St Sauver, Jennifer L

Abstract Context Metformin is the first-line drug for treating diabetes but has a high failure rate. Objective To identify demographic and clinical factors available in the electronic health record (EHR) that predict metformin failure. Methods A cohort of patients with at least 1 abnormal diabetes screening test that initiated metformin was identified at 3 sites (Arizona, Mississippi, and Minnesota). We identified 22 047 metformin initiators (48% female, mean age of 57 ± 14 years) including 2141 African Americans, 440 Asians, 962 Other/Multiracial, 1539 Hispanics, and 16 764 non-Hispanic White people. We defined metformin failure as either the lack of a target glycated hemoglobin (HbA1c) (<7%) within 18 months of index or the start of dual therapy. We used tree-based extreme gradient boosting (XGBoost) models to assess overall risk prediction performance and relative contribution of individual factors when using EHR data for risk of metformin failure. Results In this large diverse population, we observed a high rate of metformin failure (43%). The XGBoost model that included baseline HbA1c, age, sex, and race/ethnicity corresponded to high discrimination performance (C-index of 0.731; 95% CI 0.722, 0.740) for risk of metformin failure. Baseline HbA1c corresponded to the largest feature performance with higher levels associated with metformin failure. The addition of other clinical factors improved model performance (0.745; 95% CI 0.737, 0.754, P < .0001). Conclusion Baseline HbA1c was the strongest predictor of metformin failure and additional factors substantially improved performance suggesting that routinely available clinical data could be used to identify patients at high risk of metformin failure who might benefit from closer monitoring and earlier treatment intensification.

Objectives To compare the agreement between percentile ranks from 4 multi-morbidity scores. Design Population-based descriptive study. Setting Olmsted County, Minnesota (USA). Participants We used the medical records-linkage system of the Rochester Epidemiology Project (REP; http://www.rochesterproject.org ) to identify all residents of Olmsted County, Minnesota who reached one or more birthdays between 1 January 2005 and 31 December 2014 (10 years). Methods For each person, we calculated 4 multi-morbidity scores using readily available diagnostic code lists from the US Department of Health and Human Services, the Clinical Classifications Software, and the Elixhauser Comorbidity Index. We calculated scores using diagnostic codes received in the 5 years before the index birthday and fit quantile regression models across age and separately by sex to transform unweighted, simple counts of conditions into percentile ranks as compared to peers of same age and of same sex. We compared the percentile ranks of the 4 multi-morbidity scores using intra-class correlation coefficients (ICCs). Results We assessed agreement in 181,553 persons who reached a total of 1,075,433 birthdays at ages 18 years through 85 years during the study period. In general, the percentile ranks of the 4 multi-morbidity scores exhibited high levels of agreement in 6 score-to-score pairwise comparisons. The agreement increased with older age for all pairwise comparisons, and ICCs were consistently greater than 0.65 at ages 50 years and older. Conclusions The assignment of percentile ranks may be a simple and intuitive way to assess the underlying trait of multi-morbidity across studies that use different measures.

Objectives To study the association between multi-morbidity percentiles, which is a measure of clinical aging, and interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α. Methods Participants 50 to 95 years of age from the Mayo Clinic Study of Aging were assigned age- and sex-specific multi-morbidity percentiles using look-up tables that were reported previously (n = 1646). Percentiles were divided into quintiles for analysis. Plasma IL-6, IL-10, and TNF-α levels were measured in 1595 participants. Median inflammatory marker levels were compared across multi-morbidity quintiles using nonparametric tests. Results People with higher multi-morbidity percentiles had significantly higher IL-6 and TNF-α levels compared with those with lower multi-morbidity percentiles. Tests for trend across five multi-morbidity quintiles were significant among women for IL-6 and among participants 70 years of age or older for IL-6 and TNF-α. IL-10 was not associated with multi-morbidity percentiles. Conclusions Multi-morbidity percentiles may be a useful clinical index of biological age for future studies, particularly in women and people 70 years of age and older.

Objectives Sex as a biological variable affects response to opioids. However, few reports describe the prevalence of specific adverse reactions to commonly prescribed opioids in men and women separately. A large cohort was used to investigate sex differences in type and occurrence of adverse reactions associated with use of codeine, tramadol, oxycodone and hydrocodone. Design Retrospective cohort study. Setting Participants in the Right Drug, Right Dose, Right Time (RIGHT) Study. Participants The medical records of 8457 participants in the RIGHT Study who received an opioid prescription between 1 January 2004 and 31 December 2017 were reviewed 61% women, 94% white, median age (Q1–Q3)=58 (47–66). Primary and secondary outcome measures Adverse reactions including gastrointestinal, skin, psychiatric and nervous system issues were collected from the allergy section of each patient’s medical record. Sex differences in the risk of adverse reactions due to prescribed opioids were modelled using logistic regression adjusted for age, body mass index, race and ethnicity. Results From 8457 participants (of which 449 (5.3%) reported adverse reactions), more women (6.5%) than men (3.4%) reported adverse reactions to at least one opioid (OR (95% CI)=2.3 (1.8 to 2.8), p<0.001). Women were more likely to report adverse reactions to tramadol (OR (95% CI)=2.8 (1.8 to 4.4), p<0.001) and oxycodone (OR (95% CI)=2.2 (1.7 to 2.9), p<0.001). Women were more likely to report gastrointestinal (OR (95% CI)=3.1 (2.3 to 4.3), p<0.001), skin (OR (95% CI)=2.1 (1.4 to 3.3), p=0.001) and nervous system issues (OR (95% CI)=2.3 (1.3 to 4.2), p=0.004). Conclusions These findings support the importance of sex as a biological variable to be factored into pain management studies.

Objectives To describe the percentile distribution of multimorbidity across age by sex, race and ethnicity, and to demonstrate the utility of multimorbidity percentiles to predict mortality. Design Population-based descriptive study and cohort study. Setting Olmsted County, Minnesota (USA). Participants We used the medical records-linkage system of the Rochester Epidemiology Project (REP; http://www.rochesterproject.org ) to identify all residents of Olmsted County, Minnesota who reached one or more birthdays between 1 January 2005 and 31 December 2014 (10 years). Methods For each person, we obtained the count of chronic conditions (out of 20 conditions) present on each birthday by extracting all of the diagnostic codes received in the 5 years before the index birthday from the electronic indexes of the REP. To compare each person’s count to peers of same age, the counts were transformed into percentiles of the total population and displayed graphically across age by sex, race and ethnicity. In addition, quintiles 1, 2, 4 and 5 were compared with quintile 3 (reference) to predict the risk of death at 1 year, 5 years and through end of follow-up using time-to-event analyses. Follow-up was passive using the REP. Results We identified 238 010 persons who experienced a total of 1 458 094 birthdays during the study period (median of 6 birthdays per person; IQR 3–10). The percentiles of multimorbidity across age did not vary noticeably by sex, race or ethnicity. In general, there was an increased risk of mortality at 1 and 5 years for quintiles 4 and 5 of multimorbidity. The risk of mortality for quintile 5 was greater for younger age groups and for women. Conclusions The assignment of multimorbidity percentiles to persons in a population may be a simple and intuitive tool to assess relative health status, and to predict short-term mortality, especially in younger persons and in women.

Background Opioid analgesics are among the most commonly prescribed medications in the United States. Opioids are useful in the management of pain, but their use can also adversely affect patients. However, studies reporting patterns of adverse events due to use of opioid analgesics in men and women are still scarce. Understanding the individual characteristics affecting response to opioids may allow clinicians to better individualize treatments. In this study, we investigated sex differences in the patterns of adverse events as a result of opioid use. Methods We used data from 8,457 patients participating in the Mayo Clinic Biobank “Right Drug, Right Dose, Right Time (RIGHT protocol)” study of pre‐emptive genotyping who were prescribed at least one of four opioid medications (codeine, tramadol, hydrocodone, or oxycodone) between 01/01/2004 and 12/31/2017. Adverse events due to use of these medications were collected from the allergy section in each patient’s electronical medical record, and were organized into four Medical Dictionary for Regulatory Activities (MedDRA) categories: gastrointestinal (e.g. nausea, vomiting), skin and subcutaneous tissue (e.g. rash, itching), psychiatric (e.g. anxiety, hallucinations), and nervous system (e.g. headache, dizziness). We modeled sex differences in the risk of adverse events by each opioid, and sex differences in the risk of each adverse event due to any opioid using logistic regression adjusted for age, race, ethnicity, and body mass index (BMI). Results Participants with at least one opioid prescription were 60.8% female, mostly white (94.2%) and non‐Hispanic (98.9%). Women (relative to men) were younger (median = 61.6 vs. 69.1, respectively), had lower BMI (median = 27.4 vs. 28.9), and were prescribed more codeine (18.8% vs. 15.5%). Overall, 456 (5.4%) persons had a note in the allergy section of their medical record indicating a problem with an opioid medication. Women were more likely than men to have a note in the allergy section referring to at least one opioid (6.6% and 3.5%, respectively; p < 0.001). In addition, among participants who had at least one note related to opioid use in their allergy section, women were more likely to have notes regarding gastrointestinal complications (OR [95% CI] = 2.07 [1.3 – 3.2], p = 0.002), but less likely to have notes regarding psychiatric issues (OR [95% CI] = 0.30 [0.2 – 0.5], p < 0.001). Conclusion Women were more likely than men to experience adverse events due to use of codeine, tramadol, hydrocodone, and oxycodone. In addition, the types of adverse reactions differed between men and women. These data suggest that further studies are needed to ensure that both men and women have optimal responses to opioid medications. Support or Funding Information This work was supported by the Mayo Clinic Specialized Center of Research Excellent on Sex Differences, the Mayo Clinic Center for Individualized Medicine, the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, and the National Institutes of Health grants [U19 GM61388 (The Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 GM125633, R01 AG034676 (The Rochester Epidemiology Project)], and [U01 HG06379 and U01 HG06379 Supplement (The Electronic Medical Record and Genomics (eMERGE) Network)].

Introduction Population-level screening has been shown to reduce the incidence and mortality of colorectal cancer (CRC). Unfortunately, adherence to screening recommendations among eligible US adults remains below national goals. A relatively new non-invasive screening modality, the Food and Drug Administration–approved multi-target stool DNA (mt-sDNA) assay (commercialised as Cologuard), which combines the detection of haemoglobin and DNA abnormalities, has been completed by more than 3 million individuals. Given mt-sDNA’s recent availability, the effectiveness of mt-sDNA screening with respect to CRC incidence and mortality reduction has not yet been established. Methods and analysis Through an academic–industry collaboration, a prospective cohort study (Voyage) was designed with an initial enrolment target of 150 000 individuals with mt-sDNA ordered by their healthcare provider for CRC screening. Consented participants will be asked to complete a baseline questionnaire to collect sociodemographic and health information. Additional questionnaires will be provided after 1 year, and every 3 years thereafter, to collect data regarding CRC screening follow-up in order to estimate rates of CRC incidence and other health outcomes. Linkage to the National Death Index will be used to estimate mortality rates. Ethics and dissemination The Voyage study will be conducted in accordance with international guidelines and local regulatory requirements and laws. Data will be stored and retained at Mayo Clinic. Only limited data elements required for research purposes will be transmitted between Mayo Clinic and Exact Sciences Laboratories. Results of the Voyage study will be disseminated through scientific presentations and publications. Trial registration number NCT04124406.