Thacher, Tom D.

This protocol paper details a single-center, randomized trial to compare greater occipital nerve blocks (GONBs) to multiple peripheral nerve blocks (MPNBs) for acute headache relief and prophylaxis in episodic migraine. GONBs are effective for the treatment and prevention of migraine, but a combination of trigeminal and occipital nerve blocks can be effective when GONBs alone have failed. To test this hypothesis, 60 adult participants will be randomized to receive either bilateral GONB or MPNBs of the bilateral greater occipital, lesser occipital, auriculotemporal, supraorbital, and supratrochlear nerves during an acute migraine with 0.5–1.25 mL bupivacaine 0.5%. Methylprednisolone 10–20 mg will be added only for the occipital nerves. Anesthesia in the distribution of each nerve block will be tested, and reinjection with bupivacaine will be performed until anesthesia is achieved. The primary endpoint will be pain freedom 20 min after injections. Secondary endpoints include pain freedom at 2 and 24 h, headache relief at 2 h, frequency and severity of subsequent migraine, and absenteeism from work/school/life events due to headaches over a 12-week follow-up period compared to a four-week run-in period. Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04278573).

Objectives: To assess how social risk factors and socioeconomic status (SES) affect health care costs at a large, integrated health system of 45 clinics in Iowa, Minnesota, and Wisconsin. Methods: We retrospectively reviewed administrative patient cost data from January 1 through December 31, 2022. Social risk factors (lack of financial resources, food insecurity, intimate partner violence, unmet transportation needs, and housing instability) were determined with patient questionnaires. Cost z -scores were compared across all risk-factor quartiles. We used a housing-based measure to objectively determine SES. Results: We analyzed data from 410 624 patients empaneled with 689 family medicine clinicians. Self-reported risk factor data were incomplete for 219 321 patients. Costs were higher for those with higher social risk (mean cost z -score: high risk = 0.38, low risk = 0.11; P < .001). In addition, higher costs were associated with increasing age, greater medical complexity (higher Adjusted Clinical Group scores), White race, and lack of financial resources. Although we observed geographic variations in cost, urban and rural locations did not have significant cost differences. Costs were similar across all quartiles of SES, and the absolute difference in cost z -scores between the highest and lowest SES quartiles was only 0.04. The multivariate analysis, which adjusted for age, medical complexity, race, sex, and objective SES, showed that these specific associations were substantially decreased and no longer significantly associated with mean cost z -scores. Conclusions: Patient-reported social risk factors were significantly associated with increased cost of care in a large, multispecialty health system in the midwestern US. These associations were decreased in the multivariate analysis. Results should be interpreted cautiously for readers outside the midwestern US, given potential responder bias and the racial homogeneity (92% White) of the study cohort.

Introduction/Objectives: Little is known about the prevalence of patient-reported social risk factors and the use of the HOUSES Index, a simple, reliable method of assessing socioeconomic status (SES) based on publicly available housing data, in a predominantly rural, primary care population. Methods: We conducted a cross-sectional analysis of adult patients paneled to family medicine clinicians in a US Midwest health system as of December 31, 2022. Patients’ listed address determined HOUSES Index as quartile rank (Q1 lowest SES) and rural/urban status. Social risk data including housing, food, transportation, finances, and violence were collected from health record questionnaires. A mixed effect model was used to assess associations between social risk, HOUSES Index, and rurality. Results: Of the 352 355 patients included, rural patients were more likely than urban patients to report all social risk factors and had lower SES as measured by HOUSES quartiles. In the mixed effects analysis, HOUSES quartile was independently predictive of reporting an at-risk social risk factor (Q1 vs Q4 OR = 2.27, 95% CI = 2.19-2.37), but rurality was not (OR = 1.02, 95% CI = 0.97-1.07) after adjusting for HOUSES. Conclusions: The increased prevalence of social risk factors among rural residents is largely explained by individual SES measured by HOUSES Index.

Introduction: Treatment of cutaneous warts with intralesional vitamin D3 has demonstrated promising results in over 35 studies with methodological limitations. Methods: We conducted a randomized, double-blind, placebo-controlled trial in our primary care procedure clinic of intralesional vitamin D3 12 000 IU vs placebo in cutaneous warts every 4 weeks up to 3 times. Warts were assessed 4, 8, 12, and 24 weeks after the initial injection. The primary outcome was complete wart resolution. Reduction in wart size was a secondary outcome. Results: Between October 2020 and April 2023, we enrolled 77 participants with 1 or more cutaneous warts (41 and 36 in vitamin D3 and placebo groups, respectively) with untreated (32%) and recalcitrant (69%) warts. At 24 weeks, the index wart had resolved in 12 (30%) of vitamin D3 and 10 (31%) placebo participants. Treatment with vitamin D3 had no effect on wart surface area in an adjusted model nor wart resolution in analysis adjusted for baseline wart size, multiple warts, and the vehicle (OR 0.31 [95% CI] 0.01-10.3; P = 0.51). Conclusions: These results demonstrate a lack of benefit of intralesional vitamin D3 in cutaneous warts. ( ClinicalTrials.gov number NCT04278573)

Vitamin D (VitD) is an essential nutrient for preventing rickets in breastfeeding infants. Maternal supplementation is the preferred method for infant nutrition, yet concentrations of VitD and 25-hydroxyvitamin D (25OHD) in breastmilk are low unless the mother consumes substantial doses of vitamin D. Recently, we reported that sulfate-conjugated forms of vitamin D (VitD-S) and 25-hydroxyvitamin D (25OHD-S) are present in breast milk. Freshly expressed breast milk from mothers who were vitamin D-sufficient (serum 25OHD >50 nmol/L) contained approximately 6 nmol/L VitD-S and 0.5 nmol/L 25OHD-S. It is hypothesized that these sulfated metabolites are contributing to the total vitamin D nutritional value of milk; however, their physiological roles in infant nutrition are not yet understood. In order to assess their nutritional value, we evaluated two aspects that can affect the delivery and uptake of the nutrients by infants: breast milk storage and infant digestion. The United States Centers for Disease Control and Prevention recommends that breast milk can be stored safely at room temperature (22°C) for ≤4 hours, in refrigeration (4°C) for <4 days, or frozen (-20°C) for 6 months. After implementing the recommended storage conditions on breast milk samples, the metabolites, VitD-S and 25OHD-S, were measured by LC-MS/MS and UV spectroscopy. We observed that in breast milk stored at room temperature or 4°C, the metabolites undergo molecular degradation by isomerization within 24 hrs. Therefore, breast milk stored overnight (>8 h) in refrigeration will not provide the sulfated vitamin D metabolites to the infants. To evaluate molecular integrity of the sulfated metabolites during infant digestion, we collected saliva and fecal matter samples from infants, 1-6 months of age, who were either exclusively breastfed or breastfed and supplemented with formula ( ClinicalTrials.gov , NCT 06203041). The sulfatase enzymatic activity was assessed in the saliva and fecal matter samples by colorimetric assay. Overall, the sulfatase activity (mean ± SD) in saliva was 0.8 ± 0.7 nM/mg/min, ranging 0.0-2.5 nM/mg/min (n=13). The sulfatase activity in fecal samples was significantly greater than saliva ( P = 0.009), averaging 1.8 ± 1.4 nM/mg/min and ranging 0.1-4.9 nM/mg/min (n = 9) across infant samples. In a comparison between infants based on diet, we observed greater sulfatase activity in the fecal matter of exclusively breastfed infants than in infants that were breastfed with formula ( P = 0.056). This observational study is ongoing and not yet statistically powered. The presence of sulfatase activity in the infant digesta suggests that VitD-S and 25OHD-S are subject to enzymatic sulfate hydrolysis prior to absorption. Furthermore, infants who are exclusively breastfed may utilize the hydrolysis pathway more effectively than infants who are supplemented with formula. In summary, the nutritional value of VitD-S and 25OHD-S is affected by both milk storage and infant digestion. Future clinical studies investigating vitamin D nutrition in breastfed infants should consider evaluating storage of breast milk and diet of the infant as important parameters in the statistical models and analyses. The Mayo Clinic Parker D. Sanders & Isabella G. Sanders Professor of Family Medicine Endowment, Mayo Clinic Women’s Health Center Pilot Award Project. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Toxins from ingested water can significantly affect overall physical health in children and adults. In the United States, domestic water wells are not commonly tested for any heavy metal contaminants. It is well-known that chronic arsenic ingestion from water is linked to serious health effects. We surveyed patients at our academic institution via emailed questionnaires in 2023 to determine whether those with children living at home reported different patterns of behavior around well water testing as compared to those without. Survey data were collected from 8994 respondents in the U.S. Midwest who reported using residential well water. Results were used to evaluate the influence of children in the home on testing behaviors, and secondarily, whether parental demographics affected testing frequency. Respondents with children at home did not report increased testing frequency compared to those without. In parents who did report testing, having more children, being younger, and living in Wisconsin were associated with an increased frequency. Parental gender, race, and ethnicity did not correlate with testing behaviors. A total of 70% of respondents did not feel concerned about their water safety and 85% were not concerned about arsenic specifically in their water. Increased risk of toxicity to children from arsenic does not appear to influence reported well water testing behavior among parents.

Background: Arsenic is a well-known toxin which may contaminate household water. It is harmful when ingested over prolonged periods of time. As a result, public health experts recommend that water should be screened and treated to prevent arsenic ingestion. In the United States, the responsibility of testing and treatment of private wells falls on homeowners. Despite recommendations for routine screening, this is rarely done. Objectives: To assess the prevalence of well water use in a Midwestern patient population, how patients and clinicians perceive the risks of arsenic in well water, and whether additional resources on well water testing are desired. These findings will be used to influence tools for clinicians regarding symptom and examination findings of chronic arsenic exposure and potentiate the distribution of informational resources on well water testing. Methods: Surveys were sent via email to all actively practicing primary care clinicians at the Mayo Clinic in the United States Midwest, and all active adult patients at the Mayo Clinic in the same region. Our team analyzed survey data to determine whether both patients and clinicians are aware of the health effects of chronic arsenic toxicity from well water, the need for routine well water testing and whether each group wants more information on the associated risks. Results: Both patients and primary care clinicians worry about arsenic exposure. Patients with well water are concerned about their water safety yet feel uninformed about testing options. Clinicians do not know how prevalent well water use is among their patients, feel uninformed about the chronic risks of arsenic exposure and the physical examination associated with it. Both groups unanimously want more information on testing options. Conclusions: Our findings show a significant reliance on well water use in the American Midwest, and unanimous support for the need for further well water testing information and resources for patients and their clinicians.