Excess psychosocial burden in women with diabetes and premature acute coronary syndrome.

AIM: Diabetes is a stronger risk factor for acute coronary syndrome for women than men. We investigate whether behavioural and psychosocial factors contribute to the disparity in acute coronary syndrome risk and outcomes among women with diabetes relative to women without diabetes and men. METHODS: Among 939 participants in the GENESIS-PRAXY cohort study of premature acute coronary syndrome (age ≤ 55 years), we compared the prevalence of traditional and non-traditional factors by sex and Type 2 diabetes status. In a case-only analysis, we used generalized logit models to investigate the influence of traditional and non-traditional factors on the interaction of sex and diabetes. RESULTS: In 287 women (14.3% with diabetes) and 652 men (10.4% with diabetes), women and men with diabetes showed a heavier burden of traditional cardiac risk factors compared with individuals without diabetes. Women with diabetes were more likely to be the primary earner and have more anxiety relative to women without diabetes, and reported worse perceived health compared with women without diabetes and men with diabetes. The interaction term for sex and diabetes (odds ratio (OR) 1.40, 95% confidence intervals (95% CI) 0.83-2.36) was diminished after additional adjustment for non-traditional factors (OR 1.12, 95% CI 0.54-2.32), but not traditional factors alone (OR 1.41, 95% CI 0.84-2.36). CONCLUSIONS: We observed trends toward a more adverse psychosocial profile among women with diabetes and incident acute coronary syndrome compared with women without diabetes and men with diabetes, which may explain the increased risk of acute coronary syndrome in women with diabetes and may also contribute to worse outcomes.

Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures.

UNLABELLED: Hip fracture is associated with recurrent fractures and increased mortality. The results of our retrospective cohort study support the use of antiresorptive agents to prevent recurrent hip fractures in this population. INTRODUCTION: Hip fracture, the most serious consequence of osteoporosis, is associated with recurrent fractures and increased mortality. Antiresorptive therapy has proven efficacy in the prevention of fractures after vertebral fractures. It is unknown if it can prevent recurrent fractures after a hip fracture. METHODS: We designed a population based, retrospective cohort study, using administrative databases and identified patients hospitalized for a hip fracture between 1996 and 2002. The exposure was defined as being dispensed a prescription for an antiresorptive agent at any time following discharge. Multivariate Cox regression models were used to estimate the hazard ratio of recurrent hip fracture. Subgroup and propensity score analyses were performed. RESULTS: A total of 20,644 patients were identified; 6,779 filled a prescription for antiresorptive agents. There were 992 recurrent hip fractures. Patients exposed to antiresorptives had a 26% reduction in the rate of recurrent fractures (adjusted hazard ratio 0.74; 95% CI, 0.64-0.86) compared to patients who were not. All subgroups experienced a reduction in recurrent fracture, except the very elderly. Propensity score analyses were consistent with the main analysis. CONCLUSIONS: Antiresorptive therapy reduces the risk of recurrent hip fractures in elderly patients. These results provide evidence that this therapy should be considered for secondary prevention of hip fractures.

Comparative evaluation of various prostate specific antigen ratios for the early detection of prostate cancer.

OBJECTIVE: To compare the performance of various ratios using total prostate specific antigen (PSA), complexed PSA (cPSA) and free PSA (fPSA) in the early detection of prostate cancer. PATIENTS AND METHODS: The study included 535 consecutive patients evaluated at a prostate cancer detection clinic between January 1998 and October 1999. Patients had blood samples drawn before transrectal ultrasonography and prostate biopsy to measure PSA, cPSA and fPSA. Receiver operating characteristic (ROC) curves (sensitivity vs 1 - specificity) were used to evaluate the performance of PSA, cPSA, f/tPSA, cPSA/tPSA, fPSA/cPSA, tPSA/prostate volume (PV), fPSA/PV, and cPSA/PV. The areas under the curve (AUC) were calculated for each ratio. The performance of each ratio over all patients or in those with a tPSA of 4-6 or 4-10 ng/mL were evaluated. RESULTS: Of the 535 patients, 204 (38%) had biopsy-confirmed prostate cancer. The AUC obtained with tPSA alone was 0.64; when measured for all patients the cPSA/PV (0.78), PSA/PV (0.77), f/tPSA (0.76) and fPSA/cPSA (0.75) performed better than tPSA alone. Furthermore, in patients with a tPSA of 4-10 ng/mL, tPSA/PV (0.72), cPSA/PV (0.71), f/tPSA (0.69), fPSA/cPSA (0.69) and cPSA/tPSA (0.62) performed better than tPSA alone (0.52). Finally, in patients with a tPSA of 4-6 ng/mL, PSA/PV and cPSA/PV performed better than the other ratios. CONCLUSIONS: The use of PSA ratios gives a higher sensitivity and specificity for detecting prostate cancer than the use of tPSA alone.

Serum insulin-like growth factor (IGF)-1 and IGF-binding protein-3 do not correlate with Gleason score or quantity of prostate cancer in biopsy samples.

OBJECTIVE: To examine the relationship of serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3) with histological cancer characteristics in men undergoing transrectal ultrasonography (TRUS)-guided biopsy. PATIENTS AND METHODS: Patients (652), with either an elevated serum prostate-specific antigen level or an abnormal digital rectal examination, were initially evaluated by TRUS and sextant prostatic needle biopsy. Blood was drawn before biopsy, serum extracted and stored frozen until IGF-1 and IGFBP-3 were measured. In all, 241 patients had prostate cancer (37%) and were included in this study. The number of positive biopsies, the volume of tumour in each positive biopsy and the Gleason score were recorded. RESULTS: Of the 241 patients, 37 had five or six positive biopsies (from six), 128 had two to four and 76 had one. Serum IGF-1 did not correlate with the number of positive biopsies, with means of 176.7, 178.3 and 164.4 ng/mL, respectively (P = 0.3), while the mean IGFBP-3 was 2695, 2795 and 2572 ng/mL, respectively (P = 0.09). The additive percentiles of tumour volume in positive biopsies were assessed for each patient but serum IGF-1 and IGFBP-3 did not correlate (P = 0.7 and 0.9, respectively). In all, 92 patients had a Gleason score of < 7, 80 a score of 7 and 69 a score of > 7; the mean (sd) IGF-1 levels for the three groups were 181 (39), 174.6 (35) and 176 (26) ng/mL, and the mean IGFBP-3 2798 (240), 2735 (284) and 2647 (221) ng/mL, respectively, none of the differences being statistically significant. CONCLUSIONS: Serum IGF-1 and IGFBP-3 do not correlate with quantity of cancer or Gleason score in biopsy samples from patients with prostate cancer.

Comparative evaluation of total PSA, free/total PSA, and complexed PSA in prostate cancer detection.

OBJECTIVES: To compare the performance of prostate-specific antigen (PSA), the free/total PSA (F/T PSA) ratio, and complexed PSA (cPSA) in prostate cancer detection. METHODS: Five hundred thirty-five patients evaluated at the UROMED prostate cancer detection clinic had total PSA, free PSA, and cPSA measured before undergoing transrectal ultrasonography and sextant prostate biopsies. A direct comparison was performed between the different PSA assays to evaluate their ability to detect prostate cancer. RESULTS: Of the 535 patients evaluated, 38.1% had prostate cancer detected. The mean age of the entire population was 63.6 years (range 35 to 86). Abnormal digital rectal examination findings were present in 33.4% of the patients. The mean and median values of PSA and cPSA were significantly higher and the F/T PSA ratio was lower in patients with prostate cancer. The F/T PSA ratio performed better than either cPSA or total PSA. A higher specificity was observed with the F/T PSA ratio than with cPSA using either the entire patient population or subsets of patients with PSA levels between 4.0 and 10 ng/mL or 4.0 to 6.0 ng/mL. CONCLUSIONS: The use of the F/T PSA ratio offers improved prostate cancer detection compared with either cPSA or total PSA.

Relationship of p21(WAF-I) protein expression with prognosis in advanced prostate cancer treated by androgen ablation.

OBJECTIVES: The objectives of our study were (1) to characterize the expression of p21 and p53 proteins in advanced stage prostate cancer, (2) to determine the relationship between p53 and p21 protein expressions, and (3) to relate p53 and p21 expression to clinical outcome after androgen ablation. METHODS: Seventy-five patients with advanced prostate cancer (clinical stage C: 11, stage D1: 8, stage D2: 56), who all underwent androgen ablation, had tissue specimens obtained prior to hormonal therapy and studied immunohistochemicaly for p53 (Mab D07) and p21 (Mab EA10) expression. Clinical outcome was analyzed using the Kaplan-Meier method and log-rank tests. Cox proportional hazard model was used to determine the independence of multiple variables. RESULTS: About 33.3% of cases expressed p53 and 33.3% expressed p21 positive immunoreactivity. No statistically significant correlation between p21 and p53 expression either in the entire study group (N = 75) or in stage D2 cases (N = 56) was observed (P = 0.38 and P = 0.68, respectively). Disease-specific survival was significantly related to p21 expression (P = 0.0006 for entire study group and P = 0.01 for D2 cases). There was no statistically significant differences in disease-specific survival between p53 positive or negative cases (P = 0.38 overall, P = 0.7 stage D2 only). p21 expression and the number of bone lesions were independently associated with shorter survival (multivariate P = 0.001, P = 0.005, respectively). CONCLUSIONS: The data suggests that p21 expression is a strong and independent poor prognostic factor in patients with advanced stage prostate cancer treated by androgen ablation.

Are serial Holter QT, late potential, and wavelet measurement clinically useful?

Clinical centers are increasingly using new techniques such as Holter QT, late potential, and wavelet measurements. However, we lack validated databases for the assessment of the performance of the signal-processing methods and their reproducibility. Failure of the QT interval to adapt to changes in the heart rate is considered to be a more meaningful parameter than QT prolongation itself. In this study, different factors that may affect the reproducibility of QT and QTm (onset of the QRS to the maximum of T) measurement are analyzed: the incidence of sympathetic tone and parasympathetic activity on low- and high-frequency QT variability, the very low frequency dependency of the QT interval to changes in the R-R interval, changes in the heart's position, and measurement errors. Typical root-mean-square values of the beat-to-beat measurement errors in upright-position Holter recordings are only 1.5 ms for QT versus 3.4 ms for QTm. Although the dependence of the QT interval on the heart rate is well established, the method for rate correction of the QT interval remains controversial. None of the formulas for heart rate adjustment of the QT previously proposed provide complete correction for all of the rate influences involved due to "memory phenomenon"; that is, there is a time delay, ranging up to 3-4 minutes, between a change in heart rate and the subsequent change in the QT interval. This problem has been solved by developing patient-specific neural networks that are trained to "identify" the dynamic behavior of the QT interval (or QTm) as a function of the R-R interval in order to predict the beat-to-beat changes of the QT interval as a function of the measured beat-to-beat changes of the R-R interval. Computing the differences between the predicted and the measured QT interval will allow for the detection of any significant deviations, both in the steady-state and transient conditions. Recent developments in the analysis of the high-resolution electrocardiogram (HRECG) in the time domain and frequency domain, with emphasis on the assessment of the reproducibility of late potential and wavelet measurements, are also reported in this study. The two main causes of variability in HRECG analysis are physiology and, for time-domain analysis, intermanufacturer variability. Physiologic changes can be overcome by standardizing the clinical protocols and repeating the recordings. The most important technical requirement for the proper use of late potentials is to standardize the algorithm for the detection of QRS offset among different late potential analyzing machines so that clinical data can be exchanged. The recently introduced wavelet transform provides a fruitful alternative to the more classical time-domain methods. Preliminary results show an 8 to 15% performance improvement over conventional time-domain analysis for the stratification of the HRECG after myocardial infarction. Reproducibility is excellent, up to 100%, but needs to be assessed on larger populations matched for age, sex, and pathology.