The Kaiser Permanente Research Bank Cancer Cohort: a collaborative resource to improve cancer care and survivorship.

BACKGROUND: The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and surveys linked to electronic health records (EHR) from approximately 400,000 adult KP members. Within the KPRB, we developed a Cancer Cohort to address issues related to cancer survival, and to understand how genetic, lifestyle and environmental factors impact cancer treatment, treatment sequelae, and prognosis. We describe the Cancer Cohort design and implementation, describe cohort characteristics after 5 years of enrollment, and discuss future directions. METHODS: Cancer cases are identified using rapid case ascertainment algorithms, linkage to regional or central tumor registries, and direct outreach to KP members with a history of cancer. Enrollment is primarily through email invitation. Participants complete a consent form, survey, and donate a blood or saliva sample. All cancer types are included. RESULTS: As of December 31, 2020, the cohort included 65,225 cases (56% female, 44% male) verified in tumor registries. The largest group was diagnosed between 60 and 69 years of age (31%) and are non-Hispanic White (83%); however, 10,076 (16%) were diagnosed at ages 18-49 years, 4208 (7%) are Hispanic, 3393 (5%) are Asian, and 2389 (4%) are Black. The median survival time is 14 years. Biospecimens are available on 98% of the cohort. CONCLUSIONS: The KPRB Cancer Cohort is designed to improve our understanding of treatment efficacy and factors that contribute to long-term cancer survival. The cohort's diversity - with respect to age, race/ethnicity and geographic location - will facilitate research on factors that contribute to cancer survival disparities.

Demographic differences in the utilization of clinical and direct-to-consumer genetic testing.

Genetic testing has increased over the last decade due to growth in the number of clinical and direct-to-consumer (DTC) tests. However, there is uncertainty about how increased DTC genetic testing affects disparities. Between November 2017 and February 2018, a nationwide electronic survey on experiences with genetic testing was conducted among adult Kaiser Permanente members. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals comparing receipt of clinical and DTC genetic testing between groups by race and ethnicity. Invitations were sent to 57,331 members, and 10,369 surveys were completed. 22% of respondents had received genetic testing (17% DTC and 5% provider-ordered). Non-Hispanic Whites were more likely than other groups to have clinical genetic testing but were similar to Hispanics and non-Hispanic Blacks in rates of DTC genetic testing. Among those who received any health-related genetic test, 10% reported abnormal results. Of these, non-Hispanic Whites were more likely than other racial/ethnic groups to speak to a medical professional about abnormal results. Results suggest that racial/ethnic disparities in the use of clinical genetic services persist. Additional research is needed to identify lessons learned from DTC genetic testing that may increase equity in the use of clinical genetic services.

Perceptions of the appropriateness of care in California adult intensive care units.

INTRODUCTION: Increased demand for expensive intensive care unit (ICU) services may contribute to rising health-care costs. A focus on appropriate use may offer a clinically meaningful way of finding the balance. We aimed to determine the extent and characteristics of perceived inappropriate treatment among ICU doctors and nurses, defined as an imbalance between the amount or intensity of treatments being provided and the patient's expected prognosis or wishes. METHODS: This was a cross-sectional study of doctors and nurses providing care to patients in 56 adult ICUs in California between May and August 2013. In total, 1,363 doctors and nurses completed an anonymous electronic survey. RESULTS: Thirty-eight percent of 1,169 respondents (95% confidence interval (CI) 35% to 41%, 51.1% of physicians and 35.8% of nurses) identified at least one patient as receiving inappropriate treatment. Respondents most commonly reported that the amount of treatment provided was disproportionate to the patient's expected prognosis or wishes-325 out of 429 (76%, 95% CI 72% to 80%)--and that treatment was 'too much' in 93% of cases. Factors associated with perceived inappropriateness of treatment were the belief that death in their ICU is seen as a failure (odds ratio (OR) 5.75, 95% CI 2.28 to 14.53, P = 0.000), profession (doctors more than nurses) (OR 2.50, 95% CI 1.58 to 3.97, P = 0.000), lack of collaboration between doctors and nurses (OR 1.84, 95% CI 1.21 to 2.80, P = 0.004), intent to leave their job (OR 1.73, 95% CI 1.18 to 2.55, P = 0.005), and the perceived responsibility to control health-care costs (OR 1.57, 95% CI 1.05 to 2.33, P = 0.026). Providers supported formal communication training (90%, 95% CI 88% to 92%) and mandatory family meetings (89%, 95% CI 87% to 91%) as potential solutions to reduce the provision of inappropriate treatment. CONCLUSIONS: Doctors and nurses working in California ICUs frequently perceive treatment to be inappropriate. They also identified measures that could reduce the provision of inappropriate treatment.

Physician cost profiling--reliability and risk of misclassification.

BACKGROUND: Insurance products with incentives for patients to choose physicians classified as offering lower-cost care on the basis of cost-profiling tools are increasingly common. However, no rigorous evaluation has been undertaken to determine whether these tools can accurately distinguish higher-cost physicians from lower-cost physicians. METHODS: We aggregated claims data for the years 2004 and 2005 from four health plans in Massachusetts. We used commercial software to construct clinically homogeneous episodes of care (e.g., treatment of diabetes, heart attack, or urinary tract infection), assigned each episode to a physician, and created a summary profile of resource use (i.e., cost) for each physician on the basis of all assigned episodes. We estimated the reliability (signal-to-noise ratio) of each physician's cost-profile score on a scale of 0 to 1, with 0 indicating that all differences in physicians' cost profiles are due to a lack of precision in the measure (noise) and 1 indicating that all differences are due to real variation in costs of services (signal). We used the reliability results to estimate the proportion of physicians in each specialty whose cost performance would be classified inaccurately in a two-tiered insurance product in which the physicians with cost profiles in the lowest quartile were labeled as "lower cost." RESULTS: Median reliabilities ranged from 0.05 for vascular surgery to 0.79 for gastroenterology and otolaryngology. Overall, 59% of physicians had cost-profile scores with reliabilities of less than 0.70, a commonly used marker of suboptimal reliability. Using our reliability results, we estimated that 22% of physicians would be misclassified in a two-tiered system. CONCLUSIONS: Current methods for profiling physicians with respect to costs of services may produce misleading results.

Comparing Kaiser Permanente Members to the General Population: Implications for Generalizability of Research.

Introduction Insight into the characteristics of populations from which research samples are drawn is essential to understanding the generalizability of research findings. This study characterizes the membership of Kaiser Permanente and compares members to the population of the communities in which they live. Methods This study is a descriptive comparison of population distributions for Kaiser Permanente members vs the general population within counties in which Kaiser Permanente operates. Kaiser Permanente data on demographics, membership, geographically linked census data, and chronic condition prevalence were compared with community data drawn from the US Census and the Behavioral Risk Factor Surveillance System. Results Overall, Kaiser Permanente members were older (50% aged 40 or older compared to 45.8% of the general population) and more likely to be female (51.8% vs 50.5% of the general population). Distribution by race and ethnicity was similar for all Regions combined but varied somewhat within Regions. Distribution by neighborhood-linked income, education, and social vulnerability was similar between Kaiser Permanente and the community. Prevalence of 6 of 7 chronic conditions was higher in the community than in Kaiser Permanente, with differences ranging from 0.5% for depression to 7.7% for hyperlipidemia. Conclusion The demographic characteristics of Kaiser Permanente members are similar to the general population within each of the Kaiser Permanente Regions. Overall, the size and diversity of the Kaiser Permanente membership offers an effective platform for research. This approach to comparing health system members with the larger community provides valuable context for interpreting real-world evidence, including understanding the generalizability of research and of measures of system performance.

CareTrack: assessing the appropriateness of health care delivery in Australia.

OBJECTIVE: To determine the percentage of health care encounters at which a sample of adult Australians received appropriate care (ie, care in line with evidence-based or consensus-based guidelines). DESIGN, SETTING AND PARTICIPANTS: Computer-assisted telephone interviews and retrospective review of the medical records (for 2009-2010) of a sample of at least 1000 Australian adults to measure compliance with 522 expert consensus indicators representing appropriate care for 22 common conditions. Participants were selected from households in areas of South Australia and New South Wales chosen to be representative of the socioeconomic profile of Australians. Health care encounters occurred in health care practices and hospitals with general practitioners, specialists, physiotherapists, chiropractors, psychologists and counsellors. MAIN OUTCOME MEASURE: Percentage of health care encounters at which the sample received appropriate care. RESULTS: From 15 292 households contacted by telephone, 7649 individuals agreed to participate, 3567 consented, 2638 proved eligible, and 1154 were included after gaining the consent of their health care providers. The adult Australians in this sample received appropriate care at 57% (95% CI, 54%-60%) of 35 573 eligible health care encounters. Compliance with indicators of appropriate care at condition level ranged from 13% (95% CI, 1%-43%) for alcohol dependence to 90% (95% CI, 85%-93%) for coronary artery disease. For health care providers with more than 300 eligible encounters each, overall compliance ranged from 32% to 86%. CONCLUSIONS: Although there were pockets of excellence and some aspects of care were well managed across health care providers, the consistent delivery of appropriate care needs improvement, and gaps in care should be addressed. There is a need for national agreement on clinical standards and better structuring of medical records to facilitate the delivery of more appropriate care.

The distillation method: A novel approach for analyzing randomized trials when exposure to the intervention is diluted.

OBJECTIVE: To introduce a novel analytical approach for randomized controlled trials that are underpowered because of low participant enrollment or engagement. DATA SOURCES: Reanalysis of data for 805 patients randomized as part of a pilot complex care intervention in 2015-2016 in a large delivery system. In the pilot randomized trial, only 64.6% of patients assigned to the intervention group participated. STUDY DESIGN: A case study and simulation. The "Distillation Method" capitalizes on the frequently observed correlation between the probability of subjects' participation or engagement in the intervention and the magnitude of benefit they experience. The novel method involves three stages: first, it uses baseline covariates to generate predicted probabilities of participation. Next, these are used to produce nested subsamples of the randomized intervention and control groups that are more concentrated with subjects who were likely to participate/engage. Finally, for the outcomes of interest, standard statistical methods are used to re-evaluate intervention effectiveness in these concentrated subsets. DATA EXTRACTION METHODS: We assembled secondary data on patients who were randomized to the pilot intervention for one year prior to randomization and two follow-up years. Data included program enrollment status, membership data, demographics, utilization, costs, and clinical data. PRINCIPAL FINDINGS: Using baseline covariates only, Generalized Boosted Regression Models predicting program enrollment performed well (AUC 0.884). We then distilled the full randomized sample to increasing levels of concentration and reanalyzed program outcomes. We found statistically significant differences in outpatient utilization and emergency department utilization (both follow-up years), and in total costs (follow-up year two only) at select levels of population concentration. CONCLUSIONS: By offering an internally valid analytic framework, the Distillation Method can increase the power to detect effects by redefining the estimand to subpopulations with higher enrollment probabilities and stronger average treatment effects while maintaining the original randomization.

"A Gift to My Family for Their Future": Attitudes about Genetic Research Participation.

BACKGROUND: Broad participation in genetic research is needed to promote equitable advances in disease treatment and prevention. OBJECTIVES: The objective of the study was to assess motivations for, and concerns about, genetic research participation. METHODS: The Genetics in Research and Health Care Survey was sent in winter 2017-2018 to 57,331 adult Kaiser Permanente (KP) members from 7 US regions to assess attitudes about genetic testing in health care and research. The survey included an open-ended question on why members would or would not participate in genetic research. Open text responses to this question were coded in the qualitative analysis software Dedoose and analyzed using a thematic analysis approach. Code summaries were organized by major themes, subthemes, and exemplary quotes. RESULTS: Of the 10,369 participants who completed the survey, 2,645 (25%) provided a comment describing reasons they would or would not participate in research involving genetic testing. Respondents who provided a text comment were 64% female, 49% non-Hispanic (NH) White, 17% Asian/Pacific Islander, 20% Hispanic, and 14% NH Black. The primary themes identified were (1) altruism; (2) decision-making and planning; (3) data use; and (4) data security. These major themes were consistent across each race and ethnic group. CONCLUSIONS: To promote broad participation in genetic research, it is important that recruitment materials address the primary motivators for genetic research participation, including altruism and the potential use of results for personal decision-making. Study materials should also address concerns about possible misuse of genetic information and fears over potential data breaches.

Population-Based Incidence of New Ampicillin, Cephalexin, Cefaclor, and Sulfonamide Antibiotic "Allergies" in Exposed Individuals with and without Preexisting Ampicillin, Cephalexin, or Cefaclor "Allergies".

BACKGROUND: There is a theoretical concern, unconfirmed by population-based challenge data, that clinically significant, immunologically mediated hypersensitivity occurs among ß-lactams sharing side chains. OBJECTIVE: To determine the population-based allergy incidence associated with the use of ß-lactams sharing exact R1 side chains (ampicillin, cephalexin, and cefaclor [ACC]), with or without a current ACC allergy or a sulfonamide antibiotic allergy for comparison. METHODS: All courses of ACC and trimethoprim-sulfamethoxazole used by any Kaiser Permanente California members in 2017 and 2018, with follow-up through January 2019, were identified along with their preexisting antibiotic allergy status and all new antibiotic-specific allergies reported within 30 days of course initiation. RESULTS: A total of 1,167,713 courses of ACC were administered to individuals with no sulfonamide antibiotic or ACC allergy and 4,771 new ACC allergies (0.41%) were reported. Moreover, 130,032 courses of ACC were administered to individuals with a sulfonamide antibiotic allergy and no ACC allergy, and 904 new ACC allergies (0.70%) were reported. There were 5,958 courses of ACC administered to individuals with an ACC allergy, 2,341 who also had sulfonamide antibiotic allergy, and 52 new ACC allergies (0.87%) were reported. CONCLUSIONS: The incidence of new ACC allergy reports is minimally and non-specifically increased among individuals with a preexisting ACC or sulfonamide antibiotic allergy compared to the baseline incidence in the population. This argues against clinically significant, immunologically mediated cross-reactivity among ß-lactams sharing exact side chains in individuals with preexisting but unconfirmed ß-lactam allergy. Any previously reported, even unrelated antibiotic allergy appears to be a risk factor for reporting a new antibiotic allergy.

Depression and medication adherence in the treatment of chronic diseases in the United States: a meta-analysis.

OBJECTIVE: To conduct a meta-analysis of the association between depression and medication adherence among patients with chronic diseases. Poor medication adherence may result in worse outcomes and higher costs than if patients fully adhere to their medication regimens. DATA SOURCES: We searched the PubMed and PsycINFO databases, conducted forward searches for articles that cited major review articles, and examined the reference lists of relevant articles. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We included studies on adults in the United States that reported bivariate relationships between depression and medication adherence. We excluded studies on special populations (e.g., substance abusers) that were not representative of the general adult population with chronic diseases, studies on certain diseases (e.g., HIV) that required special adherence protocols, and studies on interventions for medication adherence. STUDY APPRAISAL AND SYNTHESIS METHODS: Data abstracted included the study population, the protocol, measures of depression and adherence, and the quantitative association between depression and medication adherence. Synthesis of the data followed established statistical procedures for meta-analysis. RESULTS: The estimated odds of a depressed patient being non-adherent are 1.76 times the odds of a non-depressed patient, across 31 studies and 18,245 participants. The association was similar across disease types but was not as strong among studies that used pharmacy records compared to self-report and electronic cap measures. LIMITATIONS: The meta-analysis results are correlations limiting causal inferences, and there is some heterogeneity among the studies in participant characteristics, diseases studied, and methods used. CONCLUSIONS: This analysis provides evidence that depression is associated with poor adherence to medication across a range of chronic diseases, and we find a new potential effect of adherence measurement type on this relationship. Although this study cannot assess causality, it supports the importance that must be placed on depression in studies that assess adherence and attempt to improve it.

The effect of different attribution rules on individual physician cost profiles.

BACKGROUND: Some health plans profile physicians on the basis of their relative costs and use these profiles to assign physicians to cost categories. Physician organizations have questioned whether the rules used to attribute costs to a physician affect the cost category to which that physician is assigned. OBJECTIVE: To evaluate the effect of 12 different attribution rules on physician cost profiles. DESIGN: Under each of the 12 attribution rules, a cost profile was created for the physicians in the aggregated claims database and the physicians were assigned to a cost category (high cost, average cost, low cost, or low sample size). The attribution rules differed by unit of analysis, signal for responsibility, number of physicians who can be assigned responsibility, and threshold value for assigning responsibility. SETTING: Four commercial health plans in Massachusetts. PATIENTS: 1.1 million adults continuously enrolled in 4 commercial health plans in 2004 and 2005. MEASUREMENTS: Percentage of all episodes assigned to any physician and percentage of costs billed by a physician that were included in his or her own profile were calculated under each rule. The cost category assignments from a commonly used default rule were compared with those from each of the other 11 attribution rules and the rate of disagreement was calculated. RESULTS: Percentage of episodes that could be assigned to a physician varied substantially across the 12 rules (range, 20% to 69%), as did the mean percentage of costs billed by a physician that were included in that physician's own cost profile (range, 13% to 60%). Depending on the alternate rule used, between 17% and 61% of physicians would be assigned to a different cost category than that assigned by using the default rule. LIMITATION: Results might differ if data from another state or from Medicare were used. CONCLUSION: The choice of attribution rule affects how costs are assigned to a physician and can substantially affect the cost category to which a physician is assigned. PRIMARY FUNDING SOURCE: U.S. Department of Labor.

Increasing Equity While Improving the Quality of Care: JACC Focus Seminar 9/9.

This review summarizes racial and ethnic disparities in the quality of cardiovascular care-a challenge given the fragmented nature of the health care delivery system and measurement. Health equity for all racial and ethnic groups will not be achieved without a substantially different approach to quality measurement and improvement. The authors adapt a tool frequently used in quality improvement work-the driver diagram-to chart likely areas for diagnosing root causes of disparities and developing and testing interventions. This approach prioritizes equity in quality improvement. The authors demonstrate how this approach can be used to create interventions that reduce systemic racism within the institutions and professions that deliver health care; attends more aggressively to social factors related to race and ethnicity that affect health outcomes; and examines how hospitals, health systems, and insurers can generate effective partnerships with the communities they serve to achieve equitable cardiovascular outcomes.

Association Between Removal of a Warning Against Cephalosporin Use in Patients With Penicillin Allergy and Antibiotic Prescribing.

Importance: Electronic health records (EHRs) often include default alerts that can influence physician selection of antibiotics, which in turn may be associated with a suboptimal choice of agents and increased antibiotic resistance. Objective: To examine whether removal of a default alert in the EHR to avoid cephalosporin use in patients with penicillin allergies is associated with changes in cephalosporin dispensing or administration in these patients. Design, Setting, and Participants: This retrospective cohort study of a natural experiment included data on patients who had received antibiotic treatment in the hospital or outpatient setting in 2 regions of a large, integrated health system in California from January 1, 2017, to December 31, 2018. Of 4 398 792 patients, 4 206 480 met the eligibility criteria: enrollment in the health system during antibiotic use, availability of complete demographic data, and use of antibiotics outside of the washout period. Interventions or Exposures: Oral or parenteral antibiotics dispensed or administered after removal of an EHR alert to avoid cephalosporin use in patients with a recorded penicillin allergy. Main Outcomes and Measures: Probability that an antibiotic course was a cephalosporin. A multinomial logistic regression model was used to examine the change in rates of cephalosporin use before and after an EHR penicillin allergy alert was removed in 1 of the study regions. Temporal changes in use rates were controlled for by comparing changes in cephalosporin use among patients with or without a penicillin allergy at the site that removed the warning and among patients at a comparison site that retained the warning. Regression models were used to examine adverse events. Results: Of the 4 206 480 patients who met all inclusion criteria, 2 465 849 (58.6%) were women; the mean (SD) age was 40.5 (23.2) years. A total of 10 652 014 antibiotic courses were administered or dispensed, divided approximately evenly between the period before and after removal of the warning. Before removal of an alert in the electronic health record system to avoid prescribing of cephalosporins to patients with a penicillin allergy at 1 of the 2 sites, 58 228 courses of cephalosporins (accounting for 17.9% of all antibiotic use at the site) were used among patients with a penicillin allergy; after removal of the alert, administration or dispensing of cephalosporins increased by 47% compared with cephalosporin administration or dispensing among patients without a penicillin allergy at the same site and patients at the comparison site that retained the warning (ratio of ratios of odds ratios [RROR], 1.47; 95% CI, 1.38-1.56) . No significant differences in anaphylaxis (9 total cases), new allergies (RROR, 1.02; 95% CI, 0.93-1.12), or treatment failures (RROR, 1.02; 95% CI, 0.99-1.05) were found at the course level. No significant differences were found in all-cause mortality (ratio of ratios of rate ratios [RRRR], 1.03; 95% CI, 0.94-1.13), hospital days (RRRR, 1.04; 95% CI, 0.99-1.10), and new infections (Clostridioides difficile: RRRR, 1.02; 95% CI, 0.84-1.22; methicillin-resistant Staphylococcus aureus: RRRR, 0.87; 95% CI, 0.75-1.00; and vancomycin-resistant Enterococcus: RRRR, 0.82; 95% CI, 0.55-1.22) at the patient level. Conclusions and Relevance: In this cohort study, removal of a warning in the electronic health record to avoid cephalosporin use in patients with penicillin allergies was associated with increased administration and dispensing of cephalosporin. This simple and rapidly implementable system-level intervention may be useful for improvement in antibiotic stewardship.

Relationship between number of medical conditions and quality of care.

BACKGROUND: There is emerging concern that the methods used to measure the quality of care unfairly penalize providers caring for patients with multiple chronic conditions. We therefore sought to study the relationship between the quality of care and the number of medical conditions a patient has. METHODS: We assessed measurements of the quality of medical care received in three cohorts of community-dwelling adult patients in the Community Quality Index study, the Assessing Care of Vulnerable Elders study, and the Veterans Health Administration project (7680 patients in total). We analyzed the relationship between the quality of care that patients received, defined as the percentage of quality indicators satisfied among those for which patients were eligible, and the number of chronic medical conditions each patient had. We further explored the roles of characteristics of patients, use of health care (number of office visits and hospitalizations), and care provided by specialists as explanations for the observed relationship. RESULTS: The quality of care increased as the number of medical conditions increased. Each additional condition was associated with an increase in the quality score of 2.2% (95% confidence interval [CI], 1.7 to 2.7) in the Community Quality Index cohort, of 1.7% (95% CI, 1.1 to 2.4) in the Assessing Care of Vulnerable Elders cohort, and of 1.7% (95% CI, 0.7 to 2.8) in the Veterans Health Administration cohort. The relationship between the quality of care and the number of conditions was little affected by adjustment for the difficulty of delivering the care recommended in a quality indicator and for the fact that, because of multiple conditions requiring the same care, a patient could be eligible to receive the same care process more than once. Adjustment for characteristics of patients, use of health care, and care provided by specialists diminished the relationship, but it remained positive. CONCLUSIONS: The quality of care, measured according to whether patients were offered recommended services, increases as a patient's number of chronic conditions increases.