Russell L. Rothman

Primary care research remains underused for generating pragmatic, generalizable evidence to enhance patient care. Despite the prominent national focus on addressing chronic disease and the high volume of patients seen in primary care, primary care research remains critically underfunded. In April 2025, the Duke Clinical Research Institute convened a national “Think Tank” of cross-disciplinary experts to explore how to better integrate clinical research into primary care. Primary care holds promise to improve clinical research by offering rapid recruitment of diverse patients and engagement of potential participants by trusted “front-line” providers, by allowing enhanced pragmatic data collection methods, and by addressing critical disease-specific and population health questions. However, primary care research is challenged by workforce shortages, fragmented research infrastructure, funding uncertainty, and misaligned incentives. Three key approaches were identified to bolster the future of primary care research: (1) expanding practice-based research networks, (2) leveraging digital health technologies, and (3) investing in the future of primary care research through increased funding and training opportunities. Together, these approaches can advance patient-oriented, pragmatic research in primary care to create a healthier future for all.

Background: Understanding changes in quality of life that occur with colectomy is critical to decision-making in management of recurrent diverticulitis. We hypothesized that patients choosing colectomy at surgical consultation would report better disease-specific quality of life at 1 year than those choosing observation. Objective: To investigate the association between colectomy versus observation for recurrent sigmoid diverticulitis and disease-specific quality of life at 1 year. Methods: We performed a multicenter prospective observational study including patients with recurrent uncomplicated diverticulitis choosing colectomy versus observation at initial consultation. The primary outcome was disease-specific quality of life at 1 year, measured by the Diverticulitis Quality of Life questionnaire total score. Results: A total of 113 patients were enrolled (median age 57; 64% female, 92% white); 42 (37%) chose colectomy at surgical consultation. At enrollment, median lifetime episodes of diverticulitis were similar between groups (colectomy: 5, observation: 4); the colectomy group had a higher rate of hospitalization in the past 5 years (colectomy: 71%, observation: 49%). In an adjusted linear mixed effects model, choosing colectomy was associated with better quality of life by 1.73 points (95% CI: 1.02–2.46) compared with choosing observation. 7 people (17%) who chose colectomy experienced recurrence within 1 year compared with 32 who chose observation (45%). In an adjusted model, choosing colectomy was associated with lower odds of recurrence (aOR 0.16; 95% CI: 0.05–0.48). Conclusion: For patients with recurrent sigmoid diverticulitis presenting for surgical consultation, colectomy may offer meaningful improvement in disease-specific quality of life and may be associated with reduced 1-year recurrence rates.

PCORnet ^® , a national resource funded by the Patient-Centered Outcomes Research Institute, is designed to enhance the nation’s capacity to conduct efficient, patient-centered health research. The robust and adaptable PCORnet infrastructure can be leveraged to support a variety of study designs. Within this framework, PCORnet ^® Studies, a distinguished subset of research studies that meets specific criteria and approval, serve as exemplary models of patient-centered research, standing out for their rigorous adherence to criteria that elevate the quality and impact of research. Over the past 10 years, over 300 studies have been completed using the PCORnet infrastructure, including 58 studies that have earned the distinction of being a meritorious PCORnet ^® Study, of which 19 have been completed. We explore several of these efforts, highlighting the study archetypes supported by the PCORnet infrastructure, as well as the clinical therapeutic areas of these studies, funding sources, and breadth of PCORnet institutional users. We also provide lessons learned from our accumulated experience that translates the PCORnet infrastructure into a continuously learning framework and highlight unique capabilities of the PCORnet infrastructure supporting innovation in future trials.

Background: Institutions that participate in PCORnet ^® transform their local electronic health record (EHR) data into the PCORnet ^® Common Data Model (CDM), which is then used to generate data extracts for PCORnet ^® Studies. PCORnet ^® Studies can also include institutions that do not participate in PCORnet, and for these organizations, the cost of instantiating a PCORnet ^® CDM can be prohibitive. Fast Health care Interoperability Resources (FHIR) provides an alternative method of obtaining EHR data. Objective: To determine whether data obtained through FHIR might be a viable study solution for those sites that do not participate in PCORnet. ^® This mixed-methods project had 2 objectives: (1) survey sites participating in PCORnet on the availability of FHIR (FHIR survey); (2) compare the coverage of a FHIR-based data extract using REDCap with one from the PCORnet ^® CDM across 3 sites (FHIR extract). Methods: (1) FHIR survey: A series of questions were asked about the use of FHIR in a production capacity. (2) FHIR extract: REDCap FHIR and PCORnet ^® CDM extracts were created based on study variables from 2 prior PCORnet ^® Studies. Data were extracted for 40 patients and concordance measures were computed between the 2 sources. Results: (1) FHIR survey: Of responding organizations, 73% (n=49) reported that FHIR was deployed in a production capacity. (2) FHIR extract: Results were highly variable. Cohen kappa ranged from 0.01 to 0.76 for certain diagnoses, 0.24 to 0.84 for laboratory results, and 0.1 to 0.87 for medications. Conclusions: Despite differences in data, certain studies may be well-suited for FHIR-based extracts.

Background: Scientific advances and cost efficiencies in genetics and genomics are expanding clinical application for prevention, diagnosis, and treatment. Objective: PCORnet ^® , a research network that includes participation from 78 health systems nationally and is linked to more than 47 million unique patients with at least one encounter annually, can help (1) understand the ability of genetics/genomics to predict health outcomes, (2) identify diseases impacted by genetic/genomic factors, (3) evaluate pharmacogenomics’ role in medication optimization, (4) evaluate emerging gene therapies, and (5) compare clinical genetic or genomic strategies within learning health systems to improve outcomes, while (6) facilitating patient and other partner engagement across these areas. Main Arguments: The breadth of data accessible via PCORnet represents a unique opportunity to study relationships among genetic markers and clinical and exposome-based disease risk factors, particularly as more genomic data become available. The network’s experience developing computable phenotypes for identifying specific diseases can be leveraged to evaluate the role of genetics/genomics in health. The PCORnet infrastructure can be used to identify patients with particular conditions for predictive modeling or comparative clinical effectiveness research using electronic health record data. The network can also recruit patients for observational cohorts or pragmatic clinical trials on pharmacogenomics or the return of genetic results, evaluation of emerging gene therapies, or embedded research into learning health systems to compare clinical genetics/genomics implementation approaches in health care. The partner engagement focus of the PCORnet ^® Network Partners can enrich research and improve health care delivery and outcomes. The rise of clinical genetics and genomics will profoundly impact health care in the next decade, and the PCORnet ^® Network Partners are primed to make a leading contribution in this area.

Background: The PCORnet ^® infrastructure was funded by PCORI in 2014 to streamline clinical trials, increase patient-centered research, and generate knowledge that leads to improved health care and outcomes. In this paper, we summarize the significant achievements of the infrastructure over the last decade as well as recent accomplishments. We also provide an update on the expanded patient population who receive care at sites participating in PCORnet ^® Clinical Research Networks (CRNs) and share priorities for the future. Methods: The electronic health records of 71 health systems participating in PCORnet ^® CRNs as of July 2024 were queried, and data were analyzed to describe 10 common health conditions, stratified by demographic characteristics of age, sex, race, ethnicity, and an index of social deprivation. Results: Out of over 100M total patients with activity in the last 10 years, health systems participating in PCORnet ^® CRNs had over 47 million unique patients with at least one encounter in 2023. The most common chronic conditions among these patients were hypertension (18%), anxiety disorders (10%), type 2 diabetes (8%), and asthma (5%). Over 20% of patients receiving care at a site participating in PCORnet were in the top 50% of metrics for area deprivation. The PCORnet infrastructure supported 51 PCORnet ^® studies, all of which met established guidelines for use of the PCORnet ^® Common Data Model (CDM), patient-engagement, and commitment to return of results. Discussion: PCORnet ^® CRNs represent a diverse and expanding patient population and often include data on the socioeconomic status of the communities. Through continued efforts to engage communities and patients and national-scale research, the PCORnet ^® infrastructure can help improve care and outcomes for patients affected by common and rare conditions.

Background: Guidelines recommend aspirin (75–100 mg daily) for the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, it is unknown if people with a history of ASCVD and chronic obstructive pulmonary disease (COPD) or asthma, which are independent risk factors for ASCVD, would benefit from higher dose aspirin. Methods: We evaluated the effectiveness and safety of 2 aspirin doses among individuals with and without COPD/asthma in the ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) trial. The ADAPTABLE study was an open‐label, randomized clinical trial that assigned people with ASCVD to aspirin 81 or 325 mg. We performed a secondary analysis of data from the ADAPTABLE study to investigate the difference in clinical effectiveness and safety among people with and without COPD or asthma randomized to aspirin 325 versus 81 mg. We assessed if history of COPD/asthma modified the association between aspirin dose and outcomes. Results: Among the 14 662 participants, 2778 had a history of COPD or asthma and 11 884 had no history of COPD or asthma. We observed no significant interaction between aspirin dose and history of COPD/asthma in our adjusted primary composite outcome (adjusted hazard ratio [aHR], 1.15 [95% CI, 0.92–1.43]; P value=0.349). We observed individuals with a history of COPD/asthma treated with aspirin 81 mg had a significantly higher risk of stroke (aHR, 2.41 [95% CI, 1.27–4.57]) compared with a treatment strategy of aspirin 325 mg. Conclusions: Among people with ASCVD and COPD/asthma, there were no significant differences in ASCVD outcomes based on aspirin dosing except stroke. Further evaluation of stroke prevention in this population is warranted.

Type 2 Diabetes (T2D) is a chronic multifaceted metabolic condition characterized by elevated blood glucose levels with varying degrees of insulin resistance and abnormal insulin production. Lifestyle modifications, such as those defined by the guidelines for diabetes self-management education and support (DSMES), are foundational for glycemic control. A current gap in T2D management is addressing DSMES which is tailored to best serve the diversity of patients with this disease. The purpose of this narrative review is to discuss the current literature related to lifestyle modification for T2D, the importance of culturally sensitive T2D management programs, and the impact culturally sensitive and diverse T2D management programs have on cardiometabolic health. Despite being disproportionately affected by T2D, racial and ethnic minorities have low referral rates for DSMES. This growing disparity may be exacerbated by a lack of awareness of how to adapt lifestyle modifications in a culturally competent manner and how social determinants of health (SDOH) may affect the infrastructure and resources available to diverse patient populations. Currently, there is limited research on how DSMES is addressed to include culturally and literacy-sensitive recommendations in the United States. Patient-centered care, emphasizing personalized DSMES, can lead to improved glycemic control, reduced healthcare costs, and improved cardiometabolic health. A key component of effective DSMES should include culturally and literacy-sensitive approaches with an awareness of the impact of SDOH. Understanding how ethnicity, race, and culture influence experiences with T2D management can help providers prescribe more patient-centered and sustainable recommendations.

Objectives To evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD). Design A secondary analysis of the randomised controlled trial ADAPTABLE was performed. Setting The study was conducted in 40 centres and one health plan participating in the National Patient-Centred Clinical Research Network (PCORnet) in the USA. Participants Among 15 076 participants with established ASCVD, 14 096 had self-reported race available and were included in the analysis. Participants were divided according to self-reported race as Black (n=1311, 9.3%), White (n=11 990, 85.1%) or other race (n=795, 5.6%). Interventions Participants were randomised to open-label daily aspirin doses of 81 mg versus 325 mg in a 1:1 ratio for a median of 26.2 months. Primary and secondary outcomes measures The primary effectiveness endpoint was a composite of death from any cause, hospitalisation for myocardial infarction or hospitalisation for stroke. The primary safety endpoint was hospitalisation for bleeding requiring blood product transfusion. Results Estimated cumulative incidence of the primary effectiveness endpoint at median follow-up with the 81 mg and the 325 mg daily doses were 6.70% and 7.12% in White participants (adjusted HR: 1.00 [95% CI: 0.88 to 1.15]); 12.27% and 10.69% in Black participants (adjusted HR: 1.40 [95% CI: 1.02 to 1.93]); and 6.88% and 7.69% in other participants (adjusted HR: 0.86 [95% CI: 0.54 to 1.39]) (p-interaction=0.12), respectively. There was no significant interaction between self-reported race and assigned aspirin dose regarding the secondary effectiveness and the primary safety endpoints. Conclusion Race is not an effect modifier on the impact of aspirin dosing on effectiveness and safety in patients with established ASCVD. In clinical practice, treatment decisions regarding aspirin dose in secondary prevention of ASCVD should not be influenced by race. Trial registration number NCT02697916.

Importance: The frequency and characteristics of post-acute sequelae of SARS-CoV-2 infection (PASC) may vary by SARS-CoV-2 variant. Objective: To characterize PASC-related conditions among individuals likely infected by the ancestral strain in 2020 and individuals likely infected by the Delta variant in 2021. Design: Retrospective cohort study of electronic medical record data for approximately 27 million patients from March 1, 2020-November 30, 2021. Setting: Healthcare facilities in New York and Florida. Participants: Patients who were at least 20 years old and had diagnosis codes that included at least one SARS-CoV-2 viral test during the study period. Exposure: Laboratory-confirmed COVID-19 infection, classified by the most common variant prevalent in those regions at the time. Main outcome(s) and measure(s): Relative risk (estimated by adjusted hazard ratio [aHR]) and absolute risk difference (estimated by adjusted excess burden) of new conditions, defined as new documentation of symptoms or diagnoses, in persons between 31–180 days after a positive COVID-19 test compared to persons without a COVID-19 test or diagnosis during the 31–180 days after the last negative test. Results: We analyzed data from 560,752 patients. The median age was 57 years; 60.3% were female, 20.0% non-Hispanic Black, and 19.6% Hispanic. During the study period, 57,616 patients had a positive SARS-CoV-2 test; 503,136 did not. For infections during the ancestral strain period, pulmonary fibrosis, edema (excess fluid), and inflammation had the largest aHR, comparing those with a positive test to those without a COVID-19 test or diagnosis (aHR 2.32 [95% CI 2.09 2.57]), and dyspnea (shortness of breath) carried the largest excess burden (47.6 more cases per 1,000 persons). For infections during the Delta period, pulmonary embolism had the largest aHR comparing those with a positive test to a negative test (aHR 2.18 [95% CI 1.57, 3.01]), and abdominal pain carried the largest excess burden (85.3 more cases per 1,000 persons). Conclusions and relevance: We documented a substantial relative risk of pulmonary embolism and a large absolute risk difference of abdomen-related symptoms after SARS-CoV-2 infection during the Delta variant period. As new SARS-CoV-2 variants emerge, researchers and clinicians should monitor patients for changing symptoms and conditions that develop after infection.