Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway.

BACKGROUND: New acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs). METHODS: In this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim for erenumab, fremanezumab, galcanezumab in the 6-month pre-index period) or patients without prior mAb use. Treatment patterns were assessed during the 6-month post-index period. RESULTS: Overall, 78,574 patients were identified (63% indexed on ubrogepant, 34% on rimegepant, and 3% on lasmiditan) with 26,656 patients (34%) having had prior mAb use. In the pre-index period, 79% of patients used non-mAb preventive medications and 75% of patients used acute medications. Following the index nAMSM claim, 65% of patients had ≥ 1 refill and 21% had ≥ 4 refills of their index nAMSM; 10% of patients switched to another nAMSM. Post-index mAb use was observed in 82% of patients with a prior mAb and 15% of patients without. Among patients with pre- and post-index use of acute medications, 38% discontinued ≥ 1 acute medication class in the post-index period. Among patients with concomitant use of traditional preventive medications at index, 30% discontinued ≥ 1 concomitant preventive anti-migraine medication in the post-index period. CONCLUSIONS: Most patients initiating nAMSMs had prior treatment with acute and preventive medications. Approximately one-third of patients had prior treatment with anti-CGRP pathway mAbs. After starting nAMSMs, more than one-third of patients discontinued at least one traditional acute medication and one-third of patients discontinued at least one traditional preventive medication. Despite nAMSM initiation, most patients with prior anti-CGRP pathway mAb use continued mAb use. Around 15% of patients without a prior mAb newly started a mAb. These results provide insight into how nAMSMs and mAbs have been integrated into clinical management of migraine in the real-world.

Inpatient Constipation Among Migraine Patients Prescribed Anti-calcitonin Gene-Related Peptide Monoclonal Antibodies and Standard of Care Antiepileptic Drugs: A Retrospective Cohort Study in a United States Electronic Health Record Database.

INTRODUCTION: Erenumab, an anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody (mAb), was approved by the US Food and Drug Administration in May 2018. Constipation with serious complications was added to the Warning and Precautions section in the erenumab Prescribing Information in October 2019 after events were observed during post-marketing surveillance. We aimed to assess and compare the risk of inpatient constipation, and, separately, inpatient constipation with serious complications, among patients with migraine treated with CGRP mAbs and standard of care antiepileptic drugs (AEDs). METHODS: Within Optum's Electronic Health Record Research Database, patients with migraine who initiated erenumab, other CGRP mAbs, and AEDs were identified from May 2018 through March 2020. Erenumab initiators were propensity score-matched separately to initiators of other CGRP mAbs and AEDs. Incident inpatient constipation events, and serious complications, were identified using multiple risk windows for outcome assessment (30-, 60-, 90-day risk windows, and all available follow-up). Odds ratios (ORs) were calculated comparing inpatient constipation risk among matched erenumab initiators relative to comparators. RESULTS: We identified 17,902 erenumab, 13,404 other CGRP mAb, and 49,497 AED initiators who met study criteria. Among matched initiators, the risk of inpatient constipation was 0.46% (95% confidence interval (CI) 0.35-0.60) for erenumab and 0.44% (95% CI 0.33-0.58) for other CGRP mAbs within the 90-day risk window, with a corresponding OR of 1.06 (95% CI 0.72-1.55). Among matched erenumab and AED initiators, inpatient constipation risk was 0.53% (95% CI 0.42-0.66) and 0.76% (95% CI 0.62-0.92), respectively, and the OR was 0.69 (95% CI 0.51-0.94). Few serious complications were observed. CONCLUSION: Patients initiating erenumab had similar risk of inpatient constipation within 90 days of treatment initiation versus patients initiating other CGRP mAbs, and lower risk versus patients initiating AEDs. These findings provide context to events observed during post-marketing surveillance.

Trends in characteristics and outcomes among US adults hospitalised with COVID-19 throughout 2020: an observational cohort study.

OBJECTIVES: To examine the temporal patterns of patient characteristics, treatments used and outcomes associated with COVID-19 in patients who were hospitalised for the disease between January and 15 November 2020. DESIGN: Observational cohort study. SETTING: COVID-19 subset of the Optum deidentified electronic health records, including more than 1.8 million patients from across the USA. PARTICIPANTS: There were 51 510 hospitalised patients who met the COVID-19 definition, with 37 617 in the laboratory positive cohort and 13 893 in the clinical cohort. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident acute clinical outcomes, including in-hospital all-cause mortality. RESULTS: Respectively, 48% and 49% of the laboratory positive and clinical cohorts were women. The 50- 65 age group was the median age group for both cohorts. The use of antivirals and dexamethasone increased over time, fivefold and twofold, respectively, while the use of hydroxychloroquine declined by 98%. Among adult patients in the laboratory positive cohort, absolute age/sex standardised incidence proportion for in-hospital death changed by -0.036 per month (95% CI -0.042 to -0.031) from March to June 2020, but remained fairly flat from June to November, 2020 (0.001 (95% CI -0.001 to 0.003), 17.5% (660 deaths /3986 persons) in March and 10.2% (580/5137) in October); in the clinical cohort, the corresponding changes were -0.024 (95% CI -0.032 to -0.015) and 0.011 (95% CI 0.007 0.014), respectively (14.8% (175/1252) in March, 15.3% (189/1203) in October). Declines in the cumulative incidence of most acute clinical outcomes were observed in the laboratory positive cohort, but not for the clinical cohort. CONCLUSION: The incidence of adverse clinical outcomes remains high among COVID-19 patients with clinical diagnosis only. Patients with COVID-19 entering the hospital are at elevated risk of adverse outcomes.

Rates of Vascular Events in Patients With Migraine: A MarketScan® Database Retrospective Cohort Study.

OBJECTIVE: To estimate the baseline rates of vascular events among people with migraine. BACKGROUND: Several novel medications that target the calcitonin gene-related peptide (CGRP) pathway are approved to treat people with migraine. Given that the CGRP pathway also plays a role in maintaining cardiovascular homeostasis, determining the baseline rates of vascular events among people with migraine will help inform the safety of these novel medications. METHODS: In this retrospective cohort study, patients 18- to 64-year-old patients with migraine were identified from the MarketScan® database (January 2013-December 2017) and were categorized into 4 vascular risk categories: migraine with aura; and high, medium, and low vascular risk. Event rates (per 1000 person-years [PY]) for 19 vascular events were estimated overall, by risk category, and by baseline characteristics. RESULTS: Among 1,195,696 patients with migraine, 4.8% (57,853/1,195,696) had migraine with aura, and 2.8% (33,949/1,195,696), 15.5% (184,782/1,195,696), and 77.9% (931,059/1,195,696) were at high, medium, and low risk of vascular events, respectively. Rates of ischemic stroke (per 1000 PY) were 5.1 (95% confidence interval [CI]: 5.0, 5.2) overall, 8.6 (95% CI: 8.1, 9.1) for patients with migraine aura, 47.2 (95% CI: 45.3, 49.0) in the high-risk group, 9.4 (95% CI: 9.1, 9.7) in the medium-risk group, and 2.9 (95% CI: 2.9, 3.0) in the low-risk group. Rates of acute myocardial infarction (per 1000 PY) were 1.8 (95% CI: 1.8, 1.9) overall, 1.9 (95% CI: 1.7, 2.2) for patients with migraine aura, 14.0 (95% CI: 13.0, 14.9) in the high-risk group, 3.9 (95% CI: 3.7, 4.1) in the medium-risk group, and 1.1 (95% CI: 1.0, 1.1) in the low-risk group. High-risk patients had the highest rates of each of 19 evaluated vascular events, and rates were higher for men, older age groups, and those with higher comorbidity scores, medication usage, and medical utilization. CONCLUSION: Our findings provide recent rates of vascular disease in patients with migraine. In the future, this information will be useful to help inform clinical risk:benefit decision making when assessing the use of therapies such as CGRP antagonists for migraine.

Red blood cell transfusion, hyperkalemia, and heart failure in advanced chronic kidney disease.

PURPOSE: In recent years, the use of red blood cell (RBC) transfusion for the treatment of chronic kidney disease (CKD)-related anemia has increased. We used the OptumInsight medical claims database to study the association between receiving a transfusion and hyperkalemia and heart failure events. METHODS: Persons 18-64 years of age with diagnosed stage 4 or 5 CKD (not requiring dialysis) between 2006 and 2010 were followed until their first hospitalization or emergency room visit with a diagnosis of hyperkalemia or heart failure, termination of insurance coverage, or death. We used a case-only design and conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CIs) describing associations between RBC transfusion and the risks of hyperkalemia or heart failure. We used single (1:1) and variable (1:m) self-control matching intervals, with adjustment for time-varying confounders. RESULTS: Seven thousand eight hundred twenty-nine individuals met our inclusion criteria; two-thirds were age 50 years or older; 43% were women and 51% had diabetes. Rates of hyperkalemia and heart failure were 7.9/100 person-years (95%CI: 7.3, 8.5) and 16.3/100 person-years (95%CI: 15.5, 17.2), respectively. RBC transfusion was associated with an increased risk of both hyperkalemia (single interval matched RR = 12.0, 95%CI: 1.3, 109; multiple interval matched RR = 6.1, 95%CI: 2.5, 15.1) and heart failure (single interval matched RR = 1.7, 95%CI: 0.3, 9.2; multiple interval matched RR = 3.8, 95%CI: 1.4, 10.3). CONCLUSION: In patients with advanced CKD, RBC transfusion appears to be associated with an elevated risk of hyperkalemia and heart failure; further investigation into these risks is warranted.

Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial.

Intention-to-treat (ITT) analysis is widely used to establish efficacy in randomized clinical trials. However, in a long-term outcomes study where non-adherence to study drug is substantial, the on-treatment effect of the study drug may be underestimated using the ITT analysis. The analyses presented herein are from the EVOLVE trial, a double-blind, placebo-controlled, event-driven cardiovascular outcomes study conducted to assess whether a treatment regimen including cinacalcet compared with placebo in addition to other conventional therapies reduces the risk of mortality and major cardiovascular events in patients receiving hemodialysis with secondary hyperparathyroidism. Pre-specified sensitivity analyses were performed to assess the impact of non-adherence on the estimated effect of cinacalcet. These analyses included lag-censoring, inverse probability of censoring weights (IPCW), rank preserving structural failure time model (RPSFTM) and iterative parameter estimation (IPE). The relative hazard (cinacalcet versus placebo) of mortality and major cardiovascular events was 0.93 (95% confidence interval 0.85, 1.02) using the ITT analysis; 0.85 (0.76, 0.95) using lag-censoring analysis; 0.81 (0.70, 0.92) using IPCW; 0.85 (0.66, 1.04) using RPSFTM and 0.85 (0.75, 0.96) using IPE. These analyses, while not providing definitive evidence, suggest that the intervention may have an effect while subjects are receiving treatment. The ITT method remains the established method to evaluate efficacy of a new treatment; however, additional analyses should be considered to assess the on-treatment effect when substantial non-adherence to study drug is expected or observed.

Red blood cell transfusion use in patients with chronic kidney disease.

BACKGROUND: There is limited data available on the use of red blood cell (RBC) transfusions in younger chronic kidney disease patients not on dialysis (CKD-ND), for whom the consequences of developing antibodies to foreign antigens (allosensitization) may be particularly relevant. METHODS: We used the Ingenix medical claims database, comprising data on ∼40 million commercially insured US individuals, to identify annual (2002-08) cohorts of patients 18-64 years of age with newly diagnosed CKD. We followed each cohort for 1 year to estimate RBC transfusion rates and used Cox proportional hazards regression to identify patient characteristics associated with time to first transfusion. RESULTS: We identified 120 790 newly diagnosed CKD patients for the years 2002-08; 54% were 50-64 years of age. Overall, the transfusion rate was 2.64/100 person-years (PYs) (95% CI: 2.52-2.77). Rates were higher among those with diagnosed anemia [9.80/100 PYs (95% CI: 9.31-10.3)] and among those who progressed to end-stage renal disease (ESRD) [28.0/100 PYs (95% CI: 23.7-33.0)]. For those progressing to ESRD, transfusion rates more than doubled between 2002 and 2008. Of the factors evaluated, transfusion history and the presence of heart failure and diabetes were most strongly associated with a receipt of a transfusion. CONCLUSIONS: RBC transfusions are relatively common and on the rise among younger CKD-ND patients who are anemic and progress to ESRD. Efforts to decrease the use of transfusions may be important for potential transplant candidates who progress to ESRD.

Cognitive screening for dementia and mild cognitive impairment in assisted living: comparison of 3 tests.

OBJECTIVE: Compare diagnostic characteristics of brief cognitive screening tests in residential care/assisted living (RC/AL) residents. DESIGN: Cross-sectional study involving a comprehensive clinical examination to ascertain a consensus diagnosis of probable dementia, no significant cognitive impairment, or mild cognitive impairment (MCI), including both amnestic and non-amnestic subtypes. SETTING: Fourteen RC/AL facilities in North Carolina. PARTICIPANTS: Participants were 146 RC/AL residents, aged 65 years or older, who did not have diagnosed cognitive impairment. MEASUREMENTS: Diagnostic characteristics of the Mini-Cog, the Mini-Mental State Exam (MMSE), and a new 50-point test based on expanding selected MMSE items (MMX). RESULTS: Overall, 55/146 (38%) participants were diagnosed with probable dementia, and 76 (52%) met criteria for MCI (most non-amnestic). Both the Mini-Cog and the MMSE showed high sensitivity and negative predictive value for dementia, but had relatively low sensitivity and negative predictive value for MCI. The Mini-Cog had low specificity and was less accurate as a dementia screen than either the MMSE or MMX. Reliability and validity data for the MMX were satisfactory, and it performed better as a screening test for MCI than either the MMSE or Mini-Cog. CONCLUSION: Although the MMSE and Mini-Cog are both sensitive to dementia, modest specificity and positive predictive value may limit their utility as screening tools. Preliminary MMX data suggest it improves screening for MCI compared to the Mini-Cog or MMSE, while providing a similar level of screening for dementia. Further work is needed to identify suitable instruments for cognitive screening across the range of MCI and dementia.

Calibration of two objective measures of physical activity for children.

A calibration study was conducted to determine the threshold counts for two commonly used accelerometers, the ActiGraph and the Actical, to classify activities by intensity in children 5 to 8 years of age. Thirty-three children wore both accelerometers and a COSMED portable metabolic system during 15 min of rest and then performed up to nine different activities for 7 min each, on two separate days in the laboratory. Oxygen consumption was measured on a breath-by-breath basis, and accelerometer data were collected in 15-s epochs. Using receiver operating characteristic curve (ROC) analysis, cutpoints that maximised both sensitivity and specificity were determined for sedentary, moderate and vigorous activities. For both accelerometers, discrimination of sedentary behaviour was almost perfect, with the area under the ROC curve at or exceeding 0.98. For both the ActiGraph and Actical, the discrimination of moderate (0.85 and 0.86, respectively) and vigorous activity (0.83 and 0.86, respectively) was acceptable, but not as precise as for sedentary behaviour. This calibration study, using indirect calorimetry, suggests that the two accelerometers can be used to distinguish differing levels of physical activity intensity as well as inactivity among children 5 to 8 years of age.

High-intensity environmental light in dementia: effect on sleep and activity.

OBJECTIVES: To determine whether high-intensity ambient light in public areas of long-term care facilities will improve sleeping patterns and circadian rhythms of persons with dementia. DESIGN: A cluster-unit crossover intervention trial involving four conditions: morning bright light, evening bright light, all-day bright light, and minimum standard light. SETTING: The common areas of two geriatric units in a psychiatric hospital and a dementia-specific residential care facility. PARTICIPANTS: Sixty-six older adults with dementia. INTERVENTION: Ambient bright light of approximately 2,500 lux, delivered through a low-glare lighting system installed in the dining and activity areas. Participant exposure averaged 2.5 to 3.0 hours for the morning and evening interventions and 8.4 hours for the all-day intervention. MEASUREMENTS: Nighttime sleep using wrist actigraphy and daytime activity using nonobtrusive daytime observations. RESULTS: Night-time sleep increased significantly in participants exposed to morning and all-day light, with the increase most prominent in participants with severe or very severe dementia (mean increase 16 minutes (P=.008) for morning, and 14 minutes (P=.01) for all-day). Morning light produced a mean phase advance of 29 minutes (P=.02) and evening light a mean phase delay of 15 minutes (P=.06). Effects on daytime sleepiness were inconsistent, and the number of sleep bouts, mesor, amplitude, intradaily variability, and interdaily stability were not significantly different, indicating that the overall strength of day and night activity rhythms did not change significantly under any treatment condition. CONCLUSION: Bright light appears to have a modest but measurable effect on sleep in this population, and ambient light may be preferable to stationary devices such as light boxes.

Diagnostic mammography performance and race: outcomes in Black and White women.

BACKGROUND: A previous study compared the performance (sensitivity, specificity, positive predictive value, and cancer detection rate) of screening mammography in Black and White women. No study, to the authors' knowledge, has evaluated the difference in the performance of diagnostic mammography between Black and White women. METHODS: Univariate analysis was used to evaluate differences in characteristics and cancers between Black and White women. Stratified and adjusted logistic regression analyses were used to test the association of Black and White race with performance measures of diagnostic mammography. RESULTS: The sensitivity of diagnostic mammography was higher (91% vs. 84%) and specificity was lower (86% vs. 90%) among Black women compared with White women. After controlling for age, density, self-reported breast problems, and previous mammography, sensitivity was significantly higher (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.22-2.80) and specificity was significantly lower (OR = 0.75, 95% CI = 0.70-0.81) among Black women. The crude cancer detection rate of mammography was higher for Black women (42.6/1000) than for White women (31.0/1000) and Black women had a higher proportion of cancers that were > 2.0 cm (57.4% vs. 46.2%) that were more often poorly differentiated (61.7% vs. 49.3%) and were more often estrogen-receptor and progesterone-receptor negative. CONCLUSIONS: Black women have lower specificity of diagnostic mammography and, consequently, more unnecessary workups than White women. Black women have higher sensitivity of diagnostic mammography, with cancers that are larger and more advanced than White women. Delay in responding to signs and symptoms would explain the size and later stage. However, more research is needed to understand the biologic differences of breast cancer characteristics between Black and White women.

Evaluating the quality of life of long-term care residents with dementia.

PURPOSE: This study's purpose was to better understand existing measures of quality of life in dementia residents of long-term care facilities. DESIGN AND METHODS: We gathered data from 421 residents in 45 facilities. Analyses determined the psychometric properties of each measure, estimated the relationship between measures, and identified the extent to which resident characteristics predicted scores. RESULTS: Most instruments had good to excellent dispersion and interrater reliability, and most scales had good to excellent internal consistency. Proxy measures tended to correlate best with each other, less well with observational measures, and least well with resident measures. Resident cognition and activities of daily living (ADLs) function were associated with most quality-of-life measures but predicted no more than a quarter of the observed variance in any measure. IMPLICATIONS: Various measures and sources of data provide different perspectives on quality of life. No "gold standard" exists; so a combination of methods and sources is likely to provide the most complete picture of quality of life.

Screening mammography performance and cancer detection among black women and white women in community practice.

BACKGROUND: Despite improvement in mammography screening attendance, black women continue to have poorer prognosis at diagnosis than white woman. Data from the Carolina Mammography Registry were used to evaluate whether there may be differences in mammography performance or detected cancers when comparing black women with white women who are screened by mammography. METHODS: Prospectively collected data from community-based mammography facilities on 468,484 screening mammograms (79,397 in black women and 389,087 in white women) were included for study. Mammograms were linked to a pathology data base for identification of cancers. Sensitivity, specificity, positive predictive value, and cancer detection rates were compared between black women and white women. Logistic regression methods were used to control for covariates associated with performance characteristics. Differences in cancer characteristics were compared between black women and white women using chi-square statistics. RESULTS: Screening mammography performance results for black women compared with white women were as follows: sensitivity, odds ratio (OR) = 1.07 (95% confidence interval [95% CI], 0.83-1.39); specificity, OR = 1.02 (95% CI, 0.98-1.06); and positive predictive value, OR = 1.07 (95% CI, 0.94-1.23). Among women with no previous screening, black women had a larger proportion of invasive tumors that measured > or = 2 cm (38% vs. 26%; P = 0.04). The cancer detection rate was highest among black women who reported symptoms at screening (13.9 per 1000 black women vs. 7.9 per 1000 white women). Invasive cancers in black women were poorer grade (P = 0.001), and more often had negative estrogen receptor status and progesterone receptor status (P < 0.001). CONCLUSIONS: Overall, screening mammography performed equally well in black women and white women controlling for age, breast density, and time since previous mammogram. Black women who reported symptoms had larger and higher grade tumors compared with white women. Educational efforts need to be strengthened to encourage black women to react sooner to symptoms, so that the tumors detected will be smaller and black women will have a better prognosis when they appear for mammography.