Assessing Patterns of Continuous Glucose Monitoring Use and Metrics of Glycemic Control in Type 1 Diabetes and Type 2 Diabetes Patients in the Veterans Health Care System: Integrating Continuous Glucose Monitoring Device Data with Electronic Health Records Data.

Objective: To integrate long-term daily continuous glucose monitoring (CGM) device data with electronic health records (EHR) for patients with type 1 and type 2 diabetes (T1D and T2D) in the national Veterans Affairs Healthcare System to assess real-world patterns of CGM use and the reliability of EHR-based CGM information. Research Design and Methods: This observational study used Dexcom CGM device data linked with EHR (from 2015 to 2020) for a large national cohort of patients with diabetes. We tracked the initiation and consistency of CGM use, assessed concordance of CGM use and measures of glucose control between CGM device data and EHR records, and examined results by age, ethnicity, and diabetes type. Results: The time from pharmacy release of CGM to patients to initiation of uploading CGM data to Dexcom servers averaged 3 weeks but demonstrated wide variation among individuals; importantly, this delay decreased markedly over the later years. The average daily wear time of CGM exceeded 22 h over nearly 3 years of follow-up. Patterns of CGM use were generally consistent across age, race/ethnicity groups, and diabetes type. There was strong concordance between EHR-based estimates of CGM use and Dexcom CGM wear time and between estimates of glucose control from both sources. Conclusions: The study demonstrates our ability to reliably integrate CGM devices and EHR data to provide valuable insights into CGM use patterns. The results indicate in the real-world environment that CGM is worn consistently over many years for both patients with T1D and T2D within the Veterans Affairs Healthcare System and is similar across major race/ethnic groups and age-groups.

Development of a Flavor Ingredient Wheel Linking E-Liquid Additives to the Labeled Flavor of Vaping Products.

E-liquids contain combinations of chemicals, with many enhancing the sensory attractiveness of the product. Studies are needed to understand and characterize e-liquid ingredients, particularly flavorings, to inform future research and regulations of these products. We identified common flavor ingredients in a convenience sample of commercial e-liquids using gas chromatography-mass spectrometry. E-liquid flavors were categorized by flavor descriptors provided on the product packaging. A Flavor Ingredient Wheel was developed to link e-liquid flavor ingredients with flavor categories. An analysis of 109 samples identified 48 flavor ingredients. Consistency between the labeled flavor and ingredients used to produce such flavor was found. Our novel Flavor Ingredient Wheel organizes e-liquids by flavor and ingredients, enabling efficient analysis of the link between ingredients and their flavor profiles and allowing for quick assessment of an e-liquid ingredient's flavor profile. Investigating ingredient profiles and identifying and classifying commonly used chemicals in e-liquids may assist with future studies and improve the ability to regulate these products.

Occupational Radiation Dose Trends in U.S. Radiologic Technologists Assisting with Fluoroscopically Guided Interventional Procedures, 1980-2020.

PURPOSE: To summarize dose trends from 1980 to 2020 for 19,651 U.S. Radiologic Technologists who reported assisting with fluoroscopically guided interventional procedures (FGIPs), overall and by work history characteristics. MATERIALS AND METHODS: A total of 762,310 annual personal dose equivalents at a 10-mm reference depth (doses) during 1980-2020 for 43,823 participants of the U.S. Radiologic Technologists (USRT) cohort who responded to work history questionnaires administered during 2012-2014 were summarized. This population included 19,651 technologists who reported assisting with FGIP (≥1 time per month for ≥12 consecutive months) at any time during the study period. Doses corresponding to assistance with FGIP were estimated in terms of proximity to patients, monthly procedure frequency, and procedure type. Box plots and summary statistics (eg, medians and percentiles) were used to describe annual doses and dose trends. RESULTS: Median annual dose corresponding to assistance with FGIP was 0.65 mSv (interquartile range [IQR], 0.60-1.40 mSv; 95th percentile, 6.80). Higher occupational doses with wider variability were associated with close proximity to patients during assistance with FGIP (median, 1.20 mSv [IQR, 0.60-4.18 mSv]; 95th percentile, 12.66), performing ≥20 FGIPs per month (median, 0.75 mSv [IQR, 0.60-2.40 mSv]; 95th percentile, 9.44), and assisting with high-dose FGIP (median, 0.70 mSv [IQR, 0.60-1.90 mSv]; 95th percentile, 8.30). CONCLUSIONS: Occupational doses corresponding to assistance with FGIP were generally low but varied with exposure frequency, procedure type, and proximity to patients. These results highlight the need for vigilant dose monitoring, radiation safety training, and proper protective equipment.

NCRP commentary no. 33-recommendations for stratification of equipment use and radiation safety training for fluoroscopy.

National Council on Radiation Protection and Measurements Commentary No. 33 'Recommendations for Stratification of Equipment Use and Radiation Safety Training for Fluoroscopy' defines an evidence-based, radiation risk classification for fluoroscopically guided procedures (FGPs), provides radiation-related recommendations for the types of fluoroscopes suitable for each class of procedure, and indicates the extent and content of training that ought to be provided to different categories of facility staff who might enter a room where fluoroscopy is or may be performed. For FGP, radiation risk is defined by the type and likelihood of radiation hazards that could be incurred by a patient undergoing a FGP. The Commentary also defines six training groups of facility staff based on their role in the fluoroscopy room. The training groups are based on a combination of job descriptions and the procedures in which these individuals might be involved. The Commentary recommends the extent and content of training that should be provided to each of these training groups. It also provides recommendations on training formats, training frequency, and methods for demonstrating that the learner has acquired the necessary knowledge.

Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP).

OBJECTIVE: To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS: Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011-2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS: T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and their characteristics resembled those of individuals with T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low-risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low GRS 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS: Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble those of people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.

Lipid Nanoparticle-Based Inhibitors for SARS-CoV-2 Host Cell Infection.

Purpose: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lingering threat to public health has fueled the search for effective therapeutics to treat SARS-CoV-2. This study aimed to develop lipid nanoparticle (LNP) inhibitors of SARS-CoV-2 entry to reduce viral infection in the nose and upper airway. Methods: Two types of LNP formulations were prepared following a microfluidic mixing method. The LNP-Trap consisted of DOPC, DSPC, cholesterol, and DSPE-PEG-COOH modified with various spike protein binding ligands, including ACE2 peptide, recombinant human ACE2 (rhACE2) or monoclonal antibody to spike protein (mAb). The LNP-Trim consisted of ionizing cationic DLin-MC3-DMA, DSPC, cholesterol, and DMG-PEG lipids encapsulating siACE2 or siTMPRSS2. Both formulations were assayed for biocompatibility and cell uptake in airway epithelial cells (Calu-3). Functional assessment of activity was performed using SARS-CoV-2 spike protein binding assays (LNP-Trap), host receptor knockdown (LNP-Trim), and SARS-CoV-2 pseudovirus neutralization assay (LNP-Trap and LNP-Trim). Localization and tissue distribution of fluorescently labeled LNP formulations were assessed in mice following intranasal administration. Results: Both LNP formulations were biocompatible based on cell impedance and MTT cytotoxicity studies in Calu-3 cells at concentrations as high as 1 mg/mL. LNP-Trap formulations were able to bind spike protein and inhibit pseudovirus infection by 90% in Calu-3 cells. LNP-Trim formulations reduced ACE2 and TMPRSS2 at the mRNA (70% reduction) and protein level (50% reduction). The suppression of host targets in Calu-3 cells treated with LNP-Trim resulted in over 90% inhibition of pseudovirus infection. In vivo studies demonstrated substantial retention of LNP-Trap and LNP-Trim in the nasal cavity following nasal administration with minimal systemic exposure. Conclusion: Both LNP-Trap and LNP-Trim formulations were able to safely and effectively inhibit SARS-CoV-2 pseudoviral infection in airway epithelial cells. These studies provide proof-of-principle for a localized treatment approach for SARS-CoV-2 in the upper airway.

Complexity of patients with mental healthcare needs cared for by mental health clinical pharmacist practitioners in Veterans Affairs.

PURPOSE: The complexity of patients with mental healthcare needs cared for by clinical pharmacists is not well delineated. We evaluated the complexity of patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD) in Veterans Affairs (VA) cared for by mental health clinical pharmacist practitioners (MH CPPs). METHODS: Patients at 42 VA sites with schizophrenia, bipolar disorder, or MDD in 2016 through 2019 were classified by MH CPP visits into those with 2 or more visits ("ongoing MH CPP care"), those with 1 visit ("consultative MH CPP care"), and those with no visits ("no MH CPP care"). Patient complexity for each condition was defined by medication regimen and service utilization. RESULTS: For schizophrenia, more patients in ongoing MH CPP care were complex than those with no MH CPP care, based on all measures examined: the number of primary medications (15.3% vs 8.1%), inpatient (13.7% vs 9.1%) and outpatient (42.6% vs 29.7%) utilization, and receipt of long-acting injectable antipsychotics (36.7% vs 25.8%) and clozapine (20.5% vs 9.5%). For bipolar disorder, more patients receiving ongoing or consultative MH CPP care were complex than those with no MH CPP care based on the number of primary medications (27.9% vs 30.5% vs 17.7%) and overlapping mood stabilizers (10.1% vs 11.6% vs 6.2%). For MDD, more patients receiving ongoing or consultative MH CPP care were complex based on the number of primary medications (36.8% vs 35.5% vs 29.2%) and augmentation of antidepressants (56.1% vs 54.4% vs 47.0%) than patients without MH CPP care. All comparisons were significant (P < 0.01). CONCLUSION: MH CPPs provide care for complex patients with schizophrenia, bipolar disorder, and MDD in VA.

Spatially Resolved Microglia/Macrophages in Recurrent Glioblastomas Overexpress Fatty Acid Metabolism and Phagocytic Genes.

BACKGROUND: Glioblastoma (GBM) tumors are rich in tumor-associated microglia/macrophages. Changes associated with treatment in this specific cell population are poorly understood. Therefore, we studied changes in gene expression of tumor-associated microglia/macrophages (Iba1+) cells in de novo versus recurrent GBMs. METHODS: NanoString GeoMx® Digital Spatial Transcriptomic Profiling of microglia/macrophages (Iba1+) and glial cells (Gfap+) cells identified on tumor sections was performed on paired de novo and recurrent samples obtained from three IDH-wildtype GBM patients. The impact of differentially expressed genes on patient survival was evaluated using publicly available data. RESULTS: Unsupervised analyses of the NanoString GeoMx® Digital Spatial Profiling data revealed clustering based on the transcriptomic data from Iba1+ and Gfap+ cells. As expected, conventional differential gene expression and enrichment analyses revealed upregulation of immune-function-related genes in Iba1+ cells compared to Gfap+ cells. A focused differential gene expression analysis revealed upregulation of phagocytosis and fatty acid/lipid metabolism genes in Iba1+ cells in recurrent GBM samples compared to de novo GBM samples. Importantly, of these genes, the lipid metabolism gene PLD3 consistently correlated with survival in multiple different publicly available datasets. CONCLUSION: Tumor-associated microglia/macrophages in recurrent GBM overexpress genes involved in fatty acid/lipid metabolism. Further investigation is needed to fully delineate the role of PLD phospholipases in GBM progression.

Early Mortality After the First Dose of COVID-19 Vaccination: A Target Trial Emulation.

BACKGROUND: Vaccine hesitancy persists alongside concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines. We aimed to examine the effect of COVID-19 vaccination on risk of death among US veterans. METHODS: We conducted a target trial emulation to estimate and compare risk of death up to 60 days under two COVID-19 vaccination strategies: vaccination within 7 days of enrollment versus no vaccination through follow-up. The study cohort included individuals aged ≥18 years enrolled in the Veterans Health Administration system and eligible to receive a COVID-19 vaccination according to guideline recommendations from 1 March 2021 through 1 July 2021. The outcomes of interest included deaths from any cause and excluding a COVID-19 diagnosis. Observations were cloned to both treatment strategies, censored, and weighted to estimate per-protocol effects. RESULTS: We included 3 158 507 veterans. Under the vaccination strategy, 364 993 received vaccine within 7 days. At 60 days, there were 156 deaths per 100 000 veterans under the vaccination strategy versus 185 deaths under the no vaccination strategy, corresponding to an absolute risk difference of -25.9 (95% confidence limit [CL], -59.5 to 2.7) and relative risk of 0.86 (95% CL, .7 to 1.0). When those with a COVID-19 infection in the first 60 days were censored, the absolute risk difference was -20.6 (95% CL, -53.4 to 16.0) with a relative risk of 0.88 (95% CL, .7 to 1.1). CONCLUSIONS: Vaccination against COVID-19 was associated with a lower but not statistically significantly different risk of death in the first 60 days. These results agree with prior scientific knowledge suggesting vaccination is safe with the potential for substantial health benefits.

Selective Uptake of Macromolecules to the Brain in Microfluidics and Animal Models Using the HAVN1 Peptide as a Blood-Brain Barrier Modulator.

Monoclonal antibodies (mAbs) possess favorable pharmacokinetic properties, high binding specificity and affinity, and minimal off-target effects, making them promising therapeutic agents for central nervous system (CNS) disorders. However, their development as effective therapeutic and diagnostic agents for brain disorders is hindered by their limited ability to efficiently penetrate the blood-brain barrier (BBB). Therefore, it is crucial to develop efficient delivery methods that enhance the penetration of antibodies into the brain. Previous studies have demonstrated the potential of cadherin-derived peptides (i.e., ADTC5, HAVN1 peptides) as BBB modulators (BBBMs) to increase paracellular porosities for penetration of molecules across the BBB. Here, we test the effectiveness of the leading BBBM peptide, HAVN1 (Cyclo(1,6)SHAVSS), in enhancing the permeation of various monoclonal antibodies through the BBB using both in vitro and in vivo systems. In vitro, HAVN1 has been shown to increase the permeability of fluorescently labeled macromolecules, such as a 70 kDa dextran, 50 kDa Fab1, and 150 kDa mAb1, by 4- to 9-fold in a three-dimensional blood-brain barrier (3D-BBB) microfluidics model using a human BBB endothelial cell line (i.e., hCMEC/D3). HAVN1 was selective in modulating the BBB endothelial cell, compared to the pulmonary vascular endothelial (PVE) cell barrier. Co-administration of HAVN1 significantly improved brain depositions of mAb1, mAb2, and Fab1 in C57BL/6 mice after 15 min in the systemic circulation. Furthermore, HAVN1 still significantly enhanced brain deposition of mAb2 when it was administered 24 h after the administration of the mAb. Lastly, we observed that multiple doses of HAVN1 may have a cumulative effect on the brain deposition of mAb2 within a 24-h period. These findings offer promising insights into optimizing HAVN1 and mAb dosing regimens to control or modulate mAb brain deposition for achieving desired mAb dose in the brain to provide its therapeutic effects.

Widening Gender Gap in Life Expectancy in the US, 2010-2021.

This cross-sectional study systematically examines the contributions of COVID-19 and other underlying causes of death to the widened gender life expectancy gap from 2010 to 2021.

What Goes into Patient Selection for Lung Cancer Screening? Factors Associated with Clinician Judgments of Suitability for Screening.

Rationale: Achieving the net benefit of lung cancer screening (LCS) depends on optimizing patient selection. Objective: To identify factors associated with clinician assessments that a patient was unlikely to benefit from LCS ("LCS-inappropriate") because of comorbidities or limited life expectancy. Methods: Retrospective analysis of patients assessed for LCS at 30 Veterans Health Administration facilities from January 1, 2015 to February 1, 2021. We conducted hierarchical mixed-effects logistic regression analyses to determine factors associated with clinicians' designations of LCS inappropriateness (primary outcome), accounting for 3-year predicted probability (i.e., competing risk) of non-lung cancer death. Measurements and Main Results: Among 38,487 LCS-eligible patients, 1,671 (4.3%) were deemed LCS-inappropriate by clinicians, whereas 4,383 (11.4%) had an estimated 3-year competing risk of non-lung cancer death greater than 20%. Patients with higher competing risks of non-lung cancer death were more likely to be deemed LCS-inappropriate (odds ratio [OR], 2.66; 95% confidence interval [CI], 2.32-3.05). Older patients (ages 75-80; OR, 1.45; 95% CI, 1.18-1.78) and those with interstitial lung disease (OR, 1.98; 95% CI, 1.51-2.59) were more likely to be deemed LCS-inappropriate than would be explained by competing risk of non-lung cancer death, whereas patients currently smoking (OR, 0.65; 95% CI, 0.58-0.73) were less likely to be deemed LCS-inappropriate, suggesting that clinicians over- or underweighted these factors. The probability of being deemed LCS-inappropriate varied from 0.4% to 74%, depending on the clinician making the assessment (median OR, 3.07; 95% CI, 2.89-3.25). Conclusion: Concerningly, the likelihood that a patient is deemed LCS-inappropriate is more strongly associated with the clinician making the assessment than with patient characteristics. Patient selection may be optimized by providing decision support to help clinicians assess net LCS benefit.

Process of Maintaining Self in Individuals Living With Systemic Sclerosis: A Grounded Theory Study of American Women.

BACKGROUND: People with chronic illnesses may struggle to adapt psychologically to the illness experience and have feelings of identity loss, self-diminishment, and biographical disruption. This may limit people's ability to engage in optimal self-management. Systemic sclerosis is a debilitating, stigmatizing, and life-limiting progressive chronic illness with significant disfiguring effects. Little is known about the identity management process in people with disfiguring and debilitating conditions such as systemic sclerosis. PURPOSE: The purpose of this study was to generate a grounded theory explicating the process of maintaining a sense of self in people living with systemic sclerosis. METHODS: Fifteen women with systemic sclerosis were recruited to ensure representation of a range of illness duration and progression. Semi-structured interviews were conducted, transcribed, and analyzed using open, selective, and theoretical coding. RESULTS: A basic social process of "maintaining self" was generated from the data that explained the women's experience of living with systemic sclerosis and how they tried to hold on to their identity. Three core categories were identified. Adapting to changes are the behaviors that participants struggled through to carry on with their everyday lives. Dismantling of self was a distressing internal process where participants lost their sense of self and purpose. Restoring self was a transformative process that allowed participants to rewrite and rebuild their biographies. CONCLUSIONS: Findings suggest that the management of identity was important for understanding how people adapt to life with systemic sclerosis. This study can help nurses better understand how to support patients holistically with the management of systemic sclerosis.

Trio-binning of a hinny refines the comparative organization of the horse and donkey X chromosomes and reveals novel species-specific features.

We generated single haplotype assemblies from a hinny hybrid which significantly improved the gapless contiguity for horse and donkey autosomal genomes and the X chromosomes. We added over 15 Mb of missing sequence to both X chromosomes, 60 Mb to donkey autosomes and corrected numerous errors in donkey and some in horse reference genomes. We resolved functionally important X-linked repeats: the DXZ4 macrosatellite and ampliconic Equine Testis Specific Transcript Y7 (ETSTY7). We pinpointed the location of the pseudoautosomal boundaries (PAB) and determined the size of the horse (1.8 Mb) and donkey (1.88 Mb) pseudoautosomal regions (PARs). We discovered distinct differences in horse and donkey PABs: a testis-expressed gene, XKR3Y, spans horse PAB with exons1-2 located in Y and exon3 in the X-Y PAR, whereas the donkey XKR3Y is Y-specific. DXZ4 had a similar ~ 8 kb monomer in both species with 10 copies in horse and 20 in donkey. We assigned hundreds of copies of ETSTY7, a sequence horizontally transferred from Parascaris and massively amplified in equids, to horse and donkey X chromosomes and three autosomes. The findings and products contribute to molecular studies of equid biology and advance research on X-linked conditions, sex chromosome regulation and evolution in equids.

Rule-Based Identification of Individuals with Mild Cognitive Impairment or Alzheimer's Disease Using Clinical Notes from the United States Veterans Affairs Healthcare System.

BACKGROUND: Early identification of individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a clinical and research imperative. Use of diagnostic codes for MCI and AD identification has limitations. We used clinical notes to supplement diagnostic codes in the Veterans Affairs Healthcare System (VAHS) electronic health records (EHR) to identify and establish cohorts of Veterans recorded with MCI or AD. METHODS: Targeted keyword searches for MCI ("Mild cognitive impairment;" "MCI") and AD ("Alz*") were used to extract clinical notes from the VAHS EHR from fiscal year (FY) 2010 through FY 2019. Iterative steps of inclusion and exclusion were applied until searches achieved a positive predictive value ≥ 80%. MCI and AD cohorts were identified via clinical notes and/or diagnostic codes (i.e., including Veterans recorded by "Notes Only," "Notes + Code," or "Codes Only"). RESULTS: A total of 2,134,661 clinical notes from 339,007 Veterans met the iterative search criteria for MCI due to any cause and 4,231,933 notes from 572,063 Veterans met the iterative search criteria for AD. Over the 10-year study period, the number of clinical notes recording AD was generally stable, whereas the number for MCI more than doubled. More Veterans were identified for the MCI or AD cohorts via clinical notes than by diagnostic codes, particularly in the AD cohort. Among Veterans identified by having "Notes + Code" for MCI, the number first recorded by a code was lower than the number first recorded by a note until FY 2015 and then gradually became comparable after FY 2015. Among Veterans identified by having "Notes + Code" for AD, the number first recorded by a note was more than double the number first recorded by a code AD in each of the FYs. CONCLUSIONS: Clinical note-based identification captured more Veterans recorded with MCI and AD than diagnostic code-based identification.

A new clinical opportunity: Rechallenging penicillin allergy in an outpatient pharmacy.

In the United States, approximately 27 million people have a documented penicillin allergy, but 90% of the allergies are falsely labeled. By rechallenging suspected allergies, a pharmacist can optimize patient care, fulfill antimicrobial stewardship objectives, and educate patients on true allergies. We suggest a protocol that allows pharmacists to investigate the presence of an allergy and conduct a challenge when indicated. The protocol consists of a patient interview, a risk assessment, an oral rechallenge, and the potential for a skin test. The testing and delabeling of penicillin allergies will enhance the practice of antimicrobial stewardship in the outpatient setting. In the changing landscape of pharmacy, community pharmacists can increase their services and improve patient care. Owing to limited documented experience in the outpatient pharmacy, an opportunity to set the standard and be a leader in the field is present.

Clinical pharmacist practitioners on primary care teams play an important role in caring for complex patients with diabetes.

PURPOSE: To evaluate whether clinical pharmacist practitioners (CPPs) are being utilized to care for patients with complex medication regimens and multiple chronic illnesses, we compared the clinical complexity of diabetes patients referred to CPPs in team primary care and those in care by other team providers (OTPs). METHODS: In this cross-sectional comparison of patients with diabetes in the US Department of Veterans Affairs (VA) healthcare system in the 2017-2019 period, patient complexity was based on clinical factors likely to indicate need for more time and resources in medication and disease state management. These factors include insulin prescriptions; use of 3 or more other diabetes medication classes; use of 6 or more other medication classes; 5 or more vascular complications; metabolic complications; 8 or more other complex chronic conditions; chronic kidney disease stage 3b or higher; glycated hemoglobin level of ≥10%; and medication regime nonadherence. RESULTS: Patients with diabetes referred to one of 110 CPPs for care (n = 12,728) scored substantially higher (P < 0.001) than patients with diabetes in care with one of 544 OTPs (n = 81,183) on every complexity measure, even after adjustment for age, sex, race, and marital status. Based on composite summary scores, the likelihood of complexity was 3.42 (interquartile range, 3.25-3.60) times higher for those in ongoing CPP care (ie, those with 2 or more visits) versus OTP care. Patients in CPP care also were, on average, younger, more obese, and had more prior outpatient visits and hospital stays. CONCLUSION: The greater complexity of patients with diabetes seen by CPPs in primary care suggests that CPPs are providing valuable services in comprehensive medication and disease management of complex patients.