Digital Research Alliance of Canada

BACKGROUND: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. METHODS: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. RESULTS: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. CONCLUSIONS: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

BACKGROUND: Genotype imputation can help reduce genotyping costs particularly for implementation of genomic selection. In applications entailing large populations, recovering the genotypes of untyped loci using information from reference individuals that were genotyped with a higher density panel is computationally challenging. Popular imputation methods are based upon the Hidden Markov model and have computational constraints due to an intensive sampling process. A fast, deterministic approach, which makes use of both family and population information, is presented here. All individuals are related and, therefore, share haplotypes which may differ in length and frequency based on their relationships. The method starts with family imputation if pedigree information is available, and then exploits close relationships by searching for long haplotype matches in the reference group using overlapping sliding windows. The search continues as the window size is shrunk in each chromosome sweep in order to capture more distant relationships. RESULTS: The proposed method gave higher or similar imputation accuracy than Beagle and Impute2 in cattle data sets when all available information was used. When close relatives of target individuals were present in the reference group, the method resulted in higher accuracy compared to the other two methods even when the pedigree was not used. Rare variants were also imputed with higher accuracy. Finally, computing requirements were considerably lower than those of Beagle and Impute2. The presented method took 28 minutes to impute from 6 k to 50 k genotypes for 2,000 individuals with a reference size of 64,429 individuals. CONCLUSIONS: The proposed method efficiently makes use of information from close and distant relatives for accurate genotype imputation. In addition to its high imputation accuracy, the method is fast, owing to its deterministic nature and, therefore, it can easily be used in large data sets where the use of other methods is impractical.

BACKGROUND: The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy. METHODS: We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions. RESULTS: From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group. CONCLUSIONS: In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).

IMPORTANCE: There are no known effective treatments for painful chemotherapy-induced peripheral neuropathy. OBJECTIVE: To determine the effect of duloxetine, 60 mg daily, on average pain severity. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, placebo-controlled crossover trial at 8 National Cancer Institute (NCI)-funded cooperative research networks that enrolled 231 patients who were 25 years or older being treated at community and academic settings between April 2008 and March 2011. Study follow-up was completed July 2012. Stratified by chemotherapeutic drug and comorbid pain risk, patients were randomized to receive either duloxetine followed by placebo or placebo followed by duloxetine. Eligibility required that patients have grade 1 or higher sensory neuropathy according to the NCI Common Terminology Criteria for Adverse Events and at least 4 on a scale of 0 to 10, representing average chemotherapy-induced pain, after paclitaxel, other taxane, or oxaliplatin treatment. INTERVENTIONS: The initial treatment consisted of taking 1 capsule daily of either 30 mg of duloxetine or placebo for the first week and 2 capsules of either 30 mg of duloxetine or placebo daily for 4 additional weeks. MAIN OUTCOME MEASURES: The primary hypothesis was that duloxetine would be more effective than placebo in decreasing chemotherapy-induced peripheral neuropathic pain. Pain severity was assessed using the Brief Pain Inventory-Short Form "average pain" item with 0 representing no pain and 10 representing as bad as can be imagined. RESULTS: Individuals receiving duloxetine as their initial 5-week treatment reported a mean decrease in average pain of 1.06 (95% CI, 0.72-1.40) vs 0.34 (95% CI, 0.01-0.66) among those who received placebo (P = .003; effect size, 0.513). The observed mean difference in the average pain score between duloxetine and placebo was 0.73 (95% CI, 0.26-1.20). Fifty-nine percent of those initially receiving duloxetine vs 38% of those initially receiving placebo reported decreased pain of any amount. CONCLUSION AND RELEVANCE: Among patients with painful chemotherapy-induced peripheral neuropathy, the use of duloxetine compared with placebo for 5 weeks resulted in a greater reduction in pain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00489411.

The Belgrade (b) rat has an autosomal recessively inherited, microcytic, hypochromic anemia associated with abnormal reticulocyte iron uptake and gastrointestinal iron absorption. The b reticulocyte defect appears to be failure of iron transport out of endosomes within the transferrin cycle. Aspects of this phenotype are similar to those reported for the microcytic anemia (mk) mutation in the mouse. Recently, mk has been attributed to a missense mutation in the gene encoding the putative iron transporter protein Nramp2. To investigate the possibility that Nramp2 was also mutated in the b rat, we established linkage of the phenotype to the centromeric portion of rat chromosome 7. This region exhibits synteny to the chromosomal location of Nramp2 in the mouse. A polymorphism within the rat Nramp2 gene cosegregated with the b phenotype. A glycine-to-arginine missense mutation (G185R) was present in the b Nramp2 gene, but not in the normal allele. Strikingly, this amino acid alteration is the same as that seen in the mk mouse. Functional studies of the protein encoded by the b allele of rat Nramp2 demonstrated that the mutation disrupted iron transport. These results confirm the hypothesis that Nramp2 is the protein defective in the Belgrade rat and raise the possibility that the phenotype shared by mk and b animals is unique to the G185R mutation. Furthermore, the phenotypic characteristics of these animals indicate that Nramp2 is essential both for normal intestinal iron absorption and for transport of iron out of the transferrin cycle endosome.

This paper outlines a particular approach to building theory that was employed in a recent doctoral research project (Pandit, 1995). Three aspects used in conjunction indicate the project's novelty: firstly, the systematic and rigorous application of the grounded theory method; secondly, the use of on-line computerised databases as a primary source of data; and, thirdly, the use of a qualitative data analysis software package to aid the process of grounded theory building.

The Cardiovascular Disease in Women Committee of the American College of Cardiology, in conjunction with interested parties (from the National Heart, Lung, and Blood Institute, American Heart Association, and European Society of Cardiology), convened a working group to develop a consensus on the syndrome of myocardial ischemia with no obstructive coronary arteries. In general, these patients have elevated risk for a cardiovascular event (including acute coronary syndrome, heart failure hospitalization, stroke, and repeat cardiovascular procedures) compared with reference subjects and appear to be at higher risk for development of heart failure with preserved ejection fraction. A subgroup of these patients also has coronary microvascular dysfunction and evidence of inflammation. This document provides a summary of findings and recommendations for the development of an integrated approach for identifying and managing patients with ischemia with no obstructive coronary arteries and outlines knowledge gaps in the area. Working group members critically reviewed available literature and current practices for risk assessment and state-of-the-science techniques in multiple areas, with a focus on next steps needed to develop evidence-based therapies. This report presents highlights of this working group review and a summary of suggested research directions to advance this field in the next decade.

BACKGROUND: Our goal was to estimate the rate of positive screens for bipolar I and bipolar II disorders in the general population of the United States. METHOD: The Mood Disorder Questionnaire (MDQ), a validated screening instrument for bipolar I and II disorders, was sent to a sample of 127,800 people selected to represent the U.S. adult population by demographic variables. 85,358 subjects (66.8% response rate) that were 18 years of age or above returned the survey and had usable data. Of the nonrespondents, 3404 subjects matched demographically to the 2000 U.S. Census data completed a telephone interview to estimate nonresponse bias. RESULTS: The overall positive screen rate for bipolar I and II disorders, weighted to match the 2000 U.S. Census demographics, was 3.4%. When adjusted for the nonresponse bias, the rate rose to 3.7%. Only 19.8% of the individuals with positive screens for bipolar I or II disorders reported that they had previously received a diagnosis of bipolar disorder from a physician, whereas 31.2% reported receiving a diagnosis of unipolar depression. An additional 49.0% reported receiving no diagnosis of either bipolar disorder or unipolar depression. Positive screens were more frequent in young adults and low income households. The rates of migraine, allergies, asthma, and alcohol and drug abuse were substantially higher among those with positive screens. CONCLUSION: The positive MDQ screen rate of 3.7% suggests that nearly 4% of American adults may suffer from bipolar I and II disorders. Young adults and individuals with lower income are at greater risk for this largely underdiagnosed disorder.

OBJECTIVE: To use data from the Global Burden of Disease Study between 1990 and 2017 to report the rates and trends of point prevalence, annual incidence, and years lived with disability for neck pain in the general population of 195 countries. DESIGN: Systematic analysis. DATA SOURCE: Global Burden of Diseases, Injuries, and Risk Factors Study 2017. MAIN OUTCOME MEASURES: Numbers and age standardised rates per 100 000 population of neck pain point prevalence, annual incidence, and years lived with disability were compared across regions and countries by age, sex, and sociodemographic index. Estimates were reported with uncertainty intervals. RESULTS: Globally in 2017 the age standardised rates for point prevalence of neck pain per 100 000 population was 3551.1 (95% uncertainty interval 3139.5 to 3977.9), for incidence of neck pain per 100 000 population was 806.6 (713.7 to 912.5), and for years lived with disability from neck pain per 100 000 population was 352.0 (245.6 to 493.3). These estimates did not change significantly between 1990 and 2017. The global point prevalence of neck pain in 2017 was higher in females compared with males, although this was not significant at the 0.05 level. Prevalence increased with age up to 70-74 years and then decreased. Norway (6151.2 (95% uncertainty interval 5382.3 to 6959.8)), Finland (5750.3 (5058.4 to 6518.3)), and Denmark (5316 (4674 to 6030.1)) had the three highest age standardised point prevalence estimates in 2017. The largest increases in age standardised point prevalence estimates from 1990 to 2017 were in the United Kingdom (14.6% (10.6% to 18.8%)), Sweden (10.4% (6.0% to 15.4%)), and Kuwait (2.6% (2.0% to 3.2%)). In general, positive associations, but with fluctuations, were found between age standardised years lived with disability for neck pain and sociodemographic index at the global level and for all Global Burden of Disease regions, suggesting the burden is higher at higher sociodemographic indices. CONCLUSIONS: Neck pain is a serious public health problem in the general population, with the highest burden in Norway, Finland, and Denmark. Increasing population awareness about risk factors and preventive strategies for neck pain is warranted to reduce the future burden of this condition.

The unprecedented rate of extinction calls for efficient use of genetics to help conserve biodiversity. Several recent genomic and simulation-based studies have argued that the field of conservation biology has placed too much focus on conserving genome-wide genetic variation, and that the field should instead focus on managing the subset of functional genetic variation that is thought to affect fitness. Here, we critically evaluate the feasibility and likely benefits of this approach in conservation. We find that population genetics theory and empirical results show that conserving genome-wide genetic variation is generally the best approach to prevent inbreeding depression and loss of adaptive potential from driving populations toward extinction. Focusing conservation efforts on presumably functional genetic variation will only be feasible occasionally, often misleading, and counterproductive when prioritized over genome-wide genetic variation. Given the increasing rate of habitat loss and other environmental changes, failure to recognize the detrimental effects of lost genome-wide genetic variation on long-term population viability will only worsen the biodiversity crisis.

Mid-infrared spectroscopy has been applied to zeolite structural problems. The infrared spectrum in the region of 200 to 1300 cm-1 is a sensitive tool indicating structural features of zeolite frameworks. Preliminary interpretation suggests infrared specificity for zeolite structure type and group, and for structural subunits such as double rings and large pore openings. It is proposed that the major structural groups present in zeolites can be detected from their infrared pattern. This hypothesis is based on correlation of newly determined infrared spectra of synthetic zeolites with x-ray structure data for most of the known structural classes of zeolites. Other structural information obtained from infrared studies includes framework Si/Al composition, structural changes during thermal decomposition, and cation movement during dehydration and dehydroxylation.

BACKGROUND: Tetralogy of Fallot is the most common form of congenital heart disease in implantable cardioverter-defibrillator (ICD) recipients, yet little is known about the value of ICDs in this patient population. METHODS AND RESULTS: We conducted a multicenter cohort study in high-risk patients with Tetralogy of Fallot to determine actuarial rates of ICD discharges, identify risk factors, and characterize ICD-related complications. A total of 121 patients (median age 33.3 years; 59.5% male) were enrolled from 11 sites and followed up for a median of 3.7 years. ICDs were implanted for primary prevention in 68 patients (56.2%) and for secondary prevention in 53 (43.8%), defined by clinical sustained ventricular tachyarrhythmia or resuscitated sudden death. Overall, 37 patients (30.6%) received at least 1 appropriate and effective ICD discharge, with a median ventricular tachyarrhythmia rate of 213 bpm. Annual actuarial rates of appropriate ICD shocks were 7.7% and 9.8% in primary and secondary prevention, respectively (P=0.11). A higher left ventricular end-diastolic pressure (hazard ratio 1.3 per mm Hg, P=0.004) and nonsustained ventricular tachycardia (hazard ratio 3.7, P=0.023) independently predicted appropriate ICD shocks in primary prevention. Inappropriate shocks occurred in 5.8% of patients yearly. Additionally, 36 patients (29.8%) experienced complications, of which 6 (5.0%) were acute, 25 (20.7%) were late lead-related, and 7 (5.8%) were late generator-related complications. Nine patients died during follow-up, which corresponds to an actuarial annual mortality rate of 2.2%, which did not differ between the primary and secondary prevention groups. CONCLUSIONS: Patients with tetralogy of Fallot and ICDs for primary and secondary prevention experience high rates of appropriate and effective shocks; however, inappropriate shocks and late lead-related complications are common.

Climate change arguably represents one of the greatest global health threats of our time. Health professionals can advocate for global efforts to reduce emissions and protect people from climate change; however, evidence of their willingness to do so remains scarce. In this Viewpoint, we report findings from a large, multinational survey of health professionals (n=4654) that examined their views of climate change as a human health issue. Consistent with previous research, participants in this survey largely understood that climate change is happening and is caused by humans, viewed climate change as an important and growing cause of health harm in their country, and felt a responsibility to educate the public and policymakers about the problem. Despite their high levels of commitment to engaging in education and advocacy on the issue, many survey participants indicated that a range of personal, professional, and societal barriers impede them from doing so, with time constraints being the most widely reported barrier. However, participants say various resources-continuing professional education, communication training, patient education materials, policy statements, action alerts, and guidance on how to make health-care workplaces sustainable-can help to address those barriers. We offer recommendations on how to strengthen and support health professional education and advocacy activities to address the human health challenges of climate change.

A diverse, cross-sectorial group of partners, stakeholders and researchers, collaborated to develop an evidence-informed Position Statement on active outdoor play for children aged 3-12 years. The Position Statement was created in response to practitioner, academic, legal, insurance and public debate, dialogue and disagreement on the relative benefits and harms of active (including risky) outdoor play. The Position Statement development process was informed by two systematic reviews, a critical appraisal of the current literature and existing position statements, engagement of research experts (N=9) and cross-sectorial individuals/organizations (N=17), and an extensive stakeholder consultation process (N=1908). More than 95% of the stakeholders consulted strongly agreed or somewhat agreed with the Position Statement; 14/17 participating individuals/organizations endorsed it; and over 1000 additional individuals and organizations requested their name be listed as a supporter. The final Position Statement on Active Outdoor Play states: "Access to active play in nature and outdoors--with its risks--is essential for healthy child development. We recommend increasing children's opportunities for self-directed play outdoors in all settings--at home, at school, in child care, the community and nature." The full Position Statement provides context for the statement, evidence supporting it, and a series of recommendations to increase active outdoor play opportunities to promote healthy child development.

CONTEXT: Children exposed to a traumatic event may be at higher risk for developing mental disorders. The prevalence of child psychopathology, however, has not been assessed in a population-based sample exposed to different levels of mass trauma or across a range of disorders. OBJECTIVE: To determine prevalence and correlates of probable mental disorders among New York City, NY, public school students 6 months following the September 11, 2001, World Trade Center attack. DESIGN: Survey. SETTING: New York City public schools. PARTICIPANTS: A citywide, random, representative sample of 8236 students in grades 4 through 12, including oversampling in closest proximity to the World Trade Center site (ground zero) and other high-risk areas. MAIN OUTCOME MEASURE: Children were screened for probable mental disorders with the Diagnostic Interview Schedule for Children Predictive Scales. RESULTS: One or more of 6 probable anxiety/depressive disorders were identified in 28.6% of all children. The most prevalent were probable agoraphobia (14.8%), probable separation anxiety (12.3%), and probable posttraumatic stress disorder (10.6%). Higher levels of exposure correspond to higher prevalence for all probable anxiety/depressive disorders. Girls and children in grades 4 and 5 were the most affected. In logistic regression analyses, child's exposure (adjusted odds ratio, 1.62), exposure of a child's family member (adjusted odds ratio, 1.80), and the child's prior trauma (adjusted odds ratio, 2.01) were related to increased likelihood of probable anxiety/depressive disorders. Results were adjusted for different types of exposure, sociodemographic characteristics, and child mental health service use. CONCLUSIONS: A high proportion of New York City public school children had a probable mental disorder 6 months after September 11, 2001. The data suggest that there is a relationship between level of exposure to trauma and likelihood of child anxiety/depressive disorders in the community. The results support the need to apply wide-area epidemiological approaches to mental health assessment after any large-scale disaster.

Formyl peptide receptors, abbreviated as FPRs in humans, are G-protein coupled receptors (GPCRs) mainly found in mammalian leukocytes. However, they are also expressed in cell types crucial for homeostatic brain regulation, including microglia and blood-brain barrier endothelial cells. Thus, the roles of these immune-associated receptors are extensive, from governing cellular adhesion and directed migration through chemotaxis, to granule release and superoxide formation, to phagocytosis and efferocytosis. In this review, we will describe the similarities and differences between the two principal pro-inflammatory and anti-inflammatory FPRs, FPR1 and FPR2, and the evidence for their importance in the development of neuroinflammatory disease, alongside their potential as therapeutic targets.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

In Brief Objective: To study the association between diabetes status, perioperative hyperglycemia, and adverse events in a statewide surgical cohort. Background: Perioperative hyperglycemia may increase the risk of adverse events more significantly in patients without diabetes (NDM) than in those with diabetes (DM). Methods: Using data from the Surgical Care and Outcomes Assessment Program, a cohort study (2010–2012) evaluated diabetes status, perioperative hyperglycemia, and composite adverse events in abdominal, vascular, and spine surgery at 53 hospitals in Washington State. Results: Among 40,836 patients (mean age, 54 years; 53.6% women), 19% had diabetes; 47% underwent a perioperative blood glucose (BG) test, and of those, 18% had BG ≥180 mg/dL. DM patients had a higher rate of adverse events (12% vs 9%, P < 0.001) than NDM patients. After adjustment, among NDM patients, those with hyperglycemia had an increased risk of adverse events compared with those with normal BG. Among NDM patients, there was a dose-response relationship between the level of BG and composite adverse events [odds ratio (OR), 1.3 for BG 125–180 (95% confidence interval (CI), 1.1–1.5); OR, 1.6 for BG ≥180 (95% CI, 1.3–2.1)]. Conversely, hyperglycemic DM patients did not have an increased risk of adverse events, including those with a BG 180 or more (OR, 0.8; 95% CI, 0.6–1.0). NDM patients were less likely to receive insulin at each BG level. Conclusions: For NDM patients, but not DM patients, the risk of adverse events was linked to hyperglycemia. Underlying this paradoxical effect may be the underuse of insulin, but also that hyperglycemia indicates higher levels of stress in NDM patients than in DM patients. We conducted a cohort study evaluating diabetes status, perioperative hyperglycemia, and composite adverse events in abdominal, vascular, and spine surgery at 53 hospitals in Washington State. We found that for patients without diabetes, but not for patients with diabetes, the risk of adverse events was linked to hyperglycemia.