Exploring the potential uses of value-added metrics in the context of postgraduate medical education.

CONTEXT: Increasing pressure is being placed on external accountability and cost efficiency in medical education and training internationally. We present an illustrative data analysis of the value-added of postgraduate medical education. METHOD: We analysed historical selection (entry) and licensure (exit) examination results for trainees sitting the UK Membership of the Royal College of General Practitioners (MRCGP) licensing examination (N = 2291). Selection data comprised: a clinical problem solving test (CPST); a situational judgement test (SJT); and a selection centre (SC). Exit data was an applied knowledge test (AKT) from MRCGP. Ordinary least squares (OLS) regression analyses were used to model differences in attainment in the AKT based on performance at selection (the value-added score). Results were aggregated to the regional level for comparisons. RESULTS: We discovered significant differences in the value-added score between regional training providers. Whilst three training providers confer significant value-added, one training provider was significantly lower than would be predicted based on the attainment of trainees at selection. CONCLUSIONS: Value-added analysis in postgraduate medical education potentially offers useful information, although the methodology is complex, controversial, and has significant limitations. Developing models further could offer important insights to support continuous improvement in medical education in future.

Gene-expression profiling for rejection surveillance after cardiac transplantation.

BACKGROUND: Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. METHODS: We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. RESULTS: During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P=0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P<0.001). CONCLUSIONS: Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)

Evaluation of three short-listing methodologies for selection into postgraduate training in general practice.

OBJECTIVE: This study aimed to evaluate the effectiveness and efficiency of three short-listing methodologies for use in selecting trainees into postgraduate training in general practice in the UK. METHODS: This was an exploratory study designed to compare three short-listing methodologies. Two methodologies - a clinical problem-solving test (CPST) and structured application form questions (AFQs) - were already in use for selection purposes. The third, a new situational judgement test (SJT), was evaluated alongside the live selection process. An evaluation was conducted on a sample of 463 applicants for training posts in UK general practice. Applicants completed all three assessments and attended a selection centre that used work-related simulations at final stage selection. Applicant scores on each short-listing methodology were compared with scores at the selection centre. RESULTS: Results indicate the structured AFQs, CPST and SJT were all valid short-listing methodologies. The SJT was the most effective independent predictor. Both the structured AFQs and the SJT add incremental validity over the use of the CPST alone. Results show that optimum validity and efficiency is achieved using a combination of the CPST and SJT. CONCLUSIONS: A combination of the CPST and SJT represents the most effective and efficient battery of instruments as, unlike AFQs, these tests are machine-marked. Importantly, this is the first study to evaluate a machine-marked SJT to assess non-clinical domains for postgraduate selection. Future research should explore links with work-based assessment once trainees are in post to address long-term predictive validity.

A Randomized Controlled Trial Comparing Efficacy and Safety of Insulin Glargine 300 Units/mL Versus 100 Units/mL in Older People With Type 2 Diabetes: Results From the SENIOR Study.

OBJECTIVE: SENIOR compared the efficacy and safety of insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in older people (≥65 years old) with type 2 diabetes. RESEARCH DESIGN AND METHODS: SENIOR was an open-label, two-arm, parallel-group, multicenter phase 3b trial designed to enroll ∼20% of participants aged ≥75 years. Participants were randomized 1:1 to Gla-300 or Gla-100, titrated to a fasting self-monitored plasma glucose of 5.0-7.2 mmol/L (90-130 mg/dL). RESULTS: In total, 1,014 participants were randomized (mean age: 71 years). Comparable reductions in HbA1c were observed from baseline to week 26 for Gla-300 (-0.89%) and Gla-100 (-0.91%) in the overall population (least squares mean difference: 0.02% [95% CI -0.092 to 0.129]) and for participants aged ≥75 years (-0.11% [-0.330 to 0.106]). Incidence and rates of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia events were low and similar between both treatment groups, with lower rates of documented symptomatic hypoglycemia with Gla-300. The lower risk of hypoglycemia with Gla-300 versus Gla-100 was more apparent in the subgroup aged ≥75 years versus the overall population. Significantly lower annualized rates of documented symptomatic (≤3.9 mmol/L [≤70 mg/dL]) hypoglycemia were observed (Gla-300: 1.12; Gla-100: 2.71; rate ratio: 0.45 [95% CI 0.25-0.83]). CONCLUSIONS: Efficacy and safety of Gla-300 was demonstrated in older people (≥65 years of age) with type 2 diabetes, with comparable reductions in HbA1c and similarly low or lower risk of documented symptomatic hypoglycemia versus Gla-100. A significant benefit in hypoglycemia reduction was seen in participants aged ≥75 years.

Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Using Combinations of a Basal Insulin and a Glucagon-Like Peptide-1 Receptor Agonist.

This article presents the rationale and data for combining a basal insulin with a GLP-1RA, including as fixed-ratio products.

Nodular endocardial infiltrates (Quilty lesions) cause significant variability in diagnosis of ISHLT Grade 2 and 3A rejection in cardiac allograft recipients.

BACKGROUND: Endomyocardial biopsy is used to guide therapy after heart transplantation. An accurate and reliable diagnosis of rejection is critical for proper patient management. METHODS: A sub-set of 827 biopsies from 273 patients were identified from 8 centers participating in the Cardiac Allograft Gene Expression Observational Study. These included all biopsies graded by local center pathologists as International Society for Heart and Lung Transplantation (ISHLT) Grade 1B or higher and also randomly chosen Grade 0 and 1A biopsies. Each of these cases was reviewed in a blinded manner by 3 study pathologists in the absence of clinical data. The study pathologists were assigned an ISHLT grade and noted nodular endocardial infiltrates (Quilty lesions). RESULTS: The study pathologists were significantly more likely than local pathologists to diagnose ISHLT Grade 0, 1A and 3B rejection and significantly less likely to diagnose ISHLT Grade 1B, 2 and 3A rejection. Concordance between local and study pathologists was lowest for Grade 2 (17% agreement). Quilty lesions were noted in 3.3% of local Grade 0 cases and in 31% and 37% of local Grade 2 and 3A cases, respectively. Quilty lesions were recognized by study pathologists in 35% of local Grade 2 cases "downgraded" to Grade 0 or 1, but in only 10% of local Grade 2 cases confirmed by study pathologists. CONCLUSIONS: The greatest variability between pathologists in application of the ISHLT grading system is in Grade 2 biopsies, and Quilty lesions are a major contributing factor to the lack of concordance. Accurate application of the ISHLT grading system requires improved recognition and understanding of Quilty lesions.

Concordance among pathologists in the second Cardiac Allograft Rejection Gene Expression Observational Study (CARGO II).

BACKGROUND: There has been no large evaluation of the ISHLT 2004 acute cellular rejection grading scheme for heart graft endomyocardial biopsy specimens (EMBs). METHODS: We evaluated agreement within the CARGO II pathology panel and between the panel (acting by majority) and the collaborating centers (treated as a single entity), regarding the ISHLT grades of 937 EMBs (with all grades ≥2R merged because of small numbers). RESULTS: Overall all-grade agreement was almost 71% both within the panel and between the panel and the collaborating centers but, in both cases, was largely because of agreement on grade 0: for the average pair of pathologists, fewer than a third of the EMBs assigned grade ≥2R by at least one were assigned this grade by both. CONCLUSION: The 2004 revision has done little to improve agreement on the higher ISHLT grades. An EMB grade ≥2R is not by itself sufficient as a basis for clinical decisions or as a research criterion. Steps should be taken toward greater uniformity in EMB grading, and efforts should be made to replace the ISHLT classification with diagnostic criteria--EMB based or otherwise--that correspond better with the pathophysiology of the transplanted heart.

Cellular coating of the left ventricular assist device textured polyurethane membrane reduces adhesion of Staphylococcus aureus.

OBJECTIVE: Infections are among the most common and serious complications of ventricular assist device implantation. These infections generally occur within the first 2 months after surgery. The basis for this high incidence of infection is not well established, so a murine intravascular infection model was developed with aortic implantation of the textured polyurethane patch material currently used in HeartMate ventricular assist devices (Thoratec Corporation Pleasanton, Calif). METHODS: Polyurethane patch material was placed in the wall of the mouse descending aorta. Mice were then infected with Staphylococcus aureus 1 or 14 days after implantation. In vitro adhesion studies were conducted with polyurethane membranes coated with endothelial cells and membranes coated with fibrinogen. RESULTS: Mice were susceptible to infection in both dose- and time-dependent fashions. The patch material was significantly more susceptible to infection at day 1 than day 14. Immunohistologic and morphologic studies demonstrated that the CD31+ cells deposited on the membrane surface phenotypically appeared to be endothelial cells. In vitro adhesion studies of polyurethane membranes coated with endothelial cells showed them to be less susceptible to S. aureus binding than were membranes coated with fibrinogen. CONCLUSION: Textured polyurethane membranes are less susceptible to infection as cellular deposition occurs. The time frame within which these membranes become populated with cellular material is consistent with the time-dependent clinical incidence of infection. Cellular coating of polyurethane may provide a strategy for reducing the risk of infection.

The role of Staphylococcus aureus adhesins in the pathogenesis of ventricular assist device-related infections.

Ventricular assist devices (VADs) are an important form of therapy for end-stage congestive heart failure. However, infection of the VAD, which is often caused by Staphylococcus aureus, poses a major threat to survival. Using a novel in vitro binding assay with VAD membranes and a heterologous lactococcal system of expression, we identify 3 S. aureus proteins--clumping factor A (ClfA) and fibronectin binding proteins A and B (FnBPA and FnBPB) as the main factors involved in adherence to VAD polyurethane membranes. Adherence is greatly diminished by long implantation times, reflecting a change in topological features of the VAD membrane, and is primarily mediated by the FnBPA domains in the staphylococcal proteins. We also compare the adherence of S. aureus mutant strains and show that other staphylococcal components appear to be involved in adherence to VAD membranes. Finally, we demonstrate that ClfA, FnBPA, and FnBPB mediate bacterial infection of implanted murine intra-aortic polyurethane patches.

The economic implications of noninvasive molecular testing for cardiac allograft rejection.

Endomyocardial biopsy is the mainstay for monitoring cardiac allograft rejection. A noninvasive strategy--peripheral blood gene expression profiling of circulating leukocytes--is an alternative with proven benefits, but unclear economic implications. Financial data were obtained from five cardiac transplant centers. An economic evaluation was conducted to compare the costs of outpatient biopsy with those of a noninvasive approach to monitoring cardiac allograft rejection. Hospital outpatient biopsy costs averaged 3297 US dollars, excluding reimbursement for professional fees. Costs to Medicare and private payers averaged 3581 US dollars and 4140 US dollars, respectively. A noninvasive monitoring test can reduce biopsy utilization. The savings to health care payers in the United States can be conservatively estimated at approximately 12.0 million US dollars annually. Molecular testing using gene expression profiling of peripheral circulating leukocytes is a new technology that offers physicians a noninvasive, less expensive alternative to endomyocardial biopsy for monitoring allograft rejection in cardiac transplant patients.