Patient and paramedic experiences with a direct electronic referral programme for focused hypoglycaemia education following paramedic service assist-requiring hypoglycaemia in London and Middlesex County, Ontario, Canada.

AIMS: Hypoglycaemia is a common treatment consequence in diabetes mellitus. Prior studies have shown that a large proportion of people with paramedic assist-requiring hypoglycaemia prefer not to be transported to hospital. Thus, these episodes are "invisible" to their usual diabetes care providers. A direct electronic referral programme where paramedics sent referrals focused hypoglycaemia education at the time of paramedic assessment was implemented in our region for 18 months; however, referral programme uptake was low. In this study, we examined patient and paramedic experiences with a direct electronic referral programme for hypoglycaemia education postparamedic assist-requiring hypoglycaemia, including barriers to programme referral and education attendance. METHODS: We surveyed paramedics and conducted semistructured telephone interviews of patients with paramedic-assisted hypoglycaemia who consented to the referral programme and were scheduled for an education session in London and Middlesex County, Canada. RESULTS: Paramedics and patient participants felt that the direct referral programme was beneficial. A third of paramedics who responded to our survey used the referral programme for each encounter where they treated patients for hypoglycaemia. Patients felt very positive about the referral programme and their paramedic encounter; however, they described embarrassment, guilt and prior negative experience as key barriers to attending education. CONCLUSIONS: Paramedics and patients felt that direct referral for focused hypoglycaemia education postparamedic assist-requiring hypoglycaemia was an excellent strategy. Despite this, referral programme participation was low and thus there remain ongoing barriers to implementation and attendance. Future iterations should consider how best to meet patient needs through innovative delivery methods.

Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial.

Importance: Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. Objective: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. Design, Setting, and Participants: An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. Interventions: The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. Main Outcomes and Measures: Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). Results: Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). Conclusions and Relevance: Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Trial Registration: clinicaltrials.gov Identifier: NCT00179777.

Use of n-of-1 (single patient) trials to assess the effect of age of transfused blood on health-related quality of life in transfusion-dependent patients.

BACKGROUND: The impact of age of red blood cells on health-related quality of life (HRQL) in patients who require chronic transfusions is not known. We assessed this using n-of-1 trials in patient populations where large randomized trials have not been done to date. STUDY DESIGN AND METHODS: Chronically transfusion-dependent adult patients were randomly assigned over time to four fresh (<7 days of storage) and four standard-issue (up to 42 days of storage) blood transfusions in prospective double-blinded multicrossover studies (n-of-1 trials). HRQL questionnaires were completed before and at 24 hours after each transfusion. Hemoglobin (Hb) levels were measured before each subsequent transfusion. RESULTS: Twenty transfusion-dependent patients were enrolled, of whom nine (five myelodysplastic syndromes, two myelofibrosis, one ß-thalassemia major, one Diamond-Blackfan anemia) completed at least six transfusions. Mean ages of fresh and standard-issue blood transfused were 4.0 and 23.2 days, respectively. There were no significant differences in the effect of standard and fresh blood on follow-up Hb levels or the eight HRQL dimensions assessed in all analyses. CONCLUSIONS: In chronically transfused patients, there were no significant differences in HRQL or Hb levels between fresh versus standard blood. While larger trials are needed, these results support current practices in hospital blood transfusion laboratories using a first-in, first-out model of blood utilization for these transfusion-dependent patients. Use of n-of-1 trials to determine the benefits of transfusions in single patients appears to be feasible.

N-of-1 (single-patient) trials for statin-related myalgia.

BACKGROUND: Statin-related myalgia is difficult to distinguish from other conditions causing myalgia and may often lead to statin discontinuation. OBJECTIVE: To compare the effect of statin rechallenge with placebo in patients with prior statin-related myalgia and to determine whether patients resumed statin therapy after evaluating the results. DESIGN: N-of-1 trial with 3 double-blind, crossover comparisons separated by 3-week washout periods. (Clinicaltrials.gov: NCT01259791) SETTING: Tertiary care lipid clinic. PATIENTS: Patients with prior statin-related myalgia with or without mild elevation of creatine kinase levels. INTERVENTION: Rechallenge with the statin that was previously associated with myalgia within 3 weeks of open-label use versus matching placebo. MEASUREMENTS: Weekly visual analogue scale (VAS) scores for myalgia and specific symptoms (VAS myalgia score and symptom-specific VAS score, respectively), pain interference scores, and pain severity scores were recorded during the 3-week periods when patients were receiving placebo or statin. The primary outcome was the VAS myalgia score (range, 0 to 100 mm). RESULTS: Eight patients (mean age, 66 years [SD, 8 years]; 88% women, all with high 10-year Framingham cardiovascular risk) participated in n-of-1 trials. Seven patients completed 3 treatment pairs, and 1 completed 2 treatment pairs. For each n-of-1 trial, no statistically significant differences were seen between statin and placebo in the VAS myalgia score, symptom-specific VAS score, pain interference score, and pain severity score. Five patients resumed open-label statin treatment, with a median posttrial follow-up of 10 months. LIMITATION: Results are limited by the small sample size and cannot be extended to patients with longer onset of myalgia after statin initiation. CONCLUSION: In selected patients with a history of statin-related myalgia whose symptoms are difficult to evaluate, n-of-1 trials may be a useful method for determining statin tolerability. PRIMARY FUNDING SOURCE: Western University, London, Ontario, Canada.

Effectiveness of Nonmydriatic Ultra-Widefield Retinal Imaging to Screen for Diabetic Eye Disease: A Randomized Controlled Trial (Clearsight).

OBJECTIVE: Suboptimal diabetic eye disease screening is a major cause of preventable vision loss. Screening barriers include mydriasis and the need for dedicated screening appointments. The Clearsight trial assessed whether nonmydriatic ultra-widefield (NM UWF) screening on the day of a diabetes clinic visit improved detection of clinically important eye disease versus usual screening. RESEARCH DESIGN AND METHODS: This single-center, randomized, parallel-group controlled trial was conducted at St. Joseph's Health Care, London, Ontario, Canada. Adults with diabetes due for screening were randomized to same-day, on-site screening (NM UWF imaging) on the day of a scheduled diabetes clinic visit or usual screening (encouraged to arrange optometrist screening). The primary outcome was detection of actionable eye disease (AED), defined as the need for an ophthalmology referral or increased ocular surveillance. The primary analysis (modified intention-to-screen) compared the proportions of AED between groups within 1 year of enrollment. RESULTS: Of 740 participants randomized between 7 March 2016 and 17 April 2019, 335 on-site screening and 323 usual screening participants met criteria for the primary analysis. More AED was detected in the on-site screening group than in the usual screening group (50 of 335 [14.9%] vs. 22 of 323 [6.8%]; adjusted odds ratio 2.51; 95% CI 1.49-4.36). The number needed to screen by on-site screening in order to detect 1 additional patient with AED was 13 (95% CI 8-29). CONCLUSIONS: Same-day, on-site screening by NM UWF imaging increased the detection of clinically important diabetic eye disease versus usual screening. Integration of NM UWF imaging into routine diabetes clinic visits improved screening adherence and has the potential to prevent vision loss.

Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study.

BACKGROUND: Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide. METHODS: We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations. RESULTS: From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk. CONCLUSIONS: In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.

A comparison of the baseline metabolic profiles between Diabetes Prevention Trial-Type 1 and TrialNet Natural History Study participants.

OBJECTIVE: We assessed whether differing autoantibody screening criteria for type 1 diabetes (T1D) prevention trials result in different baseline metabolic profiles of those who screen positive. METHODS: Diabetes Prevention Trial-Type 1 (DPT-1) participants were screened for islet cell autoantibodies, whereas TrialNet Natural History Study (TNNHS) participants were screened for biochemical autoantibodies. In both studies, those determined to be autoantibody positive underwent baseline oral glucose tolerance tests (OGTTs) in which glucose and C-peptide were measured. RESULTS: The percentage of those with an OGTT in the diabetic range was higher among the DPT-1 participants (10.0% of 956 vs. 6.4% of 645, p < 0.01). In a logistic regression analysis with adjustments for age and gender, the difference persisted (p < 0.01). Among those in the non-diabetic range (n = 860 for DPT-1 and n = 604 for the TNNHS), glucose levels were similar at all time points, except for higher fasting glucose levels in the TNNHS participants (p < 0.001). There was a higher percentage of impaired fasting glucose (IFG) in the TNNHS participants (10.9 vs. 6.7%, p < 0.01); however, with adjustments for age and gender, there was no longer a significant difference. There was no significant difference in the percentages with impaired glucose tolerance. C-peptide levels were much lower in the DPT-1 cohort at all OGTT time points (p < 0.001 for all). DISCUSSION: Differing criteria for autoantibody screening can result in marked differences in the baseline metabolic profiles of prospective participants of T1D prevention trials.

Hypoglycemia requiring paramedic assistance among adults in southwestern Ontario, Canada: a population-based retrospective cohort study.

BACKGROUND: People with diabetes mellitus commonly experience hypoglycemia, but they may not necessarily present to hospital after severe hypoglycemia requiring paramedic assistance. We sought to describe the incidence and characteristics of calls for hypoglycemia requiring paramedic assistance among adults in southwestern Ontario, Canada, and to determine predictors of hospital transport. METHODS: This population-based retrospective cohort study used data extracted from ambulance call reports (ACRs) of 8 paramedic services of the Southwest Ontario Regional Base Hospital Program from January 2008 to June 2014. We described calls in which treatment for hypoglycemia was administered, summarized the incidence of hypoglycemia calls and performed logistic regression to determine predictors of hospital transport. RESULTS: Out of 470 467 ACRs during the study period, 9185 paramedic calls occurred in which hypoglycemia treatment was administered to an adult (mean age 60.2 yr, 56.8% male, 81.1% with documented diabetes). Refusal of hospital transport occurred in 2243 (24.4%) of calls. Documented diabetes diagnosis (adjusted odds ratio [OR] 0.82, 95% confidence interval [CI] 0.69-0.96), higher capillary blood glucose (adjusted OR 0.31, 95% CI 0.22-0.44) and overnight calls (adjusted OR 0.80, 95% CI 0.72-0.91) were associated with lower odds of hospital transport. Higher-acuity calls (adjusted OR 2.05, 95% CI 1.58-2.66) were associated with higher odds of transport. The estimated annual incidence rate of hypoglycemia requiring paramedic assistance was 108 per 10 000 people with diabetes per year. INTERPRETATION: Hypoglycemia requiring paramedic assistance in southwestern Ontario is common, and close to 25% of calls do not result in hospital transport. Physicians managing diabetes care may be unaware of patients' hypoglycemia requiring paramedic care, suggesting a potential gap in follow-up care; we suggest that paramedics play an important role in identifying those at high recurrence risk and communicating with their care providers.

Relationship between Escherichia coli O157:H7 and diabetes mellitus.

Ingestion of Escherichia coli O157:H7 can cause a spectrum of acute illness, ranging from overt hemolytic-uremic syndrome (HUS), to gastroenteritis with bloody diarrhea, to no symptoms. This organism has been responsible for dozens of outbreaks of gastroenteritis and HUS in industrialized nations, and thus is a major public health concern. Although the acute effects of E. coli O157:H7 ingestion are well understood, the long-term complications are less well known. Here, we review the biological and empirical evidence supporting a link between E. coli O157:H7 and long-term diabetes mellitus. Survivors with diarrhea-associated HUS have a significantly increased incidence of diabetes due to complete insulin deficiency, which may recur several years after the initial infection. However, less severe forms of infection, such as E. coli O157:H7 gastroenteritis without overt HUS, do not appear to result in an increased risk of type 2 diabetes.

The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results.

OBJECTIVES: TrialNet's goal to test preventions for type 1 diabetes has created an opportunity to gain new insights into the natural history of pre-type 1 diabetes. The TrialNet Natural History Study (NHS) will assess the predictive value of existing and novel risk markers for type 1 diabetes and will find subjects for prevention trials. RESEARCH DESIGN AND METHODS: The NHS is a three-phase, prospective cohort study. In phase 1 (screening), pancreatic autoantibodies (glutamic acid decarboxylase, insulin, ICA-512, and islet cell antibodies) are measured. Phase 2 (baseline risk assessment) includes oral glucose tolerance tests (OGTTs) in antibody-positive subjects and estimation of 5-yr diabetes risks according to the OGTT and number of confirmed positive antibody tests. Phase 3 (follow-up risk assessments) requires OGTTs every 6 months. In phases 2 and 3, samples are collected for future tests of T-lymphocyte function, autoantibody isotypes, RNA gene expression, and proteomics. The primary outcome is diabetes onset. RESULTS: Of 12 636 relatives screened between March 2004 and December 2006, 605 (4.8%) were positive for at least one biochemical antibody. Of these, 322 were confirmed antibody positive and completed phase 2, of whom 296 subjects were given preliminary 5-yr diabetes risks of <25% (n = 132), > or =25% (n = 36), and > or =50% (n = 128) where the latter two categories represent different subjects based on number of confirmed positive antibodies (2, > or =25%; 3 or more, > or =50%) and/or an abnormal OGTT (> or =50%). CONCLUSIONS: The NHS is identifying potential prevention trial subjects and is assembling a large cohort that will provide new natural history information about pre-type 1 diabetes. Follow-up to diabetes will help establish the biological significance and clinical value of novel type 1 diabetes risk markers.

Closing the Gap: Results of the Multicenter Canadian Randomized Controlled Trial of Structured Transition in Young Adults With Type 1 Diabetes.

OBJECTIVE: To determine if a structured transition program for young adults with type 1 diabetes improves clinic attendance, glycemic control, diabetes-related distress, quality of life, and satisfaction with care. RESEARCH DESIGN AND METHODS: In this multicenter randomized controlled trial, young adults (17-20 years) with type 1 diabetes were randomly assigned to a transition program with a transition coordinator or to standard care. The intervention lasted 18 months (6 in pediatric and 12 in adult care). The primary outcome was the proportion of participants who failed to attend at least one adult diabetes clinic visit during the 12-month follow-up after completion of the intervention. RESULTS: We randomized 205 participants, 104 to the transition program and 101 to standard care. Clinic attendance was improved in the transition program (mean [SD] number of visits 4.1 [1.1] vs. 3.6 [1.2], P = 0.002), and there was greater satisfaction with care (mean [SD] score 29.0 [2.7] vs. 27.9 [3.4], P = 0.032) and less diabetes-related distress (mean [SD] score 1.9 [0.8] vs. 2.1 [0.8], P = 0.049) reported than in standard care. There was a trend toward improvement in mean HbA1c (8.33% [68 mmol/mol] vs. 8.80% [73 mmol/mol], P = 0.057). During the 12-month follow-up, there was no difference in those failing to attend at least one clinic visit (P = 0.846), and the mean change in HbA1c did not differ between the groups (P = 0.073). At completion of follow-up, the groups did not differ with respect to satisfaction with care or diabetes-related distress and quality of life. CONCLUSIONS: Transition support during this 18-month intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but these benefits were not sustained 12 months after completion of the intervention.

Increasing the accuracy of oral glucose tolerance testing and extending its application to individuals with normal glucose tolerance for the prediction of type 1 diabetes: the Diabetes Prevention Trial-Type 1.

OBJECTIVE: We assessed the extent to which both standard and alternative indexes from 2-h oral glucose tolerance testing predict type 1 diabetes and whether oral glucose tolerance tests (OGTTs) predict type 1 diabetes in individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS: The prediction of type 1 diabetes from baseline OGTTs was studied in 704 Diabetes Prevention Trial-Type 1 participants (islet-cell autoantibody [ICA]-positive relatives of type 1 diabetic patients). The maximum follow-up was 7.4 years. Analyses utilized receiver-operator curves (ROCs), proportional hazards models, and survival curves. RESULTS: ROC areas under the curve (ROCAUCs) for both the AUC glucose (0.73 +/- 0.02) and an OGTT prediction index (0.78 +/- 0.02) were higher (P < 0.001) than those for the fasting (0.53 +/- 0.02) and 2-h glucose (0.66 +/- 0.02). ROCAUCs for the 60- and 90-min glucose (0.71 +/- 0.02 and 0.72 +/- 0.02, respectively) were also higher (P < 0.01) than those for the fasting and 2-h glucose. Among individuals with normal glucose tolerance, OGTTs were highly predictive, with 4th versus 1st quartile hazard ratios for the 2-h glucose, AUC glucose, and OGTT prediction index ranging from 3.77 to 5.30 (P < 0.001 for all). CONCLUSIONS: Certain alternative OGTT indexes appear to better predict type 1 diabetes than standard OGTT indexes in ICA-positive relatives of type 1 diabetic patients. Moreover, even among those with normal glucose tolerance, OGTTs are strongly predictive. This suggests that subtle metabolic abnormalities are present several years before the diagnosis of type 1 diabetes.

Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial-Type 1.

OBJECTIVE: There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal of this study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type 1 diabetes over a period of approximately 2.5 years before its diagnosis. RESEARCH DESIGN AND METHODS: Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points. RESULTS: Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide-to-AUC glucose ratio (P < 0.001) values decreased in the oral group; peak C-peptide-to-2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide-to-glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide-to-fasting glucose ratio values remained constant throughout the 30-month follow-up. CONCLUSIONS: These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.

A randomised trial of non-mydriatic ultra-wide field retinal imaging versus usual care to screen for diabetic eye disease: rationale and protocol for the Clearsight trial.

INTRODUCTION: Suboptimal screening for diabetic eye disease is a major cause of preventable vision loss. Screening barriers include mydriasis and the extra time patients need to attend dedicated eye screening appointments. In the Clearsight trial, we are testing whether screening by non-mydriatic ultra-wide field (NM UWF) imaging on the day patients attend their diabetes outpatient clinic visit improves detection of clinically important eye disease compared with usual screening. METHODS AND ANALYSIS: Patients with diabetes due for a screening eye exam by the 2013 Canadian Diabetes Association (CDA) practice guidelines are being randomised to on-site screening by NM UWF imaging on the day of their clinic visit or to usual screening where, per CDA guidelines, they are encouraged to arrange an exam by an optometrist. The primary outcome is actionable eye disease (AED) based on a need for referral to ophthalmology and/or increased ocular surveillance. The primary analysis will use an intention-to-screen approach that compares the proportions of detected AED between on-site and usual screening groups under a superiority hypothesis in favour of on-site screening. With 740 randomised participants, the study will have 80% power to detect ≥5% absolute increase in the AED rate among on-site screening versus usual screening participants. This difference translates into a number-needed-to-screen by on-site screening of 20 to detect 1 additional person with AED. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board of Western University. The findings of the trial will be disseminated directly to participants and through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.Gov NCT02579837 (registered 16 October 2015). PROTOCOL ISSUE DATE: 18 November 2015.

The effectiveness of beta-blockers after myocardial infarction in patients with type 2 diabetes.

OBJECTIVE: Beta-blocker therapy has been proven to reduce mortality and reinfarction after myocardial infarction (MI), but the impact of beta-blockers on cardiac outcomes in patients with type 2 diabetes in routine practice is not clear. The purpose of this study was to determine the effectiveness of beta-blockers after MI in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using the Saskatchewan Health Databases, 12,272 patients with newly treated diabetes were identified between 1991 and 1996; 625 patients were subsequently admitted for MI. Beta-blocker exposure within 30 days of discharge was identified in 298 patients, and all were followed until death, coverage termination, or 31 December 1999. Multivariate proportional hazards models were used to assess differences in all-cause mortality, recurrent MI, and 30-day all-cause rehospitalization (the latter a proxy measure for drug safety). RESULTS: Patients were aged 69 +/- 11 years old, 66% were male, and mean follow-up was 2.7 +/- 2.1 years. Overall, beta-blockers were prescribed for 48% of patients. There were fewer deaths in the beta-blocker group versus control subjects (55 of 298 [18.5%] vs. 126 of 327 [38.5%], respectively, P < 0.001). However, beta-blockers were not associated with improved survival in multivariate analyses (hazard ratio [HR] 0.89 [95% CI 0.63-1.25]). There were no differences in rates of recurrent MI (adjusted HR 1.35 [0.93-1.95]) or rehospitalizations (adjusted odds ratio 1.40 [0.83-2.37]) between the groups. CONCLUSIONS: Beta-blocker therapy post-MI was not associated with reduced mortality or fewer recurrent events in people with type 2 diabetes in routine practice, although these medications were safe in this population.

Diabetes during diarrhea-associated hemolytic uremic syndrome: a systematic review and meta-analysis.

OBJECTIVE: To quantify the incidence of diabetes during the acute phase of diarrhea-associated hemolytic uremic syndrome (D + HUS) and to identify features associated with its development. RESEARCH DESIGN AND METHODS: A systematic review and meta-analysis of articles assessing diabetes during D + HUS was conducted. Relevant citations were identified from Medline, Embase, and Institute for Scientific Information Citation Index databases. Bibliographies of relevant articles were hand searched. All articles were independently reviewed for inclusion and data abstraction by two authors. RESULTS: Twenty-one studies from six countries were included. Only 2 studies reported a standard definition of diabetes; 14 defined diabetes as hyperglycemia requiring insulin. The incidence of diabetes during the acute phase of D + HUS could be quantified in a subset of 1,139 children from 13 studies (1966-1998, age 0.2-16 years) and ranged from 0 to 15%, with a pooled incidence of 3.2% (95% CI 1.3-5.1, random-effects model, significant heterogeneity among studies, P = 0.007). Children who developed diabetes were more likely to have severe disease (e.g., presence of coma or seizures, need for dialysis) and had higher mortality than those without diabetes. Twenty-three percent of those who developed diabetes acutely died, and 38% of survivors required long-term insulin (median follow-up 12 months). Recurrence of diabetes was possible up to 60 months after initial recovery. CONCLUSIONS: Children with D + HUS should be observed for diabetes during their acute illness. Consideration should be given to long-term screening of D + HUS survivors for diabetes.

Posterior Reversible Encephalopathy Syndrome due to High Dose Corticosteroids for an MS Relapse.

Increased blood pressure is a known adverse effect associated with corticosteroids but little is published regarding the risk with the high doses used in multiple sclerosis (MS). A 53-year-old female with known relapsing remitting MS presented with a new brainstem relapse. Standard of care treatment for an acute MS relapse, 1250 mg of oral prednisone for 5 days, was initiated. She developed an occipital headache and dizziness and felt generally unwell. These symptoms persisted after treatment was complete. On presentation to medical attention, her blood pressure was 199/110 mmHg, although she had no history of hypertension. MRI changes were consistent with posterior reversible encephalopathy syndrome (PRES), demonstrating abnormal T2 signal in both thalami, the posterior occipital and posterior parietal white matter with mild sulcal effacement. As her pressure normalized with medication, her symptoms resolved and the MRI changes improved. No secondary cause of hypertension was found. This is the first reported case of PRES secondary to high dose corticosteroid use for an MS relapse without a history of hypertension and with no other secondary cause of hypertension identified. This rare complication should be considered in MS patients presenting with a headache or other neurological symptoms during treatment for a relapse.