Impact of preexisting mental illness on breast cancer endocrine therapy adherence.

PURPOSE: Patients with estrogen receptor positive (ER+) breast cancer are often non-adherent to endocrine therapies, despite clear survival benefits. We utilized a nationally representative cancer cohort to examine the role of specific mental illnesses on endocrine therapy adherence. METHODS: Using the SEER-Medicare database, we included 21,894 women aged 68+ at their first surgically treated stage I-IV ER+ breast cancer during 2007-2013. All had continuous fee-for-service Medicare Parts A and B for 36+ months before, 18+ months after diagnosis, and continuous Part D for 4+ months before, 18+ after diagnosis. Mental illness was defined as occurring in the 36 months prior to cancer onset. We analyzed endocrine therapy adherence, initiation, and discontinuation using longitudinal linear and Cox regression models. RESULTS: Unipolar depression (11.0%), anxiety (9.5%), non-schizophrenia psychosis (4.6%), and dementias (4.6%) were the most prevalent diagnoses. Endocrine therapies were initiated by 80.0% of women. Among those with at least one year of use, 28.0% were non-adherent (< 0.80 adherence, mean = 0.84) and 25.7% discontinued. Patients with dementia or bipolar depression/psychotic/schizophrenia disorders had lower adjusted initiation probabilities by year one of follow-up, versus those without these diagnoses [0.74 95% CI (0.73-0.74) and 0.73 (0.72-0.73), respectively, reference 0.76 (0.76-0.77)]. Patients with substance use or anxiety disorders less frequently continued endocrine therapy for at least one year, after adjustment, [0.85 95% CI (0.85-0.86) and 0.88 (0.87-0.88), respectively, reference 0.90 (0.89-0.90)]. Patients with substance use disorders had 2.3% lower adherence rates (p < 0.001). CONCLUSIONS: Nearly one-quarter of female Medicare beneficiaries have diagnosed mental illness preceding invasive breast cancer. Those with certain mental illnesses have modestly reduced rates of initiation, adherence, and discontinuation and this may help define patients at higher risk of treatment abandonment. Overall, endocrine therapy adherence remains suboptimal, unnecessarily worsening recurrence and mortality risk.

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.

Intravenous immune globulin and thromboembolic adverse events: A systematic review and meta-analysis of RCTs.

Prior case reports and observational studies indicate that intravenous immune globulin (IVIg) products may cause thromboembolic events (TEEs), leading the FDA to require a boxed warning in 2013. The effect of IVIg treatment on the risk of serious TEEs (acute myocardial infarction, ischemic stroke, or venous thromboembolism) was assessed using adverse event data reported in randomized controlled trials (RCTs) of IVIg. RCTs of IVIg in adult patients from 1995 to 2015 were identified from Pubmed, Embase, ClinicalTrials.Gov, and two large prior reviews of IVIg's therapeutic applications. Trials at high risk of detection or reporting bias for serious adverse events were excluded. 31 RCTs with a total of 4,129 participants (2,318 IVIg-treated, 1,811 control) were eligible for quantitative synthesis. No evidence was found of increased TEE risk among IVIg-treated patients compared with control patients (odds ratio = 1.10, 95% CI: 0.44, 2.88; risk difference = 0.0%, 95% CI: -0.7%, 0.7%, I(2) = 0%). No significant increase in risk was found when arterial and venous TEEs were analyzed as separate endpoints. Trial publications provided little specific information concerning the methods used to ascertain potential adverse events. Care should be taken in extrapolating the results to patients with higher baseline risks of TEE. Am. J. Hematol. 91:594-605, 2016. © 2016 Wiley Periodicals, Inc.

COVID-19 pandemic effects on emotional health and substance use among urban American Indian and Alaska Native people.

OBJECTIVE: The COVID-19 pandemic has disproportionately affected American Indian and Alaska Native (AI/AN) people, who experience a 3.2 times higher age-adjusted rate of hospitalization and nearly double the attributed deaths compared to non-Hispanic Whites. We examined pandemic effects on emotional health and substance use in urban AI/AN people. METHODS: From January-May 2021 we collected cross-sectional data from 642 patients seen at five health organizations serving primarily AI/AN people in urban settings. The outcomes are self-reported, cross-sectional changes in emotional health and substance use since pandemic onset. Exposures of interest include infection history, COVID-19 risk perception, pandemic-related life disruption, and feared effects on AI/AN culture. Poisson regression was used to model adjusted multivariate associations. RESULTS: Since pandemic onset, 46% of participants reported worsened emotional health; 20% reported increased substance use. Very or extremely disruptive pandemic experiences and increasing reported feared pandemic effects on culture were associated with worse pandemic emotional health [adjusted Prevalence Ratio 1.84; 95% CI 1.44, 2.35 and 1.11; 95% CI 1.03, 1.19], respectively. COVID-19 infection and risk perception were not associated with emotional health after adjustment for other factors. The primary exposures were not associated with change in substance use. CONCLUSIONS: The COVID-19 pandemic has impacted the emotional health of urban AI/AN people. The finding that poor emotional health is associated with pandemic-related threats to AI/AN culture may signal a protective role for community and cultural resources. This warrants further study as exploratory analysis did not find hypothesized effect modification according to strength of affiliation with AI/AN culture.

Breast cancer endocrine therapy adherence in health professional shortage areas: Unique effects on patients with mental illness.

OBJECTIVE: Evaluate whether breast cancer endocrine therapy adherence is affected by access to primary and mental health care, particularly among at-risk patients with mental illness. METHODS: The study included 21,892 SEER-Medicare women aged 68 or older with stage I-IV ER+ breast cancer, 2007 to 2013. Patient home counties during breast cancer diagnosis, if evaluated for HPSA care shortage status, were categorized as least, moderate, or highest shortage; unevaluated counties (no known shortage) were a fourth category. Endocrine therapy initiation and discontinuation were analyzed with Cox regression, and daily adherence with longitudinal linear regression. RESULTS: After multivariate adjustment, patients in high primary care shortage counties were less likely to initiate endocrine therapy, reference least shortage [HR 0.92 (95% CI 0.86-0.97)]. Unevaluated counties had more oncologists per capita, fewer residents below the federal poverty level, and higher incomes. Mental health shortages were not associated with outcomes, however subgroups living in unevaluated counties were less likely to discontinue: patients with bipolar and psychotic disorders [discontinuation HR 0.35 (95% CI 0.17-0.73)], substance use [HR 0.48 (95% CI 0.24-0.95)], anxiety disorders [HR 0.56 (95% CI 0.35-0.90)]. CONCLUSIONS: Poor primary care access was associated with a lower likelihood of initiating endocrine therapy but living in counties without established mental health shortages may reduce the harmful association between mental illness and incomplete treatment receipt. Patients with mental illness may be more equipped to complete cancer treatment if given better mental health care access, suggesting a need for care coordination between primary and mental health care.

Effects of Previous Medication Regimen Factors and Bipolar and Psychotic Disorders on Breast Cancer Endocrine Therapy Adherence.

BACKGROUND: Endocrine therapy adherence remains a barrier to optimal estrogen receptor-positive breast cancer outcomes. We theorized that experience navigating difficult medication regimen factors, such as route of administration complexity, might improve subsequent adherence after stressful cancer diagnoses but not for patients with bipolar and psychotic disorders at risk of poor access and nonadherence. MATERIALS AND METHODS: We included 21,894 women aged ≥ 68 years at their first surgically treated stage I-IV estrogen receptor-positive breast cancer (2007-2013) from the Surveillance, Epidemiology, and End Results-Medicare data set, of whom 5.8% had bipolar or psychotic disorders. We required continuous fee-for-service Medicare (parts A and B) data for ≥ 36 months before and 18 months after the cancer diagnosis. The medication regimen factors in the part D claims for 4 months before included the number of all medications used, pharmacy visits, and administration complexity (medication regimen complexity index subscale). Cox regression analysis was used to model the time to initiation and discontinuation, with longitudinal linear regression for adherence to endocrine therapy. RESULTS: Women with more frequent previous medication use and pharmacy visits were more likely to initiate, 4+ medications and 2+ visits versus no medication (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.33-1.63), to adhere (6.0%; 95% CI, 4.3-7.6), and to continuously use their endocrine therapy (discontinuation HR, 0.48; 95% CI, 0.39-0.59). Medication administration complexity had modest effects. Difficult medication regimens were more common for patients with bipolar and psychotic disorders but had no statistically significant effects. CONCLUSIONS: Experience with frequent previous medication use and pharmacy visits might increase the likelihood of endocrine therapy use for most patients but not for those with bipolar and psychotic disorders.

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.