for PPCC. Provider acceptance of a PPCC hypertension clinic was generally high and sustained but varied widely among PCPs. No single reason for disapproval predominated., (©2015 Wiley Periodicals, Inc.)

Importance: National epidemiologic information from recently collected data on the new DSM-5 classification of alcohol use disorder (AUD) using a reliable, valid, and uniform data source is needed., Objective: To present nationally representative findings on the prevalence, correlates, psychiatric comorbidity, associated disability, and treatment of DSM-5 AUD diagnoses overall and according to severity level (mild, moderate, or severe)., Design, Setting, and Participants: We conducted face-to-face interviews with a representative US noninstitutionalized civilian adult (≥18 years) sample (N = 36 309) as the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III). Data were collected from April 2012 through June 2013 and analyzed in October 2014., Main Outcomes and Measures: Twelve-month and lifetime prevalences of AUD., Results: Twelve-month and lifetime prevalences of AUD were 13.9% and 29.1%, respectively. Prevalence was generally highest for men (17.6% and 36.0%, respectively), white (14.0% and 32.6%, respectively) and Native American (19.2% and 43.4%, respectively), respondents, and younger (26.7% and 37.0%, respectively) and previously married (11.4% and 27.1%, respectively) or never married (25.0% and 35.5%, respectively) adults. Prevalence of 12-month and lifetime severe AUD was greatest among respondents with the lowest income level (1.8% and 1.5%, respectively). Significant disability was associated with 12-month and lifetime AUD and increased with the severity of AUD. Only 19.8% of respondents with lifetime AUD were ever treated. Significant associations were found between 12-month and lifetime AUD and other substance use disorders, major depressive and bipolar I disorders, and antisocial and borderline personality disorders across all levels of AUD severity, with odds ratios ranging from 1.2 (95% CI, 1.08-1.36) to 6.4 (95% CI, 5.76-7.22). Associations between AUD and panic disorder, specific phobia, and generalized anxiety disorder were modest (odds ratios ranged from 1.2 (95% CI, 1.01-1.43) to 1.4 (95% CI, 1.13-1.67) across most levels of AUD severity., Conclusions and Relevance: Alcohol use disorder defined by DSM-5 criteria is a highly prevalent, highly comorbid, disabling disorder that often goes untreated in the United States. The NESARC-III data indicate an urgent need to educate the public and policy makers about AUD and its treatment alternatives, to destigmatize the disorder, and to encourage those who cannot reduce their alcohol consumption on their own, despite substantial harm to themselves and others, to seek treatment.

Exotic insects are constantly intercepted at U.S. ports-of-entry. Of these, wood-boring beetles, particularly xyleborine ambrosia beetles, are sometimes missed during port inspections and become established in the United States. Euwallacea validus (Eichhoff) and Euwallacea interjectus (Blandford) are morphologically similar Asian ambrosia beetle species that vary by their fungal associates and their potential to cause economic damage. Euwallacea validus and E. interjectus were first discovered in New York (1975) and Hawaii (1976), respectively. Euwallacea validus was collected multiple times from widely separated localities and is assumed to have spread throughout the eastern United States. The discovery of E. interjectus in Florida (2011) and Texas (2011) prompted our review of the E. validus specimens because of the potential misidentification of the species. In addition, using mitochondrial cytochrome oxidase I (COI) DNA data and phylogenetic analysis, we tested the hypothesis that multiple introductions account for the U.S. populations of E. interjectus and E. validus. Our review of 7,184 specimens revealed an earlier introduction to the mainland for E. interjectus, which was first collected from Louisiana in 1984. This species is distributed in the South while E. validus occurs in the North with a known area of syntopy in northeastern Georgia. The extent of the syntopy within the United States is unknown and further investigation is required. Phylogenetic analysis of 24 E. interjectus and 20 E. validus individuals resolved clades that associated with each species and gross geographic provenance. Four well-supported clades represented E. interjectus which included the following localities: 1) Hawaii and Thailand; 2) Vietnam, Taiwan, and Texas; 3) Okinawa (Japan); and 4) Japan and several southern U.S. states. One clade comprised all E. validus specimens from Japan and the mainland United States. Four and two haplotypes were found for the E. interjectus and E. validus specimens, respectively, in mainland United States. Except for the Texas specimen, the haplotypes differed by one nucleotide. The relationship of the haplotypes and their sequence similarity suggested that the provenance of E. validus and the majority of E. interjectus haplotypes was Japan while the Texas haplotype originated later and from a location near Taiwan. Given the high nucleotide sequence difference between the Hawaiian and Thai haplotypes, the exact origin of the Hawaiian E. interjectus is unknown but likely Southeast Asia. A broader investigation including more SE Asian individuals will help to further explain the introduction of E. interjectus into Hawaii and Texas., (© The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Optimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear., Patients and Methods: We examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses., Results: PTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I-II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34-0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22-0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14-0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17-0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission., Conclusions: This analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The impact of race/ethnicity and the additional factors of age, sex, and socioeconomic status (SES) on follicular lymphoma (FL) outcomes have not been comprehensively studied and are not well defined. We examined population-based FL data from >18,000 patients in SEER-13 (1992-2009) investigating race/ethnicity and the impact of relevant factors including sex, age, and SES. Further, we compared data over two consecutive periods: Era-1 (1992-2000, n = 8,355) and Era-2 (2001-2009, n = 10,475). We identified 18,830 FL patients (White: n = 15,116; Hispanic: n = 1,627; Asian/Pacific Islander (A/PI): n = 1,002; and Black: n = 846). Median ages (years) differed significantly by race/ethnicity: White: 62.1, Hispanic: 57.3, A/PI: 60.7, and Black: 56.8 (P < 0.01 each race versus White). Overall survival (OS) was superior in Era-2 versus Era-1 for all patients (5-year: 76.7% versus 67.4%, respectively, P < 0.001). Further, survival was significantly improved for all age groups <80 years, for males (P = 0.0019), and females (P < 0.001) across eras. Females had superior OS compared with males in Era-1 (P = 0.004), but not in Era-2. Additionally, all races, except A/PI, had improved 5-year OS rates from Era-1 to Era-2. Finally, OS improved across eras for lower and higher SES populations; however those with higher SES were superior to lower SES patients in both eras. In conclusion, and in the largest comprehensive evaluation of US-based FL patients to date, we show that despite improvements in OS for FL over time, critical disparities across races/ethnicities, sex, and age groups remain in the modern era and warrant further studies., (© 2014 Wiley Periodicals, Inc.)

Unlabelled: Current approaches to classification of chronic pain conditions suffer from the absence of a systematically implemented and evidence-based taxonomy. Moreover, existing diagnostic approaches typically fail to incorporate available knowledge regarding the biopsychosocial mechanisms contributing to pain conditions. To address these gaps, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration and the American Pain Society (APS) have joined together to develop an evidence-based chronic pain classification system called the ACTTION-APS Pain Taxonomy. This paper describes the outcome of an ACTTION-APS consensus meeting, at which experts agreed on a structure for this new taxonomy of chronic pain conditions. Several major issues around which discussion revolved are presented and summarized, and the structure of the taxonomy is presented. ACTTION-APS Pain Taxonomy will include the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors. In coming months, expert working groups will apply this taxonomy to clusters of chronic pain conditions, thereby developing a set of diagnostic criteria that have been consistently and systematically implemented across nearly all common chronic pain conditions. It is anticipated that the availability of this evidence-based and mechanistic approach to pain classification will be of substantial benefit to chronic pain research and treatment., Perspective: The ACTTION-APS Pain Taxonomy is an evidence-based chronic pain classification system designed to classify chronic pain along the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors., (Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: Women are more likely than men to develop resistant hypertension, which is associated with excess risk of major adverse outcomes; however, the impact of resistant hypertension in women with ischemia has not been explicitly studied. In this Women's Ischemia Syndrome Evaluation (WISE) analysis, we assessed long-term adverse outcomes associated with apparent treatment-resistant hypertension (aTRH) among women with suspected myocardial ischemia referred for coronary angiography., Methods and Results: Women (n=927) were grouped according to baseline blood pressure (BP): normotensive (no hypertension history, BP <140/90 mm Hg, no antihypertensive drugs); controlled (BP <140/90 mm Hg and a hypertension diagnosis or on 1 to 3 drugs); uncontrolled (BP ≥140/90 mm Hg on ≤2 drugs); or aTRH (BP ≥140/90 mm Hg on 3 drugs or anyone on ≥4 drugs). Adverse outcomes (first occurrence of death [any cause], nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure or angina) were collected over 10 years of follow-up. Apparent treatment-resistant hypertension prevalence was 10.4% among those with hypertension. Women with aTRH had a greater incidence of adverse outcomes, compared with normotensive women (adjusted hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.94 to 5.43), and women with controlled (HR, 1.77; 95% CI, 1.26 to 2.49) and uncontrolled (HR, 1.62; 95% CI, 1.15 to 2.27) hypertension; outcome differences were evident early in follow-up. Risk of all-cause death was greater in the aTRH group, compared to the normotensive women and women with controlled and uncontrolled hypertension., Conclusions: In this cohort of women with evidence of ischemia, aTRH was associated with a profoundly increased long-term risk of major adverse events, including death, that emerged early during follow-up.