Association of Direct Oral Anticoagulation Management Strategies With Clinical Outcomes for Adults With Atrial Fibrillation.

Importance: Anticoagulation management services (AMSs; ie, warfarin clinics) have evolved to include patients treated with direct oral anticoagulants (DOACs), but it is unknown whether DOAC therapy management services improve outcomes for patients with atrial fibrillation (AF). Objective: To compare outcomes associated with 3 DOAC care models for preventing adverse anticoagulation-related outcomes among patients with AF. Design, Setting, and Participants: This retrospective cohort study included 44 746 adult patients with a diagnosis of AF who initiated oral anticoagulation (DOAC or warfarin) between August 1, 2016, and December 31, 2019, in 3 Kaiser Permanente (KP) regions. Statistical analysis was conducted from August 2021 through May 2023. Exposures: Each KP region used an AMS to manage warfarin but used distinct approaches to DOAC care: (1) usual care (UC) by the prescribing clinician, (2) UC plus an automated population management tool (PMT), or (3) pharmacist-managed AMS care. Propensity scores and inverse probability of treatment weights (IPTWs) were estimated. Direct oral anticoagulant care models were first indirectly compared using warfarin as a common comparator within each region and then directly compared across regions. Main Outcomes and Measures: Patients were followed up until the first occurrence of an outcome (composite of thromboembolic stroke, intracranial hemorrhage, other major bleeding, or death), discontinuation of KP membership, or December 31, 2020. Results: Overall, 44 746 patients were included: 6182 in the UC care model (3297 DOAC; 2885 warfarin), 33 625 in the UC plus PMT care model (21 891 DOAC; 11 734 warfarin), and 4939 in the AMS care model (2089 DOAC; 2850 warfarin). Baseline characteristics (mean [SD] age, 73.1 [10.6] years, 56.1% male, 67.2% non-Hispanic White, median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex] score of 3 [IQR, 2-5]) were well balanced after IPTW. Over a median follow-up of 2 years, patients who received the UC plus PMT or AMS care model did not have significantly better outcomes than those who received UC. The incidence rate of the composite outcome was 5.4% per year for DOAC and 9.1% per year for warfarin for those in the UC group, 6.1% per year for DOAC and 10.5% per year for those in the UC plus PMT group, and 5.1% per year for DOAC and 8.0% per year for those in the AMS group. The IPTW-adjusted hazard ratios (HRs) for the composite outcome comparing DOAC vs warfarin were 0.91 (95% CI, 0.79-1.05) in the UC group, 0.85 (95% CI, 0.79-0.90) in the UC plus PMT group, and 0.84 (95% CI, 0.72-0.99) in the AMS group (P = .62 for heterogeneity across care models). When directly comparing patients receiving DOAC, the IPTW-adjusted HR was 1.06 (95% CI, 0.85-1.34) for the UC plus PMT group vs the UC group and 0.85 (95% CI, 0.71-1.02) for the AMS group vs the UC group. Conclusions and Relevance: This cohort study did not find appreciably better outcomes for patients receiving DOAC who were managed by either a UC plus PMT or AMS care model compared with UC.

Approach to Multimorbidity Burden Classification and Outcomes in Older Adults With Heart Failure.

BACKGROUND: The optimal approach to classifying multimorbidity burden in assessing treatment-associated outcomes using real-world data remains uncertain. We assessed whether 2 measurement approaches to characterize multimorbidity influenced observed associations of ß-blocker use with outcomes in adults with heart failure (HF). METHODS: We conducted a retrospective study on adults with HF from 4 integrated health care delivery systems. Multimorbidity burden was characterized by either (1) simple counts of chronic conditions or (2) a weighted multiple chronic conditions score using data from electronic health records. We assessed the impact of these 2 approaches to characterizing multimorbidity on associations between exposure to ß-blockers and subsequent all-cause death, hospitalization for HF, and hospitalization for any cause. RESULTS: The study population characterized by a count of chronic conditions included 9988 adults with HF who had a mean (SD) age of 76.4 (12.5) years, with 48.7% women and 24.7% racial/ethnic minorities. The cohort characterized by weighted multiple chronic conditions included 10,082 adults with HF who had a mean (SD) age of 76.4 (12.4) years, 48.9% women, and 25.5% racial/ethnic minorities. The multivariable associations of risks of death or hospitalizations for HF or for any cause associated with incident ß-blocker use were similar regardless of how multimorbidity burden was characterized. CONCLUSIONS: Simple counts of chronic conditions performed similarly to a weighted multimorbidity score in predicting outcomes using real-world data to examine clinical outcomes associated with ß-blocker therapy in HF. Our findings challenge conventional wisdom that more complex measures of multimorbidity are always necessary to characterize patients in observational studies examining therapy-associated outcomes.

"I really had somebody in my corner." Patient experiences with a pharmacist-led opioid tapering program.

BACKGROUND: Opioid tapering has been identified as an effective strategy to prevent the dangers associated with long-term opioid therapy for patients with chronic pain. However, many patients are resistant to tapering, and conversations about tapering can be challenging for health care providers. Pharmacists can play a role in supporting both providers and patients with the process of opioid tapering. OBJECTIVE: Qualitatively describe patient experiences with a unique phone-based and pharmacy-led opioid tapering program implemented within an integrated health care system. METHODS: In-depth telephone interviews with patients who completed the program were recorded, transcribed, and analyzed. Themes were identified through a constant comparative approach. RESULTS: We completed 25 interviews; 80% of patients were women (20), with a mean age of 58 years, and 72% (18) had been using opioids for pain management for 10 or more years. Most (60%) described a positive and satisfying experience with the tapering program. Strengths of the program reported by patients included a patient-centered and compassionate taper approach, flexible taper pace, easy access to knowledgeable pharmacist advocates, and resultant improvements in quality of life (e.g., increased energy). Challenges reported included: unhelpful or difficult-to-access nonpharmacological pain management options, negative quality of life impacts (e.g., inability to exercise), and lack of choice in the taper process. At the end of tapering, most patients (72%) described their pain as reduced or manageable rather than worse and expressed willingness to use the program in the future if a need should arise. CONCLUSIONS: Patients in a pharmacist-led opioid tapering program appreciated the program's individualized approach to care and access to pharmacist' expertise. Most interviewed patients successfully reduced their opioid use and recommended that the program should continue as an offered service. To improve the program, patients suggested increased personalization of the taper process and additional support for withdrawal symptoms and nonpharmacological pain management.

Costs and Cost-Effectiveness of Implementing a Digital Diabetes Prevention Program in a Large, Integrated Health System.

BackgroundThe Diabetes Prevention Program (DPP) has been translated into digital formats. We report an economic evaluation of a digital DPP implemented in a large, integrated health care system. MethodsPatients (n = 4148) were invited to participate in digital DPP based on clinical characteristics (HbA1c 5.7%-6.4% and body mass index ≥ 30 kg/m2) assessed using electronic medical record data. Using a propensity score we matched (1:1) enrolled and not enrolled patients for a total of 784. We identified high-risk patients (ie, above the 50th percentile of risk; n = 202) by calculating each patient's 2-year of developing diabetes. We report the cost of the intervention and the costs of medical care over 12- and 24-month follow-up, and the incremental cost-effectiveness ratio as the cost per additional kilogram weight loss at 24 months. ResultsAt 12 months, enrolled patients had lower total costs ($6,926, 95% CI $5,681-$8,171) than not enrolled patients ($7,538, 95% CI $6,293-$8,783). This pattern attenuated slightly at 24 months (enrolled = $16,255, 95% CI $14,097-$18,412; not enrolled = $16,688, 95% CI $14,531-$18,846). We found an incremental cost-effectiveness ratio of $81.92 per additional kilogram weight loss. For high-risk patients, the digital DPP group had, on average, lower costs and greater weight loss. We found a 55% chance of the digital DPP program being cost-effective at a willingness-to-pay of $150 per additional kilogram of weight loss; at the same willingness-to-pay, there is a 60% chance in the high-risk subgroup. Limitations include the nonrandomized design and potential volunteer bias. ConclusionDigital DPP had a favorable cost-effectiveness profile compared to other lifestyle interventions.

Economic Evaluation: A Randomized Pragmatic Trial of a Primary Care-based Cognitive Behavioral Intervention for Adults Receiving Long-term Opioids for Chronic Pain.

BACKGROUND: Chronic pain is prevalent and costly; cost-effective nonpharmacological approaches that reduce pain and improve patient functioning are needed. OBJECTIVE: Report the incremental cost-effectiveness ratio (ICER), compared with usual care, of cognitive behavioral therapy aimed at improving functioning and pain among patients with chronic pain on long-term opioid treatment. DESIGN: Economic evaluation conducted alongside a pragmatic cluster randomized trial. SUBJECTS: Adults with chronic pain on long-term opioid treatment (N=814). INTERVENTION: A cognitive behavioral therapy intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorists, nurses) with additional support from physical therapists, and pharmacists. OUTCOME MEASURES: Cost per quality adjusted life year (QALY) gained, and cost per additional responder (≥30% improvement on standard scale assessment of Pain, Enjoyment, General Activity, and Sleep). Costs were estimated as-delivered, and replication. RESULTS: Per patient intervention replication costs were $2145 ($2574 as-delivered). Those costs were completely offset by lower medical care costs; inclusive of the intervention, total medical care over follow-up was $1841 lower for intervention patients. Intervention group patients also had greater QALY and responder gains than did controls. Supplemental analyses using pain-related medical care costs revealed ICERs of $35,000, and $53,000 per QALY (for replication, and as-delivered intervention costs, respectively); the ICER when excluding patients with outlier follow-up costs was $106,000. LIMITATIONS: Limited to 1-year follow-up; identification of pain-related utilization potentially incomplete. CONCLUSION: The intervention was the optimal choice at commonly accepted levels of willingness-to-pay for QALY gains; this finding was robust to sensitivity analyses.

A Primary Care-Based Cognitive Behavioral Therapy Intervention for Long-Term Opioid Users With Chronic Pain : A Randomized Pragmatic Trial.

BACKGROUND: Chronic pain is common, disabling, and costly. Few clinical trials have examined cognitive behavioral therapy (CBT) interventions embedded in primary care settings to improve chronic pain among those receiving long-term opioid therapy. OBJECTIVE: To determine the effectiveness of a group-based CBT intervention for chronic pain. DESIGN: Pragmatic, cluster randomized controlled trial. (ClinicalTrials.gov: NCT02113592). SETTING: Kaiser Permanente health care systems in Georgia, Hawaii, and the Northwest. PARTICIPANTS: Adults (aged ≥18 years) with mixed chronic pain conditions receiving long-term opioid therapy. INTERVENTION: A CBT intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorist, nurse, physical therapist, and pharmacist) versus usual care. MEASUREMENTS: Self-reported pain impact (primary outcome, as measured by the PEGS scale [pain intensity and interference with enjoyment of life, general activity, and sleep]) was assessed quarterly over 12 months. Pain-related disability, satisfaction with care, and opioid and benzodiazepine use based on electronic health care data were secondary outcomes. RESULTS: A total of 850 patients participated, representing 106 clusters of primary care providers (mean age, 60.3 years; 67.4% women); 816 (96.0%) completed follow-up assessments. Intervention patients sustained larger reductions on all self-reported outcomes from baseline to 12-month follow-up; the change in PEGS score was -0.434 point (95% CI, -0.690 to -0.178 point) for pain impact, and the change in pain-related disability was -0.060 point (CI, -0.084 to -0.035 point). At 6 months, intervention patients reported higher satisfaction with primary care (difference, 0.230 point [CI, 0.053 to 0.406 point]) and pain services (difference, 0.336 point [CI, 0.129 to 0.543 point]). Benzodiazepine use decreased more in the intervention group (absolute risk difference, -0.055 [CI, -0.099 to -0.011]), but opioid use did not differ significantly between groups. LIMITATION: The inclusion of only patients with insurance in large integrated health care systems limited generalizability, and the clinical effect of change in scores is unclear. CONCLUSION: Primary care-based CBT, using frontline clinicians, produced modest but sustained reductions in measures of pain and pain-related disability compared with usual care but did not reduce use of opioid medication. PRIMARY FUNDING SOURCE: National Institutes of Health.

Bariatric Surgery and Risk of Death in Persons With Chronic Kidney Disease.

OBJECTIVE: A retrospective cohort study investigated the association between having surgery and risk of mortality for up to 5 years and if this association was modified by incident ESRD during the follow-up period. Summary of Background Data: Mortality risk in individuals with pre-dialysis CKD is high and few effective treatment options are available. Whether bariatric surgery can improve survival in people with CKD is unclear. METHODS: Patients with class II and III obesity and pre-dialysis CKD stages 3-5 who underwent bariatric surgery between January 1, 2006 and September 30, 2015 (n = 802) were matched to patients who did not have surgery (n = 4933). Mortality was obtained from state death records and ESRD was identified through state-based or healthcare system-based registries. Cox regression models were used to investigate the association between bariatric surgery and risk of mortality and if this was moderated by incident ESRD during the follow-up period. RESULTS: Patients were primarily women (79%), non-Hispanic White (72%), under 65 years old (64%), who had a body mass index > 40kg/m 2 (59%), diabetes (67%), and hypertension (89%). After adjusting for incident ESRD, bariatric surgery was associated with a 79% lower 5-year risk of mortality compared to matched controls (hazard ratio = 0.21; 95% confidence interval: 0.14-0.32; P < 0.001). Incident ESRD did not moderate the observed association between surgery and mortality (hazard ratio = 1.59; 95% confidence interval: 0.31-8.23; P =0.58). CONCLUSIONS: Bariatric surgery is associated with a reduction in mortality in pre-dialysis patients regardless of developing ESRD. These findings are significant because patients with CKD are at relatively high risk for death with few efficacious interventions available to improve survival.

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

PURPOSE: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication. METHODS: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated. RESULTS: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82). CONCLUSIONS: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI.

"We Need to Taper." Interviews with Clinicians and Pharmacists About Use of a Pharmacy-Led Opioid Tapering Program.

OBJECTIVE: To identify factors that influence or interfere with referrals by primary care providers (PCPs) to a pharmacist-led telephone-based program to assist patients undergoing opioid tapering. The Support Team Onsite Resource for Management of Pain (STORM) program provides individualized patient care and supports PCPs in managing opioid tapers. DESIGN: Qualitative interviews were conducted with referring PCPs and STORM staff. Interview guides addressed concepts from the RE-AIM framework, focusing on issues affecting referral to the STORM program. SETTING: An integrated healthcare system (HCS) in the Northwest United States. SUBJECTS: Thirty-five interviews were conducted with 20 PCPs and 15 STORM staff. METHODS: Constant comparative analysis was used to identify key themes from interviews. A codebook was developed based on interview data and a qualitative software program was used for coding, iterative review, and content analysis. Representative quotes illustrate identified themes. RESULTS: Use of the STORM opioid tapering program was influenced by PCP, patient, and HCS considerations. Factors motivating use of STORM included lack of PCP time to support chronic pain patients requiring opioid tapering and the perception that STORM is a valued partner in patient care. Impediments to referral included PCP confidence in managing opioid tapering, patient resistance to tapering, forgetting about program availability, and PCP resistance to evolving guidelines regarding opioid tapering goals. CONCLUSIONS: PCPs recognized that STORM supported patient safety and reduced clinician burden. Utilization of the program could be improved through ongoing PCP education about the service and consistent co-location of STORM pharmacists within primary care clinics.

Factors associated with opioid-tapering success: A mixed methods study.

OBJECTIVE: Opioid tapering is recommended when risks of chronic opioid use outweigh benefits. Little is known about patient characteristics or factors related to tapering success. We sought to identify characteristics that predict a 50% reduction in opioid use and qualitatively characterize factors that impact tapering success. METHODS: We used multilevel hierarchical modeling to identify predictors of a 50% reduction in opioid use among Kaiser Permanente Northwest patients who underwent pharmacist-led tapering between 2012 and 2017. We conducted qualitative interviews among patients and pharmacists to identify factors influencing tapering success. RESULTS: We identified 1384 patients who, on average, were dispensed 207 milligram morphine equivalents per day at baseline. After 12 months, 56% of patients reduced their opioid use by 50%. Increased odds of 50% reduction were associated with younger age 21-49 years (Odds ratio [OR] 1.32, P = 0.004); previous surgery (OR 2.24, P < 0.001); increased number of Addiction Medicine encounters (OR 1.25, P = 0.011); substance use disorder (OR 1.62, P = 0.001); anxiety (OR 1.32, P = 0.003); non-narcotic analgesic (OR 1.22, P = 0.025) or antipsychotic medication use (OR 1.53, P = 0.006); and opioid days supplied in the previous year (OR 1.08, P < 0.001). Patients and pharmacists noted that success was influenced by patients' willingness or resistance to change opioid use, the level of patient engagement achieved through communication with their provider, aspects of the tapering process such as pace, and external factors including health issues or caregiving responsibilities. CONCLUSIONS: Over one-half of patients who underwent tapering reduced their opioid use by 50%. Patient demographic and clinical characteristics were predictive of tapering success; however, patients and pharmacists noted that patient willingness, motivation, and personal circumstances also influence tapering outcome. Opioid tapering requires an individualized approach. Both clinical factors and personal circumstances should be considered when opioid tapering is being discussed as a possible solution for a patient.

Evaluating the Implementation of Digital and In-Person Diabetes Prevention Program in a Large, Integrated Health System: Natural Experiment Study Design.

INTRODUCTION: Implementation of a Diabetes Prevention Program (DPP) in both in-person and digital health-care settings has been increasing. The purpose of this article is to describe the protocol of a mixed-methods, natural experiment study designed to evaluate the implementation of DPP in a large, integrated health system. METHODS: Kaiser Permanente Northwest patients who were 19 to 75 years with prediabetes (hemoglobin A1c or glycated hemoglobin, 5.7-6.4) and obesity (body mass index ≥ 30 kg/m2) were invited, via the Kaiser Permanente Northwest patient portal, to participate in the digital (n = 4124) and in-person (n = 2669) DPP during 2016 through 2018. Primary (weight) and secondary (hemoglobin A1c or glycated hemoglobin level) outcome data will be obtained from electronic health records. A cost-effectiveness analysis as well as qualitative interviews with patients (enrolled and not enrolled in the DPP) and stakeholders will be conducted to examine further implementation, acceptability, and sustainability. CONCLUSION: The mixed-methods, natural experiment design we will use to evaluate Kaiser Permanente Northwest's implementation of the digital and in-person DPP builds on existing evidence related to the effectiveness of these two DPP delivery modes and will contribute new knowledge related to best practices for implementing and sustaining the DPP within large health systems over the long term.

Development of a multivariable prediction model to identify patients unlikely to complete a colonoscopy following an abnormal FIT test in community clinics.

BACKGROUND: Colorectal cancer (CRC) is the 3rd leading cancer killer among men and women in the US. The Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC) project aimed to increase CRC screening among patients in Federally Qualified Health Centers (FQHCs) through a mailed fecal immunochemical test (FIT) outreach program. However, rates of completion of the follow-up colonoscopy following an abnormal FIT remain low. We developed a multivariable prediction model using data available in the electronic health record to assess the probability of patients obtaining a colonoscopy following an abnormal FIT test. METHODS: To assess the probability of obtaining a colonoscopy, we used Cox regression to develop a risk prediction model among a retrospective cohort of patients with an abnormal FIT result. RESULTS: Of 1596 patients with an abnormal FIT result, 556 (34.8%) had a recorded colonoscopy within 6 months. The model shows an adequate separation of patients across risk levels for non-adherence to follow-up colonoscopy (bootstrap-corrected C-statistic > 0.63). The refined model included 8 variables: age, race, insurance, GINI income inequality, long-term anticoagulant use, receipt of a flu vaccine in the past year, frequency of missed clinic appointments, and clinic site. The probability of obtaining a follow-up colonoscopy within 6 months varied across quintiles; patients in the lowest quintile had an estimated 18% chance, whereas patients in the top quintile had a greater than 55% chance of obtaining a follow-up colonoscopy. CONCLUSIONS: Knowing who is unlikely to follow-up on an abnormal FIT test could help identify patients who need an early intervention aimed at completing a follow-up colonoscopy. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov ( NCT01742065 ) on December 5, 2012. The protocol is available.

A Pharmacist-Led Program to Taper Opioid Use at Kaiser Permanente Northwest: Rationale, Design, and Evaluation.

INTRODUCTION: Primary care practitioners (PCPs) are concerned about adverse effects and poor outcomes of opioid use but may find opioid tapering difficult because of a lack of pain management training or time constraints limiting patient counseling. In 2010, Kaiser Permanente Northwest implemented a pharmacist-led opioid tapering program-Support Team Onsite Resource for Management of Pain (STORM)-to address high rates of opioid use, alleviate PCPs' workload demands, and improve patient outcomes. OBJECTIVE: To describe the rationale, structure, and delivery of this unique pharmacist-led program, which partners with PCPs and provides individualized care to help patients reduce opioid use, and the Facilitating Lower Opioid Amounts through Tapering study, which examines the program's effectiveness, cost-effectiveness, and implementation. RESULTS: The STORM program includes a pain medicine physician, a social worker or nurse, and pharmacists who have received specialized clinical and communications training. The program has a 2-fold role: 1) to provide PCP education about pain management and opioid use and 2) to offer clinician and patient support with opioid tapering and pain management. After program training, PCPs are equipped to discuss the need for tapering with a patient and to refer to the program. Program pharmacists provide a range of services, including opioid taper plans, nonopioid pain management recommendations, and taper-support outreach to patients. DISCUSSION: The STORM program provides individualized care to assist patients with opioid tapering while reducing the burden on PCPs. CONCLUSION: The STORM program may be a valuable addition to health care systems and settings seeking options to address their patients' opioid tapering needs.

A reduced transferrin saturation is independently associated with excess morbidity and mortality in older adults with heart failure and incident anemia.

BACKGROUND: Low transferrin saturation (TSAT) or reduced serum ferritin level are suggestive of iron deficiency but the relationship between iron parameters and outcomes has not been systematically evaluated in older adults with heart failure (HF) and anemia. METHODS: We identified a multicenter cohort of adults age ≥ 65 years with HF and incident anemia (hemoglobin <13 g/dL [men] or < 12 g/dL [women]) between 2005 and 2012. Patients were included if ferritin (ng/mL) and TSAT (%) were evaluated within 90 days of incident anemia. HF hospitalizations and all-cause death were ascertained from electronic health records. RESULTS: Among 4103 older adults with HF and incident anemia, 47% had TSAT <20% and the median (IQR) ferritin was 126 (53, 256) ng/mL. In multivariable analyses, compared with TSAT ≥20%, patients with TSAT <20% were at increased risk of HF hospitalization for serum ferritin <100 ng/mL (adjusted HR [aHR] 1.40, 95% CI:1.16-1.70) and 100-300 ng/mL (aHR 1.24, 95% CI:1.01-1.52) but not for a ferritin >300 ng/mL (aHR 0.89, 95% CI 0.65-1.23). In addition, TSAT <20% was independently associated with an increased risk of all-cause death regardless of serum ferritin level (<100 ng/mL: aHR 1.42, 95% CI:1.20-1.68; 100-300 ng/mL: aHR 1.18, 95% CI:1.00-1.38; >300 ng/mL: aHR 1.33, 95% CI:1.06-1.69). CONCLUSIONS: Among older adults with HF and incident anemia who had iron studies tested, nearly half had a TSAT <20%, which was independently associated with higher rates of morbidity and death.

Noncardiac-Related Morbidity, Mobility Limitation, and Outcomes in Older Adults With Heart Failure.

BACKGROUND: To examine the individual and combined associations of noncardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF). METHODS: We conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of noncardiac conditions (<3 vs ≥3) and/or mobility impairment (defined by the use/nonuse of a wheelchair, cane, or walker), categorizing them into four subgroups. Outcomes included all-cause death and hospitalizations for HF or any cause. RESULTS: Among 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with <3 noncardiac conditions/no mobility limitation, adjusted hazard ratios (HR) for all-cause death among those with <3 noncardiac conditions/mobility limitation, ≥3 noncardiac conditions/no mobility limitation, ≥3 noncardiac conditions/mobility limitation (vs) were 1.40 (95% CI, 1.31-1.51), 1.72 (95% CI, 1.69-1.75), and 1.93 (95% CI, 1.85-2.01), respectively. We did not observe an increased risk of any-cause or HF-related hospitalization related to the presence of mobility limitation among those with a greater burden of noncardiac multimorbidity. Consistent findings regarding mortality were observed within groups defined according to age, gender, and HF type (preserved, reduced, mid-range ejection fraction), with the most prominent impact of mobility limitation in those <65 years of age. CONCLUSIONS: There is an additive association of mobility limitation, beyond the burden of noncardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients.

Planetary protection classification of samples returned from the martian moons: Summary of a review by the European Science Foundation and the National Academies of Sciences, Engineering and Medicine.

This work summarizes the review undertaken by a joint committee of the European Science Foundation and the National Academies of Sciences, Engineering and Medicine into the transfer of viable organisms from the surface of Mars to its moons-Phobos and Deimos-as a consequence of a giant impact on the martian surface. The possibility that viable organisms could survive ejection from Mars and subsequent deposition on Phobos and Deimos is an important consideration in determining whether samples returned from the moons by spacecraft missions be classified as restricted or unrestricted Earth return in the consensus planetary protection guidelines maintained by the Committee on Space Research (COSPAR) of the International Council for Science. Having reviewed recent research undertaken in Europe and Japan, the joint committee recommended that samples returned from the martian moons be classified as unrestricted Earth return. This paper is not intended to be a standalone work. Rather, it should be regarded as a summary of, and advertisement for, the material presented in the joint committee's formal report, Planetary Protection Classification of Samples Return Missions from the Martian Moons (the National Academies Press, 2019).

Trends in Medicare Payment Rates for Noninvasive Cardiac Tests and Association With Testing Location.

Importance: To control spending, the Centers for Medicare & Medicaid Services reduced Medicare fee-for-service (FFS) payments for noninvasive cardiac tests (NCTs) performed in provider-based office settings (ambulatory offices not administratively affiliated with hospitals) starting in 2005. Contemporaneously, payments for hospital-based outpatient testing increased. The association between differential payments by site and test location is unknown. Objectives: To quantify trends in differential Medicare FFS payments for NCTs performed in hospital-based and provider-based settings, determine the association between the hospital-based outpatient testing to provider-based office testing payment ratio and the proportion of hospital-based NCTs, and to examine trends in test location between Medicare FFS and 3 Medicare Advantage health maintenance organizations for which Centers for Medicare & Medicaid Services payments do not depend on testing location. Design, Setting, and Participants: This observational claims-based study used Medicare FFS claims from 1999 to 2015 (5% random sample) and Medicare Advantage claims from 3 large health maintenance organizations (2005-2015) among Medicare FFS beneficiaries aged 65 years or older and a health maintenance organization control group. Statistical analysis was performed from May 1, 2017, to July 15, 2019. Exposures: The weighted mean payment ratio of Medicare FFS hospital-based outpatient testing to provider-based office testing for outpatient NCTs. Main Outcomes and Measures: Proportion of outpatient NCTs performed in the hospital-based setting and Medicare FFS costs. Results: The data included a mean of 1.72 million patient-years annually in Medicare FFS (mean age, 75.2 years; 57.3% female in 2015) and a mean of 142 230 patient-years annually in the managed care control group (mean age, 74.8 years; 56.2% female in 2015). The Medicare payment ratio of FFS hospital-based outpatient testing to provider-based office testing increased from 1.05 in 2005 to 2.32 in 2015. The FFS hospital-based outpatient testing proportion increased from 21.1% in 2008 to 43.2% in 2015 and was correlated with the payment ratio (correlation coefficient with a 1-year lag, 0.767; P < .001). In contrast, the hospital-based outpatient testing proportion for the control group declined from 16.6% in 2008 to 15.2% in 2015 (correlation coefficient, -0.024, P = .95). The estimated extra costs owing to tests shifting to the hospital-based outpatient setting in the Medicare FFS group was $661 million in 2015, including $161 million in patient out-of-pocket costs. Conclusions and Relevance: In settings in which reimbursement depends on test location, increasing hospital-based payments correlated with greater proportions of outpatient NCTs performed in the hospital-based outpatient setting. Site-neutral payments may offer an incentive for testing to be performed in the more efficient location.

Influence of Multimorbidity on Burden and Appropriateness of Implantable Cardioverter-Defibrillator Therapies.

OBJECTIVE: To determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies. DESIGN: Retrospective cohort study. SETTING: Seven US healthcare delivery systems. PARTICIPANTS: Adults with left ventricular systolic dysfunction receiving an implantable cardioverter-defibrillator (ICD) for primary prevention. MEASUREMENTS: Data on 24 comorbid conditions were captured from electronic health records and categorized into quartiles of comorbidity burden (0-3, 4-5, 6-7 and 8-16). Incidence of ICD therapies (shock and antitachycardia pacing [ATP] therapies), including appropriateness, was collected for 3 years after implantation. Outcomes included time to first ICD therapy, total ICD therapy burden, and risk of inappropriate vs appropriate ICD therapy. RESULTS: Among 2235 patients (mean age = 69 ± 11 years, 75% men), the median number of comorbidities was 6 (interquartile range = 4-8), with 98% having at least two comorbidities. During a mean 2.2 years of follow-up, 18.3% of patients experienced at least one appropriate therapy and 9.9% experienced at least one inappropriate therapy. Higher comorbidity burden was associated with an increased risk of first inappropriate therapy (adjusted hazard ratio [HR] = 1.94 [95% confidence interval {CI} = 1.14-3.31] for 4-5 comorbidities; HR = 2.25 [95% CI = 1.25-4.05] for 6-7 comorbidities; and HR = 2.91 [95% CI = 1.54-5.50] for 8-16 comorbidities). Participants with 8-16 comorbidities had a higher total burden of ICD therapy (adjusted relative risk [RR] = 2.12 [95% CI = 1.43-3.16]), a higher burden of inappropriate therapy (RR = 3.39 [95% CI = 1.67-6.86]), and a higher risk of receiving inappropriate vs appropriate therapy (RR = 1.74 [95% CI = 1.07-2.82]). Comorbidity burden was not significantly associated with receipt of appropriate ICD therapies. Patterns were similar when separately examining shock or ATP therapies. CONCLUSIONS: In primary prevention ICD recipients, MCC burden was independently associated with an increased risk of inappropriate but not appropriate device therapies. Comorbidity burden should be considered when engaging patients in shared decision making about ICD implantation.

Incident anaemia in older adults with heart failure: rate, aetiology, and association with outcomes.

AIMS: Limited data exist on the epidemiology, evaluation, and prognosis of otherwise unexplained anaemia of the elderly in heart failure (HF). Thus, we aimed to determine the incidence of anaemia, to characterize diagnostic testing patterns for potentially reversible causes of anaemia, and to evaluate the independent association between incident anaemia and long-term morbidity and mortality. METHODS AND RESULTS: Within the Cardiovascular Research Network (CVRN), we identified adults age ≥65 years with diagnosed HF between 2005 and 2012 and no anaemia at entry. Incident anaemia was defined using World Health Organization (WHO) haemoglobin thresholds (<13.0 g/dL in men; <12.0 g/dL in women). All-cause death and hospitalizations for HF and any cause were identified from electronic health records. Among 38 826 older HF patients, 22 163 (57.1%) developed incident anaemia over a median (interquartile range) follow-up of 2.9 (1.2-5.6) years. The crude rate [95% confidence interval (CI)] per 100 person-years of incident anaemia was 26.4 (95% CI 26.0-26.7) and was higher for preserved ejection fraction (EF) [29.2 (95% CI 28.6-29.8)] compared with borderline EF [26.5 (95% CI 25.4-27.7)] or reduced EF [26.6 (95% CI 25.8-27.4)]. Iron indices, vitamin B12 level, and thyroid testing were performed in 20.9%, 14.9%, and 40.2% of patients, respectively. Reduced iron stores, vitamin B12 deficiency, and/or hypothyroidism were present in 29.7%, 3.2%, and 18.6% of tested patients, respectively. In multivariable analyses, incident anaemia was associated with excess mortality [hazard ratio (HR) 2.14, 95% CI 2.07-2.22] as well as hospitalization for HF (HR 1.80, 95% CI 1.72-1.88) and any cause (HR 1.77, 95% CI 1.72-1.83). CONCLUSION: Among older adults with HF, incident anaemia is common and independently associated with substantially increased risks of morbidity and mortality. Additional research is necessary to clarify the value of routine evaluation and treatment of potentially reversible causes of anaemia.

Balancing Adherence and Expense: The Cost-Effectiveness of Two-Sample vs One-Sample Fecal Immunochemical Test.

Colorectal cancer (CRC) causes more than 50,000 deaths each year in the United States but early detection through screening yields survival gains; those diagnosed with early stage disease have a 5-year survival greater than 90%, compared to 12% for those diagnosed with late stage disease. Using data from a large integrated health system, this study evaluates the cost-effectiveness of fecal immunochemical testing (FIT), a common CRC screening tool. A probabilistic decision-analytic model was used to examine the costs and outcomes of positive test results from a 1-FIT regimen compared with a 2-FIT regimen. The authors compared 5 diagnostic cutoffs of hemoglobin concentration for each test (for a total of 10 screening options). The principal outcome from the analysis was the cost per additional advanced neoplasia (AN) detected. The authors also estimated the number of cancers detected and life-years gained from detecting AN. The following costs were included: program management of the screening program, patient identification, FIT kits and their processing, and diagnostic colonoscopy following a positive FIT. Per-person costs ranged from $33 (1-FIT at 150ng/ml) to $92 (2-FIT at 50ng/ml) across screening options. Depending on willingness to pay, the 1-FIT 50 ng/ml and the 2-FIT 50 ng/ml are the dominant strategies with cost-effectiveness of $11,198 and $28,389, respectively, for an additional AN detected. The estimates of cancers avoided per 1000 screens ranged from 1.46 to 4.86, depending on the strategy and the assumptions of AN to cancer progression.