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Introduction: Vitamin D is an essential micronutrient for infant calcium metabolism and bone development. Concentrations of vitamin D in breastmilk are low, despite higher anti-rachitic activity and correlations between infant and maternal serum 25-hydroxyvitamin D (25D) (Taylor, et al., 2008; Oberhelman, et al., 2013). The sulfate-conjugated form of 25D is present in blood at concentrations approximately 40% of unmodified 25D. We hypothesized that sulfate conjugates, vitamin D3-sulfate (VitD-S) and 25-hydroxyvitamin D3-sulfate (25D-S), are present in milk and increase during supplementation. The objectives are (1) developing an LC-MS/MS assay to quantify VitD-S and 25D-S in milk, and (2) determine if these vitamin D sulfates increase with daily vitamin D supplementation. Methods: An LC-MS/MS method was developed to measure VitD-S and 25D-S in milk and in serum. Standards (Toronto Chemicals, Toronto, ON, CA) and internal standard (Glycomyr, Ames, IA) were used to optimize methods. Briefly, Milk (500 uL) and serum (250 uL) were extracted with methanol (MeOH) and resuspended in 150 uL 70% MeOH. Analytes were separated by C18 column with 70% to 100% MeOH with ammonium acetate (NH4OAc) organic phase gradient followed by MS/MS with optimized mass transitions and ESI in negative mode on SCIEX API 5000. An ongoing study is under way for breastmilk and serum collections from healthy lactating women consuming <600 IU vitamin D3/day at enrollment (day 1) and after 28 days of oral 5000 IU vitamin D3/day (day 28). This study was approved by the Mayo Clinic Institutional Review Board. Results: Preliminary analyses have been completed for 3 study participants. Serum 25D status had a trending increase from 30±2 ng/mL 25D on day 1 to 40±2 ng/mL 25D on day 28 ( P=0.1, paired t-test). Limit of detection [signal to noise (s/n) >3] for sulfates were 0.5 ng/mL 25D-S (s/n=7.3) and 0.25 ng/mL VitD-S (s/n=6.2). Upon enrollment, breastmilk sulfates were 3.25±0.12 ng/mL VitD-S (s/n=83.7±20.6) and 0.18±0.02 ng/mL 25D-S (s/n=13.6±3.3), and serum sulfates were 7.5±0.8 ng/mL VitD-S (s/n=39.4±22.5) and 53.2±10.4 ng/mL 25D-S (s/n=22.5±7.2). No statistical differences were observed between day 1 and day 28 in milk or serum sulfates for the 3 participants. However, VitD-S concentrations demonstrated a significant negative correlation between serum and milk ( r=0.87, P=0.03), and serum 25D-S was 21.3 ng/mL greater than unmodified serum 25D ( P=0.009, n=6). This study is ongoing, and data presented will include a greater number of study participants. Conclusions: We have developed an LC-MS/MS assay to measure VitD-S and 25D-S and found that VitD-S and 25D-S are present in freshly expressed breastmilk and in serum from women consuming <600 IU vitamin D3/day. F32 DK128987 & The Mayo Clinic Parker D. Sanders & Isabella G. Sanders Endowed Professorship. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction: Primary care clinicians are presented with hundreds of new clinical recommendations and guidelines. To consider practice change clinicians must identify relevant information and develop a contextual framework. Too much attention to information irrelevant to one’s practice results in wasted resources. Too little results in care gaps. A small group of primary care clinicians in a large health system sought to address the problem of vetting new information and providing peer reviewed context. This was done by engaging colleagues across the system though a primary care learning collaborative. Methods: The collaborative was a grass roots initiative between community and academic-based clinicians. They invited all the system’s primary care clinicians to participate. They selected new recommendations or guidelines and used surveys as the principal communication instrument. Surveys shared practice experience and also invited members to give narrative feedback regarding their acceptance of variation in care relate to the topic. A description of the collaborative along with its development, processes, and evolution are discussed. Process changes to address needs during the COVID-19 pandemic including expanded information sharing was necessary. Results: Collaborative membership reached across 5 states and included family medicine, internal medicine, and pediatrics. Members found involvement with the collaborative useful. Less variation in care was thought important for public health crises: the COVID pandemic and opioid epidemic. Greater practice variation was thought acceptable for adherence to multispecialty guidelines, such as diabetes, lipid management, and adult ADHD care. Process changes during the pandemic resulted in more communications between members to avoid practice gaps. Conclusion: An internet-based learning collaborative in a health system had good engagement from its members. Using novel methods, it was able to provide members with feedback related to the importance of new practice recommendations as perceived by their peers. Greater standardization was thought necessary when adopting measures to address public health crisis, and less necessary when addressing multispecialty guidelines. By employing a learning collaborative, this group was able to keep members interested and engaged. During the first year of the COVID pandemic the collaborative also served as a vehicle to share timely information.

AbstractObjectiveTo evaluate health care costs as a function of assigned primary care clinician type and care team characteristics.MethodsAdministrative data were collected for 68 family medicine clinicians (40 physicians and 28 nurse practitioners [NPs]/physician assistant [PAs]), on 11 care teams (variable MD, NP and PA on teams), caring for 77,141 patients. We performed a generalized linear mixed multivariable regression model of standardized per member per month (PMPM) median cost as the outcome, with four practice sites included as random effects.ResultsIn bivariate analysis, cost was higher in physicians than NP/PAs, in more complex patients, and associated with emergency department (ED) visit rate. On multivariate analysis, patient complexity, ED visit rate and higher patient experience ratings were independently associated with greater PMPM cost. More time in practice was associated with lower PMPM cost. In the adjusted multivariate model, physicians had 8.3% lower median PMPM costs than NP/PAs (p = 0.046).ConclusionsThe primary drivers of greater PMPM cost were patient complexity, ED visits and patient satisfaction.

Background: Perinatal factors including gestational age, birthweight, size for gestational age, delivery route, maternal parity, maternal age, maternal education, socioeconomic status, race, and sex, are associated with the future risk of obesity and co-morbid conditions. This study evaluated the relationship of birthweight for gestational age and perinatal factors with severe obesity and dyslipidemia in adulthood. Methods: We conducted a population-based, retrospective birth cohort study of infants born to residents of Olmsted County, MN between 1976 and 1982. Outcomes were assessed after age 18 years until October 2020, including severe obesity (BMI ≥ 40 kg/m 2 ) and dyslipidemia (total cholesterol ≥200 mg/dL, non-high density lipoprotein [non-HDL] cholesterol ≥145 mg/dL or HDL cholesterol <40 mg/dL). We obtained mother’s age, education level, and parity as well as newborn sex, race, type of delivery, single/multiple birth, gestational age, and birthweight from birth certificate data. Individual-level socioeconomic status (SES) of the household at birth was determined with the HOUSES index. Results: Of 10 938 birth cohort subjects, 7394 had clinic visits after age 18 years and were included, with 2630 having severe obesity (n = 798) or dyslipidemia (n = 2357) as adults. In multivariable models, female sex, singleton birth, less maternal education, and lower SES defined by HOUSES were independently associated with an increased risk of severe obesity in adulthood. Non-white race, singleton birth, and lower birthweight were independently associated with adult dyslipidemia. Birthweight for gestational age was not associated with severe obesity or dyslipidemia. Conclusion: Perinatal factors were associated with both severe obesity and dyslipidemia in adulthood. Lower SES at birth was predictive of severe obesity in adulthood, highlighting the opportunity to investigate modifiable perinatal social determinants to reduce the risk of severe obesity.

Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections. Most of the clinical studies of vitamin D in COVID-19 have been observational, and the most serious problem with observational study design is that of confounding. Observational studies typically assess the relationship of 25(OH)D values with COVID-19 outcomes. Many conditions associated with low vitamin D status are also associated with worse COVID-19 outcomes. Randomized controlled trials (RCTs) overcome the problem of confounding, typically comparing outcomes between groups receiving vitamin D supplementation or placebo. However, any benefit of vitamin D in COVID-19 may be related to the dose, duration, daily vs. bolus administration, interaction with other treatments, and timing of administration prior to or during the illness. Serum 25(OH)D values >50 nmol/L have been associated with reduced infection rates, severity of COVID-19, and mortality in observational studies. Few RCTs of vitamin D supplementation have been completed, and they have shown no benefit of vitamin D in hospitalized patients. Vitamin D may benefit those with mild or asymptomatic COVID-19, and those with greater 25(OH)D values may have lower risk of acquiring infection. Because those at greatest risk of COVID-19 are also at greatest risk of vitamin D deficiency, it is reasonable to recommend vitamin D supplementation 15–20 mcg (600–800 IU) daily for the general population during the COVID-19 pandemic. Vitamin D doses greater than 100 mcg (4000 IU) daily should not be used without monitoring serum 25(OH)D and calcium.

Research ObjectiveAn artificial intelligence (AI) algorithm based on ECG was integrated into clinical workflows to identify patients with a high likelihood of low ejection (EF), a condition that is underdiagnosed but treatable. The trial aimed to assess whether the AI‐powered clinical decision support enabled early diagnosis of low EF.Study DesignA pragmatic, cluster randomized controlled trial (RCT) was conducted in 45 primary care practices, including an academic medical center as well as community and rural clinics across Minnesota and Wisconsin. A total of 120 primary care teams, including 358 clinicians, were randomized to either intervention (access to AI results with positive results indicating a high likelihood of low EF; 181 clinicians) or control (usual care; 177 clinicians). The primary endpoint was a new diagnosis of EF≤50% within 90 days. A positive deviance qualitative study and a survey were used to assess implementation strategies.Population StudiedIn total, 22,641 adult patients (N = 11,573 intervention; N = 11,068 control) with ECG performed as part of routine care between 8/5/2019 and 3/31/2020 were included. Patients were excluded if they had known EF≤50% or a history of documented heart failure (HF) identified by clinical notes abstracted by natural language processing.Principal FindingsThe mean age of patients was 60.5 ± 17.6 years; 53.9% were women. Positive AI results were found in 6.0% of patients in both arms. Clinicians in the intervention group obtained more echocardiograms for patients with positive results (38.1% control vs. 49.6% intervention, p < 0.001), but in the overall cohort, the echocardiogram utilization was similar (18.2% vs. 19.2%, p = 0.17). The intervention increased the diagnosis of low EF in the overall cohort (1.6% vs. 2.1%, odds ratio [OR] 1.32 [1.01–1.61], p = 0.007) and among patients with positive results (14.5% vs. 19.5% OR 1.43 [1.08–1.91], p = 0.01). Results using different thresholds for low EF were consistent with the primary result. Among patients with positive results, the intervention increased echocardiography more significantly in women vs. men (p for interaction 0.02), in patients without prior echocardiogram vs. those with prior echocardiogram (p for interaction 0.04), and in patients whose ECGs were ordered in outpatient clinics (p for interaction 0.02).ConclusionsAn AI algorithm run on existing ECGs enabled the early diagnosis of low EF in a large cohort of patients managed in routine primary care practices. Because ECG is a low‐cost test frequently performed for a variety of purposes, the algorithm could improve early diagnosis and treatment of a condition that is often asymptomatic but has effective treatments, and thus, reduce the disease burden in broad populations.Implications for Policy or PracticeThe current study is one of the first RCTs that demonstrated the value of AI in routine practice. Low EF confers an increased risk of HF progression and mortality. Although there are effective therapies, low EF is undiagnosed, leading to missed opportunities for treatment. EF can be readily determined by echocardiography, but the imagining test is too resource‐intensive to screen unselected populations. The AI applied to the existing ECGs could identify high‐risk patients for further assessment.Primary Funding SourceMayo Clinic.

Background: Vitamin D deficiency may increase the risk of severe COVID-19 disease. Objectives: To determine if 25-hydroxyvitamin D [25(OH)D] levels in patients hospitalized for COVID-19 were associated with the clinical outcomes of days on oxygen, duration of hospitalization, ICU admission, need for assisted ventilation, or mortality. Methods: We conducted a retrospective study of 92 patients admitted to the hospital with SARS-CoV-2 infection between April 16, 2020 and October 17, 2020. Multivariable regression was performed to assess the independent relationship of 25(OH)D values on outcomes, adjusting for significant covariates and the hospitalization day the level was tested. Results: About 15 patients (16.3%) had 25(OH)D levels <20 ng/mL. Only 1 patient (3.4%) who had documented vitamin D supplementation prior to admission had 25(OH)D <20 ng/mL. Serum 25(OH)D concentrations were not significantly associated with any of our primary outcomes of days on oxygen, duration of hospitalization, intensive care unit (ICU) admission, need for mechanical ventilation, or mortality in any of the adjusted multivariable models. Adjusting for the hospital day of 25(OH)D sampling did not alter the relationship of 25(OH)D with any outcomes. Conclusion: Vitamin D status was not related to any of the primary outcomes reflecting severity of COVID-19 in hospitalized patients. However, our sample size may have lacked sufficient power to demonstrate a small effect of vitamin D status on these outcomes.

Vitamin D supplementation of breastfed infants is recommended because breast milk levels are low. We sought to determine if maternal supplementation would increase breast milk levels to achieve sufficiency in their infants. Forty mothers with exclusively breastfed infants were randomized to receive oral cholecalciferol (vitamin D3) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum, breast milk and urine were collected on days 0, 1, 3, 7, 14 and 28 and infant serum on days 0 and 28. In mothers receiving daily vitamin D, serum and breast milk cholecalciferol attained steady levels of 18 and 8 ng/ml, respectively, from day 3 through 28. In mothers given the single dose, serum and breast milk cholecalciferol peaked at 160 and 40 ng/ml, respectively at day 1, before rapidly declining. Breast milk and maternal serum cholecalciferol were related (r=0.87). Infant serum 25OHD (mean±SD) increased from 17±13 to 39±6 ng/ml in the single dose group and from 16±12 to 39±12 ng/ml in the daily dose group (P= 0.88). All infants achieved sufficient 25OHD serum levels (≥20ng/mL). This study suggests that maternal supplementation can achieve sufficient infant serum levels of 25OHD via breastfeeding. A large single dose of vitamin D was equivalent to daily dosing for optimizing infant vitamin D status. This research was funded by the National Center for Research Resources and Mayo Clinic. Grant Funding Source : NCRR and Mayo Clinic

Objective: The primary aim of this study was to evaluate the feasibility of collecting risk factor information and accessing digitized mammographic data in a medically marginalized population. A secondary aim was to examine the association between vitamin D status and mammographic density. Methods: Breast-screening examinations were provided for age-appropriate patients, and a referral for no-cost screening mammography was offered. Study participants were asked to undergo 25-hydroxyvitamin D testing at mammography and 1-year follow-up. Results: Of 62 women approached, 35 (56%) consented to participate. Of 32 participants who had baseline mammography, the median mammographic density measured by VolparaDensity (Volpara Solutions Limited) was 5.7%. After 1 year, 9 women obtained follow-up mammograms, with a median density of 5.7%. Vitamin D status was measured for 31 participants at baseline and 13 participants in the following year. Insufficient vitamin D status (<30 ng/mL) was noted in 77% at each time point. Mammographic density was not significantly correlated with vitamin D status ( P = .06). Conclusions: On the basis of this small pilot study, vitamin D insufficiency is common in this study population. Owing to the small sample size, an association between vitamin D insufficiency and breast density was not clear. Additional unexpected findings included substantial barriers in initial access to care and longitudinal follow-up in this population. Further study of these issues is needed.