Adjusted Indirect Treatment Comparison of Progression-Free Survival with D-Rd and VRd Based on MAIA and SWOG S0777 Individual Patient-Level Data.

INTRODUCTION: Daratumumab plus lenalidomide and dexamethasone (D-Rd) and bortezomib plus lenalidomide and dexamethasone (VRd) are commonly used treatment combinations for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). D-Rd and VRd demonstrated superior efficacy relative to lenalidomide and dexamethasone (Rd) in the MAIA and SWOG S0777 trials, respectively, but have not been compared directly in a head-to-head trial. Naïve comparisons of efficacy across the two trials may be biased because MAIA enrolled only TIE patients (median age 73 years), whereas SWOG S0777 enrolled both TIE patients and transplant-eligible patients who chose to defer/refuse frontline stem cell transplantation (median age 63 years). The present study compared progression-free survival (PFS) in TIE patients with NDMM treated with D-Rd versus VRd based on an adjusted indirect treatment comparison (ITC) that leveraged individual patient-level data from MAIA and SWOG S0777. METHODS: Harmonized inclusion/exclusion criteria (including age ≥ 65 years as a proxy for transplant ineligibility) and propensity-score weighting were used to balance the trial populations on measured baseline characteristics. After differences in trial populations were adjusted for, an anchored ITC was performed wherein within-trial PFS hazard ratios (HRs) for D-Rd versus Rd and VRd versus Rd were estimated and used to make indirect inference about PFS for D-Rd versus VRd. RESULTS: PFS HRs were 0.52 (95% confidence interval [CI] 0.41-0.67) for D-Rd versus Rd based on MAIA data, 0.88 (95% CI 0.63-1.23) for VRd versus Rd based on SWOG S0777 data, and 0.59 (95% CI 0.39-0.90) for the Rd-anchored ITC of D-Rd versus VRd. Sensitivity and subgroup analyses produced results consistent with the primary results. CONCLUSION: This anchored ITC demonstrated a greater PFS benefit for D-Rd versus VRd in TIE patients with NDMM. In the absence of head-to-head trials comparing D-Rd and VRd, the present trial may help inform treatment selection in this patient population.

Multiple drug combinations can be used to treat patients with newly diagnosed multiple myeloma (NDMM) who are not eligible for a stem cell transplant. Two of these combinations­daratumumab plus lenalidomide and dexamethasone (D-Rd) and bortezomib plus lenalidomide and dexamethasone (VRd)­have each been studied in clinical trials (MAIA and SWOG S0777) against the combination of lenalidomide plus dexamethasone (Rd), but D-Rd and VRd have not been compared directly in a head-to-head clinical trial. Our study used data from the MAIA and SWOG S0777 trials to indirectly compare outcomes observed with D-Rd and VRd. For this indirect comparison between D-Rd and VRd, we first made adjustments to the patient populations of each trial to make them more similar to each other; this helped to make sure any differences we saw in treatment outcomes between D-Rd and VRd would not be because of differences in the characteristics of the patients who participated in the trials. After we made these adjustments to the patient populations of each trial, both D-Rd and VRd lowered the risk of disease progression or death compared with Rd alone. However, when indirectly compared in our study, D-Rd lowered the risk of disease progression or death by 41% compared with VRd. As data directly comparing treatment outcomes for D-Rd and VRd are not available, this indirect comparison can contribute to the information used to make treatment decisions for patients with NDMM who are not eligible for a stem cell transplant.

Epidemiology and clinical outcomes of light-chain amyloidosis in Sweden: A nationwide population-based study.

OBJECTIVES: This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated with light-chain (AL) amyloidosis. METHODS: Patients newly diagnosed with AL amyloidosis were identified using six linked Swedish nationwide population-based registers. For each case, individuals from the general population were selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county. RESULTS: 846 patients newly diagnosed with AL amyloidosis and 4227 demographically matched individuals were identified. From 2011 to 2019, annual AL amyloidosis incidence increased from 10.5 to 15.1 cases per million. At baseline, patients with AL amyloidosis had a significantly higher disease burden including higher rates of cardiac and renal failure relative to the comparison group. Among patients with AL amyloidosis, 21.5% had incident heart failure and 17.1% had incident renal failure after initial diagnosis. Median OS for patients with AL amyloidosis was 56 months versus not reached in the matched general population comparison group. CONCLUSION: The incidence of newly diagnosed AL amyloidosis in Sweden increased over time with AL amyloidosis being associated with a higher risk of cardiac/renal failure and all-cause mortality compared with the general population.

Impact of Disease Progression, Line of Therapy, and Response on Health-Related Quality of Life in Multiple Myeloma: A Systematic Literature Review.

This systematic literature review (SLR) was conducted to better understand the impact of disease progression, line of therapy, and clinical response on health-related quality of life (HRQoL) in patients with multiple myeloma (MM). Multiple databases were searched to identify records relating to HRQoL in adult patients with MM. Titles and abstracts were independently screened by 2 reviewers for inclusion based on pre-defined criteria. Records flagged for inclusion had full texts subsequently screened using the same method. A third round of screening was then conducted to identify studies that assessed the relationship of HRQoL to disease progression, line of therapy, or clinical response. Quality assessment was conducted on utility studies using the National Institute for Health and Care Excellence Quality Assessment Checklist for Health State Utility Values. After all rounds of screening were complete, 44 records (representing 41 studies) were included in the SLR. Thirty records reported data relating HRQoL to disease progression, 5 reported data relating HRQoL to line of therapy, and 19 reported data relating HRQoL to response. Despite a lack of homogeneity and small number of studies, the data show overall that progressive disease and increasing lines of therapy were associated with worsened patient HRQoL and increasing depth of response was associated with improved patient HRQoL. The findings from this SLR support that desirable treatment outcomes such as delayed progression, fewer lines of therapy, and achieving the deepest possible clinical response result in improved HRQoL in patients with MM.

Characteristics, management, and blood pressure control in patients with apparent resistant hypertension in the US.

Background: Per treatment guidelines, resistant hypertension is defined as uncontrolled blood pressure (BP) while taking 3 concomitant antihypertensives (AHTs) or controlled BP while taking ≥4 AHTs. Characteristics, AHT therapy use, and BP control were analyzed in US patients with hypertension who were prescribed ≥3 classes of AHT medications. Methods: This retrospective analysis of the Optum® Electronic Health Record Database evaluated patients ≥18 years of age with a diagnosis of hypertension classified based on the number of prescribed AHT medication classes (3, 4, or ≥5). For the primary analysis, uncontrolled hypertension was defined as systolic BP (SBP) ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg. For secondary analyses, uncontrolled hypertension was defined as SBP ≥130 mmHg or DBP ≥80 mmHg. Results: 207,705 patients with hypertension and concurrent use of ≥3 AHT medication classes were included. Diuretics, beta blockers, ACE inhibitors and/or ARBs, and CCBs were the most prescribed classes; thiazides and thiazide-like agents were the most prescribed diuretics. Among patients who were prescribed 3, 4, or ≥5 AHT medication classes, approximately 70% achieved a BP goal of <140/90 mmHg; approximately 40% achieved BP <130/80 mmHg. After ≥1 year of follow-up, the number of concurrent AHT medication classes was unchanged from baseline in the majority of patients and the prevalence of uncontrolled hypertension (≥140/90 mmHg) was similar. Conclusions: This study illustrates suboptimal BP control in many patients with apparent resistant hypertension despite the use of multidrug regimens and suggests a need for new drug classes and regimens that effectively manage resistant hypertension.

Self-controlled assessment of thromboembolic event (TEE) risk following intravenous immune globulin (IGIV) in the U.S. (2006-2012).

Since 2013, the U.S. Food and Drug administration (FDA) has required that intravenous immune globulin (IGIV) products carry a boxed warning concerning the risk of thromboembolic events (TEEs). This study assessed the incidence of TEEs attributable to IGIV in a large population-based cohort. A self-controlled risk interval design was used to quantify the transient increase in TEE risk during the risk interval (days 0-2 and 0-13 following IGIV for arterial and venous TEEs, respectively) relative to a later control interval (days 14-27 following IGIV). Potential IGIV-exposed TEE cases from 2006 to 2012 were identified from the FDA-sponsored Sentinel Distributed Database and confirmed through medical record review. Inpatient IGIV exposures were not included in the venous TEE analysis due to concerns about time-varying confounding. 19,069 new users of IGIV who received 93,555 treatment episodes were included. Charts were retrieved for 62% and 70% of potential venous and arterial cases, respectively. There was a transient increase in the risk of arterial TEEs during days 0-2 following IGIV treatment (RR = 4.69; 95% CI 1.87, 11.90; absolute increase in risk = 8.86 events per 10,000 patients, 95% CI 3.25, 14.6), but no significant increase in venous TEE risk during days 0-13 following outpatient IGIV treatments (RR = 1.07, 95% CI 0.34, 3.48). Our results suggest there is a small increase in the absolute risk of arterial TEEs following IGIV. However, lower-than-expected chart retrieval rates and the possibility of time-varying confounding mean that our results should be interpreted cautiously. Continued pharmacovigilance efforts are warranted.

Treatment patterns, economic burden, and overall survival in US Medicare Advantage beneficiaries newly diagnosed with acute myeloid leukemia (AML) in 2015-2020.

The present study assessed changes in patient management, economic burden, and overall survival (OS) in a contemporary cohort of 2775 US Medicare Advantage beneficiaries aged ≥66 years newly diagnosed with acute myeloid leukemia (AML) between 01 January 2015 and 30 June 2020. Use of venetoclax-based therapy increased and replaced hypomethylating agent (HMA) monotherapy as the most common first-line treatment choice in 2019-2020. In newly diagnosed AML patients aged ≥75 and 66-74 years, mean per-patient 1-year healthcare expenditures were $81,818 and $156,033 (2020 USD) and median OS was 2.3 and 8.5 months, respectively. In addition, 40% of Medicare Advantage patients with newly diagnosed AML continue to receive supportive care alone. These findings indicate that at the population level clinical outcomes remain poor for older adults with AML, pointing to a continuing unmet medical need.

Daratumumab-lenalidomide-dexamethasone vs standard-of-care regimens: Efficacy in transplant-ineligible untreated myeloma.

Daratumumab in combination with lenalidomide-dexamethasone (D-Rd) recently received FDA approval for the treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The present PEGASUS study compared progression-free survival (PFS) in patients treated with D-Rd in the MAIA trial and patients treated with common standard-of-care regimens from the Flatiron Health electronic health record-derived deidentified database, which has data from patients treated primarily at community-based oncology practices in the United States. Individual-level patient data from both data sources were used to perform an anchored indirect treatment comparison (ITC) of D-Rd to bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-dexamethasone (Vd); lenalidomide-dexamethasone (Rd) was the common anchor for the ITC. Hazard ratios (HRs) reflecting direct comparisons of PFS within MAIA (D-Rd vs Rd) and Flatiron Health (VRd vs Rd; Vd vs Rd) were used to make ITCs for D-Rd vs VRd and Vd, respectively. After application of MAIA inclusion/exclusion criteria and propensity-score weighting, the Flatiron Health patients resembled the MAIA trial population on measured baseline characteristics. Based on the direct comparison within MAIA, treatment with D-Rd was associated with a significantly lower risk of progression or death compared to Rd (HR 0.54; 95% CI 0.42, 0.71). Based on the ITCs, D-Rd was associated with a significantly lower risk of progression or death compared to VRd (HR 0.68; 95% CI 0.48, 0.98) and Vd (HR 0.48; 95% CI 0.33, 0.69). In the absence of head-to-head trials comparing D-Rd to VRd or Vd, the present ITC may help inform treatment selection in transplant-ineligible patients with NDMM.

Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and stage IV-V chronic kidney disease.

BACKGROUND: There is limited evidence on the effectiveness and safety of direct-acting oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD). This study compared the risks of ischemic stroke/systemic embolism (ISSE) and major bleeding in patients with NVAF and stage IV-V CKD treated with rivaroxaban or warfarin. METHODS: Patients with NVAF and stage IV-V CKD who initiated rivaroxaban or warfarin treatment between November 2011 and June 2018 were selected from the Optum® Deidentified Electronic Health Record Database. Propensity score matching was used to balance rivaroxaban and warfarin patients on 112 measured baseline covariates. ISSE and major bleeding events over 2 years following treatment initiation were ascertained with validated end point definitions. Outcomes were analyzed as time-to-event data using Kaplan-Meier survival estimators and Cox regression. RESULTS: A total of 781 eligible rivaroxaban-treated patients were propensity score-matched to 1,536 warfarin-treated patients; baseline covariates were well balanced after matching (absolute standardized differences <0.1). The average patient age was 80 years; 60.5% were female; 81.3% and 18.7% had CKD stage IV and V, respectively. Hazard ratios for rivaroxaban compared to warfarin were 0.93 (95% CI 0.46-1.90, P = .85) for the risk of ISSE and 0.91 (95% CI 0.65-1.28, P = .60) for major bleeding. CONCLUSIONS: No statistically significant difference in the risk of ISSE or major bleeding was found between rivaroxaban- and warfarin-treated patients. Although further study is needed, rivaroxaban appears to be a reasonable alternative to warfarin for ISSE prevention in the setting of NVAF and stage IV-V CKD.

Multiple myeloma treatment patterns and clinical outcomes in the Latin America Haemato-Oncology (HOLA) Observational Study, 2008-2016.

Limited data are available regarding contemporary multiple myeloma (MM) treatment practices in Latin America. In this retrospective cohort study, medical records were reviewed for a multinational cohort of 1103 Latin American MM patients (median age, 61 years) diagnosed in 2008-2015 who initiated first-line therapy (LOT1). Of these patients, 33·9% underwent autologous stem cell transplantation (ASCT). During follow-up, 501 (45·4%) and 129 (11·7%) patients initiated second- (LOT2) and third-line therapy (LOT3), respectively. In the LOT1 setting, from 2008 to 2015, there was a decrease in the use of thalidomide-based therapy, from 66·7% to 42·6%, and chemotherapy from, 20·2% to 5·9%, whereas use of bortezomib-based therapy or bortezomib + thalidomide increased from 10·7% to 45·5%. Bortezomib-based therapy and bortezomib + thalidomide were more commonly used in ASCT patients and in private clinics. In non-ASCT and ASCT patients, median progression-free survival (PFS) was 15·0 and 31·1 months following LOT1 and 10·9 and 9·5 months following LOT2, respectively. PFS was generally longer in patients treated with bortezomib-based or thalidomide-based therapy versus chemotherapy. These data shed light on recent trends in the management of MM in Latin America. Slower uptake of newer therapies in public clinics and poor PFS among patients with relapsed MM point to areas of unmet therapeutic need in Latin America.

Assessment of obesity prevalence and validity of obesity diagnoses coded in claims data for selected surgical populations: A retrospective, observational study.

In many types of surgery, obesity may influence patient selection, prognosis, and/or management. Quantifying the accuracy of the coding of obesity and other prognostic factors is important for the design and interpretation of studies of surgical outcomes based on administrative healthcare data. This study assessed the validity of obesity diagnoses recorded in insurance claims data in selected surgical populations.This was a retrospective, observational study. Deidentified electronic health record (EHR) and linked administrative claims data were obtained for US patients age ≥20 years who underwent a qualifying surgical procedure (bariatric surgery, total knee arthroplasty [TKA], cardiac ablation, or hernia repair) in 2014Q1-2017Q1 (first = index). Patients' body mass index (BMI) as coded in the claims data (error-prone measure) during the index procedure or 180d pre-index was compared with their measured BMI as recorded in the EHR (criterion standard) to estimate the sensitivity and positive predictive value (PPV) of obesity diagnosis codes.Among patients who underwent bariatric surgery (N = 1422), TKA (N = 8670), cardiac ablation (N = 167), or hernia repair (N = 5450), obesity was present in 98%, 63%, 52%, and 54%, respectively, based on measured BMI. PPVs of obesity diagnosis codes were high: 99.3%, 96.0%, 92.8%, and 94.1% in bariatric surgery, TKA, cardiac ablation, and hernia repair, respectively. The sensitivity of obesity diagnoses was: 99.8%, 46.2%, 41.3%, and 42.3% in bariatric surgery, TKA, cardiac ablation, and hernia repair, respectively. Among false-positive patients diagnosed as obese but with measured BMI <30, the proportion with a BMI ≥28 was 40.0%, 67.6%, 60.7%, and 65.8% for bariatric surgery, TKA, cardiac ablation, and hernia repair, respectively.Our data indicate that obesity is highly prevalent in many surgical populations, obesity diagnosis codes have high PPVs, but also obesity is generally undercoded in claims data. Quantifying the validity of diagnosis codes for obesity and other important prognostic factors is important for the design and interpretation of studies of surgical outcomes based on administrative data. Further research is needed to determine the extent to which undercoding of BMI and obesity can be addressed through the use of proxies that may be better documented in claims data.

The contribution of obesity to prescription opioid use in the United States.

The prevalence of obesity has grown rapidly over the past several decades and has been accompanied by an increase in the prevalence of chronic pain and prescription opioid use. Obesity, through its association with pain, may represent an important contributor to opioid use. This cross-sectional study investigated the relationship between obesity and prescription opioid use among adults aged 35 to 79 years using data from the National Health and Nutrition Examination Survey (NHANES, 2003-2016). Relative to normal weight, body mass indices in the overweight {odds ratio (OR), 1.11 (confidence interval [CI], 0.88-1.39)}, obese I (OR, 1.26 [CI, 1.01-1.57]), obese II (OR, 1.69 [CI, 1.34-2.12]), and obese III (OR, 2.33 [CI, 1.76-3.08]) categories were associated with elevated odds of prescription opioid use. The association between excess weight and opioid use was stronger for chronic opioid use than for use with a duration of less than 90 days (P-value, <0.001). We estimated that 14% (CI, 9%-19%) of prescription opioid use at the population level was attributable to obesity, suggesting there might have been 1.5 million fewer opioid users per year under the hypothetical scenario where obese individuals were instead nonobese (CI, 0.9-2.0 million users). Back pain, joint pain, and muscle/nerve pain accounted for the largest differences in self-reported reasons for prescription opioid use across obesity status. Although interpretation is limited by the cross-sectional nature of the associations, our findings suggest that the obesity epidemic may be partially responsible for the high prevalence of prescription opioid use in the United States.

Using Machine Learning Applied to Real-World Healthcare Data for Predictive Analytics: An Applied Example in Bariatric Surgery.

OBJECTIVES: Laparoscopic metabolic surgery (MxS) can lead to remission of type 2 diabetes (T2D); however, treatment response to MxS can be heterogeneous. Here, we demonstrate an open-source predictive analytics platform that applies machine-learning techniques to a common data model; we develop and validate a predictive model of antihyperglycemic medication cessation (validated proxy for A1c control) in patients with treated T2D who underwent MxS. METHODS: We selected patients meeting the following criteria in 2 large US healthcare claims databases (Truven Health MarketScan Commercial [CCAE]; Optum Clinformatics [Optum]): underwent MxS between January 1, 2007, to October 1, 2013 (first = index); aged ≥18 years; continuous enrollment 180 days pre-index (baseline) to 730 days postindex; baseline T2D diagnosis and treatment. The outcome was no antihyperglycemic medication treatment from 365 to 730 days after MxS. A regularized logistic regression model was trained using the following candidate predictor categories measured at baseline: demographics, conditions, medications, measurements, and procedures. A 75% to 25% split of the CCAE group was used for model training and testing; the Optum group was used for external validation. RESULTS: 13 050 (CCAE) and 3477 (Optum) patients met the study inclusion criteria. Antihyperglycemic medication cessation rates were 72.9% (CCAE) and 70.8% (Optum). The model possessed good internal discriminative accuracy (area under the curve [AUC] = 0.778 [95% CI = 0.761-0.795] in CCAE test set N = 3527) and transportability (external AUC = 0.759 [95% CI = 0.741-0.777] in Optum N = 3477). CONCLUSION: The application of machine learning techniques to real-world healthcare data can yield useful predictive models to assist patient selection. In future practice, establishment of prerequisite technological infrastructure will be needed to implement such models for real-world decision support.

Body mass index and insulin use as identifiers of high-cost patients with type 2 diabetes: A retrospective analysis of electronic health records linked to insurance claims data.

AIMS: To study the association of body mass index (BMI) and insulin use with type 2 diabetes-related healthcare expenditures (T2D-HE). MATERIALS AND METHODS: Retrospective study using de-identified electronic health records linked to insurance claims data. Study included a prevalence-based sample of overweight or obese patients with antihyperglycaemic-treated T2D. Patients had ≥1 A1c measurement in 2014 (last observed = index A1c), ≥1 BMI measurement within ±90 days of index (average BMI = baseline BMI), and continuous enrolment for 180 days before (baseline) through 395 days after index (day 30-395 = follow-up). BMI was categorized as: 25 to 29.9 kg/m2 = overweight; 30 to 34.9 kg/m2 = obese class I (OCI); 35 to 39.9 kg/m2 = OCII; ≥40 kg/m2 = OCIII. Multivariable regressions were used to examine one-year follow-up T2D-HE as a function of BMI, insulin use, an interaction term between BMI and insulin use, and patient demographics. RESULTS: Study included 13 026 patients (mean age = 63.6 years; 48.1% female; 29.5% overweight, 31.6% OCI, 20.3% OCII, 18.6% OCIII; 25.3% insulin users). Baseline insulin use rates monotonically ranged from 19.7% in overweight patients to 33.0% in OCIII patients (P < 0.001). Together, BMI and insulin use were jointly associated with one-year follow-up T2D-HE, which monotonically ranged from $5842 in overweight patients with no insulin to $17 700 OCIII insulin users, P < 0.001. Within each BMI category, insulin users' one-year T2D-HE was at least double that of non-users. Additional analyses of all-cause healthcare expenditures yielded consistent results. CONCLUSIONS: BMI and insulin use represent simple stratifiers for identifying high-cost patients. OCIII insulin users incurred the greatest annual healthcare expenditures; these patients may be an ideal group for targeted interventions.

A dual-perspective analysis of the hospital and payer-borne burdens of selected in-hospital surgical complications in low anterior resection for colorectal cancer.

OBJECTIVES: The economic burden of surgical complications is borne in distinctly different ways by hospitals and payers. This study quantified the incidence and economic burden - from both the hospital and payer perspective - of selected major colorectal surgery complications in patients undergoing low anterior resection (LAR) for colorectal cancer. METHODS: Retrospective, observational study of patient undergoing LAR for colorectal cancer between 1/1/2010 and 7/1/2015. Analyses were replicated in two large healthcare administrative databases: Premier (hospital discharge and billing data; hospital perspective) and Optum (insurance claims data; payer perspective). Multivariable analyses evaluated the association between infection (surgical site or bloodstream), anastomotic leak, and bleeding complications and the following outcomes: hospital length of stay (LOS), non-home discharge, 90-day all-cause readmission, index admission costs to the hospital, index admission payer expenditures, and index admission +90-day post-discharge payer expenditures. RESULTS: 9,738 eligible LAR patients were included (7,479 in Premier; 2,259 in Optum). Overall, the incidences of infection, anastomotic leak, and bleeding complications were 6.4%, 10.6%, and 10.9%, respectively, during the index hospitalization. Each complication was associated with statistically significant longer LOS, higher risk of non-home discharge, higher risk of 90-day readmission, greater costs to the hospital, and higher payer expenditures. CONCLUSIONS: In-hospital infection, anastomotic leak, and bleeding were associated with a substantial economic burden, for both hospitals and payers, in patients undergoing LAR for colorectal cancer. This study provides information which may be used to quantify the potential economic value and impact of innovations in surgical care and delivery that reduce the incidence and burden of these complications.

Validation of body mass index (BMI)-related ICD-9-CM and ICD-10-CM administrative diagnosis codes recorded in US claims data.

PURPOSE: To quantify the sensitivity and positive predictive value (PPV) of body mass index (BMI)-related ICD-9-CM and ICD-10-CM diagnosis codes in claims data. METHODS: De-identified electronic health record (EHR) and claims data were obtained from the Optum Integrated Claims-Clinical Database for cross-sections of commercial and Medicare Advantage health plan members age ≥ 20 years in 2013, 2014, and 2016. In each calendar year, health plan members' BMI as coded in the insurance claims data (error-prone measure) was compared with their BMI as recorded in the EHR (gold standard) to estimate the sensitivity and PPV of BMI-related ICD-9-CM and ICD-10-CM diagnosis codes. The unit of analysis was the person-year. RESULTS: The study sample included 746 763 distinct health plan members who contributed 1 116 283 eligible person-years (median age 56 years; 57% female; 65% commercially insured and 35% with Medicare Advantage). BMI-related diagnoses were coded for 14.6%. The sensitivity of BMI-related diagnoses codes for the detection of underweight, normal weight, overweight, and obesity was 10.1%, 3.7%, 6.0%, and 25.2%, and the PPV was 49.0% for underweight, 89.6% for normal weight, 73.4% for overweight, and 92.4% for obesity, respectively. The sensitivity of BMI-related diagnosis codes was higher in the ICD-10-CM era relative to the ICD-9-CM era. CONCLUSIONS: The PPV of BMI-related diagnosis codes for normal weight, overweight, and obesity was high (>70%) but the sensitivity was low (<30%). BMI-related diagnoses were more likely to be coded in patients with class II or III obesity (BMI ≥35 kg/m2 ), and in 2016 relative to 2013 or 2014.

Prevalence and Determinants of Engagement with Obesity Care in the United States.

OBJECTIVE: Medical management of obesity can result in significant weight loss and reduce the burden of obesity-related complications. This report employs a new conceptual model to quantify engagement with obesity care and associated determinants in the US adult population. METHODS: Engagement with obesity care was conceptualized as a cascade comprising 5 successive steps: perceiving oneself as overweight, desiring to lose weight, attempting weight loss, seeking care from a health care professional for obesity, and seeking care from a physician specifically. RESULTS: Among adults with obesity, 7.3% did not perceive themselves as overweight, 1.5% perceived themselves as overweight but had no desire to lose weight, 29.9% wanted to lose weight but did not try in the last year, 51.3% tried to lose weight but did not consult a health professional, and 6.4% sought help for weight loss from a health professional but not a physician, implying that 96.4% of the population with obesity had an unmet need for obesity care. CONCLUSIONS: This analysis provides new insight into the most common points along the cascade at which disengagement occurs and can inform efforts to improve uptake of obesity-related health care services.

Obesity Progression Between Young Adulthood and Midlife and Incident Diabetes: A Retrospective Cohort Study of U.S. Adults.

OBJECTIVE: Understanding how changes in weight over the life course shape risk for diabetes is critical for the prevention of diabetes. Using data from the National Health and Nutrition Examination Survey (NHANES), we investigated the association between self-reported weight change from young adulthood to midlife and incident diabetes. RESEARCH DESIGN AND METHODS: We categorized individuals into four weight-change groups: those who remained nonobese (stable nonobese), those who moved from an obese BMI to a nonobese BMI (losing), those who moved from a nonobese BMI to an obese BMI (gaining), and those who remained obese (stable obese). Diabetes status was determined by self-report of a prior diagnosis, and age at diagnosis was used to establish time of diabetes onset. Hazard ratios (HRs) relating weight change to incident diabetes over 10 years of follow-up were calculated using Cox models adjusting for covariates. RESULTS: Those who were obese and lost weight exhibited a significantly lower risk (HR 0.33; 95% CI 0.14, 0.76) of diabetes compared with those with stable obesity. We also observed lower risk among those who were stable nonobese (HR 0.22; 95% CI 0.18, 0.28) and those in the gaining category (HR 0.70; 95% CI 0.57, 0.87). Further, there was evidence of an increased incidence of diabetes among obese individuals who lost weight compared with individuals who were stable nonobese; however, weight loss was rare, and the association was not statistically significant. If those who were obese had become nonobese during the 10-year period, we estimate that 9.1% (95% CI 5.3, 12.8) of observed diabetes cases could have been averted, and if the population had maintained a normal BMI during the period, 64.2% (95% CI 59.4, 68.3) of cases could have been averted. CONCLUSIONS: The findings from this study underscore the importance of population-level approaches to the prevention and treatment of obesity across the life course of individuals.

Chart validation of inpatient ICD-9-CM administrative diagnosis codes for acute myocardial infarction (AMI) among intravenous immune globulin (IGIV) users in the Sentinel Distributed Database.

BACKGROUND: The Sentinel Distributed Database (SDD) is a large database of patient-level administrative health care records, primarily derived from insurance claims and electronic health records, and is sponsored by the US Food and Drug Administration for medical product safety evaluations. Acute myocardial infarction (AMI) is a common study endpoint for drug safety studies that rely on health records from the SDD and other administrative databases. PURPOSE: In this chart validation study, we report on the positive predictive value (PPV) of inpatient International Classification of Diseases, Ninth Revision, Clinical Modification AMI administrative diagnosis codes (410.x1 and 410.x0) in the SDD. METHODS: As part of an assessment of thromboembolic adverse event risk following treatment with intravenous immune globulin, charts were obtained for 103 potential post-intravenous immune globulin AMI cases. Charts were abstracted by trained nurses and physician-adjudicated based on prespecified diagnostic criteria. RESULTS: Acute myocardial infarction status could be determined for 89 potential cases. The PPVs for the inpatient AMI diagnoses recorded in the SDD were 75% overall (95% CI, 65-84%), 93% (95% CI, 78-99%) for principal-position diagnoses, 88% (95% CI, 72-97%) for secondary diagnoses, and 38% (95% CI, 20-59%) for position-unspecified diagnoses (eg, diagnoses originating from separate physician claims associated with an inpatient stay). Of the confirmed AMI cases, demand ischemia was the suspected etiology more often for those coded in secondary or unspecified positions (72% and 40%, respectively) than for principal-position AMI diagnoses (21%). CONCLUSIONS: The PPVs for principal and secondary AMI diagnoses were high and similar to estimates from prior chart validation studies. Position-unspecified diagnosis codes were less likely to represent true AMI cases.

Chart validation of inpatient International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) administrative diagnosis codes for venous thromboembolism (VTE) among intravenous immune globulin (IGIV) users in the Sentinel Distributed Database.

The Sentinel Distributed Database (SDD) is a database of patient administrative healthcare records, derived from insurance claims and electronic health records, sponsored by the US Food and Drug Administration for evaluation of medical product outcomes. There is limited information on the validity of diagnosis codes for acute venous thromboembolism (VTE) in the SDD and administrative healthcare data more generally.In this chart validation study, we report on the positive predictive value (PPV) of inpatient administrative diagnosis codes for acute VTE-pulmonary embolism (PE) or lower-extremity or site-unspecified deep vein thrombosis (DVT)-within the SDD. As part of an assessment of thromboembolic adverse event risk following treatment with intravenous immune globulin (IGIV), charts were obtained for 75 potential VTE cases, abstracted, and physician-adjudicated.VTE status was determined for 62 potential cases. PPVs for lower-extremity DVT and/or PE were 90% (95% CI: 73-98%) for principal-position diagnoses, 80% (95% CI: 28-99%) for secondary diagnoses, and 26% (95% CI: 11-46%) for position-unspecified diagnoses (originating from physician claims associated with an inpatient stay). Average symptom onset was 1.5 days prior to hospital admission (range: 19 days prior to 4 days after admission).PPVs for principal and secondary VTE discharge diagnoses were similar to prior study estimates. Position-unspecified diagnoses were less likely to represent true acute VTE cases.