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.

Diagnostic delay and characterization of the clinical prodrome in AL amyloidosis among 1523 US adults diagnosed between 2001 and 2019.

Light-chain (AL) amyloidosis is a multisystem disorder with a high early mortality and diagnostic delays of >1 year from symptom onset. This retrospective observational study sought to characterize the clinical prodrome and diagnostic delay to inform early detection. We identified 1523 adults with newly diagnosed AL amyloidosis in the Optum de-identified Clinformatics® Datamart US healthcare claims database as those with ≥2 new diagnosis codes for AL or other amyloidosis in 90 days with ≥1 multiple myeloma treatment within 730 days, excluding patients with prior hereditary or secondary amyloidosis and Familial Mediterranean Fever. We considered 34 signs/symptoms using diagnosis codes in all observable time on or before AL amyloidosis diagnosis. Sign/symptom prevalence was compared to that of 1:4 matched population controls. The overlap and sequence of signs/symptoms and the median time from first sign/symptom to AL amyloidosis diagnosis were explored. Healthcare utilization was summarized. The most common individual AL amyloidosis signs/symptoms were malaise/fatigue (61%) and dyspnea (59%). Cardiac signs/symptoms were observed in 77% of patients, followed by renal (62%) and neurologic (59%) signs/symptoms. Multisystem involvement (≥3 systems) was present in 54%. Monoclonal gammopathy was detected in 29% before diagnosis. Median time from symptom onset to AL amyloidosis diagnosis was 2.7 years. Healthcare utilization was high between first AL amyloidosis signs/symptoms and diagnosis, with 50% visiting ≥5 physician types. AL amyloidosis patients have a lengthy and complex clinical prodrome. Novel approaches to early diagnosis are needed to improve outcomes.

Cause-specific mortality among Medicare beneficiaries with newly diagnosed non-Hodgkin lymphoma subtypes.

BACKGROUND: As the US population ages and non-Hodgkin lymphoma (NHL)-specific mortality declines, deaths from causes other than NHL will become increasingly important in treatment decision making for older patients with NHL. The objective of the current study was to describe how the 5-year cumulative incidence of NHL-specific and other-cause mortality varies by subtype, age, comorbidity level, and time since diagnosis in older patients. METHODS: Using the Surveillance, Epidemiology, and End Results cancer registry data linked to Medicare claims, patients aged ≥66 years were identified at the time of diagnosis with a first, primary NHL diagnosis from 2004 through 2013. Death certificate data and Fine-Gray competing risks models were used to estimate the 5-year cumulative incidence of NHL-specific and other-cause mortality by NHL subtype, age, and comorbidity level. Estimates were displayed over time using stacked cumulative incidence curves. RESULTS: Among 30,666 patients with NHL, 32% died of NHL and 13% died of other causes within 5 years of diagnosis. The cumulative incidence of other-cause mortality increased with age and comorbidity level for all subtypes. Among patients with aggressive NHL subtypes, NHL-specific mortality exceeded other-cause mortality across all age groups, comorbidity levels, and number of years after diagnosis. For patients with indolent NHL subtypes, other-cause mortality was similar to or exceeded NHL-specific mortality, especially among older patients with severe comorbidity or with the indolent marginal zone, lymphoplasmacytic, and mycosis fungoides subtypes. CONCLUSIONS: The findings of the current study suggest that mortality from causes other than NHL are important for patients of an older age, with a higher comorbidity level, and with indolent disease. Evidence from the current study can guide the development of tools for estimating individual prognosis that inform treatment discussions in patients with NHL.

Comparison of Medicare Claims-based Proxy Measures of Poor Function and Associations With Treatment Receipt and Mortality in Older Colon Cancer Patients.

BACKGROUND: Multiple claims-based proxy measures of poor function have been developed to address confounding in observational studies of drug effects in older adults. We evaluated agreement between these measures and their associations with treatment receipt and mortality in a cohort of older colon cancer patients. METHODS: Medicare beneficiaries age 66+ diagnosed with stage II-III colon cancer were identified in the Surveillance, Epidemiology, and End Results-Medicare database (2004-2011). Poor function was operationalized by: (1) summing the total poor function indicators for each model; and (2) estimating predicted probabilities of poor function at diagnosis. Agreement was evaluated using Fleiss' κ and Spearman's correlation. Associations between proxy measures and: (1) laparoscopic versus open surgery; (2) chemotherapy versus none; (3) 5-fluorouracil (5FU)+oxaliplatin (FOLFOX) versus 5FU monotherapy; and (4) 1-year mortality were estimated using log-binomial regression, controlling for age, sex, stage, and comorbidity. Survival estimates were stratified by functional group, age, and comorbidity. RESULTS: Among 29,687 eligible colon cancer patients, 67% were 75+ years and 45% had stage III disease. Concordance across the poor function indicator counts was moderate (κ: 0.64) and correlation of predicted probability measures varied (ρ: 0.21-0.74). Worse function was associated with lower chemotherapy and FOLFOX receipt, and higher 1-year mortality. Within age and comorbidity strata, poor function remained associated with mortality. CONCLUSIONS: While agreement varied across the claims-based proxy measures, each demonstrated anticipated associations with treatment receipt and mortality independent of comorbidity. Claims-based comparative effectiveness studies in older populations should consider applying one of these models to improve confounding control.

Update on prevalence of diagnosed systemic lupus erythematosus (SLE) by major health insurance types in the US in 2016.

OBJECTIVE: To provide current estimates of the number of patients with prevalent systemic lupus erythematosus (SLE) by major health insurance types in the US and to describe patient characteristics. Four large US health insurance claims databases were analyzed to represent different types of insurance coverage, including private insurance, Medicaid, and Medicare Supplemental. RESULTS: Overall unadjusted SLE prevalence per 100,000 persons in the US ranged from 150.1 (private insurance) to 252.9 (Medicare Supplemental insurance). Extrapolating to the US civilian population in 2016, we estimated roughly 345,000 to 404,000 prevalent SLE patients with private/Medicare insurance and 99,000 prevalent SLE patients with Medicaid insurance. Comorbidities, including renal failure/dialysis were commonly observed across multiple organ systems in SLE patients (8.4-21.1%). We estimated a larger number of prevalent SLE cases in the US civilian population than previous reports and observed extensive disease burden based on a 1-year cross-sectional analysis.

Publication of comparative effectiveness research has not increased in high-impact medical journals, 2004-2013.

OBJECTIVE: To explore the impact of increasing interest and investment in patient-centered research, this study sought to describe patterns of comparative effectiveness research (CER) and patient-reported outcomes (PROs) in pharmacologic intervention studies published in widely read medical journals from 2004-2013. DESIGN AND SETTING: We identified 2335 articles published in five widely read medical journals from 2004-2013 with ≥1 intervention meeting the US Food and Drug Administration's definitions for a drug, biologic, or vaccine. Six trained reviewers extracted characteristics from a 20% random sample of articles (468 studies). We calculated the proportion of studies with CER and PROs. Trends were summarized using locally-weighted means and 95% confidence intervals. RESULTS: Of the 468 sampled studies, 30% used CER designs and 33% assessed PROs. The proportion of studies using CER designs did not meaningfully increase over the study period. However, we observed an increase in the use of PROs. CONCLUSIONS: Among pharmacological intervention studies published in widely read medical journals from 2004-2013, we identified no increase in CER. Randomized, placebo-controlled trials continue to be the dominant study design for assessing pharmacologic interventions. Increasing trends in PRO use may indicate greater acceptance of these outcomes as evidence for clinical benefit.

Methodologic Issues When Estimating Risks in Pharmacoepidemiology.

Risk is an important parameter to describe the occurrence of health outcomes over time. However, many outcomes of interest in healthcare settings, such as disease incidence, treatment initiation, and cause-specific mortality, may be precluded from occurring by other events, often referred to as competing events. Here, we review straightforward approaches to estimate risk in the presence of competing events. We illustrate the application of these methods using timely examples in pharmacoepidemiologic research and compare results to those obtained using analytic simplifications commonly used to handle competing events. These examples demonstrate how the analytic methods used to account for competing events affect the interpretation of results from pharmacoepidemiologic studies.

Applying the Social Ecological Model to Creating Asthma-Friendly Schools in Louisiana.

BACKGROUND: In 2010, the Louisiana Asthma Management and Prevention Program (LAMP) implemented the Asthma-Friendly Schools Initiative in high-risk Louisiana populations. The social ecological model (SEM) was used as a framework for an asthma program implemented in 70 state K-12 public schools over 2 years. METHODS: Activities included a needs assessment, identification of students with asthma, individualized asthma action plans (AAP), staff trainings, environmental quality improvement, and school system policy changes to address the asthma burden. RESULTS: There were 522 new or existing asthma cases recognized. Asthma knowledge/awareness was measurably improved among school personnel. School indoor air quality was improved across all locations. School-level policies were adopted that improved AAP collection, compliance to bus-idling restrictions, and asthma medication self-carry. CONCLUSIONS: The SEM framework can be used for school-based programs to address successfully and improve asthma-related issues from the individual through policy levels.

Roles of the state asthma program in implementing multicomponent, school-based asthma interventions.

BACKGROUND: Asthma is a leading chronic childhood disease in the United States and a major contributor to school absenteeism. Evidence suggests that multicomponent, school-based asthma interventions are a strategic way to address asthma among school-aged children. The Centers for Disease Control and Prevention (CDC) encourages the 36 health departments (34 states, District of Columbia, and Puerto Rico) in the National Asthma Control Program (NACP) to implement multicomponent, school-based asthma interventions on a larger scale. METHODS: To gain a better understanding of replicable best practices for state-coordinated asthma interventions in schools, an NACP evaluation team conducted evaluability assessments of promising interventions run by state asthma programs in Louisiana, Indiana, and Utah. RESULTS: The team found that state asthma programs play a critical role in implementing school-based asthma interventions due to their ability to (1) use statewide surveillance data to identify asthma trends and address disparities; (2) facilitate connections between schools, school systems, and school-related community stakeholders; (3) form state-level connections; (4) translate policies into action; (5) provide resources and public health practice information to schools and school systems; (6) monitor and evaluate implementation. CONCLUSIONS: This article presents evaluability assessment findings and illustrates state roles using examples from the 3 participating state asthma programs.