Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma.

BACKGROUND: Black and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations. METHODS: In this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 µg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed. RESULTS: Of 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P = 0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups. CONCLUSIONS: Among Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.).

Association of GLP-1 Receptor Agonists and Hepatocellular Carcinoma Incidence and Hepatic Decompensation in Patients With Type 2 Diabetes.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer death. HCC is preventable with about 70% of HCC attributable to modifiable risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), Food and Drug Administration-approved medications for treating type 2 diabetes mellitus (T2DM), have pleiotropic effects on counteracting risk factors for HCC. Here we evaluate the association of GLP-1RAs with incident HCC risk in a real-world population. METHODS: This retrospective cohort included 1,890,020 patients with a diagnosis of T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications and had no prior diagnosis of HCC. Incident (first-time) diagnosis of HCC and hepatic decompensating events during a 5-year follow-up was compared between cohorts of patients prescribed GLP-1 RAs vs other anti-diabetes medications. Time-to-first-event analysis was performed using Kaplan-Meier survival analysis with hazard ratio and 95% confidence interval calculated. RESULTS: GLP-1RAs were associated with a lower risk of incident HCC with hazard ratio of 0.20 [0.14-0.31], 0.39 [0.21-0.69], 0.63 [0.26-1.50] compared with insulin, sulfonylureas, and metformin, respectively. GLP-1RAs were associated with a significantly lower risk of hepatic decompensation compared with 6 other anti-diabetes medications. Reduced risks were observed in patients without and with different stages of fatty liver diseases, with more profound effects in patients without liver diseases. Similar findings were observed in patients with and without obesity and alcohol or tobacco use disorders. GLP-1RA combination therapies were associated with decreased risk for HCC and hepatic decompensations compared with monotherapies. CONCLUSIONS: GLP-1RAs were associated with a reduced risk of incident HCC and hepatic decompensation compared with other anti-diabetes medications in patients with T2DM. These findings provide supporting evidence for future studies to investigate the underlying mechanisms and their clinical use.

Risk for diagnosis or treatment of mood or anxiety disorders in adults after SARS-CoV-2 infection, 2020-2022.

COVID-19 is associated with increased risks for mood or anxiety disorders, but it remains uncertain how the association evolves over time or which patient groups are most affected. We conducted a retrospective cohort study using a nationwide database of electronic health records to determine the risk of depressive or anxiety disorder diagnoses after SARS-CoV-2 infection by 3-month blocks from January 2020 to April 2022. The study population comprised 822,756 patients (51.8% female; mean age 42.8 years) with COVID-19 and 2,034,353 patients with other respiratory tract infections (RTIs) (53.5% female, mean age 30.6 years). First time diagnoses of depressive or anxiety disorders 14 days to 3 months after infection, as well as new or new plus recurrent prescriptions of antidepressants or anxiolytics, were compared between propensity score matched cohorts using Kaplan-Meier survival analysis, including hazard ratio (HR) and 95% confidence interval (CI). Risk of a new diagnosis or prescription was also stratified by age, sex, and race to better characterize which groups were most affected. In the first three months of the pandemic, patients infected with SARS-CoV-2 had significantly increased risk of depression or anxiety disorder diagnosis (HR 1.65 [95% CI, 1.30-2.08]). October 2021 to January 2022 (HR, 1.12 [95% CI, 1.06-1.18]) and January to April 2022 (HR, 1.08 [95% CI, 1.01-1.14]). Similar temporal patterns were observed for antidepressant and anxiolytic prescriptions, when the control group was patients with bone fracture, when anxiety and depressive disorders were considered separately, when recurrent depressive disorder was tested, and when the test period was extended to 6 months. COVID-19 patients ≥65 years old demonstrated greatest absolute risk at the start of the pandemic (6.8%), which remained consistently higher throughout the study period (HR, 1.20 [95% CI, 1.13-1.27]), and overall, women with COVID-19 had greater risk than men (HR 1.35 [95% CI 1.30-1.40]).

Association of semaglutide with reduced incidence and relapse of cannabis use disorder in real-world populations: a retrospective cohort study.

Cannabis is the most frequently used illicit drug in the United States with more than 45 million users of whom one-third suffer from a cannabis use disorder (CUD). Despite its high prevalence, there are currently no FDA-approved medications for CUD. Patients treated with semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for treating type 2 diabetes (T2D) and for weight management have reported reduced desire to drink and smoke. Preclinical studies have shown that semaglutide decreased nicotine and alcohol consumption. Preclinical and preliminary clinical evidence of semaglutide's potential beneficial effects on various substance use disorders led us to evaluate if it pertained to CUD. In this retrospective cohort study of electronic health records (EHRs) from the TriNetX Analytics Network, a global federated health research network of approximately 105.3 million patients from 61 large healthcare organizations in the US, we aimed to assess the associations of semaglutide with both incident and recurrent CUD diagnosis compared to non-GLP-1RA anti-obesity or anti-diabetes medications. Hazard ratio (HR) and 95% confidence intervals (CI) of incident and recurrent CUD were calculated for 12-month follow-up by comparing propensity-score matched patient cohorts. The study population included 85,223 patients with obesity who were prescribed semaglutide or non-GLP-1RA anti-obesity medications, with the findings replicated in 596,045 patients with T2D. In patients with obesity (mean age 51.3 years, 65.6% women), semaglutide compared with non-GLP-1RA anti-obesity medications was associated with lower risk for incident CUD in patients with no prior history CUD (HR: 0.56, 95% CI: 0.42-0.75), and recurrent CUD diagnosis in patients with a prior history CUD (HR: 0.62, 95% CI: 0.46-0.84). Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without T2D. Similar findings were replicated in the study population with T2D when comparing semaglutide with non-GLP-1RA anti-diabetes medications for incident CUD (HR: 0.40, 95% CI: 0.29-0.56) and recurrent CUD (HR: 0.66, 95% CI: 0.42-1.03). While these findings provide preliminary evidence of the potential benefit of semaglutide in CUD in real-world populations, further preclinical studies are warranted to understand the underlying mechanism and randomized clinical trials are needed to support its use clinically for CUD.

Asthma morbidity measures across Black ethnic subgroups.

BACKGROUND: Black adults are disproportionately affected by asthma and are often considered a homogeneous group in research studies despite cultural and ancestral differences. OBJECTIVE: We sought to determine if asthma morbidity differs across adults in Black ethnic subgroups. METHODS: Adults with moderate-severe asthma were recruited across the continental United States and Puerto Rico for the PREPARE (PeRson EmPowered Asthma RElief) trial. Using self-identifications, we categorized multiethnic Black (ME/B) participants (n = 226) as Black Latinx participants (n = 146) or Caribbean, continental African, or other Black participants (n = 80). African American (AA/B) participants (n = 518) were categorized as Black participants who identified their ethnicity as being American. Baseline characteristics and retrospective asthma morbidity measures (self-reported exacerbations requiring systemic corticosteroids [SCs], emergency department/urgent care [ED/UC] visits, hospitalizations) were compared across subgroups using multivariable regression. RESULTS: Compared with AA/B participants, ME/B participants were more likely to be younger, residing in the US Northeast, and Spanish speaking and to have lower body mass index, health literacy, and <1 comorbidity, but higher blood eosinophil counts. In a multivariable analysis, ME/B participants were significantly more likely to have ED/UC visits (incidence rate ratio [IRR] = 1.34, 95% CI = 1.04-1.72) and SC use (IRR = 1.27, 95% CI = 1.00-1.62) for asthma than AA/B participants. Of the ME/B subgroups, Puerto Rican Black Latinx participants (n = 120) were significantly more likely to have ED/UC visits (IRR = 1.64, 95% CI = 1.22-2.21) and SC use for asthma (IRR = 1.43, 95% CI = 1.06-1.92) than AA/B participants. There were no significant differences in hospitalizations for asthma among subgroups. CONCLUSIONS: ME/B adults, specifically Puerto Rican Black Latinx adults, have higher risk of ED/UC visits and SC use for asthma than other Black subgroups.

Association between systemic lupus erythematosus and myasthenia gravis: A population-based National Study.

BACKGROUND: Systemic lupus erythematosus (SLE) and myasthenia gravis (MG) are autoimmune diseases. Previous case reports and case series suggest an association may exist between these diseases, as well as an increased risk of SLE after thymectomy for MG. We undertook this study to determine whether SLE and MG were associated in large cohorts. METHODS: We searched the IBM Watson Health Explorys platform and the Department of Veterans Affairs Million Veteran Program (MVP) database for diagnoses of SLE and MG. In addition, we examined subjects enrolled in the Lupus Family Registry and Repository (LFRR) as well as controls for a diagnosis of MG. RESULTS: Among 59,780,210 individuals captured in Explorys, there were 25,750 with MG and 65,370 with SLE. 370 subjects had both. Those with MG were >10 times more likely to have SLE than those without MG. Those with both diseases were more likely to be women, African American, and at a younger age than MG subjects without SLE. In addition, the MG patients who underwent thymectomy had an increased risk of SLE compared to MG patients who had not undergone thymectomy (OR 3.11, 95% CI: 2.12 to 4.55). Autoimmune diseases such as pernicious anemia and miscellaneous comorbidities such as chronic kidney disease were significantly more common in MG patients who developed SLE. In the MVP, SLE and MG were also significantly associated. Association of SLE and MG in a large SLE cohort with rigorous SLE classification confirmed the association of SLE with MG at a similar level. CONCLUSION: While the number of patients with both MG and SLE is small, SLE and MG are strongly associated together in very large databases and a large SLE cohort.

Preexisting Psychiatric Conditions as Risk Factors for Diagnosed Long COVID-19 Syndrome Within Aggregated Electronic Health Record Data.

OBJECTIVE: This study aimed to investigate the frequency of long COVID diagnosis among patients infected with severe acute respiratory syndrome coronavirus 2 with preexisting psychiatric conditions versus those without preexisting psychiatric conditions. METHODS: The TriNetX Analytics platform, an aggregated electronic health record research network containing the deidentified electronic health record data of more than 90 million patients, was queried for patients who were diagnosed with COVID-19 infection based on International Classifications of Disease, Tenth Revision codes. Patients were stratified based on their preexisting psychiatric conditions, and new diagnoses of long COVID were recorded and reported as the primary outcome. RESULTS: Among 1,180,948 patients previously diagnosed with COVID-19, 17,990 patients (1.52%) were diagnosed with long COVID based on the newly implemented International Classifications of Disease, Tenth Revision code "U09: post-COVID-19 condition." After propensity score matching, patients with any preexisting psychiatric diagnosis had a 1.52 (95% confidence interval [CI] = 1.47-1.58) times greater prevalence of diagnosed long COVID within 180 days of infection than patients without preexisting psychiatric diagnoses. Patients with diagnosed anxiety disorders (relative risk [RR] = 1.64; 95% CI = 1.57-1.71), mood disorders (RR = 1.65; 95% CI = 1.57-1.72), bipolar disorder (RR = 1.37; 95% CI = 1.21-1.54), major depressive disorder (RR = 1.69; 95% CI = 1.56-1.83), psychotic disorders (RR = 1.23; 95% CI = 1.06-1.44), and substance use disorders (RR = 1.28; 95% CI = 1.22-1.36) had higher risks for long COVID diagnoses when compared with patients without preexisting psychiatric illness at the time of diagnosis. CONCLUSIONS: Multiple preexisting psychiatric diagnoses are associated with an increased risk of being diagnosed with long COVID after COVID-19 infection.

Association of COVID-19 with endocarditis in patients with cocaine or opioid use disorders in the US.

The incidence of endocarditis in the US is increasing, driven in part by the rise in intravenous drug use, mostly opioids and stimulant drugs (cocaine and methamphetamine). Recent reports have documented that individuals with COVID-19 are at increased risk for cardiovascular diseases. However, it is unknown whether COVID-19 is associated with increased risk for endocarditis in patients with opioid or stimulant use disorders. This is a retrospective cohort study based on a nationwide database of electronic health records (EHRs) of 109 million patients in the US, including 736,502 patients with a diagnosis of opioid use disorder (OUD) and 379,623 patients with a diagnosis of cocaine use disorder (CocaineUD). Since Metamphetamine use disorder is not coded we could not analyze it. We show that the incidence rate of endocarditis among patients with OUD or CocaineUD significantly increased from 2011 to 2022 with acceleration during 2021-2022. COVID-19 was associated with increased risk of new diagnosis of endocarditis among patients with OUD (HR: 2.23, 95% CI: 1.92-2.60) and with CocaineUD (HR: 2.24, 95% CI: 1.79-2.80). Clinically diagnosed COVID-19 was associated with higher risk of endocarditis than lab-test confirmed COVID-19 without clinical diagnosis. Hospitalization within 2 weeks following COVID-19 infection was associated with increased risk of new diagnosis of endocarditis. The risk for endocarditis did not differ between patients with and without EHR-recorded vaccination. There were significant racial and ethnic differences in the risk for COVID-19 associated endocarditis, lower in blacks than in whites and lower in Hispanics than in non-Hispanics. Among patients with OUD or CocaineUD, the 180-day hospitalization risk following endocarditis was 67.5% in patients with COVID-19, compared to 58.7% in matched patients without COVID-19 (HR: 1.21, 95% CI: 1.07-1.35). The 180-day mortality risk following the new diagnosis of endocarditis was 9.2% in patients with COVID-19, compared to 8.0% in matched patients without COVID-19 (HR: 1.16, 95% CI: 0.83-1.61). This study shows that COVID-19 is associated with significantly increased risk for endocarditis in patients with opioid or cocaine use disorders. These results highlight the need for endocarditis screening and for linkage to infectious disease and addiction treatment in patients with opioid or cocaine use disorders who contracted COVID-19. Future studies are needed to understand how COVID-19 damages the heart and the vascular endothelium among people who misuse opioids or cocaine (presumably also methamphetamines).

A Comprehensive Global Population-Based Analysis on the Coexistence of Eosinophilic Esophagitis and Inflammatory Bowel Disease.

BACKGROUND: We explored inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE) coexistence using a global dataset. Investigating their epidemiology, risks, and impact, we aimed to enhance the understanding of concurrent diagnoses and patient outcomes. METHODS: A retrospective population-based cohort study was conducted using deidentified patient data from the TriNetX database (2011-2022). We estimated the incidence and prevalence of EoE in patients with IBD, including both Crohn's disease (CD) and ulcerative colitis (UC), and vice versa. Risks of select immune-mediated conditions and disease complications were compared among patients with EoE, IBD, or concurrent diagnoses. RESULTS: Our results included 174,755 patients with CD; 150,774 patients with UC; and 44,714 patients with EoE. The risk of EoE was significantly higher among patients with CD (prevalence ratio [PR] 11.2) or UC (PR 8.7) compared with individuals without IBD. The risk of IBD was higher in patients with EoE (CD: PR 11.6; UC: PR 9.1) versus those without EoE. A propensity-matched analysis of IBD patients revealed that, when comparing patients with and without EoE, the relative risk of immune-mediated comorbidities was significantly greater for celiac disease, IBD-related inflammatory conditions, eczema and asthma (CD: n = 1896; UC: n = 1231; p < 0.001). Patients with a concurrent diagnosis of EoE and IBD had a higher composite risk of IBD-related complications (CD: adjusted HR (aHR) 1.14, p < 0.005; UC: aHR 1.17, p < 0.01) and lower risk of food bolus impaction (aHR 0.445, p = 0.0011). CONCLUSION: Simultaneous EoE and IBD increased IBD-related complications risk, needing more treatment (glucocorticoids, biologic therapy, abdominal surgery), while reducing EoE-related issues like food bolus impaction.

Five-Year Incidence of Progression to Osteoarthritis and Total Joint Arthroplasty in Patients Prescribed Glucagon-Like Peptide 1 Receptor Agonists.

BACKGROUND: Research has suggested that glucagon-like peptide-1 receptor agonists (GLP-1-RAs) may have therapeutic effects on osteoarthritis of the hip and knee, in addition to managing diabetes and obesity. However, there is a lack of understanding regarding the association between GLP-1-RA use and the diagnosis of osteoarthritis (OA) of the hip and knee. METHODS: A collaborative network analytics platform was queried for obese diabetic (n = 1,094,198), obese nondiabetic (n = 916,235), and nonobese diabetic (n = 157,305) patients who had an index visit between 2015 and 2017. Patients who had pre-existing hip and/or knee OA were excluded. A 1:1 propensity score matching was used to balance GLP-1-RA use in stratified cohorts for age, sex, race, body mass index, and hemoglobin A1c. The primary outcomes were rates of progression to hip OA, knee OA, major joint injections, total hip arthroplasty, and total knee arthroplasty. Cox proportional hazards models determined hazard ratios (HRs) between cohorts prescribed and not prescribed GLP-1-RAs. RESULTS: All patients had a five-year follow-up. Rates of progression to hip and knee OA were higher among the GLP-1-RA users in both obese diabetic (hip HR: 1.63, 95% confidence interval [CI]: 1.46 to 1.82; knee HR: 1.52, CI: 1.41 to 1.64) and nonobese diabetic (hip HR: 1.78, CI: 1.50 to 2.10; knee HR: 1.58, CI: 1.39 to 1.80) cohorts. These diabetic cohorts received higher rates of major joint injections, though there was no difference in rates of total hip arthroplasty or total knee arthroplasty. No differences in five-year outcomes were seen when comparing obese, nondiabetic patients who were prescribed GLP-1-RAs with obese, nondiabetic patients not exposed to GLP-1-RAs. CONCLUSIONS: This five-year analysis found a greater risk of progression to hip and knee OA among obese and non-obese diabetic GLP-1-RA users. Further studies should explore GLP-1-RA effects upon glucose management, weight loss, and lower extremity arthritis development. LEVEL OF EVIDENCE: III, retrospective cohort study.

Epidemiological Trends and Outcomes of Unicompartmental Knee Arthroplasty Among 104 Million Patients in the United States.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty (TKA) for localized osteoarthritis. Recent advancements in UKA implant design and expanding patient criteria may have increased its utilization. However, few studies have examined the use of UKA in the United States. Thus, this study assessed the current and projected future trends of UKA and robotic UKA in the United States through 2035, along with postoperative outcomes. METHODS: A collaborative healthcare research network was queried to identify patients who had undergone UKA. Primary outcomes measured included prevalence (P), incidence proportion (IP), and incidence rate (IR) from 2012 to 2022. Chi-squared analyses were done to compare outcomes across categorical data. Regression modeling was performed to project UKA to the year 2035. Statistical significance was held at P < .05 for all analyses. RESULTS: In 2022, 1,662 UKAs were performed within the network, a 590% increase from 2012 (241 performed). The IP increased on an average annual basis by 41.8%, the IR by 50%, and the P by 51.3%. A year following UKA, conversion to TKA was the most common orthopaedic complication (39.9%). As of 2022, there were 68 robotic UKAs performed, a 518% increase from the 11 performed in 2012. Regression analysis for UKA through 2035 showed that IP will be 0.04%, IR will be 1.75 × 10-6 cases/person-day, and P will be 0.3%. CONCLUSIONS: These findings are consistent with prior studies indicating a higher utilization of UKA over the past decade. Reported complications were not uncommon, as nearly 40% of patients required a conversion to a TKA. Further research is needed to optimally identify criteria for appropriate patients and determine the benefits robotic UKA may provide, specifically reducing the risk of conversion to a TKA.

Cardiovascular Outcomes After Tixagevimab and Cilgavimab use for Pre-Exposure Prophylaxis Against Coronavirus Disease 2019: A Population-Based Propensity-matched Cohort Study.

Tixagevimab and cilgavimab treatment was associated with higher rates of cardiovascular events in a post hoc analysis of a phase 3 trial. In this large population-based propensity-matched study, we found no increased risk of cardiovascular events up to 90 days after tixagevimab and cilgavimab administration, including in patients with pre-existing cardiovascular disease.

Reducing Disparities in No Show Rates Using Predictive Model-Driven Live Appointment Reminders for At-Risk Patients: a Randomized Controlled Quality Improvement Initiative.

BACKGROUND: Appointment no shows are prevalent in safety-net healthcare systems. The efficacy and equitability of using predictive algorithms to selectively add resource-intensive live telephone outreach to standard automated reminders in such a setting is not known. OBJECTIVE: To determine if adding risk-driven telephone outreach to standard automated reminders can improve in-person primary care internal medicine clinic no show rates without worsening racial and ethnic show-rate disparities. DESIGN: Randomized controlled quality improvement initiative. PARTICIPANTS: Adult patients with an in-person appointment at a primary care internal medicine clinic in a safety-net healthcare system from 1/1/2022 to 8/24/2022. INTERVENTIONS: A random forest model that leveraged electronic health record data to predict appointment no show risk was internally trained and validated to ensure fair performance. Schedulers leveraged the model to place reminder calls to patients in the augmented care arm who had a predicted no show rate of 15% or higher. MAINE MEASURES: The primary outcome was no show rate stratified by race and ethnicity. KEY RESULTS: There were 5840 appointments with a predicted no show rate of 15% or higher. A total of 2858 had been randomized to the augmented care group and 2982 randomized to standard care. The augmented care group had a significantly lower no show rate than the standard care group (33% vs 36%, p < 0.01). There was a significant reduction in no show rates for Black patients (36% vs 42% respectively, p < 0.001) not reflected in white, non-Hispanic patients. CONCLUSIONS: In this randomized controlled quality improvement initiative, adding model-driven telephone outreach to standard automated reminders was associated with a significant reduction of in-person no show rates in a diverse primary care clinic. The initiative reduced no show disparities by predominantly improving access for Black patients.

A Cluster Randomized Trial of Primary Care Practice Redesign to Integrate Behavioral Health for Those Who Need It Most: Patients With Multiple Chronic Conditions.

PURPOSE: Patient outcomes can improve when primary care and behavioral health providers use a collaborative system of care, but integrating these services is difficult. We tested the effectiveness of a practice intervention for improving patient outcomes by enhancing integrated behavioral health (IBH) activities. METHODS: We conducted a pragmatic, cluster randomized controlled trial. The intervention combined practice redesign, quality improvement coaching, provider and staff education, and collaborative learning. At baseline and 2 years, staff at 42 primary care practices completed the Practice Integration Profile (PIP) as a measure of IBH. Adult patients with multiple chronic medical and behavioral conditions completed the Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey. Primary outcomes were the change in 8 PROMIS-29 domain scores. Secondary outcomes included change in level of integration. RESULTS: Intervention assignment had no effect on change in outcomes reported by 2,426 patients who completed both baseline and 2-year surveys. Practices assigned to the intervention improved PIP workflow scores but not PIP total scores. Baseline PIP total score was significantly associated with patient-reported function, independent of intervention. Active practices that completed intervention workbooks (n = 13) improved patient-reported outcomes and practice integration (P ≤ .05) compared with other active practices (n = 7). CONCLUSION: Intervention assignment had no effect on change in patient outcomes; however, we did observe improved patient outcomes among practices that entered the study with greater IBH. We also observed more improvement of integration and patient outcomes among active practices that completed the intervention compared to active practices that did not. Additional research is needed to understand how implementation efforts to enhance IBH can best reach patients.

Total Hip Arthroplasty Outcomes in Patients Who Have a History of Prior Radiation.

BACKGROUND: The purpose of this study was to assess the odds of developing medical and surgical adverse events following total hip arthroplasty (THA) in patients who have a history of radiation therapy (RT) for cancer. METHODS: A retrospective cohort study was conducted using a national database to identify patients who underwent primary THA (Current Procedural Terminology code 27130) from 2002 to 2022. Patients who had a prior RT were identified by International Classification of Diseases, Tenth Revision, Clinical Modification codes Z51.0 (encounter for antineoplastic RT), Z92.3 (personal history of irradiation), or Current Procedural Terminology code 101843 (radiation oncology treatment). One-to-one propensity score matching was conducted to generate 3 pairs of cohorts: 1) THA with/without a history of RT; 2) THA with/without a history of cancer; and 3) THA patients who have a history of cancer treated with/without RT. Surgical and medical complications were assessed at the 30-day, 90-day, and 1-year postoperative periods. RESULTS: Patients who have a history of RT had higher odds of developing anemia, deep vein thrombosis, pneumonia, pulmonary embolism, and prosthetic joint infection at all intervals. When controlling for a history of cancer, RT was associated with an increased risk of pulmonary embolism, heterotrophic ossification, prosthetic joint infection, and periprosthetic fracture at all postoperative time points. There was additionally an increased risk of aseptic loosening at 1 year (odds ratio: 2.0, 95% confidence interval: 1.2 to 3.1). CONCLUSION: These findings suggest that patients who have a history of antineoplastic RT are at an increased risk of developing various surgical and medical complications following THA.

COVID-19 breakthrough infections and hospitalizations among vaccinated patients with dementia in the United States between December 2020 and August 2021.

INTRODUCTION: There is lack of data on COVID-19 breakthrough infections in vaccinated patients with dementia in the United States. METHODS: This is a retrospective cohort study of 262,847 vaccinated older adults (age 73.8 ± 6.81 years old) between December 2020 and August 2021. RESULTS: Among the fully vaccinated patients with dementia, the overall risk of COVID-19 breakthrough infections ranged from 8.6% to 12.4%. Patients with dementia were at increased risk for breakthrough infections compared with patients without dementia, with the highest odds for patients with Lewy body dementia (LBD) (adjusted odds ratio or AOR: 3.06, 95% confidence interval or CI [1.45 to 6.66]), followed by vascular dementia (VD) (AOR: 1.99, 95% CI [1.42 to 2.80]), Alzheimer's disease (AD) (1.53, 95% CI [1.22 to 1.92]), and mild cognitive impairment (MCI) (AOR: 1.78, 95% CI [1.51 to 2.11]). The incidence rate of breakthrough infections among fully vaccinated patients with dementia increased since December 2020 and accelerated after May 2021. The overall risk for hospitalization after breakthrough infections in patients with dementia was 39.5% for AD, 46.2% for VD, and 30.4% for MCI. DISCUSSION: These results highlight the need to continuously monitor breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and outcomes in vaccinated patients with dementia.

Treacher Collins Syndrome Associated with Disproportionate Nervous System, Cardiovascular, Otologic Complications Among 1,114 Patients.

OBJECTIVE: To compare the rates of selected nervous system, cardiovascular, and otologic abnormalities in patients with and without Treacher Collins Syndrome (TCS). DESIGN: Retrospective TriNetX platform cohort study. SETTING: Aggregated and deidentified electronic health record (EHR) data from across the United States. PATIENTS, PARTICIPANTS: Patients with TCS (n = 1,114) and a propensity matched control cohort without TCS (n = 1,114 matched from n = 110,368,585). MAIN OUTCOME MEASURED: Prevalence and relative risk (RR) of selected diagnoses in a propensity-matched cohort. RESULTS: The RR of congenital malformations of the circulatory system in patients with TCS was 8.5 (95% CI 4.44-16.28). Patients with TCS also had higher rates of otologic abnormalities including conductive hearing loss (RR 44, 95% CI 24-83) and nervous system disorders including movement disorders (RR 2.60, 95% CI 1.27-5.50) and recurrent seizures (RR 4.2, 95% CI 2.12-8.33). CONCLUSIONS: We found a significantly elevated risk in TCS patients within all three systems. We postulate that the nervous system effects may be the result of one of the TCS-linked genes, for which a mutation has also been associated with progressive ataxia, cerebellar atrophy, hypomyelination, and seizures. As the previously-identified causal genes influence neural crest cells that form the head and face, these cells may also populate cardiac structures, resulting in cardiovascular abnormalities. Finally, the characteristic craniofacial abnormalities identified in TCS impair hearing and are associated with increased risk of otitis media. Our findings may help researchers to hypothesize the function of the genes underlying TCS, as well as to inform the care of affected individuals.

Cardiac and mortality outcome differences between methadone, buprenorphine and naltrexone prescriptions in patients with an opioid use disorder.

IMPORTANCE: More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely used medications for opioid use disorders (MOUD) and the most effective intervention for preventing overdose deaths. However, there is a concern that methadone results in long QT syndrome, which increases the risk for fatal cardiac arrythmias. Currently few studies have systematically evaluated both the short-term and long-term differences in cardiac and mortality outcomes between MOUD. OBJECTIVES: To compare the risks of cardiac arrythmias, long QT syndrome and overall mortality between patients with opioid use disorders (OUD) who were prescribed methadone, buprenorphine or naltrexone. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study based on a multicenter and nationwide database of electronic health records (EHRs) in the United States. The study population was comprised of 144,141 patients who had medical encounters for OUD in 2016-2022, were prescribed MOUD within 1 month following a medical encounter for OUD diagnosis and had no diagnosis of cardiac arrythmias or long QT syndrome before any MOUD prescription. The study population was divided into three cohorts: (1) Methadone cohort (n = 40,938)-who were only prescribed methadone. (2) Buprenorphine cohort (n = 80,055)-who were only prescribed buprenorphine. (3) Naltrexone cohort (n = 5,738)-who were only prescribed naltrexone. EXPOSURES: methadone, buprenorphine, or naltrexone. MAIN OUTCOMES AND MEASURES: Cardiac arrythmias, long QT syndrome, and death. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes at six different follow-up time frames (1-month, 3-month, 6-month, 1-year, 3-year, and 5-year) by comparing propensity-score matched cohorts using Kaplan-Meier survival analysis. RESULTS: Patients with OUD who were prescribed methadone had significantly higher risks of cardiac arrhythmias, long QT syndrome and death compared with propensity-score matched patients with OUD who were prescribed buprenorphine or naltrexone. For the 1-month follow-up, the overall risk for cardiac arrythmias was 1.03% in the Methadone cohort, higher than the 0.87% in the matched Buprenorphine cohort (HR: 1.20, 95% CI: 1.04-1.39); The overall risk for long QT syndrome was 0.35% in the Methadone cohort, higher than the 0.15% in the matched Buprenorphine cohort (HR: 2.40, 95% CI: 1.75-3.28); The overall mortality was 0.59% in the Methadone cohort, higher than the 0.41% in the matched Buprenorphine cohort (HR: 1.48, 95% CI: 1.21-1.81). The increased risk persisted for 5 years: cardiac arrhythmias (HR: 1.31, 95% CI: 1.23-1.38), long QT syndrome (HR: 3.14, 95% CI: 2.76-3.58), death (HR: 1.50, 95% CI: 1.41-1.59). CONCLUSIONS AND RELEVANCE: Methadone was associated with a significantly higher risk for cardiac and mortality outcomes than buprenorphine and naltrexone. These findings are relevant to the development of guidelines for medication selection when initiating MOUD treatment and inform future medication development for OUD that minimizes risks while maximizing benefits.

Improving Timeliness of Antibiotic Administration Using a Provider and Pharmacist Facing Sepsis Early Warning System in the Emergency Department Setting: A Randomized Controlled Quality Improvement Initiative.

OBJECTIVES: Results of pre-post intervention studies of sepsis early warning systems have been mixed, and randomized clinical trials showing efficacy in the emergency department setting are lacking. Additionally, early warning systems can be resource-intensive and may cause unintended consequences such as antibiotic or IV fluid overuse. We assessed the impact of a pharmacist and provider facing sepsis early warning systems on timeliness of antibiotic administration and sepsis-related clinical outcomes in our setting. DESIGN: A randomized, controlled quality improvement initiative. SETTING: The main emergency department of an academic, safety-net healthcare system from August to December 2019. PATIENTS: Adults presenting to the emergency department. INTERVENTION: Patients were randomized to standard sepsis care or standard care augmented by the display of a sepsis early warning system-triggered flag in the electronic health record combined with electronic health record-based emergency department pharmacist notification. MEASUREMENTS AND MAIN RESULTS: The primary process measure was time to antibiotic administration from arrival. A total of 598 patients were included in the study over a 5-month period (285 in the intervention group and 313 in the standard care group). Time to antibiotic administration from emergency department arrival was shorter in the augmented care group than that in the standard care group (median, 2.3 hr [interquartile range, 1.4-4.7 hr] vs 3.0 hr [interquartile range, 1.6-5.5 hr]; p = 0.039). The hierarchical composite clinical outcome measure of days alive and out of hospital at 28 days was greater in the augmented care group than that in the standard care group (median, 24.1 vs 22.5 d; p = 0.011). Rates of fluid resuscitation and antibiotic utilization did not differ. CONCLUSIONS: In this single-center randomized quality improvement initiative, the display of an electronic health record-based sepsis early warning system-triggered flag combined with electronic health record-based pharmacist notification was associated with shorter time to antibiotic administration without an increase in undesirable or potentially harmful clinical interventions.

COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States.

The global pandemic of COVID-19 is colliding with the epidemic of opioid use disorders (OUD) and other substance use disorders (SUD) in the United States (US). Currently, there is limited data on risks, disparity, and outcomes for COVID-19 in individuals suffering from SUD. This is a retrospective case-control study of electronic health records (EHRs) data of 73,099,850 unique patients, of whom 12,030 had a diagnosis of COVID-19. Patients with a recent diagnosis of SUD (within past year) were at significantly increased risk for COVID-19 (adjusted odds ratio or AOR = 8.699 [8.411-8.997], P < 10-30), an effect that was strongest for individuals with OUD (AOR = 10.244 [9.107-11.524], P < 10-30), followed by individuals with tobacco use disorder (TUD) (AOR = 8.222 ([7.925-8.530], P < 10-30). Compared to patients without SUD, patients with SUD had significantly higher prevalence of chronic kidney, liver, lung diseases, cardiovascular diseases, type 2 diabetes, obesity and cancer. Among patients with recent diagnosis of SUD, African Americans had significantly higher risk of COVID-19 than Caucasians (AOR = 2.173 [2.01-2.349], P < 10-30), with strongest effect for OUD (AOR = 4.162 [3.13-5.533], P < 10-25). COVID-19 patients with SUD had significantly worse outcomes (death: 9.6%, hospitalization: 41.0%) than general COVID-19 patients (death: 6.6%, hospitalization: 30.1%) and African Americans with COVID-19 and SUD had worse outcomes (death: 13.0%, hospitalization: 50.7%) than Caucasians (death: 8.6%, hospitalization: 35.2%). These findings identify individuals with SUD, especially individuals with OUD and African Americans, as having increased risk for COVID-19 and its adverse outcomes, highlighting the need to screen and treat individuals with SUD as part of the strategy to control the pandemic while ensuring no disparities in access to healthcare support.