Enhancing clinical decision support with genomic tools in breast cancer: A Scottish perspective.

INTRODUCTION: The Oncotype DX Breast RS test has been adopted in Scotland and has been the subject of a large population-based study by a Scottish Consensus Group to assess the uptake of the recurrence score (RS), evaluate co-variates associated with the RS and to analyse the effect it may have had on clinical practice. MATERIALS & METHODS: Pan-Scotland study between August 2018-August 2021 evaluating 833 patients who had a RS test performed as part of their diagnostic pathway. Data was extracted retrospectively from electronic records and analysis conducted to describe change in chemotherapy administration (by direct comparison with conventional risk assessment tools), and univariate/multivariate analysis to assess relationship between covariates and the RS. RESULTS: Chemotherapy treatment was strongly influenced by the RS (p < 0.001). Only 30 % of patients received chemotherapy treatment in the intermediate and high risk PREDICT groups, where chemotherapy is considered. Additionally, 55.5 % of patients with a high risk PREDICT had a low RS and did not receive chemotherapy. There were 17 % of patients with a low risk PREDICT but high RS who received chemotherapy. Multivariate regression analysis showed the progesterone receptor Allred score (PR score) to be a strong independent predictor of the RS, with a negative PR score being associated with high RS (OR 4.49, p < 0.001). Increasing grade was also associated with high RS (OR 3.81, p < 0.001). Classic lobular pathology was associated with a low RS in comparison to other tumour pathology (p < 0.01). Nodal disease was associated with a lower RS (p = 0.012) on univariate analysis, with menopausal status (p = 0.43) not influencing the RS on univariate or multivariate analysis. CONCLUSIONS: Genomic assays offer the potential for risk-stratified decision making regarding the use of chemotherapy. They can help reduce unnecessary chemotherapy treatment and identify a subgroup of patients with more adverse genomic tumour biology. A recent publication by Health Improvement Scotland (HIS) has updated guidance on use of the RS test for NHS Scotland. It suggests to limit its use to the intermediate risk PREDICT group. Our study shows the impact of the RS test in the low and high risk PREDICT groups. The implementation across Scotland has resulted in a notable shift in practice, leading to a significant reduction in chemotherapy administration in the setting of high risk PREDICT scores returning low risk RS. There has also been utility for the test in the low risk PREDICT group to detect a small subgroup with a high RS. We have found the PR score to have a strong independent association with high risk RS. This finding was not evaluated by the key RS test papers, and the potential prognostic information provided by the PR score as a surrogate biomarker is an outstanding question that requires more research to validate.

Clinical Experience of Axillary Radiotherapy for Node-positive Breast Cancer.

AIMS: Patients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer. MATERIALS AND METHODS: We evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan-Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model. RESULTS: Locoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20-0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45-14.0, P = 0.009). CONCLUSION: We support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology.

Characteristics of adult- compared to childhood-onset type 1 diabetes.

AIMS: To compare diagnosis characteristics, diabetes management and comorbidities in a population diagnosed with type 1 diabetes in childhood with those in a similar population diagnosed in adulthood to identify disease differences related to the age of diabetes onset. METHODS: This analysis was performed using the T1D Exchange Clinic Registry, a cross-sectional survivor cohort. Retrospectively collected characteristics were compared across the following age-at-diagnosis groups: <10, 10-17, 18-24, 25-39 and ≥40 years. RESULTS: The entire cohort included 20 660 participants [51% female, median (interquartile range) age 18 (14-36) years, 82% non-Hispanic white]. Diabetic ketoacidosis at diagnosis was more common among those with onset in childhood. Participants diagnosed as adults were more likely to be overweight/obese at diagnosis and to have used oral agents preceding type 1 diabetes diagnosis (57%). Current insulin pump use was less frequent in participants diagnosed at older ages. Current glycaemic control, measured by HbA1c , insulin requirements and use of a continuous glucose monitor were not different by age at diagnosis. Coeliac disease was the only comorbidity that was observed to have a different frequency by age at diagnosis, being more common in the participants diagnosed at a younger age. CONCLUSIONS: These results show differences and similarities between type 1 diabetes diagnosed in childhood vs adulthood; notably, there was a tendency for there was a higher frequency of diabetic ketoacidosis at onset in children and a higher frequency of use of oral antidiabetes agents in adults. The data indicate that there is little distinction between the clinical characteristics and outcomes of type 1 diabetes diagnosed in childhood vs adulthood. Optimizing glycaemic control remains a challenge in all age groups, with lower use of insulin pumps impacting those diagnosed as adults.

A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach.

AIMS: To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. METHODS: We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. RESULTS: The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. CONCLUSIONS: We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way.

Donor characteristics do not influence transfusion-related acute lung injury incidence in a secondary analysis of two case-control studies.

OBJECTIVE: To investigate the relation between donor characteristics and TRALI incidence. BACKGROUND: Transfusion-related acute lung injury (TRALI) is a potentially fatal complication of transfusion. In pre-clinical studies and several clinical studies, TRALI has been related to loss of product quality during red blood cell (RBC) storage, called the "storage lesion". Donor characteristics, as for example age, genetics and life style choices influence this "storage lesion". We hypothesized that donor sex, age and blood type is related to TRALI incidence. METHODS/MATERIALS: We performed a secondary analysis of two cohort studies, designed to identify TRALI risk factors by matching TRALI patients to transfused controls. We obtained donor sex, age and blood type from the Dutch Blood Bank Sanquin and investigated TRALI incidence in patients who were exposed to a certain donor characteristic. We used Kruskal-Wallis testing to compare the number of transfused products and Chi2 testing to compare proportions of TRALI patients and transfused control. RESULTS: After implementation of the male-donor only plasma strategy, patients received more transfusion products from male donors. However, we did not detect a relation between TRALI incidence and donor sex. Both TRALI patients and transfused controls received mainly products from donors over 41 years old, but donor age did not influence TRALI risk. Donor blood type, the transfusion of blood type-compatible and blood type-matched products also had no influence on TRALI incidence. CONCLUSION: We conclude that in two cohorts of TRALI patients, donor age, donor sex and donor blood type are unrelated to TRALI.

The practice of diagnosing and reporting transfusion-associated circulatory overload: a national survey among physicians and haemovigilance officers.

OBJECTIVES: This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion-associated circulatory overload ('TACO'). BACKGROUND: TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion. METHODS: A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B-coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0- to 100-point scale. RESULTS: One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [ß 0·4(-0·1-1·0)], positive fluid balance [ß 0·9(0·4-1·5)] and history of renal failure [ß 0·6(0·1-1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [ß 0·3(-0·2-0·7) resp. 0·5(-0·1-1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [ß 0·3(-0·8-1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60 (IQR 50-80)]. No differences were observed between disciplines involved. CONCLUSION: When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes.

The role of endothelium in the onset of antibody-mediated TRALI.

Transfusion Related Acute Lung Injury (TRALI) is one of the leading causes of mortality and morbidity following blood transfusion. The mechanisms behind the disease are not yet fully understood but seem to involve many different activating pathways and donor factors, in synergy with patient susceptibility. Studies have focused mostly on neutrophil activation, as aggregates of neutrophils and edema in lungs are found in post-mortem histological sections. This review aims to highlight the role of the endothelium in TRALI, as activated endothelium is the main promoter of leukocyte transmigration, and creates the barrier between blood and tissue. Since recent evidence suggests that a strong endothelial barrier prevents leukocyte transmigration and vascular leakage, we suggest that strengthening this barrier may be key to TRALI prevention.

Diabetes distress is linked with worsening diabetes management over time in adults with Type 1 diabetes.

AIM: To determine the cross-sectional and longitudinal associations between diabetes distress and diabetes management. METHODS: In a non-interventional study, 224 adults with Type 1 diabetes were assessed for diabetes distress, missed insulin boluses, hypoglycaemic episodes, and HbA1c at baseline and 9 months. RESULTS: At baseline, greater distress was associated with higher HbA1c and a greater percentage of missed insulin boluses. Longitudinally, elevated baseline distress was related to increased missed insulin boluses, and decreases in distress were associated with decreases in HbA1c . In supplementary analyses, neither depression symptoms nor a diagnosis of major depressive disorder was associated with missed insulin boluses, HbA1c or hypoglycaemic episodes in cross-sectional or longitudinal analyses. CONCLUSIONS: Significant cross-sectional and longitudinal associations were found between diabetes distress and management; in contrast, no parallel associations were found for major depressive disorder or depression symptoms. Findings suggest that elevated distress may lead to more missed insulin boluses over time, suggesting a potential intervention target. The covarying association between distress and HbA1c points to the complex and likely interactive associations between these constructs. Findings highlight the need to address distress as an integral part of diabetes management in routine care.

The practice of platelet transfusion prior to central venous catheterization in presence of coagulopathy: a national survey among clinicians.

BACKGROUND: Correction of coagulopathy prior to central venous catheter (CVC) placement is advocated by guidelines, while retrospective studies support restrictive use of transfusion products. STUDY DESIGN AND METHODS: We conducted a mixed vignette and questionnaire web survey to investigate current practice and preferences for CVC placement. Clinical vignettes were used to quantify the tendency to administer platelet concentrate. A positive ß-coefficient is in favour of administering platelet concentrate. RESULTS: Ninety-seven physicians answered the survey questions (36 critical care physicians, 14 haematologists, 20 radiologists and 27 anaesthesiologist). Eighty-six physicians subsequently completed the clinical vignettes (response rate 71%). Preferences in favour of correcting thrombocytopenia prior CVC placement were platelet counts of 10 × 109 /L and 20 × 109 /L (ß = 3·9; ß = 3·2, respectively), the subclavian insertion site (ß = 0·8). An elevated INR (INR = 3; ß = 0·6) and an elevated aPTT (aPTT = 60 s; ß = 0·4) showed a positive trend towards platelet transfusion. Platelet transfusion was less likely in an emergency setting (ß = -0·4). Reported transfusion thresholds for CVC placement varied from <10 × 109 /L to 80 × 109 /L for platelet count, from 1·0 to 10·0 for INR and from 25 s to 150 s for aPTT. Implementation of ultrasound guidance as standard practice was limited. CONCLUSION: Current transfusion practice prior to CVC placement is highly variable. Physicians adjust the decision to correct coagulopathy prior CVC placement based on clinical parameters, insertion site and technique applied.

Non-polar lipids accumulate during storage of transfusion products and do not contribute to the onset of transfusion-related acute lung injury.

BACKGROUND AND OBJECTIVES: The accumulation of non-polar lipids arachidonic acid, 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE and 15-HETE during storage of transfusion products may play a role in the onset of transfusion-related acute lung injury (TRALI), a syndrome of respiratory distress after transfusion. MATERIALS AND METHODS: We investigated non-polar lipid accumulation in red blood cells (RBCs) stored for 42 days, plasma stored for 7 days at either 4 or 20°C and platelet (PLT) transfusion products stored for 7 days. Furthermore, we investigated whether transfusion of RBCs with increased levels of non-polar lipids induces TRALI in a 'two-hit' human volunteer model. All products were produced following Dutch Blood Bank protocols and are according to European standards. Non-polar lipids were measured with high-performance liquid chromotography followed by mass spectrometry. RESULTS: All non-polar lipids increased in RBCs after 21 days of storage compared to baseline. The non-polar lipid concentration in plasma increased significantly, and the increase was even more pronounced in products stored at 20°C. In platelets, baseline levels of 5-HETE and 15-HETE were higher than in RBCs or plasma. However, the non-polar lipids did not change significantly during storage of PLT products. Infusion of RBCs with increased levels of non-polar lipids did not induce TRALI in LPS-primed human volunteers. CONCLUSION: We conclude that non-polar lipids accumulate in RBC and plasma transfusion products and that accumulation is temperature dependent. Accumulation of non-polar lipids does not appear to explain the onset of TRALI (Dutch Trial Register - NTR4455).

Underdiagnosing of antibody-mediated transfusion-related acute lung injury: evaluation of cellular-based versus bead-based techniques.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To support the diagnosis of antibody-mediated TRALI, HLA and HNA antibodies are tested in involved blood donors. Identification of antibody positive donors is important as exclusion of these donors is part of preventative strategies against TRALI. We compared cellular-based versus bead-based techniques for diagnosis of antibody-mediated TRALI. MATERIALS AND METHODS: All reported TRALI cases in the Netherlands during a 5-year period were evaluated. Donors were screened for the presence of HLA class I and class II antibodies using both cellular-based and bead-based techniques. RESULTS: In total, 100 TRALI cases were reported of which 91 were fully tested. In 113 donors, HLA antibodies were detected of which 84 were only detected by bead-based techniques, 12 only by cellular-based tests and 17 by both assays. Antibody-mediated TRALI was diagnosed in 44 of 91 reported cases. Twenty-one (48%) of these cases would not have been identified using only cellular-based assays. CONCLUSION: Bead-based techniques show a higher sensitivity for detecting incompatible donors in TRALI cases than cellular-based assays. These results suggest that the use of bead-based assays will result in a significant reduction of future TRALI reactions as more antibody positive donors will be excluded from future donations.

Prevalence of depression in Type 1 diabetes and the problem of over-diagnosis.

AIMS: To determine the prevalence of depression and diabetes distress in adults with Type 1 diabetes and the rate of false-positives when compared with rates of major depressive disorder. METHODS: The sample consisted of 368 individuals with Type 1 diabetes, aged > 19 years. Individuals completed: the eight-item Patient Health Questionnaire depression scale (PHQ8), which was coded using four scoring criteria (scores > 10, >12 and >15, and Diagnostic and Statistical Manual of Mental Disorders 5 (DSM) algorithm scores); the Type 1 Diabetes Distress Scale; and the Structured Clinical Interview for DSM Disorders (SCID) to assess major depressive disorder. RESULTS: The prevalence rates of depression according to the eight-item Patient Health Questionnaire were: score >10, 11.4%; score >12, 7.1%; score >15, 3.8%; and positive algorithm result, 4.6%. The prevalence of major depressive disorder was 3.5%; and the prevalence of at least moderate diabetes distress was 42.1%. Depending on the criterion used, the false-positive rate when using the Patient Health Questionnaire compared with the results when using the SCID varied from 52 to 71%. Of those classified as depressed on the PHQ-8 or Structured Clinical Interview for DSM Disorders, between 92.3 and 96.2% also reported elevated diabetes distress. No significant association was found between any group classed as having depression according to the PHQ8 or the SCID and HbA1c concentration. Depression was significantly associated with more other life stress, more complications and a lower level of education. CONCLUSIONS: We found an unexpectedly low rate of current depression and major depressive disorder in this diverse sample of adults with Type 1 diabetes, and a very high rate of false-positive results using the Patient Health Questionnaire. Considering the high prevalence of diabetes distress, much of what has been considered depression in adults with Type 1 diabetes may be attributed to the emotional distress associated with managing a demanding chronic disease and other life stressors and not necessarily to underlying psychopathology.

Challenges contributing to disrupted transition from paediatric to adult diabetes care in young adults with type 1 diabetes.

AIM: To examine challenges contributing to disruptions in care during the transition from paediatric to adult care among young adults with Type 1 diabetes who are primarily in ethnic minority groups and have low socio-economic status. METHODS: Participants (n = 20) were newly enrolled patients in a transition clinic for young adults with Type 1 diabetes with a history of loss to medical follow-up. Participants completed qualitative semi-structured interviews detailing their transition experiences in addition to demographic, HbA1c and psychosocial measures. Descriptive statistics were completed for quantitative data, and narrative thematic analysis of interviews was used to identify common themes. A mixed-method analysis was used to identify the associations between stressors identified in interviews and clinical and psychosocial variables. RESULTS: Three categories of challenges contributing to loss to follow-up were identified: psychosocial challenges, health provider and health system challenges and developmental challenges. Participants experienced a high degree of stressful life circumstances which were associated with higher HbA1c (r = 0.60, P = 0.005), longer duration of loss to follow-up (r = 0.51, P = 0.02), greater emergency department utilization (r = 0.45, P = 0.05), and lower life satisfaction (r = -0.62, P = 0.003). CONCLUSIONS: A confluence of challenges, including stressful life circumstances, healthcare system barriers and the developmental trajectory of young adulthood, contributes to a high risk of loss to follow-up and poor health in this population of young adults with Type 1 diabetes. An integrated approach to transition addressing medical and psychosocial needs may facilitate improved follow-up and health outcomes in clinical settings.

The properties of an improvised piston pump for the rapid delivery of intravenous fluids.

To maximise the effect of a small fluid load, it is occasionally desirable to bolus manually with multiple depressions of a large-capacity syringe. This is usually achieved by placing the syringe on the side port of a three-way tap. We modified this technique by placing two-one-way valves in line with the three-way tap, effectively creating a piston pump, the infusion rates via which we compared with those achieved by an inflatable pressure-infuser in a simulated resuscitation. Fluid flow was faster using the piston pump than with the pressure-infuser (mean (SD) time to infuse 2000 ml saline 0.9% via a 16-G cannula 352 (10) s vs 495 (19) s, respectively, p < 0.0001). The piston pump appears to have potential for both tight control of fluid delivery and major high-volume resuscitation. The lightweight nature of the pump and its lack of reliance on gravity may also make it suitable for the pre-hospital setting.

Disclosure of psychosocial stressors affecting diabetes care among uninsured young adults with Type 1 diabetes.

AIMS: To determine the disclosure rates of psychosocial issues affecting routine diabetes care. METHODS: A total of 20 young adults were interviewed regarding the impact of psychosocial stressors on their diabetes care. The interviewer, endocrinologist and case manager reported the prevalence rates of psychosocial stressors. Disclosure rates were compared to determine the prevalence of psychosocial issues and the different patterns of disclosure. RESULTS: Participants reported a high number of psychosocial stressors, which were associated with poorer glycaemic control (r = 0.60, P = 0.005). Approximately half of all disclosed stressors (50.9%) were identified in routine care; other stressors were identified only through intensive case management and/or in-depth interviews. CONCLUSIONS: Identifying psychosocial stressors in routine care, and providing referrals to psychological or social services, is a significant unmet need and may improve glycaemic control among certain populations with diabetes. Systematic mechanisms of capturing this information, such as by screening surveys, should be considered.

Using thiazolidinediones: rosiglitazone and pioglitazone in clinical practice.

Type 2 diabetes is a disorder that has numerous components, including insulin resistance, an insulin secretory defect, and an increase in hepatic glucose production. Until recently, only the insulin secretory defect could be treated. Within recent years, the thiazolidinedione (TZD) class of drugs, which targets primarily insulin resistance, was released. Originally developed in Japan as triglyceride-lowering agents, TZDs were found to be more effective in lowering blood glucose levels instead. The actions of 2 TZDs--rosiglitazone and pioglitazone--are discussed, and their glucose- and nonglucose-lowering effects are explained. Four case histories are presented to illustrate various patients' responses to TZDs in clinical practice. Although TZDs have been demonstrated to be effective in dealing with many different aspects of type 2 diabetes, further study, involving multiple clinical trials, is needed.

Revisiting the oral glucose tolerance test criterion for the diagnosis of diabetes.

OBJECTIVE: The Expert Committee on the Diagnosis and Classification of Diabetes retained the 2-hour glucose concentration on an oral glucose tolerance test of >/=11.1 mmol/L (200 mg/dL) as a criterion to diagnose diabetes. Since glycated hemoglobin levels have emerged as the best measure of long-term glycemia and an important predictor of microvascular and neuropathic complications, we evaluated the distribution of hemoglobin A1C (Hb A1C) levels in individuals who had undergone an oral glucose tolerance test to determine how well 2-hour values could identify those with normal versus increased Hb A1C levels. DESIGN: A cross-sectional analysis of 2 large data sets was performed. We cross-tabulated 2-hour glucose concentrations on an oral glucose tolerance test separated into 4 intervals (<7.8 mmol/L [140 mg/dL], 7.8-11.0 mmol/L [140-199 mg/dL], 11.1-13.3 mmol/L [200-239 mg/dL], and >/=13.3 mmol/L [240 mg/dL]) with Hb A1C levels separated into 3 intervals (normal; <1% above the upper limit of normal; and greater than or equal to the upper limit of normal + 1%). RESULTS: Approximately two thirds of patients in both data sets with 2-hour glucose concentrations of 11.1 to 13.3 mmol/L (200-239 mg/dL) had normal Hb A1C levels. In contrast, 60% to 80% of patients in both data sets with 2-hour glucose concentrations >/=13.3 mmol/L (240 mg/dL) had elevated Hb A1C levels. CONCLUSION: Since Hb A1C levels are the best measures presently available that reflect long-term glycemia, we conclude that the 2-hour glucose concentration criterion on an oral glucose tolerance test for the diagnosis of diabetes should be raised from >/= 11.1 mmol/L (200 mg/dL) to >/= 13.3 mmol/L (240 mg/dL) to remain faithful to the concept that diagnostic concentrations of glucose should predict the subsequent development of specific diabetic complications (e.g., retinopathy).