Sleep medication use and risk of fractures in breast cancer survivors.

PURPOSE: Sleep problems are more common in breast cancer survivors than those without a cancer history. Our goal was to examine the risk of fractures among breast cancers survivors who used prescription sleep aids. METHODS: We conducted a retrospective cohort study of 21,346 adult women diagnosed with stage 0-III breast cancer between 2009 and 2016 and followed them through 2017. We examined person-year rates of fractures by sleep medication use and calculated adjusted hazard ratios (HR) and 95% confidence intervals (CI) with Cox proportional hazards models using time-dependent variables for sleep medications and covariate medications (antidepressants, anti-anxiety medications, and bisphosphonates) adjusted for demographics, comorbidities, and tumor characteristics and cancer treatments. RESULTS: The sleep medication use was common (40%) in breast cancer survivors and was associated with a 33% increased risk of fractures (adjusted HR = 1.33, 95% CI: 1.20-1.49). Further, in a sensitivity analysis based on new use of sleep medication, the fracture risk was even stronger (adjusted HR = 1.44, 95% CI: 1.26-1.64). CONCLUSION: Given the high use of sleep medications and the high risk of fractures in breast cancer survivors, this study suggests that non-pharmacologic management of sleep problems might be considered as alternative therapy.

SARS-CoV-2 Testing, Positivity Rates, and Healthcare Outcomes in a Cohort of 22,481 Breast Cancer Survivors.

PURPOSE: As health inequities during the pandemic have been magnified, we evaluated how use of SARS-CoV-2 testing differed by race or ethnicity in a large cohort of breast cancer survivors and examined the correlates of testing positive. METHODS: We conducted a retrospective cohort study of 22,481 adult breast cancer survivors who were active members of a large California integrated healthcare plan in 2020. We collected data on their breast cancer diagnosis, comorbidity, and demographic characteristics. We examined SARS-CoV-2 testing utilization between March 2020 and September 2020 by race or ethnicity, comorbidity, and other patient characteristics. We also examined the correlates of a having a positive SARS-CoV-2 test result. We conducted bivariable and multivariable logistic regression to identify correlates of testing utilization and test positivity. RESULTS: Of these 22,481 women, 3,288 (14.6%) underwent SARS-CoV-2 testing. The cohort included 51.8% women of color. Of the 3,288 tested, 264 (8.0%) women had a positive test result. In multivariable analyses, Latinx survivors were more likely (adjusted odds ratio [OR], 1.23; 95% CI, 1.12 to 1.34) to undergo testing than White survivors; however, Asian or Pacific Islander survivors were 16% less likely to get tested (adjusted OR, 0.84; 95% CI, 0.75 to 0.94). Compared to White survivors, Latinx survivors were 3.5 times (adjusted OR, 3.47; 95% CI, 2.52 to 4.77) and Asian or Pacific Islander or Other survivors were 2.2-fold (adjusted OR, 2.23; 95% CI, 1.49 to 3.34) more likely to test positive. Being overweight (adjusted OR, 1.83; 95% CI, 1.24 to 2.72) or obese (adjusted OR, 2.04; 95% CI, 1.39 to 2.98) were also strongly associated with SARS-CoV-2 positivity. CONCLUSION: Even in an integrated healthcare system, Asian or Pacific Islander patients were less likely to undergo SARS-CoV-2 testing than White survivors, but more likely to test positive. Additionally, Latinx ethnicity and high body mass index were strongly correlated with a greater odds of SARS-CoV-2 test positivity.

Healthcare Effectiveness Data and Information Set (HEDIS) measures of alcohol and drug treatment initiation and engagement among people living with the human immunodeficiency virus (HIV) and patients without an HIV diagnosis.

Background: Problematic use of alcohol and other drugs (AOD) is highly prevalent among people living with the human immunodeficiency virus (PLWH), and untreated AOD use disorders have particularly detrimental effects on human immunodeficiency virus (HIV) outcomes. The Healthcare Effectiveness Data and Information Set (HEDIS) measures of treatment initiation and engagement are important benchmarks for access to AOD use disorder treatment. To inform improved patient care, we compared HEDIS measures of AOD use disorder treatment initiation and engagement and health care utilization among PLWH and patients without an HIV diagnosis. Methods: Patients with a new AOD use disorder diagnosis documented between October 1, 2014, and August 15, 2015, were identified using electronic health records (EHR) and insurance claims data from 7 health care systems in the United States. Demographic characteristics, clinical diagnoses, and health care utilization data were also obtained. AOD use disorder treatment initiation and engagement rates were calculated using HEDIS measure criteria. Factors associated with treatment initiation and engagement were examined using multivariable logistic regression models. Results: There were 469 PLWH (93% male) and 86,096 patients without an HIV diagnosis (60% male) in the study cohort. AOD use disorder treatment initiation was similar in PLWH and patients without an HIV diagnosis (10% vs. 11%, respectively). Among those who initiated treatment, few engaged in treatment in both groups (9% PLWH vs. 12% patients without an HIV diagnosis). In multivariable analysis, HIV status was not significantly associated with either AOD use disorder treatment initiation or engagement. Conclusions: AOD use disorder treatment initiation and engagement rates were low in both PLWH and patients without an HIV diagnosis. Future studies need to focus on developing strategies to efficiently integrate AOD use disorder treatment with medical care for HIV.

Novel tumor markers provide improved prediction of survival after diagnosis of human immunodeficiency virus (HIV)-related diffuse large B-cell lymphoma.

Existing prognostic tools for HIV + diffuse large B-cell lymphoma (DLBCL) fail to accurately predict patient outcomes. To develop a novel prognostic algorithm incorporating molecular tumor characteristics and HIV disease factors, we included 80 patients with HIV-related DLBCL diagnosed between 1996 and 2007. Immunohistochemistry staining was used to analyze the expression of 26 tumor markers. Clinical data were collected from medical records. Logistic regression and bootstrapping were used to select and assess stability of the prognostic model, respectively. Of the tumor markers examined, expression of cMYC, Ki 67, CD44, EBV, SKP2, BCL6, p53, CD20 and IgM were associated with two-year mortality. The final prognostic model, confirmed in bootstrapped samples, included IPI, circulating CD4 cell count, history of clinical AIDS, and expression of CD44, p53, IgM and EBV. This model incorporating HIV disease history and tumor markers, achieved better prediction for two-year mortality [AUC = 0.87, 95% CI: 0.78-0.96] compared with IPI alone [AUC = 0.63 (0.51-0.75)].

Stromal immune infiltration in HIV-related diffuse large B-cell lymphoma is associated with HIV disease history and patient survival.

OBJECTIVE: Understanding tumor microenvironment and its impact on prognosis of HIV-related lymphomas may provide insight into novel therapeutic strategies. DESIGN: We characterized the relationship between infiltrating immune cells with tumor characteristics, HIV disease history and survival in 80 patients with HIV-related diffuse large B-cell lymphoma (DLBCL) diagnosed in the era of combined antiretroviral therapy (1996-2007) at Kaiser Permanente California. Eighty patients with HIV-unrelated DLBCL were included for comparison. METHODS: Data on patients' clinical history were obtained from Kaiser Permanente's electronic health records. The density of stromal CD4, CD8 and FOXP3 T cells and CD68 macrophages, as well as tumor molecular characteristics were examined using immunohistochemistry. The associations between stromal immune infiltration and patient's clinical history or tumor characteristics were examined using Kruskal-Wallis tests or Pearson's correlation coefficient. The effect of stromal immune infiltration on 2-year mortality was evaluated in multivariable logistic regression. RESULTS: Compared with HIV-unrelated DLBCL, patients with HIV-related DLBCL had significantly reduced stromal CD4 and FOXP3 T cells, but increased density of macrophages. Increased density of stromal macrophages was correlated with lower circulating CD4 cell count at DLBCL diagnosis. Tumor molecular characteristics, including BCL6, p53 and cMYC expression, but not Epstein-Barr virus infection status, were significantly correlated with stromal immune infiltration, particularly FOXP3 T cells. A higher density of infiltrating CD8 T cell was significantly associated with reduced mortality in patients with HIV-related DLBCL (odds ratio = 0.30 [0.09-0.97] for ≥25 vs. <10%). CONCLUSION: These data provide evidence for the prognostic significance of cytotoxic T cells in determining outcomes of HIV-related lymphoma.

A comparative study of molecular characteristics of diffuse large B-cell lymphoma from patients with and without human immunodeficiency virus infection.

PURPOSE: HIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically different from DLBCL in the general population. We compared, by HIV status, the expression and prognostic significance of selected oncogenic markers in DLBCL diagnosed at Kaiser Permanente in California, between 1996 and 2007. EXPERIMENTAL DESIGN: Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected DLBCL patients by age, gender, and race. Twenty-three markers in the following categories were examined using IHC: (i) cell-cycle regulators, (ii) B-cell activators, (iii) antiapoptotic proteins, and (iv) others, such as IgM. Tumor marker expression was compared across HIV infection status by Fisher exact test. For markers differentially expressed in HIV-related DLBCL, logistic regression was used to evaluate the association between tumor marker expression and 2-year overall mortality, adjusting for International Prognostic Index, cell-of-origin phenotype, and DLBCL morphologic variants. RESULTS: Expression of cMYC (% positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%), PKC-ß2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) was significantly elevated in HIV-related DLBCLs, whereas expression of p27 (39% vs. 75%) was significantly reduced. Of these, cMYC expression was independently associated with increased 2-year mortality in HIV-infected patients [relative risk = 3.09 (0.90-10.55)] in multivariable logistic regression. CONCLUSIONS: These results suggest that HIV-related DLBCL pathogenesis more frequently involves cMYC and BCL6 among other factors. In particular, cMYC-mediated pathogenesis may partly explain the more aggressive clinical course of DLBCL in HIV-infected patients.

Implantable defibrillators for secondary prevention of sudden cardiac death in cardiac surgery patients with perioperative ventricular arrhythmias.

BACKGROUND: Randomized studies of implantable cardioverter defibrillators (ICD) have excluded sudden cardiac death survivors who had revascularization before or after an arrhythmic event. To evaluate the role of ICD and the effects of clinical variables including degree of revascularization, we studied cardiac surgery patients who had an ICD implanted for sustained perioperative ventricular arrhythmias. METHODS AND RESULTS: The electronic database for Southern California Kaiser Foundation hospitals was searched for patients who had cardiac surgery between 1999 and 2005 and an ICD implanted within 3 months of surgery. One hundred sixty-four patients were identified; 93/164 had an ICD for sustained pre- or postoperative ventricular tachycardia or fibrillation requiring resuscitation. Records were reviewed for the following: presenting arrhythmia, ejection fraction, and degree of revascularization. The primary end point was total mortality (TM) and/or appropriate ICD therapy (ICD-T), and secondary end points are TM and ICD-T. During the mean follow up of 49 months, the primary endpoint of TM+ICD-T and individual end points of TM and ICD-T were observed in 52 (56%), 35 (38%), and 28 (30%) patients, respectively, with 55% of TM, and 23% of ICD-T occurring within 2 years of implant. In multivariate risk analysis, none of the following was associated with any of the end points: incomplete revascularization, presenting ventricular arrhythmia, and timing of arrhythmias. CONCLUSION: Our data supports the recent guidelines for ICD in this cohort of patients, as the presence of irreversible substrate and triggers of ventricular arrhythmias, cannot be reliably excluded even with complete revascularization. Further studies are needed to understand this complex group of patients.

The accuracy and trends of smoking history documentation in electronic medical records in a large managed care organization.

The accuracy of smoking history documentation in the electronic medical records was examined at a large managed care organization among 36,494 male members who self-reported smoking history in mailed surveys. The sensitivity of electronic smoking history documentation for ever-smoking status was 0.19 in years 2003-2005 (using ICD-9/CPT code only), 0.80 in 2006-2008 and 0.84 in 2009-2010 (combination of ICD-9/CPT codes and risk factor module used after 2006). The positive predictive value was 0.96, 0.90, and 0.95 in these periods, respectively. Among self-reported ever-smokers, increased healthcare utilization and smoking intensity/duration were associated with higher likelihood of having electronic smoking history documentation, while Asian race and Spanish language preference were associated with lower likelihood. These data suggest that enhanced efforts may be needed to screen for and document smoking among racial/ethnic minorities.