Multimorbidity trajectories in early adulthood and middle age: Findings from the CARDIA prospective cohort study.

Background: Multimorbidity research has focused on the prevalence and consequences of multimorbidity in older populations. Less is known about the accumulation of chronic conditions earlier in the life course. Methods: We identified patterns of longitudinal multimorbidity accumulation using 30 years of data from in-person exams, annual follow-ups, and adjudicated end-points among 4,945 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Chronic conditions included arthritis, asthma, atrial fibrillation, cancer, end stage renal disease, chronic obstructive pulmonary disease, coronary heart disease, diabetes, heart failure, hyperlipidemia, hypertension, and stroke. Trajectory patterns were identified using latent class growth curve models. Results: Mean age (SD) at baseline (1985-6) was 24.9 (3.6), 55% were female, and 51% were Black. The median follow-up was 30 years (interquartile range 25-30). We identified six trajectory classes characterized by when conditions began to accumulate and the rapidity of accumulation: (1) early-fifties, slow, (2) mid-forties, fast, (3) mid-thirties, fast, (4) late-twenties, slow, (5) mid-twenties, slow, and (6) mid-twenties, fast. Compared with participants in the early-fifties, slow trajectory class, participants in mid-twenties, fast were more likely to be female, Black, and currently smoking and had a higher baseline mean waist circumference (83.6 vs. 75.6 cm) and BMI (27.0 vs. 23.4 kg/m2) and lower baseline physical activity (414.1 vs. 442.4 exercise units). Conclusions: A life course approach that recognizes the heterogeneity in patterns of accumulation of chronic conditions from early adulthood into middle age could be helpful for identifying high risk subgroups and developing approaches to delay multimorbidity progression.

Deprescribing electronic case reviews for older veterans at risk for falls: Effects on drug burden and falls.

BACKGROUND: Falls are the most common medication-related safety event in older adults. Deprescribing fall risk-increasing drugs (FRIDs) may mitigate fall risk. This study assesses the effects of an innovative deprescribing program in reducing FRID burden and falls-related acute visits over 1 year. METHODS: The Falls Assessment of Medications in the Elderly (FAME) Program is a pilot deprescribing program designed to improve medication safety in Veterans aged ≥65, screening positive for high fall risk at the Durham Veterans Affairs Health Care System. Central case finding and electronic case reviews with deprescribing recommendations were completed by an interdisciplinary team, forwarded to prescribers for approval, then implemented during follow-up telephone visits by FAME team. Primary outcome was change in FRID burden calculated by modified Drug Burden Index (DBI) at 1 year and an exploratory outcome was 1-year fall-related acute visits. RESULTS: Overall, 472 patients (236 intervention cases, 236 matched controls) were included in the study. Of the 236 patients receiving a FAME deprescribing plan, 147 had recommendations approved by prescriber and patient. In the intention-to-treat analysis, the 1-year change in modified DBI was -0.15 (95% CI -0.23, -0.08) in the intervention cohort and -0.11 (-0.21, -0.00) in the matched control cohort (p = 0.47). The odds of increasing DBI by a clinically important threshold of 0.5 was significantly lower in the FAME cohort (OR 0.37, 0.21, 0.66). Fall-related acute events occurred in 6.3% of patients in the intervention group versus 11.0% in control patients over a one-year period (p = 0.10). CONCLUSIONS: The program was associated with a significantly lower odds of further increasing FRID burden at 1 year compared to matched controls. An electronic case review and telephone counseling program has the potential to reduce drug-related falls in high-risk older adults.

Surgery Clerkship Directors' Perceptions of the COVID-19 Pandemic's Impact on Medical Student Education.

BACKGROUND: This study assessed the national impact of the COVID-19 pandemic on the education of medical students assigned to surgery clerkship rotations, as reported by surgery clerkship directors(CDs). STUDY DESIGN: In the spring of 2020 and 2021, the authors surveyed 164 CDs from 144 LCME-accredited US medical schools regarding their views of the pandemic's impact on the surgery clerkship curriculum, students' experiences, outcomes, and institutional responses. RESULTS: Overall survey response rates, calculated as no. respondents/no. surveyed were 44.5%(73/164) and 50.6%(83/164) for the spring 2020 and 2021 surveys, respectively. Nearly all CDs(>95%) pivoted to virtual platforms and solutions. Most returned to some form of in-person learning by winter 2020, and pre-pandemic status by spring 2021(46%, 38/83). Students' progression to the next year was delayed by 12%(9/73), and preparation was negatively impacted by 45%(37/83). Despite these data, CDs perceived students' interest in surgical careers was not significantly affected(89% vs. 77.0%, p=0.09). Over the one-year study, the proportion of CDs reporting a severe negative impact on the curriculum dropped significantly(p<0.0001) for most parameters assessed except summative evaluations(40.3% vs. 45.7%,p=0.53). CDs(n=83) also noted the pandemic's positive impact with respect to virtual patient encounters(21.7%), didactics(16.9%), student test performance(16.9%), continuous personal learning(14.5%), engagement in the clerkship(9.6%) and student interest in surgery as a career(7.2%). CONCLUSION: During the pandemic, the severe negative impact on student educational programs lessened and novel virtual curricular solutions emerged. Student interest in surgery as a career was sustained. Measures of student competency and effectiveness of new curriculum, including telehealth, remain areas for future investigation.

One-Year Follow-Up of COVID-19 Impact on Surgical Education: Clinical Training Restored but Surgical Trainee Emotional Well-Being Still at Risk.

BACKGROUND: A previous survey documented the severe disruption of the coronavirus disease 2019 pandemic on surgical education and trainee well-being during the initial surge and systemic lockdowns. Herein, we report the results of a follow-up survey inclusive of the 2020 to 2021 academic year. STUDY DESIGN: A survey was distributed to education leaders across all surgical specialties in summer 2021. We compared the proportion of participants reporting severe disruption in key areas with those of the spring 2020 survey. Aggregated differences by year were assessed using chi-square analysis. RESULTS: In 2021, severe disruption of education programs was reported by 14% compared with 32% in 2020 (p < 0.0001). Severe reductions in nonemergency surgery were reported by 38% compared with 87% of respondents in 2020. Severe disruption of expected progression of surgical trainee autonomy by rank also significantly decreased to 5% to 8% in 2021 from 15% to 23% in 2020 among respondent programs (p < 0.001). In 2021 clinical remediation was reported for postgraduate year 1 to 2 and postgraduate year 3 to 4, typically through revised rotations (19% and 26%) and additional use of simulation (20% and 19%) maintaining trainee promotion and job placement. In 2021, surgical trainees' physical safety and health were reported as less severely impacted compared with 2020; however, negative effects of isolation (77%), burnout (75%), and the severe impact on emotional well-being (17%) were prevalent. CONCLUSIONS: One year after the initial coronavirus disease 2019 outbreak, clinical training and surgical trainee health were less negatively impacted. Disruption of emotional well-being remained high. Future needs include better objective measures of clinical competence beyond case numbers and the implementation of novel programs to promote surgical trainee health and well-being.

Impact of the COVID-19 pandemic on surgical trainee education and well-being spring 2020-winter 2020: A path forward.

BACKGROUND: The time course and longitudinal impact of the COVID -19 pandemic on surgical education(SE) and learner well-being (LWB)is unknown. MATERIAL AND METHODS: Check-in surveys were distributed to Surgery Program Directors and Department Chairs, including general surgery and surgical specialties, in the summer and winter of 2020 and compared to a survey from spring 2020. Statistical associations for items with self-reported ACGME Stage and the survey period were assessed using categorical analysis. RESULTS: Stage 3 institutions were reported in spring (30%), summer (4%) [p < 0.0001] and increased in the winter (18%). Severe disruption (SD) was stage dependent (Stage 3; 45% (83/184) vs. Stages 1 and 2; 26% (206/801)[p < 0.0001]). This lessened in the winter (23%) vs. spring (32%) p = 0.02. LWB severe disruption was similar in spring 27%, summer 22%, winter 25% and was associated with Stage 3. CONCLUSIONS: Steps taken during the pandemic reduced SD but did not improve LWB. Systemic efforts are needed to protect learners and combat isolation pervasive in a pandemic.

Factors Associated With Adherence to Osteoporosis Medications Among Male Veterans.

Risk factors for nonadherence to osteoporosis medication have been well described for cohorts of women with osteoporosis, but little is known about predictors or mediators of nonadherence in men. We conducted a secondary analysis of a national cohort of male veterans to explore factors associated with nonadherence to osteoporosis medications. We included veterans with a prescription for an oral bisphosphonate or calcitonin between 2000 and 2010. We identified demographic, comorbid, and fracture-related risk factors by their International Classification of Diseases-9 (ICD-9) and Current Procedural Terminology (CPT) codes and used multivariable logistic regression to evaluate their association with adherence. Adherence was measured by medication possession ratio (MPR) over 5 years, starting at the time of their first prescription during the study period and censoring at death or end of study period. Of 135,306 men identified with at least one prescription for an osteoporosis medication during the study period, 90,406 (67%) were nonadherent (MPR < 0.80). The median duration of therapy was 3.2 years (interquartile range [IQR] = 1.7-5.0). In the fully adjusted model, the odds of adherence were lower in those aged <65 years (odds ratio [OR] = 0.87; 95% confidence interval [CI] 0.84-0.89), with no copay (OR = 0.78; 95% CI 0.76-0.80), dementia (OR = 0.87; 95% CI 0.83-0.91), anxiety/depression (OR = 0.92; 95% CI 0.90-0.95), tobacco use (OR = 0.91; 95% CI 0.89-0.94), alcohol abuse (OR = 0.91; 95% CI 0.89-0.94), rheumatoid arthritis (OR = 0.92; 95% CI 0.87-0.97), and on androgen deprivation therapy (OR = 0.89; 95% CI 0.83-0.95). The odds of adherence were higher in whites (OR = 1.14; 95% CI 1.11-1.17), with a prior screening colonoscopy (OR = 1.12; 95% CI 1.09-1.14), on alendronate versus other agents (OR = 1.61; 95% CI 1.55-1.67), with a dual-energy X-ray absorptiometry (DXA) (OR = 1.14; 95% CI 1.12-1.17), on glucocorticoids (OR = 1.08; 95% CI 1.02-1.14), and with recent fracture (OR = 1.07; 95% CI 1.04-1.10). In conclusion, adherence to oral bisphosphonates/calcitonin is poor, with particular subgroups at greatest risk. These findings may help tailor approaches for supporting adherence in men prescribed osteoporosis medications. © 2021 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Impact of Supervised Exercise on One-Year Medication Use in Older Veterans with Multiple Morbidities.

Exercise is touted as the ideal prescription to treat and prevent many chronic diseases. We examined changes in utilization and cost of medication classes commonly prescribed in the management of chronic conditions following participation in 12-months of supervised exercise within the Veterans Affairs Gerofit program. Gerofit enrolled 480 veterans between 1999 and 2017 with 12-months participation, with 453 having one or more active prescriptions on enrollment. Active prescriptions overall and for five classes of medications were examined. Changes from enrollment to 12 months were calculated, and cost associated with prescriptions filled were used to estimate net cost changes. Active prescriptions were reduced for opioids (77 of 164, 47%), mental health (93 of 221, 42%), cardiac (175 of 391, 45%), diabetes (41 of 166, 25%), and lipid lowering (56 of 253, 22%) agents. Cost estimates resulted in a net savings of $38,400. These findings support the role of supervised exercise as a favorable therapeutic intervention that has impact across chronic conditions.

Impact of the COVID-19 Pandemic on Surgical Training and Learner Well-Being: Report of a Survey of General Surgery and Other Surgical Specialty Educators.

BACKGROUND: The COVID-19 pandemic disrupted the delivery of surgical services. The purpose of this communication was to report the impact of the pandemic on surgical training and learner well-being and to document adaptations made by surgery departments. STUDY DESIGN: A 37-item survey was distributed to educational leaders in general surgery and other surgical specialty training programs. It included both closed- and open-ended questions and the self-reported stages of GME during the COVID-19 pandemic, as defined by the ACGME. Statistical associations for items with stage were assessed using categorical analysis. RESULTS: The response rate was 21% (472 of 2,196). US stage distribution (n = 447) was as follows: stage 1, 22%; stage 2, 48%; and stage 3, 30%. Impact on clinical education significantly increased by stage, with severe reductions in nonemergency operations (73% and 86% vs 98%) and emergency operations (8% and 16% vs 34%). Variable effects were reported on minimal expected case numbers across all stages. Reductions were reported in outpatient experience (83%), in-hospital experience (70%), and outside rotations (57%). Increases in ICU rotations were reported with advancing stage (7% and 13% vs 37%). Severity of impact on didactic education increased with stage (14% and 30% vs 46%). Virtual conferences were adopted by 97% across all stages. Severity of impact on learner well-being increased by stage-physical safety (6% and 9% vs 31%), physical health (0% and 7% vs 17%), and emotional health (11% and 24% vs 42%). Regardless of stage, most but not all made adaptations to support trainees' well-being. CONCLUSIONS: The pandemic adversely impacted surgical training and the well-being of learners across all surgical specialties proportional to increasing ACGME stage. There is a need to develop education disaster plans to support technical competency and learner well-being. Careful assessment for program advancement will also be necessary. The experience during this pandemic shows that virtual learning and telemedicine will have a considerable impact on the future of surgical education.

Hospitalization Risk Among Older Adults with Sensory Impairments: Development of a Prognostic Model.

OBJECTIVES: To develop a prognostic model for hospital admissions over a 1-year period among community-dwelling older adults with self-reported hearing and/or vision impairments based on readily obtainable clinical predictors. DESIGN: Retrospective cohort study. SETTING: Medicare Current Beneficiary Survey from 1999 to 2006. PARTICIPANTS: Community-dwelling Medicare beneficiaries, aged 65 years and older, with self-reported hearing and/or vision impairment (N = 15,999). MEASUREMENTS: The primary outcome was any hospital admission over a predefined 1-year study period. Candidate predictors included demographic factors, prior healthcare utilization, comorbidities, functional impairment, and patient-level factors. We analyzed the association of all candidate predictors with any hospital admission over the 1-year study period using multivariable logistic regression. The final model was created using a penalized regression method known as the least absolute shrinkage and selection operator. Model performance was assessed by discrimination (concordance statistic (c-statistic)) and calibration (evaluated graphically). Internal validation was performed via bootstrapping, and results were adjusted for overoptimism. RESULTS: Of the 15,999 participants, the mean age was 78 years and 55% were female. A total of 2,567 participants (16.0%) had at least one hospital admission in the 1-year study period. The final model included seven variables independently associated with hospitalization: number of inpatient admissions in the previous year, number of emergency department visits in the previous year, activities of daily living difficulty score, poor self-rated health, and self-reported history of myocardial infarction, stroke, and nonskin cancer. The c-statistic of the final model was 0.717. The optimism-corrected c-statistic after bootstrap internal validation was 0.716. A calibration plot suggested that the model tended to overestimate risk among patients at the highest risk for hospitalization. CONCLUSION: This prognostic model can help identify which community-dwelling older adults with sensory impairments are at highest risk for hospitalization and may inform allocation of healthcare resources.

Association of Sustained Blood Pressure Control with Multimorbidity Progression Among Older Adults.

BACKGROUND/OBJECTIVES: Due to the high costs and excess mortality associated with multimorbidity, there is a need to develop approaches for delaying its progression. High blood pressure (BP) is a common chronic condition and a risk factor for many additional chronic conditions, making it an ideal target for intervention. The purpose of this analysis was to determine the association between the level of sustained BP control and the progression of multimorbidity. DESIGN: Retrospective cohort study. SETTING: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare claims. PARTICIPANTS: A total of 6,591 ALLHAT participants with Medicare who had systolic BP (SBP) measurements at eight or more study visits. MEASUREMENTS: SBP control was categorized as lower than 140 mm Hg at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits. Multimorbidity progression was defined by the number of incident chronic conditions, including arthritis, asthma, atrial fibrillation, cancer, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, dementia, depression, diabetes mellitus, heart failure, hyperlipidemia, osteoporosis, and stroke. Recurrent event survival analysis was used to calculate rate ratios (RRs) for the association of sustained SBP control with progression of multimorbidity. RESULTS: Rates of incident conditions per 10 person-years (95% CIs) were 5.2 (5.1-5.4), 4.7 (4.5-4.8), 4.4 (4.2-4.5), and 4.0 (3.8-4.2) for participants with SBP control at less than 50%, 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively, over a median follow-up of 9.0 years. Compared with participants with SBP control at less than 50% of visits, adjusted RRs (95% CIs) for multimorbidity progression were 0.90 (0.86-0.95), 0.85 (0.81-0.89), and 0.77 (0.72-0.82) for those with SBP control at 50% to less than 75%, 75% to less than 100%, and 100% of visits, respectively. CONCLUSIONS: Sustaining BP control may be an effective approach to slow multimorbidity progression and may reduce the population burden of multimorbidity.

Understanding Social Determinants of Cardiometabolic Disease Risk in Rural Women.

Women living in rural America experience significant disparities in cardiometabolic diseases warranting research to aid in understanding the contextual factors that underlie the rural and urban disparity and in planning effective primary prevention interventions. While research has established a general understanding of cardiometabolic risks individually, the combination or bundling of these risk behaviors is not clearly understood. The purpose of this study is to explore the association of social determinants of health on obesity and adiposity related cardiometabolic disease risk among rural women. Data were from the multi-state Rural Families Speak about Health Study. A total of 399 women were included in the analyses. Data were collected using a self-administered questionnaire on women's demographics, economic stability, education, and health and healthcare. Food insecurity, education, healthcare access and comprehension health literacy were associated with higher obesity and adiposity-related cardiometabolic risk. Health behaviors, tobacco use and physical activity were not associated with higher cardiometabolic risk in this sample of rural women. This is one of the first studies to focus on multiple social determinants of health and cardiometabolic risk in rural American women. Understanding combinations of risk behaviors can assist health care providers and community health professionals in tailoring multiple health behavior change interventions to prevent cardiometabolic disease among rural women. The findings support a focus on community and societal level factors may be more beneficial for improving the cardiometabolic health of rural women.

Acetylcholinesterase Inhibitors Are Associated with Reduced Fracture Risk among Older Veterans with Dementia.

Acetylcholinesterase inhibitors (AChEIs) have been noted to increase bone density and quality in mice. Human studies are limited but suggest an association with improved bone healing after hip fracture. We examined the relationship between AChEI use and fracture risk in a national cohort of 360,015 male veterans aged 65 to 99 years with dementia but without prior fracture using Veterans Affairs (VA) hospital, Medicare, and pharmacy records from 2000 to 2010. Diagnosis of dementia, any clinical fracture (excluding facial and digital), comorbidities, and medications were identified using ICD-9 and drug class codes. Cox proportional hazard models considering AChEI use as a time-varying covariate and adjusting for fall and fracture risk factors compared the time-to-fracture in AChEI users versus non-AChEI users. Potential confounders included demographics (age, race, body mass index), comorbidities associated with fracture or falls (diabetes, lung disease, stroke, Parkinson's, seizures, etc.) and medications associated with fracture or falls (bisphosphonates, glucocorticoids, androgen deprivation therapy [ADT], proton pump inhibitors [PPIs], selective serotonin receptor inhibitors [SSRIs], etc.). Competing mortality risk was considered using the methods of Fine and Gray. To account for persistent effects on bone density or quality that might confer protection after stopping the medication, we completed a secondary analysis using the medication possession ratio (MPR) as a continuous variable in logistic regression models and also compared MPR increments of 10% to minimal/no use (MPR 0 to <0.10). Among older veterans with diagnosis of dementia, 20.1% suffered a fracture over an average of 4.6 years of follow-up. Overall, 42.3% of the cohort were prescribed AChEIs during the study period. The hazard of any fracture among AChEI users compared with those on other/no dementia medications was significantly lower in fully adjusted models (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.75-0.88). After considering competing mortality risk, fracture risk remained 18% lower in veterans using AChEIs (HR = 0.82; 95% CI 0.76-0.89). © 2019 American Society for Bone and Mineral Research. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.

Glycemic Control and Insulin Treatment Alter Fracture Risk in Older Men With Type 2 Diabetes Mellitus.

Diabetes mellitus among older men has been associated with increased bone mineral density but paradoxically increased fracture risk. Given the interactions among medication treatment, glycemic control, and diabetes-associated comorbidities, the relative effects of each factor remains unclear. This retrospective study includes 652,901 male veterans aged ≥65 years with diabetes and baseline hemoglobin A1c (HbA1c) value. All subjects received primary care in the Veterans Health Administration (VHA) from 2000 to 2010. Administrative data included ICD9 diagnoses and pharmacy records and was linked to Medicare fee-for-service data. Hazard ratios (HR) for any clinical fracture and hip fracture were calculated using competing risk hazards models, adjusted for fracture risk factors including age, race/ethnicity, body mass index (BMI), alcohol and tobacco use, rheumatoid arthritis, corticosteroid use, as well as diabetes-related comorbidities including cardiovascular disease, chronic kidney disease, and peripheral neuropathy. HbA1c <6.5% was associated with a higher risk of any clinical fracture (HR = 1.08, 95% confidence interval [CI] 1.06-1.11) compared with the reference HbA1c of 7.5% to 8.5%. Fracture risk was not increased among those with A1c ≥8.5%, nor among those with A1c 6.5% to 7.5%. Use of insulin was independently associated with greater risk of fracture (HR = 1.10, 95% CI 1.07-1.12). There was a significant interaction between insulin use and HbA1c level, (p < 0.001), such that those using insulin with HbA1c <6.5% had HR = 1.23 and those with HbA1c 6.5% to 7.5% had HR = 1.15. Metformin use was associated with decreased fracture risk (HR = 0.88, 95% CI 0.87-0.90). We conclude that among older men with diabetes, those with HbA1c lower than 6.5% are at increased risk for any clinical and hip fracture. Insulin use is associated with higher fracture risk, especially among those with tight glycemic control. Our findings demonstrate the importance of the treatment regimen and avoiding hypoglycemia for fracture prevention in older men with diabetes. © 2019 American Society for Bone and Mineral Research.

Rural-urban differences in health behaviors and outcomes among older, overweight, long-term cancer survivors in the RENEW randomized control trial.

PURPOSE: Rural cancer survivors (RCS) have poorer health outcomes and face multiple challenges-older age, and limited transportation, education, income, and healthcare access. Yet, RCS are understudied. The Reach-out to ENhancE Wellness(RENEW) trial, a home-based, diet and exercise intervention among 641 breast, prostate, and colorectal cancer survivors addressed many of these challenges. METHODS: We examined whether rural and urban participants differed in their response to the RENEW intervention (e.g., physical functioning, quality-of-life, intakes of fruits and vegetables (F&V) and saturated fat, body mass index(BMI), physical activity, and adverse events). RESULTS: Rural versus urban survivors report significantly more favorable mean (SE) changes in physical functioning [- 0.66 (1.47) v - 1.71 (1.00)], physical health [+ 0.14 (0.71) v - 0.74 (0.50)], and fewer adverse events [1.58 (0.08) v 1.64 (0.06)]. Rural versus urban survivors reported smaller increases in F&Vs [+ 1.47 (0.23) v + 1.56(0.16); p = 0.018], and lower percentages achieved goal behavior for endurance exercise and intakes of F&Vs and saturated fat. CONCLUSIONS: The RENEW intervention reduced declines in physical health and functioning among RCS to a significantly greater extent than for urban cancer survivors. All survivors significantly improved intakes of F&V and saturated fat, and endurance exercise; however, lower percentages of rural versus urban survivors met goal suggesting that more intensive interventions may be needed for RCS.

Influence of Weight Reduction and Enhanced Protein Intake on Biomarkers of Inflammation in Older Adults with Obesity.

Both aging and obesity are associated with increased levels of pro-inflammatory metabolites, while weight reduction is associated with improvements in inflammatory status. However, few studies have explored the response of key inflammatory markers to the combined settings of weight reduction in an aging population. There are also few studies that have investigated the potential impact of diet composition on inflammatory marker responses. In the MEASUR-UP trial, we evaluated changes in baseline levels of inflammatory markers with post-study levels for a traditional weight loss control group versus a group with generous, balanced protein intake. In this 6-month randomized controlled trial (RCT), older (≥60 years) adults with obesity (BMI ≥30 kg/m2) and Short Physical Performance Battery (SPPB) score of 4-10 were randomly assigned to either a traditional weight loss regimen, (Control, n = 14) or one with higher protein intake (≥30 g) at each meal (Protein, n = 25). All participants were prescribed a hypo-caloric diet and attended weekly support and education groups and weigh-ins. Protein participants consumed ≥30 g of high-quality protein/meal, including lean and extra lean beef provided to them for two of the three meals per day. Protein intakes were 0.8 and 1.2 g/kg/day for Control and Protein, respectively. Adiponectin, leptin, C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6, IL-8, serum amyloid A (SAA), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and glycated serum protein (GSP) levels were measured at 0 and 6-month time points. At the 6-month endpoint, there was significant weight loss and decrease in BMI in both the Control (-4.8 ± 8.2 kg; -2.3 ± 2.4 kg/m2; p = 0.05) and Protein (-8.7 ± 7.4 kg; -2.9 ± 2.3 kg/m2; p < 0.0001) groups. SPPB scores improved in both arms, with a superior functional response in Protein (p < 0.05). Body fat (%) at baseline was positively correlated with leptin, hs-CRP, VCAM-1, ICAM-1, and GSP. Several markers of inflammation responded to the Protein group: leptin (p < 0.001), hs-CRP (p < 0.01), and ICAM-1 (p < 0.01) were decreased and adiponectin increased (p < 0.01). There were no significant changes in any inflammatory markers in the Control arm. In the between group comparison, only adiponectin trended towards a group difference (more improvement in Protein; p < 0.07). Our findings in the MEASUR-UP trial show that a weight loss diet with enhanced protein intake is comparable to an adequate protein diet in terms of weight loss success and that it can lead to improvements in inflammatory status, specifically for adiponectin, leptin, hs-CRP, and ICAM-1. These findings are important given current recommendations for higher protein intakes in older adults and justify the additional study of the inflammatory impact of an enhanced protein diet. (ClinicalTrials.gov identifier: NCT01715753).

Age-Related Adverse Inflammatory and Metabolic Changes Begin Early in Adulthood.

Aging is characterized by deleterious immune and metabolic changes, but the onset of these changes is unknown. We measured immune and metabolic biomarkers in adults beginning at age 30. To our knowledge, this is the first study to evaluate these biomarkers in adults aged 30 to over 80. Biomarkers were quantified in 961 adults. Tumor necrosis factor alpha (TNF-α), tumor necrosis factor receptor I (TNFR-I), tumor necrosis factor receptor II (TNFR-II), interleukin (IL)-2, IL-6, VCAM-I, D-Dimer, G-CSF, regulated on activation, normal T cell expressed and secreted (RANTES), matrix metalloproteinase-3 (MMP-3), adiponectin, and paraoxonase activity were measured by ELISA. Acylcarnitines and amino acids (AAs) were measured by mass spectrometry and reduced to a single factor using principal components analysis (PCA). Glycine was analyzed separately. The relationship between age and biomarkers was analyzed by linear regression with sex, race, and body mass index (BMI) as covariates. Age was positively correlated with TNF-α, TNFR-I, TNFR-II, IL-6, IL-2, VCAM-1, D-Dimer, MMP-3, adiponectin, acylcarnitines, and AAs. Age was negative correlated with G-CSF, RANTES, and paraoxonase activity. BMI was significant for all biomarkers except IL-2, VCAM-1, RANTES, paraoxonase activity, and the AA factor. Excluding MMP-3, greater BMI was associated with potentially adverse changes in biomarker concentrations. Age-related changes in immune and metabolic biomarkers, known to be associated with poor outcomes in older adults, begin as early as the thirties.

Transition to adult care in sickle cell disease: A longitudinal study of clinical characteristics and disease severity.

BACKGROUND: Sickle cell disease (SCD) is a chronic blood disorder in which mortality has increased for adolescents and young adults (AYA). PROCEDURE: A longitudinal analysis of medical records was conducted to describe the clinical course among AYAs (ages 12-27 years) during transition to adult care. Measures included sociodemographic, complications, SCD severity (modified pediatric SCD severity index), comorbidities, and transfer. Group-based trajectory modeling (GBTM) to identify subgroups with distinct severity trajectories and chi-square and unpaired Student t test to explore subgroup differences were used. RESULTS: Overall, 339 AYAs (97% black, 56% male, 69% hemoglobin SS) had 10 848 clinic, 3840 hospital, and 3152 emergency department visits. Complications included vaso-occlusive crises (80%) and acute chest syndrome (41%). Comorbidities included depression (19%) and anxiety (14%). Most AYAs transferred to adult care (n = 220) at 19 years. Fourteen AYAs died, 10 within seven years from transfer. GBTM identified both stable and increasing severity trajectory groups: stable-low (n = 31, 23%), stable-medium (n = 61, 46%), stable-high (n = 6, 4.5%), low-increasing (n = 13, 10%), and medium-increasing (n = 22, 17%). AYAs with increasing severity (25%) were older, lived closer to the clinic, and had higher risk for SCD complications and comorbidities. They had fewer pediatric clinic visits; however, they were more likely to transfer and remain longer in adult SCD care. CONCLUSIONS: Whereas most AYAs had stable severity, nearly a quarter had increasing severity, over time. AYAs with increasing severity had more complications, were more likely to transfer to adult care, and demonstrated higher and longer adult SCD care utilization compared with AYAs with stable severity.

Preoperative Cognitive Impairment As a Predictor of Postoperative Outcomes in a Collaborative Care Model.

OBJECTIVES: To compare postoperative outcomes of individuals with and without cognitive impairment enrolled in the Perioperative Optimization of Senior Health (POSH) program at Duke University, a comanagement model involving surgery, anesthesia, and geriatrics. DESIGN: Retrospective analysis of individuals enrolled in a quality improvement program. SETTING: Tertiary academic center. PARTICIPANTS: Older adults undergoing surgery and referred to POSH (N = 157). MEASUREMENTS: Cognitive impairment was defined as a score less than 25 out of 30 (adjusted for education) on the St. Louis University Mental Status (SLUMS) Examination. Median length of stay (LOS), mean number of postoperative complications, rates of postoperative delirium (POD, %), 30-day readmissions (%), and discharge to home (%) were compared using bivariate analysis. RESULTS: Seventy percent of participants met criteria for cognitive impairment (mean SLUMS score 20.3 for those with cognitive impairment and 27.7 for those without). Participants with and without cognitive impairment did not significantly differ in demographic characteristics, number of medications (including anticholinergics and benzodiazepines), or burden of comorbidities. Participants with and without cognitive impairment had similar LOS (P = .99), cumulative number of complications (P = .70), and 30-day readmission (P = .20). POD was more common in those with cognitive impairment (31% vs 24%), but the difference was not significant (P = .34). Participants without cognitive impairment had higher rates of discharge to home (80.4% vs 65.1%, P = .05). CONCLUSION: Older adults with and without cognitive impairment referred to the POSH program fared similarly on most postoperative outcomes. Individuals with cognitive impairment may benefit from perioperative geriatric comanagement. Questions remain regarding the validity of available measures of cognition in the preoperative period.

Association of Integrated Care Coordination With Postsurgical Outcomes in High-Risk Older Adults: The Perioperative Optimization of Senior Health (POSH) Initiative.

Importance: Older adults undergoing elective surgery experience higher rates of preventable postoperative complications than younger patients. Objective: To assess clinical outcomes for older adults undergoing elective abdominal surgery via a collaborative intervention by surgery, geriatrics, and anesthesia focused on perioperative health optimization. Design, Setting, and Participants: Perioperative Optimization of Senior Health (POSH) is a quality improvement initiative with prospective data collection. Participants in an existing geriatrics-based clinic within a single-site academic health center were included if they were at high risk for complications (ie, older than 85 years or older than 65 years with cognitive impairment, recent weight loss, multimorbidity, or polypharmacy) undergoing elective abdominal surgery. Outcomes were compared with a control group of patients older than 65 years who underwent similar surgeries by the same group of general surgeons immediately before implementation of POSH. Main Outcomes and Measures: Primary outcomes included length of stay, 7- and 30-day readmissions, and level of care at discharge. Secondary outcomes were delirium and other major postoperative complications. Outcomes data were derived from institutional databases linked with electronic health records and billing data sets. Results: One hundred eighty-three POSH patients were compared with 143 patients in the control group. On average, patients in the POSH group were older compared with those in the control group (75.6 vs 71.9 years; P < .001; 95% CI, 2.27 to 5.19) and had more chronic conditions (10.6 vs 8.5; P = .001; 95% CI, 0.86 to 3.35). Median length of stay was shorter among POSH patients (4 days vs 6 days; P < .001; 95% CI, -1.06 to -4.21). Patients in the POSH group had lower readmission rates at 7 days (5 of 180 [2.8%] vs 14 of 142 [9.9%]; P = .007; 95% CI, 0.09 to 0.74) and 30 days (14 of 180 [7.8%] vs 26 of 142 [18.3%]; P = .004; 95% CI, 0.19 to 0.75) and were more likely to be discharged home with self-care (114 of 183 [62.3%] vs 73 of 143 [51.1%]; P = .04; 95% CI, 1.02 to 2.47). Patients in the POSH group experienced fewer mean number of complications (0.9 vs 1.4; P < .001; 95% CI, -0.13 to -0.89) despite higher rates of documented delirium (52 of 183 [28.4%] vs 8 of 143 [5.6%]; P < .001; 95% CI, 3.06 to 14.65). A greater proportion of POSH patients underwent laparoscopic procedures (92 of 183 [50%] vs 55 of 143 [38.5%]; P = .001; 95% CI, 1.04 to 2.52). Tests for interactions between POSH patients and procedure type were insignificant for all outcomes. Conclusions and Relevance: Despite higher mean age and morbidity burden, older adults who participated in an interdisciplinary perioperative care intervention had fewer complications, shorter hospitalizations, more frequent discharge to home, and fewer readmissions than a comparison group.

Clinical Fractures Among Older Men With Diabetes Are Mediated by Diabetic Complications.

Introduction: Type 2 diabetes mellitus among older women has been associated with increased bone mineral density, but paradoxically with increased fracture risk. Findings among older men have varied, and potential mechanisms have not been fully elucidated. Methods: A retrospective study of male veterans 65 to 99 years of age who received primary care in the Veterans Health Administration from 2000 to 2010, using administrative data from all 146 Veterans Health Administration medical centers linked to Centers for Medicare and Medicaid Services Medicare fee-for-service data. Potential mediating factors of the diabetes-associated risk were evaluated using negative binomial regression models with the outcomes of any clinical fracture and hip fracture. Results: Of 2,798,309 Veterans included in the cohort, 900,402 (32.3%) had a diagnosis of diabetes. After adjusting for age, race, ethnicity, body mass index, alcohol and tobacco use, rheumatoid arthritis, and corticosteroid use, the risk of any clinical fracture associated with diabetes was 1.22 (95% confidence interval, 1.21 to 1.23) and that of hip fracture was 1.21 (95% confidence interval, 1.19 to 1.23). Significant mediating factors included peripheral neuropathy, cardiovascular disease, and congestive heart failure, with 45.5% of the diabetes-associated fracture risk explained by these diagnoses. Conclusions: Older male Veterans with diabetes have a 22% increased risk of incident clinical fracture compared with those without. A significant portion of this risk is explained by diabetes-related comorbidities, specifically peripheral neuropathy and congestive heart failure. Identification of these mediating factors suggests possible mechanisms, as well as potential interventions.