Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness.

Rheumatoid arthritis (RA) T cells drive autoimmune features via metabolic reprogramming that reduces oxidative metabolism. Exercise training improves cardiorespiratory fitness (i.e., systemic oxidative metabolism) and thus may impact RA T cell oxidative metabolic function. In this pilot study of RA participants, we took advantage of heterogeneous responses to a high-intensity interval training (HIIT) exercise program to identify relationships between improvements in cardiorespiratory fitness with changes in peripheral T cell and skeletal muscle oxidative metabolism. In 12 previously sedentary persons with seropositive RA, maximal cardiopulmonary exercise tests, fasting blood, and vastus lateralis biopsies were obtained before and after 10 weeks of HIIT. Following HIIT, improvements in RA cardiorespiratory fitness were associated with changes in RA CD4 + T cell basal and maximal respiration and skeletal muscle carnitine acetyltransferase (CrAT) enzyme activity. Further, changes in CD4 + T cell respiration were associated with changes in naïve CD4 + CCR7 + CD45RA + T cells, muscle CrAT, and muscle medium-chain acylcarnitines and fat oxidation gene expression profiles. In summary, modulation of cardiorespiratory fitness and molecular markers of skeletal muscle oxidative metabolism during exercise training paralleled changes in T cell metabolism. Exercise training that improves RA cardiorespiratory fitness may therefore be valuable in managing pathologically related immune and muscle dysfunction.Trial registration: ClinicalTrials.gov, NCT02528344. Registered on 19 August 2015.

Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis.

BACKGROUND: Exercise training, including high-intensity interval training (HIIT), improves rheumatoid arthritis (RA) inflammatory disease activity via unclear mechanisms. Because exercise requires skeletal muscle, skeletal muscle molecular pathways may contribute. The purpose of this study was to identify connections between skeletal muscle molecular pathways, RA disease activity, and RA disease activity improvements following HIIT. METHODS: RA disease activity assessments and vastus lateralis skeletal muscle biopsies were performed in two separate cohorts of persons with established, seropositive, and/or erosive RA. Body composition and objective physical activity assessments were also performed in both the cross-sectional cohort and the longitudinal group before and after 10 weeks of HIIT. Baseline clinical assessments and muscle RNA gene expression were correlated with RA disease activity score in 28 joints (DAS-28) and DAS-28 improvements following HIIT. Skeletal muscle gene expression changes with HIIT were evaluated using analysis of covariance and biological pathway analysis. RESULTS: RA inflammatory disease activity was associated with greater amounts of intramuscular adiposity and less vigorous aerobic exercise (both p < 0.05). HIIT-induced disease activity improvements were greatest in those with an older age, elevated erythrocyte sedimentation rate, low cardiorespiratory fitness, and a skeletal muscle molecular profile indicative of altered metabolic pathways (p < 0.05 for all). Specifically, disease activity improvements were linked to baseline expression of RA skeletal muscle genes with cellular functions to (1) increase amino acid catabolism and interconversion (GLDC, BCKDHB, AASS, PYCR, RPL15), (2) increase glycolytic lactate production (AGL, PDK2, LDHB, HIF1A), and (3) reduce oxidative metabolism via altered beta-oxidation (PXMP2, ACSS2), TCA cycle flux (OGDH, SUCLA2, MDH1B), and electron transport chain complex I function (NDUFV3). The muscle mitochondrial glycine cleavage system (GCS) was identified as critically involved in RA disease activity improvements given upregulation of multiple GCS genes at baseline, while GLDC was significantly downregulated following HIIT. CONCLUSION: In the absence of physical activity, RA inflammatory disease activity is associated with transcriptional remodeling of skeletal muscle metabolism. Following exercise training, the greatest improvements in disease activity occur in older, more inflamed, and less fit persons with RA. These exercise training-induced immunomodulatory changes may occur via reprogramming muscle bioenergetic and amino acid/protein homeostatic pathways. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02528344 . Registered on 19 August 2015.

Effect of dairy consumption and its fat content on glycemic control and cardiovascular disease risk factors in patients with type 2 diabetes: a randomized controlled study.

BACKGROUND: Dietary Guidelines for Americans recommend the consumption of 3 servings/d of low-fat/nonfat dairy. The effects of higher dairy consumption and its fat content are unknown in patients with type 2 diabetes. OBJECTIVE: Evaluate the impact of higher consumption of high- compared with low-fat dairy on glycated hemoglobin (HbA1c), body weight, and cardiovascular disease risk factors in patients with type 2 diabetes. METHODS: We enrolled 111 subjects with type 2 diabetes (aged 58.5 ± 8.9 y, 47% females, diabetes duration 13.2 ± 8.3 y, HbA1c 8.09 ± 0.96%) who consumed <3 servings of dairy/d. We randomly assigned them into 3 groups: control group maintained baseline dairy intake, low-fat (LF) group incorporated ≥3 servings/d of LF dairy, and the high-fat (HF) group incorporated ≥3 servings/d of HF dairy. We evaluated HbA1c, body weight, BMI, body composition parameters, blood pressure (BP), lipid parameters, homeostatic model assessment of insulin resistance (HOMA-IR), and total energy and macronutrient intake at baseline, and after 12 and 24 wk. RESULTS: At 24 wk, percent energy from saturated fat increased from baseline in the HF group by 3.6%, (95% CI: 2.2, 5.1) and decreased in the LF group by -1.9% (95% CI: -3.3, -0.4). The LF group increased their percent energy from protein by 4.5% (95% CI: 2.6, 6.4), whereas the HF group decreased their percent energy from carbohydrates by -3.4% (95% CI: -0.2, -6.7). There were no differences in the mean changes in HbA1c, body weight, BMI, body composition or lipid parameters, or BP between the 3 groups at 24 wk. CONCLUSION: In patients with type 2 diabetes, increased dairy consumption to ≥3 servings/d compared with <3 servings/d, irrespective of its fat content, while maintaining energy intake has no effect on HbA1c, body weight, body composition, lipid profile, or BP. This trial was registered at clinicaltrials.gov as NCT02895867.

Effect of diabetes-specific nutrition formulas on satiety and hunger hormones in patients with type 2 diabetes.

OBJECTIVES: Diabetes-specific nutritional formulas (DSNFs) are frequently used by patients with type 2 diabetes (T2D) as part of nutrition therapy to improve glycemic control and reduce body weight. However, their effects on hunger and satiety hormones when compared to an isocaloric standardized breakfast are not fully understood. This study aims to evaluate the postprandial effects of two DSNFs-Glucerna (GL) and Ultra Glucose Control (UGC)-versus oatmeal on selected satiety and hunger hormones. METHOD: After an overnight fast, 22 patients with T2D (mean age 62.3 ± 6.8 years, A1C 6.8 ± 0.7%, body weight 97.4 ± 21.3 kg, and BMI 33.2 ± 5.9 kg/m²) were given 200 kcal of each meal on three separate days. Blood samples for amylin, cholecystokinin (CCK), ghrelin, glucagon, leptin, and peptide-YY (PYY) were collected at baseline and 30, 60, 90, 120, 180, and 240 min after the start of each meal. Incremental area under the curve (iAUC0-240) for each hormone was calculated. RESULTS: iAUC0-240 for glucagon and PYY were significantly higher after GL and UGC than after oatmeal (p < 0.001 for both). No difference was observed between the three meals on postprandial amylin, CCK, ghrelin, and leptin hormones. CONCLUSIONS: Intake of DSNFs significantly increases secretion of PYY and glucagon, two important satiety hormones. While subjective satiety was not directly evaluated, the increased effect on satiety hormones may partially explain the mechanism of body weight loss associated with DSNF use.

Frequency of self-monitoring of blood glucose in relation to weight loss and A1C during intensive multidisciplinary weight management in patients with type 2 diabetes and obesity.

Objective: We evaluated the relationship between frequency of self-monitoring of blood glucose (SMBG) and body weight, A1C, and cardiovascular risk factors in patients with type 2 diabetes (T2D) and obesity enrolled in a 12-week intensive multidisciplinary weight management (IMWM) program. Research design and methods: We conducted a retrospective analysis of 42 patients who electronically uploaded their SMBG data over 12 weeks of an IMWM program and divided them into tertiles based on their average frequency of SMBG per day. Mean (range) SMBG frequencies were 2.3 (1.1-2.9) times/day, 3.4 (3-3.9) times/day, and 5 (4-7.7) times/day in the lowest, middle, and highest tertiles, respectively. Anthropometric and metabolic parameters were measured at baseline and after 12 weeks of intervention. Results: Participants in the highest tertile achieved a median change (IQR) in body weight of -10.4 kg (-7.6 to -14.4 kg) compared with -8.3 kg (-5.2 to -12.2 kg), and -6.9 kg (-4.2 to -8.9 kg) in the middle and lowest tertiles, respectively (p=0.018 for trend). Participants in the highest tertile had a median change (IQR) in A1C of -1.25% (-0.6 to -3.1%) compared with -0.8% (-0.3% to -2%) and -0.5% (-0.2% to -1.2%) in the middle and lowest tertiles, respectively (p=0.048 for trend). The association between change in body weight and SMBG frequency remained significant after adjusting for age, sex, baseline body mass index, diabetes duration, and use of insulin therapy. Conclusions: Increased frequency of SMBG during IMWM is associated with significantly better weight loss and improvement of A1C in patients with T2D and obesity. These findings may suggest future clinical recommendations aimed at increasing SMBG frequency to achieve the most favorable outcomes.

Retinol binding protein 3 is increased in the retina of patients with diabetes resistant to diabetic retinopathy.

The Joslin Medalist Study characterized people affected with type 1 diabetes for 50 years or longer. More than 35% of these individuals exhibit no to mild diabetic retinopathy (DR), independent of glycemic control, suggesting the presence of endogenous protective factors against DR in a subpopulation of patients. Proteomic analysis of retina and vitreous identified retinol binding protein 3 (RBP3), a retinol transport protein secreted mainly by the photoreceptors, as elevated in Medalist patients protected from advanced DR. Mass spectrometry and protein expression analysis identified an inverse association between vitreous RBP3 concentration and DR severity. Intravitreal injection and photoreceptor-specific overexpression of RBP3 in rodents inhibited the detrimental effects of vascular endothelial growth factor (VEGF). Mechanistically, our results showed that recombinant RBP3 exerted the therapeutic effects by binding and inhibiting VEGF receptor tyrosine phosphorylation. In addition, by binding to glucose transporter 1 (GLUT1) and decreasing glucose uptake, RBP3 blocked the detrimental effects of hyperglycemia in inducing inflammatory cytokines in retinal endothelial and Müller cells. Elevated expression of photoreceptor-secreted RBP3 may have a role in protection against the progression of DR due to hyperglycemia by inhibiting glucose uptake via GLUT1 and decreasing the expression of inflammatory cytokines and VEGF.

Characterization of Glycolytic Enzymes and Pyruvate Kinase M2 in Type 1 and 2 Diabetic Nephropathy.

OBJECTIVE: Elevated glycolytic enzymes in renal glomeruli correlated with preservation of renal function in the Medalist Study, individuals with ≥50 years of type 1 diabetes. Specifically, pyruvate kinase M2 (PKM2) activation protected insulin-deficient diabetic mice from hyperglycemia-induced glomerular pathology. This study aims to extend these findings in a separate cohort of individuals with type 1 and type 2 diabetes and discover new circulatory biomarkers for renal protection through proteomics and metabolomics of Medalists' plasma. We hypothesize that increased glycolytic flux and improved mitochondrial biogenesis will halt the progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS: Immunoblots analyzed selected glycolytic and mitochondrial enzymes in postmortem glomeruli of non-Medalists with type 1 diabetes (n = 15), type 2 diabetes (n = 19), and no diabetes (n = 5). Plasma proteomic (SOMAscan) (n = 180) and metabolomic screens (n = 214) of Medalists with and without stage 3b chronic kidney disease (CKD) were conducted and significant markers validated by ELISA. RESULTS: Glycolytic (PKM1, PKM2, and ENO1) and mitochondrial (MTCO2) enzymes were significantly elevated in glomeruli of CKD- versus CKD+ individuals with type 2 diabetes. Medalists' plasma PKM2 correlated with estimated glomerular filtration rate (r 2 = 0.077; P = 0.0002). Several glucose and mitochondrial enzymes in circulation were upregulated with corresponding downregulation of toxic metabolites in CKD-protected Medalists. Amyloid precursor protein was also significantly upregulated, tumor necrosis factor receptors downregulated, and both confirmed by ELISA. CONCLUSIONS: Elevation of enzymes involved in the metabolism of intracellular free glucose and its metabolites in renal glomeruli is connected to preserving kidney function in both type 1 and type 2 diabetes. The renal profile of elevated glycolytic enzymes and reduced toxic glucose metabolites is reflected in the circulation, supporting their use as biomarkers for endogenous renal protective factors in people with diabetes.

Plasma FGF-19 Levels are Increased in Patients with Post-Bariatric Hypoglycemia.

BACKGROUND: Hypoglycemia is an increasingly recognized complication of bariatric surgery. Mechanisms contributing to glucose lowering remain incompletely understood. We aimed to identify differentially abundant plasma proteins in patients with post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB), compared to asymptomatic post-RYGB. METHODS: Proteomic analysis of blood samples collected after overnight fast and mixed meal challenge in individuals with PBH, asymptomatic RYGB, severe obesity, or overweight recruited from outpatient hypoglycemia or bariatric clinics. RESULTS: The top-ranking differentially abundant protein at 120 min after mixed meal was fibroblast growth factor 19 (FGF-19), an intestinally derived hormone regulated by bile acid-FXR signaling; levels were 2.4-fold higher in PBH vs. asymptomatic post-RYGB (mean + SEM, 1094 ± 141 vs. 428 ± 45, P < 0.001, FDR < 0.01). FGF-19 ELISA confirmed 3.5-fold higher concentrations in PBH versus asymptomatic (360 ± 70 vs. 103 ± 18, P = 0.025). To explore potential links between increased FGF-19 and GLP-1, residual samples from other human studies in which GLP-1 was modulated were assayed. FGF-19 levels did not change in response to infusion of GLP-1 and PYY in overweight/obese individuals. Infusion of the GLP-1 receptor antagonist exendin 9-39 in recently operated asymptomatic post-RYGB did not alter FGF-19 levels after mixed meal. By contrast, GLP-1 receptor antagonist infusion yielded a significant increase in FGF-19 levels after oral glucose in individuals with PBH. While plasma bile acids did not differ between PBH and asymptomatic post-RYGB, these data suggest unique interrelationships between GLP-1 and FGF-19 in PBH. CONCLUSIONS: Taken together, these data support FGF-19 as a potential contributor to insulin-independent pathways driving postprandial hypoglycemia in PBH.

Characterization of periodontitis in people with type 1 diabetes of 50 years or longer duration.

BACKGROUND: Periodontitis is more common and severe in people with diabetes than the general population. We have reported in the Joslin Medalist Study that people with type 1 diabetes of ≥50 years (Medalists) may have endogenous protective factors against diabetic nephropathy and retinopathy. METHODS: In this cross-sectional study, the prevalence of periodontitis according to the Centers for Disease Control/American Academy of Periodontology classification in a subset (n = 170, mean age = 64.6 ± 6.9 years) of the Medalist cohort, and its associations to various criteria of periodontitis and diabetic complications were assessed. RESULTS: The prevalence of severe periodontitis in Medalists was only 13.5% which was lower than reported levels in diabetic patients of similar ages. Periodontal parameters, including bleeding on probing, plaque index, gingival index, and demographic traits, including male sex, chronological age, and age at diagnosis were significantly associated with severity of periodontitis, which did not associate with diabetes duration, hemoglobin A1c (HbA1c), body mass index, and lipid profiles. Random serum C-peptide levels inversely associated with severity of periodontitis (P = 0.03), lower probing depth (P = 0.0002), and clinical attachment loss (P = 0.03). Prevalence of cardiovascular diseases (CVD) and systemic inflammatory markers, plasma interleukin-6 (IL-6), and serum immunoglobulin G titer against Porphyromonas gingivalis positively associated with severity of periodontitis (P = 0.002 and 0.02, respectively). Antibody titer to P. gingivalis correlated positively and significantly with CVD, serum IL-6, and high-sensitivity C-reactive protein. CONCLUSIONS: Some Medalists could be protected from severe periodontitis even with hyperglycemia. Endogenous protective factors for periodontitis could possibly be related to residual insulin production and lower levels of chronic inflammation.

Metabolic Effects of Betaine: A Randomized Clinical Trial of Betaine Supplementation in Prediabetes.

Context: Plasma betaine correlates with insulin sensitivity in humans. Betaine supplementation improves metabolic effects in mice fed a high-fat diet. Objective: To assess metabolic effects of oral betaine in obese participants with prediabetes. Design: A 12-week, parallel arm, randomized, double-masked, placebo-controlled trial. Setting: University-affiliated hospital. Participants and Interventions: Persons with obesity and prediabetes (N = 27) were randomly assigned to receive betaine 3300 mg orally twice daily for 10 days, then 4950 mg twice daily for 12 weeks, or placebo. Main Outcome Measures: Changes from baseline in insulin sensitivity, glycemia, hepatic fat, and endothelial function. Results: There was a 16.5-fold increase in plasma dimethylglycine [dimethylglycine (DMG); P < 0.0001] levels, but modest 1.3- and 1.5-fold increases in downstream serine and methionine levels, respectively, in the betaine vs placebo arm. Betaine tended to reduce fasting glucose levels (P = 0.08 vs placebo) but had no other effect on glycemia. Insulin area under curve after oral glucose was reduced for betaine treatment compared with placebo (P = 0.038). Insulin sensitivity, assessed by euglycemic hyperinsulinemic clamp, was not improved. Serum total cholesterol levels increased after betaine treatment compared with placebo (P = 0.032). There were no differences in change in intrahepatic triglyceride or endothelial function between groups. Conclusion: DMG accumulation supports DMG dehydrogenase as rate limiting for betaine metabolism in persons with prediabetes. Betaine had little metabolic effect. Additional studies may elucidate mechanisms contributing to differences between preclinical and human responses to betaine, and whether supplementation of metabolites downstream of DMG improves metabolism.

Effects of nutrition therapy on HbA1c and cardiovascular disease risk factors in overweight and obese patients with type 2 diabetes.

BACKGROUND: Nutrition Therapy (NT) is essential in type 2 diabetes (T2D) management. Standards of care recommend that each patient engages with a nutritionist (RDN) to develop an individualized eating plan. However, it is unclear if it is the most efficient method of NT. This study evaluates the effects of three different methods of NT on HbA1c and cardiovascular disease risk factors in overweight and obese patients with T2D. METHODS: We randomized 108 overweight and obese patients with T2D (46 M/62F; age 60 ± 10 years; HbA1c 8.07 ± 1.05%; weight 101.4 ± 21.1 kg and BMI 35.2 ± 7.7 kg/m2) into three groups. Group A met with RDN to develop an individualized eating plan. Group B met with RDN and followed a structured meal plan. Group C did similar to group B and received weekly phone support by RDN. RESULTS: After 16 weeks, all three groups had a significant reduction of their energy intake compared to baseline. HbA1c did not change from baseline in group A, but decreased significantly in groups B (- 0.66%, 95% CI -1.03 to - 0.30) and C (- 0.61%, 95% CI -1.0 to - 0.23) (p value for difference among groups over time < 0.001). Groups B and C also had significant reductions in body weight, body fat percentage and waist circumference. CONCLUSION: Structured NT alone improves glycemia in comparison to individualized eating plans in overweight and obese patients with T2D. It also reduces other important cardiovascular disease risk factors like body fat percentage and waist circumference. TRIAL REGISTRATION: The trial was retrospectively registered at clinicaltrials.gov( NCT02520050 ).

Depressive Symptoms at Critical Times in Youth With Type 1 Diabetes: Following Type 1 Diabetes Diagnosis and Insulin Pump Initiation.

PURPOSE: Depressive symptoms occur at various times during the life cycle in persons with type 1 diabetes. We investigated depressive symptoms prospectively in youth with new-onset type 1 diabetes and in those beginning pump therapy. METHODS: Youth with type 1 diabetes (N = 96), ages 10-17 years, completed the Children's Depression Inventory (CDI) at baseline and at 1, 6, and 12 months after diabetes onset or pump start; scores ≥13 indicated clinical elevation. The change in depressive symptoms and the association between CDI score and hemoglobin A1c (HbA1c) level were assessed over 1 year. RESULTS: The new-onset group (n = 54) had an HbA1c level of 11.4% ± 2.5%. The pump group (n = 42) had a diabetes duration of 4.1 ± 3.4 years and an HbA1c level of 8.3% ± 1.3%. The baseline median CDI was 5.0 in both groups and remained low over time (ranging from 2.0 to 3.5). Most youth (new onset 72%, pump 81%) scored <13 at all times. Those with a CDI score of ≥13 in month 1 had 9-fold (95% confidence interval: 3-28) and 11-fold (95% confidence interval: 3-38) higher risks of CDI score of ≥13 at 6 and 12 months, respectively, than those with a CDI score of <13. New-onset youth with a CDI score of ≥13 in month 1 had a higher HbA1c level at 6 months (8.3% ± 1.7%) than new-onset youth with a CDI score of <13 (7.2% ± 1.6%, p = .04). CONCLUSIONS: CDI scores over 1 year were similar in the new-onset and pump groups. Youth with elevated CDI in the first month after diagnosis or pump start were significantly more likely to have a CDI score of ≥13 at 6 or 12 months, supporting recommendations to screen for depressive symptoms because of persistence over time. Those with new-onset diabetes and depressive symptoms in the first month had higher HbA1c at 6 months; confirmatory research is needed.

Improving patients' home cooking - A case series of participation in a remote culinary coaching program.

This case series describes and examines the outcomes of a remote culinary coaching program aimed at improving nutrition through home cooking. Participants (n = 4) improved attitudes about the perceived ease of home cooking (p < 0.01) and self-efficacy to perform various culinary skills (p = 0.02); and also improved in confidence to continue online learning of culinary skills and consume healthier food. We believe this program might be a viable response to the need for effective and scalable health-related culinary interventions.

Impact of Diabetes-Specific Nutritional Formulas versus Oatmeal on Postprandial Glucose, Insulin, GLP-1 and Postprandial Lipidemia.

Diabetes-specific nutritional formulas (DSNFs) are frequently used as part of medical nutrition therapy for patients with diabetes. This study aims to evaluate postprandial (PP) effects of 2 DSNFs; Glucerna (GL) and Ultra Glucose Control (UGC) versus oatmeal (OM) on glucose, insulin, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and triglycerides (TG). After an overnight fast, 22 overweight/obese patients with type 2 diabetes were given 200 kcal of each of the three meals on three separate days in random order. Blood samples were collected at baseline and at 30, 60, 90, 120, 180 and 240 min. Glucose area under the curve (AUC0-240) after GL and UGC was lower than OM (p < 0.001 for both). Insulin positive AUC0-120 after UGC was higher than after OM (p = 0.02). GLP-1 AUC0-120 and AUC0-240 after GL and UGC was higher than after OM (p < 0.001 for both). FFA and TG levels were not different between meals. Intake of DSNFs improves PP glucose for 4 h in comparison to oatmeal of similar caloric level. This is achieved by either direct stimulation of insulin secretion or indirectly by stimulating GLP-1 secretion. The difference between their effects is probably related to their unique blends of amino acids, carbohydrates and fat.

Physician styles of decision-making for a complex condition: Type 2 diabetes with co-morbid mental illness.

RATIONALE AIMS AND OBJECTIVES: Variation in physician decisions may reflect personal styles of decision-making, as opposed to singular clinical actions and these styles may be applied differently depending on patient complexity. The objective of this study is to examine clusters of physician decision-making for type 2 diabetes, overall and in the presence of a mental health co-morbidity. METHOD: This randomized balanced factorial experiment presented video vignettes of a "patient" with diagnosed, but uncontrolled type 2 diabetes. "Patients" were systematically varied by age, sex, race and co-morbidity (depression, schizophrenia with normal or bizarre affect, eczema as control). Two hundred and fifty-six primary care physicians, balanced by gender and experience level, completed a structured interview about clinical management. RESULTS: Cluster analysis identified 3 styles of diabetes management. "Minimalists" (n=84) performed fewer exams or tests compared to "middle of the road" physicians (n=84). "Interventionists" (n=88) suggested more medications and referrals. A second cluster analysis, without control for co-morbidities, identified an additional cluster of "information seekers" (n=15) who requested more additional information and referrals. Physicians ranking schizophrenia higher than diabetes on their problem list were more likely "minimalists" and none were "interventionists" or "information seekers". CONCLUSIONS: Variations in clinical management encompass multiple clinical actions and physicians subtly shift these decision-making styles depending on patient co-morbidities. Physicians' practice styles may help explain persistent differences in patient care. Training and continuing education efforts to encourage physicians to implement evidence-based clinical practice should account for general styles of decision-making and for how physicians process complicating comorbidities.

Orthopedic grand rounds can change resident practice.

This study sought to determine whether a grand rounds presentation could change resident practice. A 6-month review of all hip fracture patients 65 years and older at a single academic medical center was performed. The rate of addressing advanced directives and code status as documented in the medical record was noted. A grand rounds presentation was then given to the orthopedic department, and the medical records of hip fracture patients for the 12 months following the grand rounds were reviewed. In the 6 months prior to the grand rounds, orthopedic residents did not document code status or advanced directives in any of their admission or consultation notes. Following the grand rounds, orthopedic residents addressed advanced directives, code status, and contact person in 76% of their admission notes. There was a marked difference in the rate of documentation among residents who attended the grand rounds (88%), compared with residents who did not attend grand rounds (20%). Based on the results of this study, specifically whether residents attended grand rounds, this form of teaching can lead to changes in resident behavior.

How do emergency department physicians rate their orthopaedic on-call coverage?

PURPOSE: Throughout the United States, the lack of orthopaedic on-call coverage at many institutions has been described as a "crisis." This study sought to understand how emergency department (ED) physicians perceive their orthopaedic on-call coverage. Specifically, the study looked at availability of orthopaedic coverage, adequacy of coverage, and reasons for patient transfers. METHODS: After Institutional Review Board approval, written questionnaires were mailed to the ED directors at 39 of the 41 emergency departments in New Hampshire and Vermont. The instrument consisted of 25 items. Survey domains included ED physician demographics, availability and adequacy of orthopaedic coverage, and reasons for patient transfer. All responses were anonymous. RESULTS: A total of 31 questionnaires was returned. Approximately one third (36%) of ED physicians reported they had full-time orthopaedic coverage with 8% reporting they "never" had coverage. Almost two thirds (64%) of respondents felt their daytime orthopaedic coverage was adequate, but this number dropped to 52% for night coverage and 48% for weekend coverage. Over half (55%) of respondents felt their orthopaedist was reluctant to come in to evaluate a patient when the ED physician felt the patient warranted orthopaedic consultation. Approximately half (52%) felt it was often the case that a patient's care could have been improved if they had been evaluated by an orthopaedist. Only 29% of respondents said their orthopaedist always came in when asked to evaluate a patient. The top three reasons ED physicians felt their orthopaedist declined to care for a patient were complexity of the injury, the time of day/night, and if it was a weekend. CONCLUSION/IMPLICATIONS: The findings in this study suggest there is substantial room for improvement in orthopaedic on-call coverage for emergency departments.

Best practices for using physical activity monitors in population-based research.

The use of physical activity monitors in population-based research has increased dramatically in the past decade. In this report, we review the major purpose for using physical activity monitors in different types of population-based studies (i.e., surveillance, intervention, association studies) and discuss the strengths and weaknesses for the various behavioral outcomes derived from monitors for each study type. We also update and extend previous recommendations for use of these instruments in large-scale studies, particularly with respect to selecting monitor systems in the context of technological advances that have occurred in recent years. The current state of the science with respect to optimal measurement schedules for use of physical activity monitors is also discussed. A checklist and flowchart are provided so that investigators have more guidance when reporting key elements of monitor use in their studies.

Validity of the Omron HJ-112 pedometer during treadmill walking.

PURPOSE: The purpose of this investigation was to examine the validity of step counts measured with the Omron HJ-112 pedometer and to assess the effect of pedometer placement. METHODS: Ninety-two subjects (44 males and 48 females; 71 with body mass index [BMI] <30 kg.m and 21 with BMI >or=30 kg.m) completed three, 12-min bouts of treadmill walking at speeds of 1.12, 1.34, and 1.56 mxs. A subset (21 males and 23 females; 38 BMI <30 kg.m and 6 BMI >or=30 kg.m) completed a variable walking condition. For all conditions, participants wore an Omron HJ-112 pedometer on the hip, in the pants pocket, in the chest shirt pocket, and around the neck. Hip pedometer placement was alternated between right and left sides with the Yamax Digiwalker SW-701. During each walk, an investigator recorded actual steps with a manual hand counter. RESULTS: There was no substantial bias with the Omron in any speed condition (-0.1% to 0.5%). Bias was larger with the Yamax (-3.6% to 2.0%). The largest random error for the Omron was 3.7% in the variable-speed condition for the BMI <30 kg.m group, whereas random errors for the Yamax were larger and up to 20%. None of the Omron placement positions produced statistically significant bias. Hip mounting produced the smallest random error (1.2%), followed by shirt pocket (1.7%), neck (2.2%), and pants pocket (5.8%). CONCLUSION: The Omron HJ-112 pedometer validly assesses steps in different BMI groups during constant- and variable-speed walking; other than that in the pants pocket, placement of the pedometer has little effect on validity.

Development of novel techniques to classify physical activity mode using accelerometers.

PURPOSE: Use of accelerometers to assess physical activity (PA) is widespread in public health research, but their utility is often limited by the accuracy of data-processing techniques. We hypothesized that more sophisticated approaches to data processing could distinguish between activity types based on accelerometer data, providing a more accurate picture of PA. METHODS: Using data from MTI Actigraphs worn by six subjects during four activities (walking, walking uphill, vacuuming, working at a computer), quadratic discriminant analysis (QDA) was performed, and a hidden Markov model (HMM) was trained to recognize the activities. The ability of the new analytic techniques to accurately classify PA was assessed. RESULTS: The mean (SE) percentage of time points for which the QDA correctly identified activity mode was 70.9% (1.2%). Computer work was correctly recognized most frequently (mean (SE) percent correct = 100% (0.01%)), followed by vacuuming (67.5% (1.5%)), uphill walking (58.2% (3.5%)), and walking (53.6% (3.3%)). The mean (SE) percentage of time points for which the HMM correctly identified activity mode was 80.8% (0.9%). Vacuuming was correctly recognized most frequently (mean (SE) percent correct = 98.8% (0.05%)), followed by computer work (97.3% (0.7%)), walking (62.6% (2.3%)), and uphill walking (62.5% (2.3%)). In contrast to a traditional method of data processing that misidentified the intensity level of 100% of the time spent vacuuming and walking uphill, the QDA and HMM approaches correctly estimated the intensity of activity 99% of the time. CONCLUSION: The novel approach of estimating activity mode, rather than activity level, may allow for more accurate field-based estimates of physical activity using accelerometer data, and this approach warrants more study in a larger and more diverse population of subjects and activities.