Jacobson, Debra J.

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.

Background Persons who accumulate chronic conditions at a rate faster than their peers may experience accelerated aging and poor health outcomes, including functional limitations. Methods Adults aged ≥40 years who resided in Olmsted County, Minnesota on 1 January 2006 were identified. The prevalence of 21 chronic conditions was ascertained, and age-specific quartiles of the number of chronic conditions was estimated within 4 age groups: 40–54, 55–64, 65–74, and ≥75 years. Difficulty with nine patient-reported functional limitations (including basic and instrumental activities of daily living and mobility activities) were ascertained through 31 October 2018. Cox regression was used to model associations of chronic condition quartiles with new-onset functional limitations considered separately. We estimated absolute risk differences and hazard ratios stratified by age group, and adjusted for sex, race, ethnicity, marital status, education, and the residual effect of age. Results Among 39,624 persons (44.5% men, 93.2% white), the most common reported new functional limitations were difficulty with climbing stairs, walking, and housekeeping. For all functional limitations, the absolute risk differences were largest among the oldest age group (≥75 years). Approximately twofold increased hazard ratios were observed among those in the highest vs. lowest quartile for the three oldest age groups, and approximately threefold or higher hazard ratios were observed for persons aged 40-54 years. Conclusion Persons with increased accumulation of chronic conditions experience increased risks of developing functional limitations compared to their peers. These findings underscore the importance of assessing health status and of employing interventions to prevent and effectively manage multi-morbidity at all ages.

Abstract Introduction End‐of‐life care differs by serious illness diagnosis. Cancer and dementia are serious illnesses that have been associated with less intensive end‐of‐life health care use. It is not known how health care utilization varies in the presence of >1 serious illness. Methods We used the Rochester Epidemiology Project to identify persons living in a midwestern area who died on July 1, 2017–June 30, 2018 at age ≥65 years, and were seriously ill. We examined the number of emergency department (ED), hospital, and intensive care unit (ICU) stays in the last 6 months and the last 30 days of life. We used Poisson regression to determine the incidence rate ratio for ED, hospital, and ICU stay in the last 6 months and 30 days of life by number of serious illness diagnoses. For cancer and dementia, we examined the effect of an additional serious illness. Results We included a population of 1372 adults who were, on average, 84 years, 52% female, and 96% white. Approximately 41% had multiple serious illnesses. Compared to older adults with 1 serious illness diagnosis, rates of hospitalization, and ICU stay for adults with 2 or ≥3 serious illness diagnoses were at least 1.5 times higher in the last 6 months and the last 30 days of life. Rates of ED visits were significantly higher for older adults with 2 or ≥3 serious illness diagnoses in the last 6 months of life, but only higher for those with ≥3 versus 1 serious illness diagnosis in the last 30 days of life. For both cancer and dementia, rates of ED visits, hospitalization and ICU stay were lower for the condition alone than when an additional serious illness diagnosis was present. Conclusion Having multiple serious illnesses increases the risk of health care utilization at the end of life.

Objective: This study determined the incidence rates for obesity among adult patients ages 20 and older empaneled in primary care practice in Midwest United States to potentially identify an optimum timeframe for initiating intervention. Background: Primary care practice patients are likely to reflect underlying community trends in overweight and obesity; however, data on overweight and obesity in primary care patients is limited. While childhood incidence rates of obesity have been well reported, there is still a paucity of data on the incidence of obesity among adult population; literature has mainly focused on its prevalence. Methods: Medical record review of identified cohort with BMI data was conducted. Population was stratified by age and sex and overweight category was subdivided into tertiles. Results: Majority of 40 390 individuals who comprised the final population and had follow-up data, consisted of adults ages 40 to 69 years (47.5%), female (59.8%) of non-Hispanic ethnicity (95.9%) with 21 379 (52.8%) falling in weight category of overweight. Incidence of obesity was 7% at 1 year and 16% at 3 years follow-up. Highest percentages of individuals who became obese at 1 and 3 years were in age category of 40 to 69 years among men and 20 to 39 years among women. In Cox regression analysis, there was statistically significant association to developing obesity among all tertile groups in the overweight category. Age and particularly gender appeared to be modifying factors to likelihood of developing obesity. Conclusion: Study results suggest that while obesity incidence is higher among certain age groups in both genders, middle-aged women, and men in all tertiles of overweight category are at highest risk and may be the optimum population to target for weight loss interventions. Findings support the initiation of population-based interventions before onset of obesity.

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.

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)].