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The Pooled Cohort Equations (PCEs) do not accurately estimate atherosclerotic cardiovascular disease (ASCVD) risk in certain populations. The 2018 AHA/ACC cholesterol guideline identified risk-enhancing factors as a supplement to PCEs-based risk assessment. However, the role of each risk-enhancing factor in ASCVD risk assessment has not been well quantified. Further, social determinants of health (SDOH) are not included in the PCEs nor considered as risk-enhancing factors in the US cholesterol guideline. We sought to evaluate ASCVD risk associated with each risk-enhancing factor and commonly collected SDOH including education, income, and employment status, and to assess if adding risk-enhancing factors and SDOH to the PCEs improve ASCVD risk prediction. We included individuals aged 40 to 75 years, without ASCVD or diabetes at baseline, and with low-density lipoprotein cholesterol 70-189 mg/dL from two contemporary prospective cohort studies (MESA and REGARDS) and from Kaiser Permanente Southern California (KPSC). The primary endpoint was incident ASCVD defined as nonfatal myocardial infarction, fatal coronary heart disease, or fatal or nonfatal stroke over a 10-year period (median follow-up 10 years). We used Cox proportional hazards models to estimate associations between risk-enhancing factors and SDOH with ASCVD. We also assessed changes in model performance after adding risk-enhancing factors and SDOH to the PCEs. We included 13,863 adults (mean age 60.7 years) from the prospective cohorts and 307,931 adults (mean age 54.8 years) from KPSC. Risk-enhancing factors including hypercholesterolemia, hypertriglyceridemia, metabolic syndrome, and chronic kidney disease were associated with a higher ASCVD risk, independent of 10-year risk estimated by the PCEs. Low education, low income, and unemployment were also associated with higher ASCVD risk. While adding individual risk-enhancing factors or SDOH to the PCEs had limited impact on model performance, adding multiple risk-enhancing factors and SDOH simultaneously led to modest improvements in discrimination (C-index increased by up to 0.07), calibration (integrated Brier score reduced by up to 2.3%), and net reclassification improvement up to 41.4%. These findings suggest including SDOH and risk-enhancing factors may improve ASCVD risk assessment.

The effectiveness of bisphosphonates (BP) in reducing risk of second breast cancer and recurrence in observational studies has been minimally studied. We examined the association of oral BP use on risk of contralateral breast cancer (CBC) and recurrence in 16,781 women diagnosed with early-stage breast cancer from 1996 to 2007, treated with tamoxifen, and followed through December 31, 2009 at Kaiser Permanente Northern California (KPNC, n  = 8857) and Southern California (KPSC, n  = 7924). Sociodemographic, clinical, and pharmacy information were extracted from electronic medical records and cancer registries. CBC was identified from cancer registries, and recurrences from electronic health records and chart reviews. Multivariate Cox regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) treating BP use and hormonal therapy as time-varying variables. After mean 6.4 years of follow-up, 494 (3.0 %) women developed CBC. BP use post-breast cancer diagnosis (>93 % alendronate) ranged from 14.5 to 24.9 % at both study sites. Overall, there was no association of BP use with reduced risk of CBC (ever use, HR = 0.96; 95 % CI 0.67–1.38 and continuous use, HR = 1.03; 95 % CI 0.88, 1.20). Similar null associations were observed for recurrence (ever use, HR = 0.98; 95 % CI 0.82, 1.17 and continuous use, HR = 1.00; 95 % CI 0.92, 1.09). Associations varied somewhat by site yet confidence intervals overlapped. BP use was not associated with reduced risk of recurrence or new primary disease among women diagnosed with early breast cancer and treated with tamoxifen.

Background The utility of procalcitonin (PCT)-guided algorithms to decrease antibiotic use has been extensively studied in clinical trials. The guidance that PCT provides as it translates into real-world practice is unclear. This study aims to describe real-world antibiotic prescribing practices in relation to PCT in patients admitted to our US-based health system with acute respiratory infections. Methods Retrospective cohort study of 1,606 adults admitted within our US health system from January 1, 2016 to December 31, 2018 with a primary diagnosis of acute upper or lower respiratory infection with at least one PCT measurement. Antibiotic practice patterns were evaluated using pharmacy analytic information and antibiotic status to note antibiotics given prior to and 36 hours after PCT result. Analysis of discordance with initial PCT level was defined as continuing or starting antibiotics after a low PCT level (PCT ≤0.25 μg/L) and withholding or discontinuing antibiotics after a high PCT level (PCT > 0.25 μg/L). Results Antibiotic prescription patterns after the result of initial PCT level are summarized in Table 1. Only 242 patients (15%) had more than one PCT-level checked. Overall, antibiotic discordance with initial PCT result was 45%; mostly attributed to continuing or starting antibiotics despite a low PCT level (77%). (Figure 1) There were 496 patients who were initially started and continued on antibiotics despite a low PCT result. Of this subgroup, only one patient had a serial PCT measured, and 12 were admitted for Chronic Obstructive Pulmonary Disease (COPD) exacerbation and continued on azithromycin/doxycycline after result of the low PCT. Conclusion Utilization of antibiotics went against well-studied PCT cutoffs 45% of the time, primarily driven by antibiotic use at low PCT levels. Only a small number were continued on azithromycin/doxycycline for anti-inflammatory effect in COPD exacerbations, indicating that most patients received antibiotics for presumed bacterial infection despite the high negative predictive value of PCT. This study illustrates PCT use in real-world practice did not significantly alter prescribing practices, potentially from lack of confidence or knowledge in interpreting PCT results and lack of serial measurements to aid in decision-making. Disclosures All authors: No reported disclosures.

Purpose We evaluated the influence of race/ethnicity and geocoded socioeconomic status (SES) on all-cause mortality in cancer patients with health insurance. Methods We identified adults diagnosed with eight common cancers from 2009 to 2014 from the California Cancer Registry and followed them through 2017 (8 years maximum). We calculated person-year mortality rates by race/ethnicity and SES. Adjusted hazard ratios for the association between overall mortality and race/ethnicity and SES were estimated using Cox proportional hazards models accounting for other demographics, stage at diagnosis, and cancer treatments. Results A total of 164,197 adults were diagnosed with cancer originating from breast, prostate, lung, colon, skin melanoma, uterus, kidney, and bladder. For all race/ethnic groups combined, the mortality rates from lowest to highest SES groups were 112.1/1000 PY (lowest); 100.2/1000 PY (lower-middle); 91.2/1000 PY (middle); 79.1/1000 PY (upper-middle); and 63.5/1000 PY (upper). These rates suggest that person with lowest SES have a markedly increased mortality risk after cancer diagnosis even if they have health insurance. In multivariable analyses, those in the lowest SES group had a 40–78% increased risk of all-cause mortality compared to those in the upper SES group across all race/ethnicities. For example, within African Americans, the adjusted mortality risk was up to 61% higher (HR 1.61, 95% CI 1.41–1.83) in the lowest SES group compared to the highest SES group. Conclusion This study suggests disparities in overall mortality risk after cancer diagnoses persist even in a cohort with health insurance, and that SES is an important driver of this disparity.

BackgroundThis study evaluates associations of commonly co-occurring childhood adversities with physical violence in dating relationships to identify potential strategies for refining and targeting dating violence prevention programmes.MethodsData on 5130 adult respondents to a nationally representative survey with at least one dating relationship before the age of 21 years were analysed. Logistic regression models assessed associations between 12 childhood adversities and physical dating violence (PDV).ResultsAdjusting for the number of co-occurring adversities, 10 of the 12 childhood adversities were significantly associated with PDV perpetration or victimisation (OR 1.5–2.8). The population attributable risk proportion of PDV due to all 12 childhood adversities was 53.4%. Childhood adversities with the highest attributable risk proportions were sexual abuse (13.8%), interparental violence (11.6%) and parent mental illness (10.7%). Multivariate prediction equations ranked respondents by their childhood adversity risk profiles; 46.4% of PDV cases occurred in the top two risk deciles.ConclusionsAssessment of a broad range of childhood exposures to familial adversities may help to identify adolescents at particularly high risk of PDV and to guide prevention efforts.

We compared all-cause mortality in insured patients with cancer who were diagnosed in Kaiser Permanente Southern California (KPSC), the largest integrated health care delivery system in southern California, with that in patients diagnosed in hospitals that serve other private insurance (OPI) plans. Retrospective cohort study. Using the California Cancer Registry, we conducted a cohort analysis of all insured adults diagnosed between 2009 and 2014 with 8 common cancers (breast, prostate, lung, colon, melanoma, endometrium, kidney, and bladder) and followed them through December 2017. The cohort comprised 164,197 patients with cancer. We calculated person-year mortality rates by health care system (KPSC and OPI), and we estimated adjusted HRs for the association between overall mortality and health care system using Cox proportional hazards models accounting for race/ethnicity, demographics, cancer site, tumor characteristics, payer, cancer treatments, and socioeconomic status. We observed 41,727 deaths during the 9 years of follow-up. We found that the patients diagnosed in KPSC had lower overall mortality rates than in the OPI group, a difference that also held within each age category, racial/ethnic group, and stage at diagnosis. In multivariable models adjusting for relevant covariates, African American/Black patients (adjusted HR, 1.14; 95% CI, 1.06-1.21) and Hispanic patients (adjusted HR, 1.23; 95% CI, 1.16-1.30) in the OPI group had dramatically higher mortality risks than those diagnosed in KPSC. Among insured patients with cancer in southern California, those diagnosed within KPSC had lower overall mortality compared with the OPI group. Furthermore, this protective effect was greatest for African American/Black patients and Hispanic patients.

Purpose: American Joint Committee on Cancer (AJCC) Tumor (T), Nodal (N), and Metastatic (M) staging is commonly used in clinical practice for treatment decisions, yet before 2004, Surveillance Epidemiology and End Results (SEER)-affiliated cancer registries did not routinely include TNM staging defined by AJCC criteria, reporting instead SEER Summary Staging. Methods: We developed and validated an algorithm to determine AJCC TNM staging from Extent of Disease information for 17,133 female breast cancer cases diagnosed from 1988 to 2003 in the cancer registries of Kaiser Permanente Northern and Southern California. Test characteristics (percent agreement, Cohen's kappa, sensitivity, specificity) were calculated to compare derived TNM with gold-standard TNM available in the registry. Results: Agreement for TNM variables was excellent (range 0.91-1.00 for percent agreement and Cohen's kappa). The sensitivity and specificity, respectively, of the algorithm for AJCC TNM Version 6 staging were as follows: Stage 0 (0.99, 1.00), Stage I (0.97, 0.98), Stage II (0.91, 0.96), Stage III (0.69, 0.99), and Stage IV (0.92, 1.00). Stage III had lower sensitivity due to reclassification of supraclavicular lymph node positivity from M1 (Stage IV) to N3 (Stage IIIC) in AJCC Version 6. Conclusions: Derived AJCC staging for breast tumors diagnosed before 2004 is feasible and accurate using cancer registry data.

The COVID-19 pandemic necessitated a rapid adoption of telehealth (TH); however, its safety in subspecialty clinical practice remains uncertain. To assess the clinical outcomes associated with TH use in patients with coronary artery disease and/or heart failure during the initial phase of the COVID-19 pandemic, eligible adult patients who saw cardiologists from March 1, 2020, to August 31, 2020 (TH period) were identified. Patients were divided into two 3-month subcohorts (TH1, TH2) and compared with corresponding 2019 prepandemic subcohorts. The primary outcome was cardiovascular (CV) events within 3 months after index visits. Secondary analysis was CV events in patients aged ≥75 years within 3-month follow-up associated with TH use. Multivariable logistic regression was used to evaluate the association between TH use and CV outcomes. The study cohort included 6,485 TH and 7,557 prepandemic patients. The mean age was 70 years, with 40% of patients aged ≥75 years and 35% women. TH visits accounted for 0% of visits during the prepandemic period, compared with 68% during the TH period. Telephone visits comprised ≥92% of all TH encounters. Compared with the prepandemic period, patients seen during the TH period had fewer overall CV events (adjusted odds ratio 0.78, 95% confidence interval 0.67 to 0.90). Patients aged ≥75 years had similar findings (adjusted odds ratio 0.70, 95% confidence interval 0.55 to 0.89). Additional analysis of CV outcome events within 6 months after index visits showed similar findings. In conclusion, TH largely by way of telephone encounters can be safely incorporated into the ambulatory cardiology practice regardless of age.

Advances in gene sequencing of mutations related to hereditary cancers have enabled expansion of this testing to patients cared for in community clinics. Our goal was to report on the prevalence of pathogenic/likely pathogenic variants (PV/LPV) and the distribution of mutations by cancer history in a diverse cohort. We evaluated 3162 women in a large non-profit health plan who were referred for cancer genetic counseling and tested them via the same multigene cancer panel. We examined the pathogenic variant/likely pathogenic variant (PV/LPV) prevalence for 20 genes by clinical factors, demographics, and personal or family cancer history. We calculated adjusted odds ratios for the association between race/ethnicity and mutation results. The majority of women (65.4%) were referred post-breast or ovarian cancer diagnosis. The overall prevalence of any PV/LPV result was 11.7%. Overall, nearly 5.4% had BRCA1/2 mutations, while 6.3% had at least one mutation in non-BRCA genes. In the subset with any PV/LPV result, 55.0% of the total mutations were in non-BRCA genes. The distribution of mutations was similar in those with or without a personal cancer history. Latina women were somewhat less likely to have mutations in non-BRCA genes implicated with breast cancer (OR = 0.55, 95% CI 0.36–0.87). Given that 55.0% of the PV/LPV results were in genes other than BRCA1/2, regardless personal or family cancer history, the study suggests that multigene cancer panel testing may be appropriate for detecting germline mutations in a high-risk cohort in a managed care or public health setting.

Substantial variation exists in surgeon decision making. In response, multiple specialty societies have established criteria for the appropriate use of spine surgery. Yet few strategies exist to facilitate routine use of appropriateness criteria by surgeons. Behavioral science nudges are increasingly used to enhance decision making by clinicians. We sought to design \"surgical appropriateness nudges\" to support routine use of appropriateness criteria for degenerative lumbar scoliosis and spondylolisthesis. The work reflected Stage I of the NIH Stage Model for Behavioral Intervention Development and involved an iterative, multi-method approach, emphasizing qualitative methods. Study sites included two large referral centers for spine surgery. We recruited spine surgeons from both sites for two rounds of focus groups. To produce preliminary nudge prototypes, we examined sources of variation in surgeon decision making (Focus Group 1) and synthesized existing knowledge of appropriateness criteria, behavioral science nudge frameworks, electronic tools, and the surgical workflow. We refined nudge prototypes via feedback from content experts, site leaders, and spine surgeons (Focus Group 2). Concurrently, we collected data on surgical practices and outcomes at study sites. We pilot tested the refined nudge prototypes among spine surgeons, and surveyed them about nudge applicability, acceptability, and feasibility (scale 1-5, 5 = strongly agree). Fifteen surgeons participated in focus groups, giving substantive input and feedback on nudge design. Refined nudge prototypes included: individualized surgeon score cards (frameworks: descriptive social norms/peer comparison/feedback), online calculators embedded in the EHR (decision aid/mapping), a multispecialty case conference (injunctive norms/social influence), and a preoperative check (reminders/ salience of information/ accountable justification). Two nudges (score cards, preop checks) incorporated data on surgeon practices and outcomes. Six surgeons pilot tested the refined nudges, and five completed the survey (83%). The overall mean score was 4.0 (standard deviation [SD] 0.5), with scores of 3.9 (SD 0.5) for applicability, 4.1 (SD 0.5) for acceptability, and 4.0 (SD 0.5), for feasibility. Conferences had the highest scores 4.3 (SD 0.6) and calculators the lowest 3.9 (SD 0.4). Behavioral science nudges might be a promising strategy for facilitating incorporation of appropriateness criteria into the surgical workflow of spine surgeons. Future stages in intervention development will test whether these surgical appropriateness nudges can be implemented in practice and influence surgical decision making.