Hepatocellular Carcinoma in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Importance: In the US, hepatocellular carcinoma (HCC) has been the most rapidly increasing cancer since 1980, and metabolic dysfunction-associated steatotic liver disease (MASLD) is expected to soon become the leading cause of HCC. Objective: To develop a prediction model for HCC incidence in a cohort of patients with MASLD. Design, Setting, and Participants: This prognostic study was conducted among patients aged at least 18 years with MASLD, identified using diagnosis of MASLD using International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis codes; natural language processing of radiology imaging report text, which identified patients who had imaging evidence of MASLD but had not been formally diagnosed; or the Dallas Steatosis Index, a risk equation that identifies individuals likely to have MASLD with good precision. Patients were enrolled from Kaiser Permanente Northern California, an integrated health delivery system with more than 4.6 million members, with study entry between January 2009 and December 2018, and follow-up until HCC development, death, or study termination on September 30, 2021. Statistical analysis was performed during February 2023 and January 2024. Exposure: Data were extracted from the electronic health record and included 18 routinely measured factors associated with MASLD. Main Outcome and Measures: The cohort was split (70:30) into derivation and internal validation sets; extreme gradient boosting was used to model HCC incidence. HCC risk was divided into 3 categories, with the cumulative estimated probability of HCC 0.05% or less classified as low risk; 0.05% to 0.09%, medium risk; and 0.1% or greater, high risk. Results: A total of 1 811 461 patients (median age [IQR] at baseline, 52 [41-63] years; 982 300 [54.2%] female) participated in the study. During a median (range) follow-up of 9.3 (5.8-12.4) years, 946 patients developed HCC, for an incidence rate of 0.065 per 1000 person-years. The model achieved an area under the curve of 0.899 (95% CI, 0.882-0.916) in the validation set. At the medium-risk threshold, the model had a sensitivity of 87.5%, specificity of 81.4%, and a number needed to screen of 406. At the high-risk threshold, the model had a sensitivity of 78.4%, a specificity of 90.1%, and a number needed to screen of 241. Conclusions and Relevance: This prognostic study of more than 1.8 million patients with MASLD used electronic health record data to develop a prediction model to discriminate between individuals with and without incident HCC with good precision. This model could serve as a starting point to identify patients with MASLD who may need intervention and/or HCC surveillance.

Race and ethnicity and pharmacy dispensing of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes.

Background: Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) improve cardiorenal outcomes in patients with type 2 diabetes. Equitable use of SGLT2i and GLP-1 RA has the potential to reduce racial and ethnic health disparities. We evaluated trends in pharmacy dispensing of SGLT2i and GLP-1 RA by race and ethnicity. Methods: Retrospective cohort study of patients (≥18 years) with type 2 diabetes using 2014-2022 electronic health record data from six US care delivery systems. Entry was at earliest pharmacy dispensing of any type 2 diabetes medication. We used multivariable logistic regression to evaluate the association between pharmacy dispensing of SGLT2i and GLP1-RA and race and ethnicity. Findings: Our cohort included 687,165 patients (median 6 years of dispensing data; median 60 years; 0.3% American Indian/Alaska Native (AI/AN), 16.6% Asian, 10.5% Black, 1.4% Hawaiian or Pacific Islander (HPI), 31.1% Hispanic, 3.8% Other, and 36.3% White). SGLT2i was lower for AI/AN (OR 0.80, 95% confidence interval 0.68-0.94), Black (0.89, 0.86-0.92) and Hispanic (0.87, 0.85-0.89) compared to White patients. GLP-1 RA was lower for AI/AN (0.78, 0.63-0.97), Asian (0.50, 0.48-0.53), Black (0.86, 0.83-0.90), HPI (0.52, 0.46-0.57), Hispanic (0.69, 0.66-0.71), and Other (0.78, 0.73-0.83) compared to White patients. Interpretation: Dispensing of SGLT2is, and GLP-1 RAs was lower in minority group patients. There is a need to evaluate approaches to increase use of these cardiorenal protective drugs in patients from racial and ethnic minority groups with type 2 diabetes to reduce adverse cardiorenal outcomes and improve health equity. Funding: Patient-Centered Outcomes Research Institute and National Institutes of Health.

Ovarian cancer risk among older patients with stable adnexal masses.

BACKGROUND: Few studies have evaluated the risk of cancer among older patients with stable adnexal masses in community-based settings to determine the duration of observation time needed. OBJECTIVE: This study aimed to assess the ovarian cancer risk among older patients with stable adnexal masses on ultrasound. STUDY DESIGN: This was a retrospective cohort study of patients in a large community-based health system aged ≥50 years with an adnexal mass <10 cm on ultrasound between 2016 and 2020 who had at least 1 follow-up ultrasound performed ≥6 weeks after initial ultrasound. Masses were considered stable on follow-up examination if they did not exhibit an increase of >1 cm in the greatest dimension or a change in standardized reported ultrasound characteristics. Ovarian cancer risk was determined at increasing time intervals of stability after initial ultrasound. RESULTS: Among 4061 patients with stable masses, the average age was 61 years (range, 50-99), with an initial mass size of 3.8 cm (range, 0.2-9.9). With a median follow-up of 3.7 years, 11 cancers were detected, with an absolute risk of 0.27%. Ovarian cancer risk declined with longer duration of stability, from 0.73 (95% confidence interval, 0.30-1.17) per 1000 person-years at 6 to 12 weeks, 0.63 (95% confidence interval, 0.19-1.07) at 13 to 24 weeks, 0.44 (95% confidence interval, 0.01-0.87) at 25 to 52 weeks, and 0.00 (95% confidence interval, 0.00-0.00) at >52 weeks. Expressed as number needed to reimage, ongoing ultrasound imaging would be needed for 369 patients whose masses show stability at 6 to 12 weeks, 410 patients at 13 to 24 weeks, 583 patients at 25 to 52 weeks, and >1142 patients with stable masses at 53 to 104 weeks to detect 1 case of ovarian cancer. CONCLUSION: In a diverse community-based setting, among patients aged ≥50 years with an adnexal mass that was stable for at least 6 weeks after initial ultrasound, the risk of ovarian cancer was very low at 0.27%. Longer demonstrated duration of stability was associated with progressively lower risk, with no cancer cases observed after 52 weeks of stability. These findings suggest that the benefit of ultrasound monitoring of stable masses beyond 12 months is minimal and may be outweighed by potential risks of repeated imaging.

Prenatal detection rates for congenital heart disease using abnormal obstetrical screening ultrasound alone as indication for fetal echocardiography.

OBJECTIVE: To determine the live born prenatal detection rate of significant congenital heart disease (CHD) in a large, integrated, multi-center community-based health system using a strategy of referral only of patients with significant cardiac abnormalities on obstetrical screening ultrasound for fetal echocardiography. Detection rates were assessed for screening in both radiology and maternal fetal medicine (MFM). The impact on fetal echocardiography utilization was also assessed. METHODS: This was a retrospective cohort study using an electronic health record, outside claims databases and chart review to determine all live births between 2016 and 2020 with postnatally confirmed sCHD that were prenatally detectable and resulted in cardiac surgery, intervention, or death within 1 year. RESULTS: There were 214,486 pregnancies resulting in live births. Prenatally detectable significant CHD was confirmed in 294 infants. Of those 183 were detected for an overall live-born detection rate of 62%. Detection rates in MFM were 75% and in radiology were 52%. The number of fetal echocardiograms needed to detect (NND) sCHD was 7. CONCLUSIONS: A focus on quality and standardization of obstetrical screening ultrasound with referral to fetal echocardiography for cardiac abnormalities alone achieves benchmark targets for live-born detection of significant CHD requiring fewer fetal echocardiograms.

Principles for Stakeholder Engagement in Observational Health Research.

This Viewpoint advocates for the inclusion of patients and other stakeholders in interpreting data for observational research studies.

Adolescent utilization of eating disorder higher level of care: roles of family-based treatment adherence and demographic factors.

BACKGROUND: Outpatient family-based treatment (FBT) is effective in treating restrictive eating disorders among adolescents. However, little is known about whether FBT reduces higher level of care (HLOC) utilization or if utilization of HLOC is associated with patient characteristics. This study examined associations between utilization of eating disorder related care (HLOC and outpatient treatment) and reported adherence to FBT and patient characteristics in a large integrated health system. METHODS: This retrospective cohort study examined 4101 adolescents who received care for restrictive eating disorders at Kaiser Permanente Northern California. A survey was sent to each medical center to identify treatment teams as high FBT adherence (hFBT) and low FBT adherence (lFBT). Outpatient medical and psychiatry encounters and HLOC, including medical hospitalizations and higher-level psychiatric care as well as patient characteristics were extracted from the EHR and examined over 12 months post-index. RESULTS: 2111 and 1990 adolescents were treated in the hFBT and lFBT, respectively. After adjusting for age, sex, race/ethnicity, initial percent median BMI, and comorbid mental health diagnoses, there were no differences in HLOC or outpatient utilization between hFBT and lFBT. Females had higher odds of any utilization compared with males. Compared to White adolescents, Latinos/Hispanics had lower odds of HLOC utilization. Asian, Black, and Latino/Hispanic adolescents had lower odds of psychiatric outpatient care than Whites. CONCLUSIONS: Reported FBT adherence was not associated with HLOC utilization in this sample. However, significant disparities across patient characteristics were found in the utilization of psychiatric care for eating disorders. More efforts are needed to understand treatment pathways that are accessible and effective for all populations with eating disorders.

Adolescents with restrictive eating treated by Family-Based Treatment (FBT) teams had better early weight gain but no differences in the use of intensive outpatient, residential, partial hospital programs or inpatient psychiatry care when compared to those treated by teams with a low adherence to the FBT approach. Factors such as sex, race, ethnicity, mood disorders, and suicidality were associated with the use of psychiatric services. These findings are consistent with previously documented systematic disparities in accessing psychiatric services across patient demographics and should be used to inform the development of proposed care models that are more inclusive and accessible to all patients.

Training the next generation of delivery science researchers: 10-year experience of a post-doctoral research fellowship program within an integrated care system.

Introduction: Learning health systems require a workforce of researchers trained in the methods of identifying and overcoming barriers to effective, evidence-based care. Most existing postdoctoral training programs, such as NIH-funded postdoctoral T32 awards, support basic and epidemiological science with very limited focus on rigorous delivery science methods for improving care. In this report, we present the 10-year experience of developing and implementing a Delivery Science postdoctoral fellowship embedded within an integrated health care delivery system. Methods: In 2012, the Kaiser Permanente Northern California Division of Research designed and implemented a 2-year postdoctoral Delivery Science Fellowship research training program to foster research expertise in identifying and addressing barriers to evidence-based care within health care delivery systems. Results: Since 2014, 20 fellows have completed the program. Ten fellows had PhD-level scientific training, and 10 fellows had clinical doctorates (eg, MD, RN/PhD, PharmD). Fellowship alumni have graduated to faculty research positions at academic institutions (9), and research or clinical organizations (4). Seven alumni now hold positions in Kaiser Permanente's clinical operations or medical group (7). Conclusions: This delivery science fellowship program has succeeded in training graduates to address delivery science problems from both research and operational perspectives. In the next 10 years, additional goals of the program will be to expand its reach (eg, by developing joint research training models in collaboration with clinical fellowships) and strengthen mechanisms to support transition from fellowship to the workforce, especially for researchers from underrepresented groups.

Hospital Readmissions Among Patients Experiencing Homelessness: An Electronic Health Record Data Study.

BACKGROUND: Population-level tracking of hospital use patterns with integrated care organizations in patients experiencing homelessness has been difficult. A California law implemented in 2019 (Senate Bill 1152) aimed to ensure safety for this population after discharge from the hospital by requiring additional documentation for patients experiencing homelessness, which provides an opportunity to evaluate hospital use by this population. METHODS: In a large integrated health system in California, patients experiencing homelessness were identified through documentation change requirements associated with this law and compared with a matched group from the general population. RESULTS: Patients experiencing homelessness had increased rates of hospital readmission after discharge compared to the general population matched on demographics and medical comorbidity in 2019 and 2020. Any address change in the prior year for patients was associated with increased odds of emergency department readmission. Patients experiencing homelessness, both enrolled in an integrated delivery system and not, were successfully identified as having higher readmission rates compared with their housed counterparts. CONCLUSION: Documentation of housing status following Senate Bill 1152 has enabled improved study of hospital use among those with housing instability. Understanding patterns of hospital use in this vulnerable group will help practitioners identify timely points of intervention for further social and health care support.

Identifying Predictors of Homelessness Among Adults in a Large Integrated Health System in Northern California.

Introduction Homelessness contributes to worsening health and increased health care costs. There is little published research that leverages rich electronic health record (EHR) data to predict future homelessness risk and inform interventions to address it. The authors' objective was to develop a model for predicting future homelessness using individual EHR and geographic data covariates. Methods This retrospective cohort study included 2,543,504 adult members (≥ 18 years old) from Kaiser Permanente Northern California and evaluated which covariates predicted a composite outcome of homelessness status (hospital discharge documentation of a homeless patient, medical diagnosis of homelessness, approved medical financial assistance application for homelessness, and/or "homeless/shelter" in address name). The predictors were measured in 2018-2019 and included prior diagnoses and demographic and geographic data. The outcome was measured in 2020. The cohort was split (70:30) into a derivation and validation set, and logistic regression was used to model the outcome. Results Homelessness prevalence was 0.35% in the overall sample. The final logistic regression model included 26 prior diagnoses, demographic, and geographic-level predictors. The regression model using the validation set had moderate sensitivity (80.4%) and specificity (83.2%) for predicting future cases of homelessness and achieved excellent classification properties (area under the curve of 0.891 [95% confidence interval = 0.884-0.897]). Discussion This prediction model can be used as an initial triage step to enhance screening and referral tools for identifying and addressing homelessness, which can improve health and reduce health care costs. Conclusions EHR data can be used to predict chance of homelessness at a population health level.

Using Peer Support to Prevent Diabetes: Results of a Pragmatic RCT.

INTRODUCTION: High-contact structured diabetes prevention programs are effective in lowering weight and HbA1cs, yet their intensity level can create barriers to participation. Peer support programs improve clinical outcomes among adults with Type 2 diabetes, but their effectiveness in diabetes prevention is unknown. This study examined whether a low-intensity peer support program improved outcomes more than enhanced usual care in a diverse population with prediabetes. STUDY DESIGN: The intervention was tested in a pragmatic 2-arm RCT. SETTING/PARTICIPANTS: Participants were adults with prediabetes at three healthcare centers. INTERVENTION: Participants randomized to the enhanced usual care arm received educational materials. Participants in the Using Peer Support to Aid in Prevention and Treatment in Prediabetes arm were matched with a peer supporter: another patient who had made healthy lifestyle changes and was trained in autonomy-supportive action planning. Peer supporters were instructed to provide weekly telephone support to their peers on specific action steps toward behavioral goals for 6 months, then monthly support for 6 months. MAIN OUTCOME MEASURES: Changes in primary outcomes of weight and HbA1c and secondary outcomes of enrollment in formal diabetes prevention programs, self-reported diet, physical activity, health-specific social support, self-efficacy, motivation, and activation at 6 and 12 months were examined. RESULTS: Data collection occurred from October 2018 to March 2022, with analyses completed in September 2022. Among 355 randomized patients, in intention-to-treat analyses, there were no between-group differences in HbA1c or weight changes at 6 and 12 months. Using Peer Support to Aid in Prevention and Treatment in Prediabetes participants were more likely to enroll in structured programs at 6 (AOR=2.45, p=0.009) and 12 (AOR=2.21, p=0.016) months and to report eating whole grains at 6 (4.49, p=0.026) and 12 (4.22, p=0.034) months. They reported greater improvements in perceived social support for diabetes prevention behaviors at 6 (6.39, p<0.001) and 12 (5.48, p<0.001) months, with no differences in other measures. CONCLUSIONS: A stand-alone, low-intensity peer support program improved social support and participation in formal diabetes prevention programs but not weight or HbA1c. It will be important to examine whether peer support could effectively complement higher-intensity, structured diabetes prevention programs. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT03689530. Full protocol available at https://clinicaltrials.gov/ct2/show/NCT03689530.

Effects of COVID-19 shelter-in-place confinement on diabetes prevention health behaviors among US adults with prediabetes: A cross-sectional survey.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in significant lifestyle changes due to shelter-in-place confinement orders. The study's purpose was to assess if the COVID-19 pandemic affected self-reported diabetes prevention behaviors among American adults with prediabetes. As part of a randomized clinical trial among adults with prediabetes and overweight/obesity, questions were added to existing study surveys to assess the effect of the COVID-19 pandemic on diabetes prevention behaviors and stress. Survey responses were summarized using frequencies. 259 study participants completed seven COVID-19 survey questions from June 2020 to June 2021. Participants were 62.9% female, 42.5% White, 31.3% Black, 11.6% Asian, 8.1% Hispanic, and 6.6% Other. Over 75% of participants reported that the COVID-19 pandemic affected physical activity levels, with 82.1% of those affected reporting decreased physical activity; 70.3% reported that the pandemic affected their eating habits, with 61.7% of those affected reporting their eating habits became less healthy; 73.7% reported that the pandemic affected their level of stress, with 97.4% of those affected reporting that their level of stress had increased; 60% reported that the pandemic affected their motivation to adopt/maintain healthy habits, with 72.9% of those affected reporting their motivation decreased. A high percentage of study participants with prediabetes reported decreases in health promotion behaviors and increases in stress due to the COVID-19 pandemic. Consequently, the pandemic could lead to increased diabetes incidence. Strategies to improve diabetes prevention behaviors and address mental health concerns among those at-risk for diabetes are critical during and after the COVID-19 pandemic.

Association of Surgical Timing with Outcomes in Early Stage Lung Cancer.

BACKGROUND: Optimal time to surgery for lung cancer is not well established. We aimed to assess whether time to surgery correlates with outcomes. METHODS: We assessed patients 18-84 years old who were diagnosed with stage I/II lung cancer at our integrated healthcare system from 2009 to 2019. Time to surgery was defined to start with disease confirmation (imaging or biopsy) prior to the surgery scheduling date. Outcomes of unplanned return to care within 30 days of lung cancer surgery, all-cause mortality, and disease recurrence were compared based on time to surgery before and after 2, 4, and 12 weeks. RESULTS: Of 2861 included patients, 70% were over 65 years old and 61% were female. Time to surgery occurred in 1-2 weeks for 6%, 3-4 weeks for 31%, 5-12 weeks for 58%, and 13-26 weeks for 5% of patients. Patients with time to surgery > 4 (vs. ≤ 4) weeks had greater risk of both death (hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.39) and recurrence (HR 1.33, 95% CI 1.10-1.62). Associations were not statistically significant when dichotomizing time to surgery at 2 or 12 weeks for death (2 week HR 1.23, 95% CI 0.93-1.64; 12 week HR 1.35, 95% CI 0.97-1.88) and recurrence (2 week HR 1.54, 95% CI 0.85-2.80; 12 week HR 2.28, 95% CI 0.80-6.46). CONCLUSIONS: Early stage lung cancer patients with time to surgery within 4 weeks experienced lower rates of recurrence. Optimal time to surgical resection may be shorter than previously reported.

Incidence and Medical Hospitalization Rates of Patients With Pediatric Eating Disorders.

Objective Eating disorders typically onset in preadolescence and adolescence and cause negative mental and physical health sequelae over the life span. This study examined the incidence and medical hospitalization rates of pediatric eating disorders in an integrated health system in the United States. Methods This retrospective cohort study examined 4883 Kaiser Permanente Northern California members 8-18 years of age with an eating disorder diagnosis from January 2015 to June 2019. Medical hospitalizations include admissions at any of the 13 Kaiser Permanente Northern California hospitals with a primary or secondary eating disorder diagnosis. Results Incidence rates ranged between 177 and 205 per 100,000 adolescents per year. More than half the adolescents were non-White: 10.8% Asian, 4.3% Black, 26.7% Hispanic/Latinx, 8.4% multiracial, 0.3% Native American/Alaskan Native, and 0.5% Native Hawaiian/Pacific Islander. Thirteen percent had a body mass index (BMI) below the 5th percentile, 61.8% had a BMI between the 5th and the 84th percentiles, 19.7% had a BMI above the 85th percentile, and 5.6% had an unknown BMI. During the 12-month follow-up period, 5.4% of adolescents had medical hospitalizations. Conclusions This study adds to the evidence that eating disorders affect children/adolescents across all weight/BMI ranges and racial/ethnic backgrounds. Future studies call for exploration on treatment strategies that tailor to the diverse populations.

Address Changes Are Associated With Unmet Glycemic Targets: Opportunities to Improve Processes and Outcomes of Care Among People With Type 2 Diabetes.

Introduction The objective of this study was to identify and operationalize measures of potential housing insecurity within existing electronic health record data and to quantify the association between address changes and diabetes management goals among patients with type 2 diabetes. Methods We conducted a retrospective cohort study to measure potential housing insecurity in electronic health record data by quantifying the number of address changes in 2018. We considered at least one address change as a potential marker for housing insecurity. We used multivariable modified Poisson regressions to analyze the association between address change and clinical, utilization and preventive care outcomes while adjusting for patient and health system factors. Results We identified 274,123 adults with type 2 diabetes who were members of Kaiser Permanente Northern California in 2018 and 6% (N = 17,317) had at least one address change during 2018. In multivariate analyses, we found that one or more address changes was associated with greater chance of hemoglobin A1C < 9 (ARR: 1.12, 95% CI: 1.09, 1.15), lower chance of hemoglobin A1C < 8 (ARR: 0.95, 95% CI; 0.94, 0.96), lower chance of controlled blood pressure (ARR: 0.99, 95% CI: 0.98-0.99), greater chance of emergency department visits (ARR: 1.25, 95% CI: 1.23, 1.27), and lower chance of having a flu shot (ARR: 0.94, 95% CI: 0.93, 0.95) when compared to no address change. Discussion Changes in address are associated with worse diabetes management outcomes. Conclusion Identifying patients with potential housing insecurity and providing resources aimed at continuity of care and stable health care access could improve diabetes management for vulnerable populations.

Psychosocial and diabetes risk factors among racially/ethnically diverse adults with prediabetes.

Psychosocial factors such as self-efficacy may be important in helping high-risk adults prevent diabetes. We aimed to describe psychosocial and diabetes risk factors in adults with prediabetes and evaluate if these varied by demographic characteristics. Cross-sectional data came from baseline surveys and electronic health records (2018-2021) of adults with prediabetes enrolled in a randomized study of peer support for diabetes prevention at Kaiser Permanente Northern California and Michigan Medicine. Linear regression was used to compare differences between racial/ethnic groups, adjusting for age, sex, and clinic. Of 336 participants in the study, 62% were female; median age was 57; 41% were White, 35% African American, 9% Hispanic. Mean autonomous motivation was 6.6 and self-efficacy to prevent diabetes was 6.0 (1-7 scale); mean perceived social support was 47 (12-72 scale). Hispanic adults reported higher autonomous motivation and African American adults reported higher self-efficacy compared to White adults. Hispanic and African American adults had more diabetes risk factors than White adults, including greater family history of diabetes, hypertension, sugar-sweetened beverage consumption, physical inactivity and food insecurity. In conclusion, participants reported high levels of autonomous motivation and self-efficacy at baseline, with Hispanic and African American adults reporting higher levels of some psychosocial factors related to behavior change, suggesting a significant opportunity to engage a diverse population of adults with prediabetes in diabetes prevention strategies. However, Hispanic and African American participants showed greater diabetes risk factors levels. Diabetes prevention efforts should address both to reduce diabetes incidence.

Spinal corticosteroid injections are not associated with increased influenza risk.

BACKGROUND CONTEXT: Spinal corticosteroid injections (CSI) are often used to treat radicular and axial pain arising from the spine. Systemic corticosteroids are well known to cause immunosuppression, and locally injected spinal CSI are known to have some systemic absorption. However, it is unknown whether spinal CSI increases the risk of systemic viral infections, such as influenza. PURPOSE: To determine whether spinal CSI causes an increased risk for influenza infection and whether they reduce the protective effect of vaccination STUDY DESIGN/SETTING: A retrospective cohort study was performed at Kaiser Permanente Northern California, a large healthcare system with a diverse population. PATIENT SAMPLE: Adults (n=60,880) who received a spinal CSI during influenza seasons from 2016 to 2019. A comparison was made with 121,760 case-matched individuals who did not receive a spinal CSI. OUTCOME MEASURES: The primary outcome was odds of influenza diagnosis following spinal CSI compared with case-matched controls. Secondary analysis examined odds of influenza diagnosis based on vaccination status, multiple same-day injections, and epidural versus non-epidural route of injection. METHODS: The electronic health record and associated research databases were analyzed to identify patients who received a spinal CSI during three consecutive flu seasons, 2016 through 2019. Injections were stratified into epidural versus non-epidural CSI and single injections versus multiple same-day injections. Additionally, the rate of influenza in vaccinated versus non-vaccinated individuals was examined. Inpatient flu diagnosis was used as a proxy for severe disease. After case matching was completed, odds ratios for flu diagnosis were calculated using a logistical regression model. RESULTS: The odds of flu diagnosis following spinal CSI were not increased compared with controls (OR 0.93 [0.87-1.01, 95% Wald CL]). For epidural CSI the OR was 0.91 (0.83-1.00, 95% Wald CL), and non-epidural it was 1.00 (0.89-1.13, 95% Wald CL). There were similar findings for multiple same-day injections and when looking at inpatient flu diagnosis. For vaccinated individuals, the OR for flu following spinal CSI was 0.86 (0.80-0.92, 95% Wald CL), which indicates a protective effect in these patients. CONCLUSIONS: Spinal CSI did not increase the odds of subsequently receiving a diagnosis of influenza, regardless of vaccination status, location of injection, single versus multiple same-day injection, or co-morbidity. Vaccination had a protective effect against influenza, and this was not adversely affected by receiving spinal CSI during the flu season.

Association of Cardiovascular Outcomes and Mortality With Sustained Long-Acting Insulin Only vs Long-Acting Plus Short-Acting Insulin Treatment.

Importance: Cardiovascular events and mortality are the principal causes of excess mortality and health care costs for people with type 2 diabetes. No large studies have specifically compared long-acting insulin alone with long-acting plus short-acting insulin with regard to cardiovascular outcomes. Objective: To compare cardiovascular events and mortality in adults with type 2 diabetes receiving long-acting insulin who do or do not add short-acting insulin. Design, Setting, and Participants: This retrospective cohort study emulated a randomized experiment in which adults with type 2 diabetes who experienced a qualifying glycated hemoglobin A1c (HbA1c) level of 6.8% to 8.5% with long-acting insulin were randomized to continuing treatment with long-acting insulin (LA group) or adding short-acting insulin within 1 year of the qualifying HbA1c level (LA plus SA group). Retrospective data in 4 integrated health care delivery systems from the Health Care Systems Research Network from January 1, 2005, to December 31, 2013, were used. Analysis used inverse probability weighting estimation with Super Learner for propensity score estimation. Analyses took place from April 1, 2018, to June 30, 2019. Exposures: Long-acting insulin alone or with added short-acting insulin within 1 year from the qualifying HbA1c level. Main Outcomes and Measures: Mortality, cardiovascular mortality, acute myocardial infarction, stroke, and hospitalization for heart failure. Results: Among 57 278 individuals (39 279 with data on cardiovascular mortality) with a mean (SD) age of 60.6 (11.5) years, 53.6% men, 43.5% non-Hispanic White individuals, and 4 years of follow-up (median follow-up of 11 [interquartile range, 5-20] calendar quarters), the LA plus SA group was associated with increased all-cause mortality compared with the LA group (hazard ratio, 1.27; 95% CI, 1.05-1.49) and a decreased risk of acute myocardial infarction (hazard ratio, 0.89; 95% CI, 0.81-0.97). Treatment with long-acting plus short-acting insulin was not associated with increased risks of congestive heart failure, stroke, or cardiovascular mortality. Conclusions and Relevance: Findings of this retrospective cohort study suggested an increased risk of all-cause mortality and a decreased risk of acute myocardial infarction for the LA plus SA group compared with the LA group. Given the lack of an increase in major cardiovascular events or cardiovascular mortality, the increased all-cause mortality with long-acting plus short-acting insulin may be explained by noncardiovascular events or unmeasured confounding.