Myelodysplastic syndrome and acute myeloid leukemia after receipt of granulocyte colony-stimulating factors in older patients with non-Hodgkin lymphoma.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL). METHODS: This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication. RESULTS: Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (Ptrend < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45). CONCLUSIONS: A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.

Impact of a Medication Therapy Management Clinic on Glycosylated Hemoglobin, Blood Pressure, and Resource Utilization.

BACKGROUND: Medication therapy management is widely promoted to improve care. However, few well-controlled studies have evaluated its impact. OBJECTIVES: We evaluated whether enrollment in a comprehensive medication therapy management clinic (MTMC) was associated with improved 12-month outcomes. METHODS: This institutional review board approved study was a retrospective controlled cohort study in an academic health center serving low-income, African American and Latino populations. Between 2001 and 2011 MTMC patients were matched to control patients by age, gender, and comorbidities. Outcomes were mean change in glycosylated hemoglobin (A1C), diastolic (DBP) and systolic blood pressure (SBP), and emergency department (ED) and hospital admissions at 6 and 12 months. A difference-in-difference analysis was conducted for each outcome of interest, adjusting for observed, unmatched confounders. RESULTS: Patients with diabetes and receiving MTMC had greater A1C improvements, compared with controls, of 0.54% (P = 0.0067) at 6 months and 0.63% (P = 0.0160) at 12 months. At 6 months, SBP and DBP decreased in MTMC patients by 6.5 mm Hg (P = 0.0108) and 3.8 mm Hg (P = 0.0136) more than controls, respectively. At 12 months, those receiving MTMC services had SBP and DBP decreases, respectively, of 8.2 mm Hg (P = 0.0018) and 1.7 mm Hg (P = 0.2691) compared with controls. ED and hospital visits were not statistically significantly different between groups. Conclusion and Relevance: This MTMC potentially improved outcomes for referred patients in whom target goals were difficult to achieve and can serve as a model for other similar medication management programs.

Competencies for Patient Safety and Quality Improvement: A Synthesis of Recommendations in Influential Position Papers.

BACKGROUND: There is limited conformity among patient safety and quality improvement (QI) competencies of the knowledge, skills, and attitudes (KSA), by stage of skill acquisition, essential for all health professionals. A study was conducted to identify, categorize, critically appraise, and discuss implications of competency recommendations published in influential position papers. METHODS: A literature search was conducted of competency recommendations in position papers published by national and international professional associations, expert panels, consortia, centers and institutes, and convened committees, in the domain of patient safety and QI. To be included in the analysis, the competency had to be recommended in at least 20% (rounded) of the position papers. Qualitative content analysis was used to identify themes among the published competencies for the skill acquisition levels of competent and expert, using Dreyfus's definitions. RESULTS: On the basis of the 22 papers that met the inclusion criteria, 17 themes were identified among the 59 competencies for the skill level competent. Among the 23 competencies for the skill level expert, 13 themes were identfied. Competencies within the theme "Evidence-Based Practice" were most frequently recommended across both skill levels. The themes "Interdisciplinary Teamwork and Collaboration" and "Evidence-Based Practice" were the themes identified among the greatest number of position papers for the skill level competent and expert, respectively. CONCLUSIONS: The identified themes for competencies in patient safety and QI have implications for curriculum development and assessment of competence in education and practice. The findings in this study demonstrate a need to discourage publication of recommendations of yet more competencies and to instead encourage development of an international consensus on the essential KSA for patient safety and QI across all health professions and all levels of skill acquisition.

Risk of fall-related injury and all-cause hospitalization of select concomitant central nervous system medication prescribing in older adult persistent opioid users: A case-time-control analysis.

BACKGROUND: Concomitant use of central nervous system (CNS) medications frequently occurs in older adults with persistent opioid use. The risks of adverse outcomes associated with combinations of opioids, sedative hypnotics, or skeletal muscle relaxants have not been sufficiently described in this population. OBJECTIVE: To compare the overall and incremental risk of (1) fall-related injury and (2) all-cause hospitalization associated with sedative hypnotics and skeletal muscle relaxants among older persistent opioid users. METHODS: A case-time-control study was conducted using administrative claims of adults ages ≥66 years with a history of persistent (≥90 days) opioid use. Cases included those with first (1) emergency department, hospital, or outpatient visit for a fall-related injury, or (2) all-cause hospitalization. Exposure to CNS medications prior to the case event versus earlier periods, and the risk associated with CNS drug class combinations and sequence of use, was estimated using conditional logistic regression, adjusted for time trends and time-varying covariates. RESULTS: Among 140,101 older persistent opioid users, 20,723 experienced fall-related injury and 39,444 were hospitalized during follow-up. Skeletal muscle relaxant use was associated with an increased risk of fall-related injury (Odds ratio [OR] 1.28) and all-cause hospitalization (OR 1.11). Statistically significant associations were observed for the joint effects of interactions involving skeletal muscle relaxants on fall-related injury (with opioid: OR 1.25; with sedative hypnotic: OR 1.24), and interactions involving opioids on all-cause hospitalization (with sedative hypnotic: OR 1.10; with skeletal muscle relaxant: OR 1.17). The addition of a skeletal muscle relaxant to an opioid regimen was associated with a 25% increased risk of fall-related injury. Additions of other CNS medications did not have apparent incremental effects on the risk of all-cause hospitalization. CONCLUSION: The excess risks of fall-related injury and hospitalization associated with various combinations of CNS medications among older persistent opioid users should be considered in therapeutic decision making. Further research is needed to confirm these findings.

Retrospective Claims Analysis Indirectly Comparing Medication Adherence and Persistence Between Intravenous Biologics and Oral Small-Molecule Therapies in Inflammatory Bowel Diseases.

INTRODUCTION: Patients' adherence to and persistence on treatment for inflammatory bowel disease (IBD) can vary, depending on type and distribution of disease and treatment modality. We aim to identify differences in adherence and persistence with treatments with different administration routes (intravenous vs oral) in IBD. METHODS: A retrospective cohort analysis of a claims database of adult patients diagnosed with IBD or rheumatoid arthritis (RA) who began treatment with vedolizumab, tofacitinib, or infliximab from January 2015 through December 2015. Adherence evaluated by proportion of days covered (PDC) and cumulative days with gaps at least 20% beyond expected interval (CG20) using multivariable generalized linear equation models. Persistence assessed as time to treatment discontinuation over 12 months of follow-up using Kaplan-Meier estimates and Cox proportional hazards models; proportion of persistent patients determined via multivariable logistic regression. Indirect comparisons across disease states adjusted using infliximab data. RESULTS: After indirect adjustment by disease, mean PDC difference was significantly higher (difference of 4.7%; P = 0.0376) and mean CG20 was lower (difference of 15 days; P = 0.0646) but not statistically significant in vedolizumab/IBD than tofacitinib/RA. CONCLUSION: We describe a novel adjustment method for interdisease treatment differences using infliximab treatment patterns to bridge differences between IBD and RA. After adjustment, adherence was higher with infusions than oral medications, which may affect outcomes. Indirect comparisons between vedolizumab and tofacitinib are not generalizable and should be confirmed in tofacitinib-treated IBD patients. FUNDING: Takeda Pharmaceuticals U.S.A., Inc.

Effect of Comprehensive Care Coordination on Medicaid Expenditures Compared With Usual Care Among Children and Youth With Chronic Disease: A Randomized Clinical Trial.

Importance: Medicaid spending on children and young adults with chronic disease could be decreased through care coordination programs by reducing unnecessary hospital and emergency care. Objective: To assess whether a comprehensive care coordination program reduces Medicaid expenditures by decreasing hospital and emergency department (ED) utilization. Design, Setting, and Participants: This randomized clinical trial included 6259 children and young adults with chronic disease who received public insurance through Illinois Medicaid. In April 2016, eligible youth were randomized to receive comprehensive care coordination through the Coordinated Healthcare for Complex Kids (CHECK) program (n = 3126) or usual care (n = 3119) to measure the effect of the CHECK program on Medicaid expenditures and health care utilization using a difference-in-differences (DID) approach. Data were collected from May 1, 2014, to April 30, 2017, and analyzed in May 2018. Interventions: Care coordination, mental health care, education, and social support were provided to CHECK participants and their family members. Services were tailored based on family and participant need. Main Outcomes and Measures: Mean annual Medicaid expenditures, mean annual health care utilization by category (ED and inpatient), and chronic disease type and risk level. Results: A total of 6259 participants (mean [SD] age, 11.3 [6.4] years; 2918 [46.6%] female; 2594 [41.4%] with medium and high risk) were randomized. Following the exclusion of 14 outliers, 6245 participants were analyzed. The mean (SD) annual Medicaid expenditure before the intervention was $1633 ($4006) for the intervention group and $1703 ($4466) for the usual care group, which decreased to a mean (SD) of $1341 ($3004) and $1413 ($3785), respectively, after the intervention (DID, -$1; 95% CI, -$199 to $196; P = .99). The mean (SD) inpatient utilization before the intervention was 63.0 (344.4) per 1000 person-years (PYs) for the intervention group and 69.3 (370.9) per 1000 PYs for the usual care group, which decreased to 43.5 (297.2) per 1000 PYs and 47.8 (304.9) per 1000 PYs, respectively, after the intervention (DID, 2.0; 95% CI, -17.9 to 21.8; P = .85). Among participants with asthma, those in the intervention group had a greater mean (SD) decrease in ED utilization compared with usual care, but the difference was not significant (-225.9 [65.3] vs -104.5 [80.0] visits per 1000 PY; DID, -121.5; 95% CI, -268.9 to 26.0; P = .11). Similarly, enrolled participants with sickle cell disease had a smaller but not significant mean (SD) increase in ED utilization compared with usual care (583.3 [839.0] vs 3761.9 [4611.2] visits per 1000 PYs; DID, -3178.6; 95% CI, -10 724.3 to 4367.2; P = .41). Conclusions and Relevance: Overall Medicaid expenditures and health care utilization (hospital and ED) decreased similarly for both CHECK participants and the usual care group. Trial Registration: ClinicalTrials.gov identifier: NCT04057521.

Mediation analyses of socioeconomic factors determining racial differences in the treatment of diffuse large B-cell lymphoma in a cohort of older adults.

Despite near universal health coverage under Medicare, racial disparities persist in the treatment of diffuse large B-cell lymphoma (DLBCL) among older patients in the United States. Studies evaluating DLBCL outcomes often treat socioeconomic status (SES) measures as confounders, potentially introducing biases when SES factors are mediators of disparities in cancer treatment.To examine differences in DLBCL treatment, we performed causal mediation analyses of SES measures, including: metropolitan statistical area (MSA) of residence; census-tract poverty level; and private Medicare supplementation using the Surveillance, Epidemiology and End Results-Medicare linked database between 2001 and 2011. In this retrospective cohort study of DLBCL patients ages 66+ years, we conducted a series of multivariable logistic regression analyses estimating odds ratios (OR) and 95% confidence intervals (CI) relating chemo- and/or immuno-therapy treatment and each SES measure, comparing non-Hispanic (NH)-black, Hispanic/Latino, and Asian/Pacific Islander (API) to NH-white patients.Compared to NH-white patients, racial/ethnic minority patients had lower odds of receiving chemo- and/or immuno-therapy treatment (NH-black: OR 0.84, 95% CI 0.65, 1.08; API: OR 0.80, 95% CI 0.64, 1.01; Hispanic/Latino: OR 0.78, 95% CI 0.64, 0.96) and higher odds of lacking private Medicare supplementation and residence within an urban MSA and poor census tracts. Adjustment for SES measures as confounders nullified observed racial differences. In causal mediation analyses, between 31% and 38% of race/ethnicity differences were mediated by having private Medicare supplementation.Providing equitable access to Medicare supplementation may reduce disparities in receipt of chemo- and/or immuno-therapy treatment in older DLBCL patients.