The influence of measurement error on calibration,discrimination, and overall estimation of a risk prediction model

Background

Self-reported height and weight are commonly collected at the population level; however, they can be subject to measurement error. The impact of this error on predicted risk, discrimination, and calibration of a model that uses body mass index (BMI) to predict risk of diabetes incidence is not known. The objective of this study is to use simulation to quantify and describe the effect of random and systematic error in self-reported height and weight on the performance of a model for predicting diabetes.

Methods

Two general categories of error were examined: random (nondirectional) error and systematic (directional) error on an algorithm relating BMI in kg/m² to probability of developing diabetes. The cohort used to develop the risk algorithm was derived from 23,403 Ontario residents that responded to the 1996/1997 National Population Health Survey linked to a population-based diabetes registry. The data and algorithm were then simulated to allow for estimation of the impact of these errors on predicted risk using the Hosmer-Lemeshow goodness-of-fit χ² and C-statistic. Simulations were done 500 times with sample sizes of 9,177 for males and 10,618 for females.

Results

Simulation data successfully reproduced discrimination and calibration generated from population data. Increasing levels of random error in height and weight reduced the calibration and discrimination of the model. Random error biased the predicted risk upwards whereas systematic error biased predicted risk in the direction of the bias and reduced calibration; however, it did not affect discrimination.

Conclusion

This study demonstrates that random and systematic errors in self-reported health data have the potential to influence the performance of risk algorithms. Further research that quantifies the amount and direction of error can improve model performance by allowing for adjustments in exposure measurements.

     

Evaluation of the prevention programs that work curriculum to teach use of public health evidence to community practitioners

Training on use of evidence may increase the adoption of evidence-based strategies in communities. The purpose of this study was to evaluate the Prevention Programs That Work training. This article summarizes the training modules and evaluation results from three trainings conducted in Spring 2009. The training teaches practitioners from community-based organizations to locate, choose, adopt or adapt, and evaluate an evidence-based program. Participants completed a pretest and posttest that covered competencies related to use of evidence, demographics, and feedback on training. A total of 47 participants attended three trainings. They represented coordinators, directors, nurses, and outreach workers. Participants showed the greatest increases in the following competencies: locate evidence-based resources, narrow search results of potential programs or strategies to reflect programmatic specifics, define steps in the adaptation process, and discuss factors during each phase of implementation. According to participants, the most useful aspects of the training content were the areas that covered program implementation, adaptation, and evaluation. A workshop can increase competencies to use evidence-based strategies among community practitioners. Building competencies is a critical initial step in promoting the dissemination of evidence-based strategies and helping practitioners use a systematic process to select an evidence-based intervention and implement the programs with fidelity.     

Prevalence of Hepatic Granulomas in Chronic Hepatitis B

An increasing frequency of hepatic granulomas, up to 10%, in chronic hepatitis C patients is reported, and their presence is considered to be a predictor of treatment success. However, there is only one prevalence study on granuloma in chronic hepatitis B, and its significance for treatment outcome is unknown. We aimed to determine the prevalence of hepatic granulomas in a larger group of chronic hepatitis B patients and to compare their presence with the response to interferon therapy. Biopsy specimens of chronic hepatitis B patients were reevaluated for the presence of hepatic granulomas. All patients with hepatic granuloma were screened for other granulomatous diseases by tuberculin skin test, chest X-ray and computed tomography, venereal disease research laboratory, Brucella agglutination tests, and exposure to hepatotoxic agents. We screened 663 cases of chronic hepatitis B. Hepatic granulomas were found in 10 cases (1.5%). The granulomas could not be ascribed to any other reason. Of the 10 patients with hepatic granulomas, 4 responded to interferon therapy, 2 dropped out, and 4 were nonresponders. We conclude that hepatic granuloma is a rare finding in chronic hepatitis B and its presence does not seem to predict the response to interferon therapy.     

Effects of Glycoprotein IIb/IIIa Inhibition on QT Dispersion in Patients with Unstable Angina and Non-Q-Wave Myocardial Infarction

Acute coronary ischemia augments inhomogeneity in ventricular repolarization, which significantly correlates with ventricular fibrillation. The effects of glycoprotein IIb/IIIa receptor inhibition on QT interval dispersion (QTd), and the effects of QTd changes on in-hospital, 30 day, and long-term cardiac events in patients with unstable angina (UA) and non-Q-wave myocardial infarction (MI) have not been investigated previously. Eighty-three patients presenting with Braunwald class IIIB UA or non-Q-wave MI were randomized to standard therapy (aspirin and unfractionated heparin, 42 patients) or tirofiban therapy: addition to standard therapy (41 patients). QT interval dispersion (QTd) and corrected QTd (QTcd) were measured prior to therapy, and 6, 24, 48, 72, and 96 hours after the initiation of the treatment. In both groups QTd and QTcd were higher than normal limits during the admission, prior to therapy. The first QTd and QTcd were not different between two groups; the remaining values were significantly lower in tirofiban group except the first and last QTd (p values for QTd at 6, 24, 48, 72, and 96 hours are 0.057, 0.045, 0.0006, 0.04, and NS, respectively, and for QTcd, they are 0.017, 0.046, 0.0004, 0.012, and 0.01, respectively). When the first QTd and QTcd compared to the following measurements in each group, the first significant decrease occurred at 6th hour (p = 0.004 for QTd, and 0.004 for QTcd) in tirofiban group, whereas in standard therapy group it was occurred at 48th hour (p = 0.02) for QTd, and 72nd hour (p = 0.019) for QTcd. While the incidence of in-hospital acute MI, recurrent refractory angina, and total major cardiac events were significantly lower in the tirofiban group (p = 0.03, 0.04, and 0.01, respectively) that early QTd recovery observed, the 30 day and long-term incidence of major cardiac events were not different between the two groups. GP IIb/IIIa receptor inhibition in addition to heparin treatment causes a faster recovery of increased QT dispersion, and the early recovery of QTd is associated with a reduction in in-hospital major cardiac events.     

Imatinib mesylate (STI571) treatment in patients with chronic-phase chronic myelogenous leukaemia previously submitted to autologous stem cell transplantation

Imatinib mesylate (STI571) is a highly effective and well-tolerated treatment for patients with chronic-phase chronic myeloid leukaemia (CML), but information on its efficacy and tolerance in intensively pretreated patients is scarce. Thirty-three chronic-phase CML patients who were resistant or intolerant to interferon (IFN) and had been previously submitted to autologous stem cell transplantation were treated with imatinib for a median of 14 months (range: 6-19 months). Seven patients were in haematological response (HR) at the start of treatment; the remaining 26 attained a HR at a median of 3 weeks (range: 1-4 weeks). Major cytogenetic response rates at 3, 6 and 12 months were 42%, 45% and 55%, respectively, including 21%, 24% and 33% complete responses. Grade 3-4 neutropenia, thrombocytopenia and anaemia developed in 33%, 27% and 12% of patients respectively. Non-haematological toxicity included superficial oedema (21% of patients), gastrointestinal symptoms (18%), muscle cramps (15%), skin rash and liver enzyme increase (3% each). These results were not significantly different from those in 65 chronic-phase CML patients, resistant or intolerant to interferon without a previous ASCT, who were included in the same protocol. Imatinib mesylate is effective and safe in chronic-phase CML patients with a previous history of intensive treatment.     

Malformations due to warfarin: A case report

We report a 5-month-old infant with severe growth retardation who was exposed to in utero warfarin for the first 4 months. She had a dysmorphic face with depressed nasal hypoplasia and low-set ears. Cranial computerized tomography revealed bifrontal atrophy, agenesis of corpus callosum, and dilation of lateral ventricles. In addition she had patent ductus arteriosus with pulmonary hypertension, which had to be ligated.     

Alcoholism among inpatients in a general hospital in Barcelona, Spain

This cross-sectional study in a general hospital revealed that 37.5% of inpatients were alcoholics, excessive drinkers, or probable alcoholics; when only males were considered, that proportion increased to 61.3%. Most of the physical disorders were associated with the amount of alcohol consumed. The age-adjusted mortality rate in the hospital was three times higher in alcoholics than in nonalcoholics. A large number of alcohol problems were not detected by the patients' medical team. An interview about alcohol and drug consumption, the CAGE, the MAST Brief, and the MALT were utilized to diagnose alcoholism; for our population, the former was shown as the most effective instrument.     

Effects of glycoprotein IIb/IIIa inhibition on clinical stabilization parameters in patients with unstable angina and non-Q-wave myocardial infarction

Glycoprotein IIb/IIIa receptor inhibition prevents the major cardiac events and improves the prognosis of patients with acute coronary syndromes. The purpose of the study was to evaluate the effects of tirofiban on clinical stabilization parameters in patients with unstable angina (UA) and non-Q-wave myocardial infarction (MI). Eighty-three patients presenting with prolonged ongoing chest pain and ST segment depression were included in the study. Forty-two patients were randomized to aspirin and heparin therapy, and 41 patients to tirofiban therapy in addition to the aspirin and heparin therapy. The interval between the initiation of the treatment and the disappearance of angina, recovery time of ST segment depression, creatine kinase-MB (CK-MB) levels, onset of decrease and normalization of CK-MB, and frequency of in-hospital major cardiac events were compared. The interval between initiation of the treatment and the disappearance of angina was significantly shorter in the tirofiban group (3.5 ± 4.2 vs 9.1 ± 8.6h, P 0.001). Recovery time of ST depression was also significantly shorter in the tirofiban group (5.1 ± 7.3 vs 12.3 ± 11.5h, P 0.05). The peak CK-MB values were significantly lower in the non-Q-wave MI and UA subgroups of tirofiban than in the heparin group (P = 0.04 for both). The onset of the CK-MB decrease was significantly earlier in the tirofiban group (15 ± 14 vs 24 ± 15h, P = 0.02). The normalization time of the CK-MB was relatively shorter in the tirofiban group but without statistical significance (50 ± 22 vs 60 ± 25h). The tirofiban group had a lower frequency of total major cardiac events (26% vs 54%, P = 0.01), acute MI (2.4% vs 19%, P = 0.03), and recurrent angina (26% vs 50%, P = 0.04). The frequency of death and urgent revascularization did not differ between the groups. Tirofiban, in addition to heparin, provides earlier clinical stability and prevents major in-hospital cardiac events in patients with UA and non-Q-wave MI as compared to heparin therapy alone.     

Cardiac troponin-I in the serum of infants of diabetic mothers

A transient form of hypertrophic cardiomyopathy has been previously described in infants of diabetic mothers. When it occurs, it is generally benign. The purpose of our study was to establish the extent of injury to the cardiomyocytes in symptomatic and asymptomatic patients with and without hypertrophic cardiomyopathy. Thus, we compared 35 consecutive patients to 20 healthy controls, establishing the significance, if any, of differences in cardiac troponin-I and creatine kinase, including its MB-fraction, and seeking to establish the value of these parameters in the diagnosis of cardiac injury. We also determined to levels of glucose and insulin in the serum, and took note of electrocardiographic and echocardiographic investigations. Values were determined at the 1st and 7th days after admission in the patients, while parameters were measured in the control group only on the first day. We found that the levels of cardiac troponin-I in the serum, known to be a marker for cardiac injury, were significantly elevated in symptomatic patients with life-threatening respiratory or haemodynamic distress. We speculate that transient ventricular hypertrophy is neither the cause nor the consequence of damage to the cardiomyocytes. It would be interesting, nonetheless, to determine the relationship, if any, between cardiomyocytic damage and clinical outcome.