Editor's Choice -- Survival, Limb Salvage, and Management of Patients with Lower Limb Acute Ischaemia: A French National Retrospective Observational Study.

OBJECTIVE: The aim was to describe the baseline characteristics of French patients referred with acute limb ischaemia (ALI), and their clinical management and outcome (death, amputation). METHODS: This retrospective observational cohort study used the National Health Data System. All adults hospitalised for ALI who underwent revascularisation with an endovascular or open surgical approach between 1 January 2015 and 31 December 2020 were included and followed up until death or the end of the study (31 December 2021). A one year look back period was used to capture patients' medical history. The risks of death, and major and minor amputations were described using Kaplan-Meier and Aalen-Johansen estimators. A Cox model was used to report the adjusted association between groups and risk of death and Fine-Gray models for the risk of amputations considering the competing risk of death. RESULTS: Overall, 51 390 patients (median age 70 years, 69% male) were included and had a median follow up of 2.7 years: 39 411 (76.7%) were treated with an open approach and 11 979 (23.3%) with a percutaneous endovascular approach. The preferred approach for the revascularisation varied between French regions. The one year overall survival was 78.0% and 85.2% in the surgery and endovascular groups, respectively. The surgery group had a higher risk of death (hazard ratio [HR] 1.17, 95% CI 1.12 - 1.21), a higher risk of major amputation (sub-distribution HR 1.20, 95% CI 1.10 - 1.30) and lower risk of minor amputation (sub-distribution HR 0.66, 95% CI 0.60 - 0.71) than the endovascular group. Diabetes and dialysis increased the risk of major amputation by 52% and 78%, respectively. Subsequent ALI was the third most common cause of hospital re-admission within one year. CONCLUSION: ALI remains a condition at high risk of death and amputation. Individual risk factors and ALI severity need to be considered to choose between approaches. Continued prevention efforts, improved management, and access to the most suitable approach are necessary.

Systems Metabolomics for Prediction of Metabolic Syndrome.

The evolution of human health is a continuum of transitions, involving multifaceted processes at multiple levels, and there is an urgent need for integrative biomarkers that can characterize and predict progression toward disease development. The objective of this work was to perform a systems metabolomics approach to predict metabolic syndrome (MetS) development. A case-control design was used within the French occupational GAZEL cohort (n = 112 males: discovery study; n = 94: replication/validation study). Our integrative strategy was to combine untargeted metabolomics with clinical, sociodemographic, and food habit parameters to describe early phenotypes and build multidimensional predictive models. Different models were built from the discriminant variables, and prediction performances were optimized either when reducing the number of metabolites used or when keeping the associated signature. We illustrated that a selected reduced metabolic profile was able to reveal subtle phenotypic differences 5 years before MetS occurrence. Moreover, resulting metabolomic markers, when combined with clinical characteristics, allowed improving the disease development prediction. The validation study showed that this predictive performance was specific to the MetS component. This work also demonstrates the interest of such an approach to discover subphenotypes that will need further characterization to be able to shift to molecular reclassification and targeting of MetS.

Primary Cardiovascular Disease Risk Factors Predicted by Poor Working Conditions in the GAZEL Cohort.

The mechanisms by which work environment might influence cardiovascular disease (CVD) risk are still a matter of debate. In particular, the involvement of the main behavioral and clinical risk factors and their relationships with working conditions are not always clear, despite an abundant body of literature. Most studies have investigated the impact of a limited number of characteristics of the work environment on the occurrence of 1 or a few risk factors. In contrast, in this study we used a global approach in which 30 objective and subjective indicators of working conditions were tested as predictors of 9 modifiable CVD risk factors in a well-characterized cohort of 20,625 middle-aged French workers who were followed from the 1990s until they retired or until December 31, 2013. The incidence of 3 CVD risk factors (obesity, sleep complaints, and depression) was predicted by a large number of indicators of working conditions in both age- and sex-adjusted and multivariate-adjusted Cox regression models, whatever the significance threshold retained. These results suggest the existence of close relationships between a poor work environment and a higher risk of developing obesity, sleep complaints, or depression. These risk factors may contribute to increased CVD risk not only when workers are exposed to poor working conditions but also after retirement, as predictors of the appearance of other risk factors.

Daily alcohol consumption and sickness absence in the GAZEL cohort.

Background: : Previous studies that examined the association between daily alcohol consumption and sickness absences (SA) were mostly retrospective and did not take into account the characteristics of SA. : A total of 9907 daily drinkers (8442 men and 1465 women) of the GAZEL prospective cohort were included. Daily alcohol consumption over the three previous years was self-reported at baseline and categorized as low, moderate, high or very high risk according to the World Health Organization. Duration of SA (short: ≤7 days; moderate: 8-28; long: >28) was collected from administrative records as well as causes for long SA. Negative binomial regression models were used to estimate Risk Ratios of SA according to alcohol consumption with low-risk category as reference. : Duration of follow-up (in years) for SA was 8.4 ± 3.7 in men and 11.2 ± 5.4 in women. Increasing alcohol consumption predicted increasing risk of SA with a dose-response relationship ( P < 0.01 for men; P = 0.01 for women). In men, strength of this association increased with SA duration [e.g. RRs from 1.41 (95% CI: 1.12-1.79) to 2.12 (95% CI: 1.49-3.00) in the very high-risk category, for short and long SA, respectively]. In men, even a moderate consumption predicted increased risk of SA whatever their duration (RR = 1.15; 95% CI: 1.07-1.23). In women, a moderate consumption predicted only long SA (RR = 1.22; 95% CI: 1.00-1.50). Daily alcohol consumption was associated with almost all causes of long SA in men, and with respiratory diseases, digestive diseases and injury in women. : We found a dose-response relationship between daily alcohol consumption and the risk of SA. Even moderate consumption could increase this risk, particularly in men.

Is physically arduous work associated with limitations after retirement? Findings from the GAZEL cohort.

INTRODUCTION: In the context of delayed retirement age, we aimed to study the association between a score for global evaluation of perceived physical strain (PPS) at work and limitations after retirement in the GAZEL cohort. METHODS: At baseline in 1989 and every year since then, the PPS question, 'Do you find that your work is physically strenuous?' was used as a proxy measure of general occupational physical exertion or load; it was coded into a score, and divided into four categories for men and three for women. The self-report question about limitations was asked in 1989 and 2012 (difficulties performing some daily life activities). Among men and women without limitations at baseline, relationships were studied between reported limitations in 2012 and a cumulative score based on PPS since 1989, allowing examination of the dose-effect relationship, and adjusted for age and perceived state of health at baseline. RESULTS: From 1989 to 2012, 9326 participants without limitations at baseline were followed and filled out the 2012 questionnaire. In 2012, 12.1% of men (n=845) and 12.9% of women (n=302) reported limitations. Limitations in 2012 were associated with very high categorical PPS in men (OR 1.7 (1.4 to 2.2)) and high/very high categorical PPS in women (OR 1.6 (1.2 to 2.2)), with a significant trend. CONCLUSIONS: A positive association was found between preretirement physically arduous working conditions and limitations in daily activities after retirement. Findings offer a new insight for global evaluation of physical exposures during working life.

More than Light Alcohol Consumption Predicts Early Cessation from Employment in French Middle-Aged Men.

AIMS: To investigate the association between alcohol consumption and different causes of work cessation and estimate the loss of occupational activity among high consumers compared with low consumers. METHODS: From the prospective study of men employed in the French gas and electric company, 8442 men during a median follow-up of 8.4 years reported on their alcohol consumption. Information on work cessation was collected from the company administrative records. Hazard Ratios (HRs) by cause of work cessation (death, disability, retirement before or after age 55) were estimated using a competing risk method. RESULTS: An increasing quantity of daily alcohol consumption was associated with an increased risk of death, disability and retirement before age 55 (P trend ≤ 0.01, = 0.03 and ≤ 0.01, respectively), but not of retirement after age 55 (P trend = 0.56). Moreover, compared with low consumption, moderate, high or very high daily intakes were associated with an increased risk of early work cessation (combination of the three causes: death, disability and retirement before age 55) (HR = 1.14, 95% confidence interval (CI) = 1.05-1.25; HR = 1.23, 95% CI = 1.12-1.35 and HR = 1.49, 95% CI = 1.15-1.92 respectively). Between ages 50 and 60, we estimated that high or very high consumers could gain 6.04 months of occupational activity if they drank like low consumers. CONCLUSIONS: Our results provide evidence of a dose-effect relationship between alcohol consumption and early work cessation.

Incidence of Chronic and Other Knee Pain in Relation to Occupational Risk Factors in a Large Working Population.

OBJECTIVES: The aim of this study was to estimate the incidence of chronic and other knee pain (KP) in relation to occupational and personal risk factors among workers representative of a general working population. METHODS: Of 3710 workers in a French region included in a surveillance network for musculoskeletal disorders (2002-2005), 2332 completed a follow-up questionnaire in 2007-2009 (Cosali cohort). The questionnaires included questions on musculoskeletal symptoms, and personal and occupational exposure. Incident cases of KP in 2007-2009 (i.e. with KP at follow-up but not at baseline) were dichotomized into chronic KP (>30 days in the previous year) and other KP. Associations between incident KP and personal and occupational factors at baseline were studied separately according to sex using multinomial logistic regression. RESULTS: Of the 1616 respondents without KP at baseline, 122 (7.5%) reported chronic KP and 243 (15.0%) reported other KP. The incidence rate of chronic KP was estimated at 19.6 per 1000 worker-years (95% CI: 16.3-23.5). After adjustment for age and body mass index, significant associations were found between incident chronic KP and handling loads >4kg [odds ratio (OR) 2.1 (1.2-3.6) for men, OR 2.3 (1.1-5.0) for women] and kneeling >2h a day for men [OR 1.8 (1.0-3.0)]. CONCLUSIONS: This study highlights the high frequency of chronic KP in the working population and the role of occupational factors in its incidence, in particular those kneeling and handling loads.

Long-term persistence of knee pain and occupational exposure in two large prospective cohorts of workers.

BACKGROUND: The persistence of knee pain (KP) and its relationship with occupational factors were investigated in two prospective cohorts of French workers: retirees of the Gazel cohort and workers in the Cosali cohort. METHODS: KP was defined according to the Nordic questionnaire (>1 day in the last year), and the information was extracted from two questionnaires in 2006 and 2012 for the Gazel cohort, and in 2002-2005 and 2007-2010 for the Cosali cohort. The personal and occupational factors and the severity of KP were measured at baseline. Of the 4590 members of the Gazel cohort with KP at baseline, 4140(90.2%) were followed up, as were 637(63.1%) members of the Cosali cohort. Logistic models were used to evaluate associations (ORs) between occupational exposure and the persistence of KP separately by sex, adjusted on indicators of severity of KP. RESULTS: KP was no longer present at follow-up for 38.3% of Gazel men and 46.0% of Cosali men (33.4% of Gazel women and 50.6% of Cosali women). The persistence of KP in men was associated with carrying or handling heavy loads on univariate analyses and with kneeling on multivariate analyses, with ORs of 1.3(1.0-1.6) (Gazel) and 1.6(1.0-2.6) (Cosali). Climbing stairs was not significantly associated with the persistence of knee pain among men. The persistence of KP in women was not significantly associated with such occupational exposure. CONCLUSIONS: This study highlights the role of occupational factors in the persistence of KP for men, in particular kneeling and handling/carrying loads.

Impact of hospitalized vaso-occlusive crises in the previous calendar year on mortality and complications in adults with sickle cell disease: a French population-based study.

Background: Historically, sickle cell disease (SCD) patients experiencing frequent hospitalized vaso-occlusive crises (HVOC) have been associated with increased mortality, yet recent data reflecting the widespread use of hydroxyurea and advancements in disease management remain limited. Our study aims to assess the association between HVOC and mortality or severe complications in patients with SCD in this new treatment landscape. Methods: This was a retrospective observational cohort study using the French national health data system. Between 01-01-2012 and 12-31-2018, all SCD patients ≥16 years old (ICD-10 codes D57.0-2) were included and followed until 12-31-2018. HVOC was defined as a hospitalization of ≥1 night with primary diagnosis of SCD with crisis, following an emergency room visit. The association between HVOC and severe complications was assessed with a Cox proportional hazards model. Findings: In total, 8018 patients (56.6% females; 4538/8018) were included. The 2018 SCD standardized one-year period prevalence was 17.9 cases/100,000 person-years [17.4; 18.3]. The mean rate was 0.84 (1.88) HVOC/person-year. In 2018, 70% (5323/7605), 22% (1671/7605), and 8% (611/7605) of patients experienced 0, 1-2, or 3+ HVOCs, respectively. The median survival time between HVOCs was 415 days [386; 439]. Overall, 312 patients died (3.9%) with a mean age of 49.8 (19.4). Compared to patients without HVOC, the hazard ratios of death in patients with 1-2 or 3+ HVOCs the year prior to death were 1.67 [1.21; 2.30] and 3.70 [2.30; 5.93], respectively. Incidence of acute chest syndrome, pulmonary embolism, osteonecrosis, and sepsis increased with the HVOCs category, but not stroke. In 2018, 29.5% (180/611) of patients with 3+ HVOCs did not take hydroxyurea. Interpretation: Patients must be closely monitored during their hospitalizations to intensify treatment and check treatment compliance. Innovative therapies are also required. Funding: The study was funded by Novartis.

Self-reported physical exposure association with medial and lateral epicondylitis incidence in a large longitudinal study.

INTRODUCTION: Although previous studies have related occupational exposure and epicondylitis, the evidence is moderate and mostly based on cross-sectional studies. Suspected physical exposures were tested over a 3-year period in a large longitudinal cohort study of workers in the USA. METHOD: In a population-based study including a variety of industries, 1107 newly employed workers were examined; only workers without elbow symptoms at baseline were included. Baseline questionnaires collected information on personal characteristics and self-reported physical work exposures and psychosocial measures for the current or most recent job at 6 months. Epicondylitis (lateral and medial) was the main outcome, assessed at 36 months based on symptoms and physical examination (palpation or provocation test). Logistic models included the most relevant associated variables. RESULTS: Of 699 workers tested after 36 months who did not have elbow symptoms at baseline, 48 suffered from medial or lateral epicondylitis (6.9%), with 34 cases of lateral epicondylitis (4.9%), 30 cases of medial epicondylitis (4.3%) and 16 workers who had both. After adjusting for age, lack of social support and obesity, consistent associations were observed between self-reported wrist bending/twisting and forearm twisting/rotating/screwing motion and future cases of medial or lateral epicondylitis (ORs 2.8 (1.2 to 6.2) and 3.6 (1.2 to 11.0) in men and women, respectively). CONCLUSIONS: Self-reported physical exposures that implicate repetitive and extensive/prolonged wrist bend/twisting and forearm movements were associated with incident cases of lateral and medial epicondylitis in a large longitudinal study, although other studies are needed to better specify the exposures involved.

Work-related risk factors for lateral epicondylitis and other cause of elbow pain in the working population.

BACKGROUND: This study was designed to assess the relationship between work-related combined physical and psychosocial factors and elbow disorders (lateral epicondylitis and non-specific disorders without lateral epicondylitis) in the working population. METHODS: A total of 3,710 workers (58% men) in a French region in 2002-2005 participated in physical examinations by occupational health physicians and assessed their personal factors and work exposure by self-administered questionnaire. Statistical associations between elbow disorders and risks factors were analyzed using multinomial logistic regression. RESULTS: A total of 389 (10.5%) workers had elbow pain without lateral epicondylitis and 90 (2.4%) workers had lateral epicondylitis. Age, body mass index (>25), and low social support (only for men) were significant risks factors. Hard perceived physical exertion combined with elbow flexion/extension (>2 hr/day) and wrist bending (>2 hr/day) was a strong significant risk factor for elbow pain and epicondylitis: among men, adjusted Odds Ratio (ORa) = 2.6 (1.9-3.7) and ORa = 5.6 (2.8-11.3), respectively; among women, ORa = 1.4 (0.9-2.2) and ORa = 2.9 (1.3-6.5). CONCLUSIONS: This study emphasizes the strength of the associations between combined physical exertion and elbow movements and lateral epicondylitis. Certain observed differences in associations with lateral epicondylitis and elbow pain only indicate the need for additional longitudinal studies on different stages of elbow disorders and known risk factors.

Accounting for genetic heterogeneity in homozygosity mapping: application to Mendelian susceptibility to mycobacterial disease.

INTRODUCTION: Genome-wide homozygosity mapping is a powerful method for locating rare recessive Mendelian mutations. However, statistical power decreases dramatically in the presence of genetic heterogeneity. METHODS: The authors applied an empirical approach to test for linkage accounting for genetic heterogeneity by calculating the sum of positive per-family multipoint LOD scores (S) across all positions, and obtaining corresponding empirical p values (EmpP) through permutations. RESULTS: The statistical power of the approach was found to be consistently higher than the classical heterogeneity LOD by simulations. Among 21 first-cousin matings with a single affected child, for five families linked to a locus of interest and 16 families to other loci, S/EmpP achieved a power of 40% versus 28% for heterogeneity LOD at an α level of 0.001. The mean size of peak linkage regions was markedly higher for true loci than false positive regions. The S/EmpP approach was applied to a sample of 17 consanguineous families with Mendelian susceptibility to mycobacterial disease, leading to the identification of two mutations in IL12RB1 and TYK2 from the largest of six linkage regions at p<10(-3). CONCLUSIONS: The S/EmpP approach is a flexible and powerful approach that can be applied to linkage analysis of families with suspected Mendelian disorders.

Safety Attitude of Operating Room Personnel Associated With Accurate Completion of a Surgical Checklist: A Cross-sectional Observational Study.

OBJECTIVE: How the checklist is executed in routine practice may reflect the teamwork and safety climate in the operating room (OR). This cross-sectional study aimed to identify whether the presence of a fully completed checklist in medical records was associated with teams' safety attitudes. METHODS: Data from 29 French hospitals, including 5677 operated patients and 834 OR professionals, were prospectively collected. The degree of checklist compliance was categorized for each patient in 1 of 4 ways: full, incomplete, inaccurate, and no checklist completed. The members of OR teams were invited to complete a questionnaire including teamwork climate measurement (Safety Attitudes Questionnaire) and their opinion regarding checklist use, checklist audibly reading, and communication change with checklist. Multilevel modeling was performed to investigate the effect of variables related to hospitals and professionals on checklist compliance, after adjustment for patient characteristics. RESULTS: A checklist was present for 83% of patients, but only 35% demonstrated full completion. Compared with no checklist, full completion was associated with higher safety attitude (high teamwork climate [adjusted odds ratio for full completion, 4.14; 95% confidence interval, 1.75-9.76]; communication change [1.31, 1.04-1.66]; checklist aloud reading [1.16, 1.02-1.32]) and was reinforced by the designation of a checklist coordinator (2.43, 1.06-5.55). Incomplete completion was also associated with enhanced safety attitude contrary to inaccurate completion. CONCLUSIONS: Compliance with checklists is associated with safer OR team practice and can be considered as an indicator of the extent of safety in OR practice.

Performance curves of medical researchers during their career: analysis of scientific production from a retrospective cohort.

OBJECTIVES: To establish the pattern of change in individual scientific production over the career of medical researchers. DESIGN: Retrospective cohort based on prospectively collected data in a hospital information system. SETTING: Multicentre university hospital in France. PARTICIPANTS: Two distinct populations of 1835 researchers (full professors vs non-academic physicians) having produced 44 723 publications between 1995 and 2014. MAIN OUTCOME MEASURES: Annual number of publications referenced in Medline/PubMed with a sensitivity analysis based on publications as first/last author and in high impact journals. The individual volume of publications was modelled by age using generalised estimating equations adjusted for birth cohort, biomedical discipline and academic position of researchers. RESULTS: Averaged over the whole career, the annual number of publications was 5.28 (95% CI 4.90 to 5.69) among professors compared to 0.82 (95% CI 0.76 to 0.89) among non-academic physicians (p<0.0001). The performance curve of professors evolved in three successive phases, including an initiation phase with a sharp increase in scientific production between 25 and 35 years (adjusted incidence rate ratio 102.20, 95% CI 60.99 to 171.30), a maturation phase with a slower increase from 35 to 50 years (2.10, 95% CI 1.75 to 2.51) until a stabilisation phase with constant production followed by a potential decline at the end of career (0.90, 95% CI 0.77 to 1.06). The non-academic physicians experienced a slower pace of learning curve at the beginning of their careers (42.38, 95% CI 25.37 to 70.81) followed by a smaller increase in the annual number of publications (1.29, 95% CI 1.11 to 1.51). CONCLUSIONS: Compared to full professors, non-academic physicians had a poor capacity to publish, indicating a low productivity when medical doctors have limited time or little interest in undertaking research. This finding highlights the potential for rethinking the missions of medical doctors towards an enlargement of scientific prerogatives in favour of progress in global knowledge.

A Global View of the Relationships between the Main Behavioural and Clinical Cardiovascular Risk Factors in the GAZEL Prospective Cohort.

Although it has been recognized for a long time that the predisposition to cardiovascular diseases (CVD) is determined by many risk factors and despite the common use of algorithms incorporating several of these factors to predict the overall risk, there has yet been no global description of the complex way in which CVD risk factors interact with each other. This is the aim of the present study which investigated all existing relationships between the main CVD risk factors in a well-characterized occupational cohort. Prospective associations between 12 behavioural and clinical risk factors (gender, age, parental history of CVD, non-moderate alcohol consumption, smoking, physical inactivity, obesity, hypertension, dyslipidemia, diabetes, sleep disorder, depression) were systematically tested using Cox regression in 10,736 middle-aged individuals free of CVD at baseline and followed over 20 years. In addition to independently predicting CVD risk (HRs from 1.18 to 1.97 in multivariable models), these factors form a vast network of associations where each factor predicts, and/or is predicted by, several other factors (n = 47 with p<0.05, n = 37 with p<0.01, n = 28 with p<0.001, n = 22 with p<0.0001). Both the number of factors associated with a given factor (1 to 9) and the strength of the associations (HRs from 1.10 to 6.12 in multivariable models) are very variable, suggesting that all the factors do not have the same influence within this network. These results show that there is a remarkably extensive network of relationships between the main CVD risk factors which may have not been sufficiently taken into account, notably in preventive strategies aiming to lower CVD risk.

Work-related risk factors for incidence of lateral epicondylitis in a large working population.

OBJECTIVES: This study aims to estimate the association between repeated measures of occupational risk factors and the incidence of lateral epicondylitis in a large working population. METHODS: A total of 3710 workers in a French region were included in 2002-2005, and among them 1046 had a complete follow-up in 2007-2010. At both stages, occupational health physicians assessed the presence of lateral epicondylitis and workers self-reported their occupational exposures. Poisson models were performed to assess the incidence rate ratios (IRR) separately by sex using multiple imputed data. RESULTS: The annual incidence rate of lateral epicondylitis was estimated as 1.0 [95% confidence interval (95% CI) 0.7-1.3] per 100 workers among men and 0.9 (95% CI 0.6-1.3) among women. Workers aged >45 years had higher incidence than those aged <30 years (significant at 10%). Among men, high physical exertion combined with elbow flexion/extension or extreme wrist bending (>2 hours/day) was a risk factor, with an age-adjusted IRR of 3.2 (95% CI 1.5-6.4) for workers exposed at both questionnaires [3.3 (95% CI 1.4-7.6) among women]. CONCLUSIONS: This study highlights the importance of temporal dimensions for occupational risk factors on the incidence of lateral epicondylitis. Further research should evaluate the risk associated with the duration and repetition of occupational exposure on the incidence of lateral epicondylitis.

Impact of diabetes on work cessation: data from the GAZEL cohort study.

OBJECTIVE: To measure the impact of diabetes on work cessation, i.e., on the risks of work disability, early retirement, and death while in the labor force. RESEARCH DESIGN AND METHODS: We used data from the GAZEL prospective cohort of 20,625 employees of the French national gas and electricity company "EDF-GDF." We identified 506 employees with diabetes and randomly selected 2,530 nondiabetic employed control subjects matched for major sociodemographic and occupational characteristics. Using a multistate Cox model, we estimated hazard ratios (HRs) comparing the risks of transition from employment to disability, retirement, and death over time between participants with versus without diabetes. RESULTS: Employment rate decreased more rapidly in participants with diabetes (51.9 and 10.1% at 55 and 60 years, respectively) compared with nondiabetic participants (66.5 and 13.4%, respectively). Participants with diabetes had significantly increased risks of transition from employment to disability (HR 1.7 [95% CI 1.0-2.9]), retirement (HR 1.6 [1.5-1.8]), and death (HR 7.3 [3.6-14.6]) compared with participants without diabetes. Between 35 and 60 years, each participant with diabetes lost an estimated mean time of 1.1 year in the workforce (95% CI 0.99-1.14) compared with a nondiabetic participant. CONCLUSIONS: Our results provide evidence for a profound negative impact of diabetes on workforce participation in France. Social and economic consequences are major for patients, employers, and society-a burden that is likely to increase as diabetes becomes more and more common in the working-aged population.