Karen Belkić

Lipoprotein(a) as a Determinant of Coronary Heart Disease in Young Women

BACKGROUND Lipoprotein(a) [Lp(a)] appears to be a risk factor for coronary heart disease (CHD) in men. The role of Lp(a) in women, however, is less clear. METHODS AND RESULTS We examined the ability of Lp(a) to predict CHD in a population-based case-control study of women 65 years of age or younger who lived in the greater Stockholm area. Subjects were all patients hospitalized for an acute CHD event between February 1991 and February 1994. Control subjects were randomly selected from the city census and were matched to patients by age and catchment area. Lp(a) was measured 3 months after hospitalization by use of an immunoturbidometric method (Incstar) calibrated to the Northwest Lipid Research Laboratories (coefficient of variation was < 9%). Of the 292 consecutive patients, 110 (37%) were hospitalized for an acute myocardial infarction, and 182 were hospitalized (63%) for angina pectoris. The mean age for both patients and control subjects was 56 +/- 7 years. Of participants, 74 patients (25%) and 84 control subjects (29%) were premenopausal. The distributions of Lp(a) were highly skewed in both patients and control subjects, with a range from 0.001 to 1.14 g/L. Age-adjusted odds ratio for CHD in the highest versus the lowest quartile of Lp(a) was 2.3 (95% confidence interval [CI], 1.4 to 3.7). After adjustment for age, smoking, education, body mass index, systolic blood pressure, total cholesterol, triglycerides, and HDL, the odds ratio was 2.9 (95% CI, 1.6 to 5.0). The odds ratios were similar when myocardial infarction and angina patients were compared with their respective control subjects. The odds ratios were 5.1 (95% CI, 1.4 to 18.4) and 2.4 (95% CI, 1.3 to 4.5) in premenopausal and postmenopausal women, respectively. CONCLUSIONS These results suggest that Lp(a) is a determinant of CHD in both premenopausal and postmenopausal women.

What Prevents Professional Drivers from Following Physicians’ Cardiologic Advice?

Background: There is a scarcity of published studies of the effects of cardiac counselling among professional drivers (PD). Aims of the study were: (1) to examine explanatory variables for two classical ‘driver’ risk factors – body mass index (BMI), and smoking – and to analyse the interrelations among smoking cessation, losing weight and work-related life changes; (2) to assess the effectiveness of risk factor counselling after 6 months, and (3) to gain insight into possible discrepancies between PD perception of needed changes and compliance with the physician’s advice. Methods: There were 4 groups of male PD: 13 with ischemic heart disease, 12 hypertensives, 10 borderline hypertensives and 34 normotensives. Baseline cardiovascular risk factors as well as occupational and behavioral data were assessed via questionnaire. The counselling was aimed at smoking cessation, weight loss and promoting leisure-time physical activity. Qualitative methods were used to assess PD perceptions about the work environment and health promotion. Results: Baseline smoking intensity was best predicted by the total burden of occupational stress and number of smoking years. Baseline BMI was best predicted by long work hours behind the wheel, low availability of attachment outside work and low self-reported job strain. Self-initiated smoking cessation was best predicted by few smoking years, low coffee intake and admitting fear during driving. Physical activity was significantly increased after 6 months. Losing weight was associated with: quitting or diminishing smoking and making other, work-related, life changes. None of the heavy smokers decreased their daily number of cigarettes after 6 months, although expressing the need to do so in self-generated statements. Conclusions: Exposure to occupational stressors, mainly, long work hours and the concomitant denial of job strain, in combination with low availability of social attachment outside work, could contribute to maintenance of maladaptive behavior in PD. These findings could serve as a basis for designing standardized intervention trials and suggest that modification of the work environment, with participation of the drivers, is a needed component of such trials. Particular attention should be paid to the length and scheduling of work shifts.

The fast Padé transform in magnetic resonance spectroscopy for potential improvements in early cancer diagnostics.

The convergence rates of the fast Padé transform (FPT) and the fast Fourier transform (FFT) are compared. These two estimators are used to process a time-signal encoded at 4 T by means of one-dimensional magnetic resonance spectroscopy (MRS) for healthy human brain. It is found systematically that at any level of truncation of the full signal length, the clinically relevant resonances that determine concentrations of metabolites in the investigated tissue are significantly better resolved in the FPT than in the FFT. In particular, the FPT has a better resolution than the FFT for the same signal length. Moreover, the FPT can achieve the same resolution as the FFT by using twice shorter signals. Implications of these findings for two-dimensional magnetic resonance spectroscopy as well as for two- and three-dimensional magnetic resonance spectroscopic imaging are highlighted. Self-contained cross-validation of all the results from the FPT is secured by using two conceptually different, equivalent algorithms (inside and outside the unit-circle), that are both valid in the entire complex frequency plane. The difference between the results from these two variants of the FPT is indistinguishable from the background noise. This constitutes robust error analysis of proven validity. The FPT shows promise in applications of MRS for early cancer detection.

Survey on Recent Suicidal Ideation Among Female University Hospital Physicians in Sweden and Italy (The HOUPE Study): Cross-Sectional Associations With Work Stressors

BACKGROUND Suicide rates among physicians are higher than in the general population, and rates among female physicians are particularly high. More female than male physicians report suicidal thoughts, with suicidal ideation being a well-recognized precursor of suicide. The urgent need to find the reasons for suicide risk in female physicians is underscored by societys increasing dependence on this group of health care providers. OBJECTIVE The aim of this paper was to identify potential risk and protective factors associated with recent suicidal ideation in female physicians. METHODS A cross-sectional survey analysis of work-related health, organizational culture, career paths, and working conditions was performed among permanently employed female physicians from the HOUPE (Health and Organisation among University Physicians in four European countries) study: 385 in Sweden and 126 in Italy. The main outcome measure was recent (within the prior 12 months) suicidal thoughts. RESULTS Overall, 13.7% and 14.3% of the participants from Sweden and Italy, respectively, reported suicidal thoughts within the prior 12 months. Among the physicians from Sweden, the most powerful multivariate model for such thoughts included 2 independent variables related to work: degrading experiences/harassment at work (odds ratio [OR], 3.03; 95% CI, 1.48-6.23), and work meetings to discuss stressful situations (OR, 0.36; 95% CI, 0.19-0.69). The model included self-diagnosis and self-treatment as a significant factor. Work meetings to discuss stressful situations were also in the multivariate model for the Italian physicians (OR, 0.21; 95% CI, 0.05-0.86), together with being given work assignments without adequate resources (OR, 5.0; 95% CI, 1.32-18.8). Significant non-work-related factors in the Italian model were younger age and seeking professional help for depression or burnout. CONCLUSIONS In both Sweden and Italy, work stressors have been identified that may increase the risk for suicide for female physicians. A potential protective factor was meetings to discuss stressful work experiences. These findings suggest that such meetings should be more broadly implemented.

The Etiology of Syncope in Pacemaker Patients

A total of 46 patients with syncopal episodes after VVI pacemaker implantation were studied. Of these, 92% had one to three syncopal episodes and 8% more than three. All underwent a thorough clinical examination, which included chest X ray, echocardiogram, neurological exam, and the following protocol: 24‐hour Holler monitoring, EEG, blood pressure (BP) measurement in three positions, Doppler exam of the carotid vessels, fasting blood glucose, and head‐up tilt table test (60 minutes, 60°). Holter monitoring showed exit block in two patients (4.3%) and failed sensing in one (2.1%). In two patients there was unilateral slowing on EEG. Orthostatic hypotension was found in four patients (8.6%), and hypoglycemia in three insulin‐dependent diabetics. An ocdusive atherosclerotic plaque in the carotid artery was found in three patients (6,5%). Syncope was induced in 17 patients (36,9%) by the tilt table test, after a mean standing time of 47 ± 11 minutes. The mean resting systolic BP of these patients was 140 ± 24 mmHg, and fell to a mean level of 56 ± 8 mmHg (mean systolic BP drop was 79 ± 8 mmHg). Sixteen of these 17 patients with positive tilt table were being paced at the time of syncope and one had a spontaneous heart rate of 73 beats/min. In 14 cases (30.4%) the cause of syncopai episodes after this extensive workup remained unexplained. These results indicate that pacemaker dysfunction is a not major cause of syncopal episodes in pacemaker patients and that these are most often due to vasovagal syncope. Long‐term follow‐up is warranted to determine the prognostic significance of various types of syncope in pacemaker patients.

In vivo magnetic resonance spectroscopy by the fast Padé transform

The fast Padé transform (FPT) is thoroughly illustrated on two in vivo time signals encoded at 4 T and 7 T via magnetic resonance spectroscopy (MRS). The exact quantum-mechanical spectrum as the Green function series truncated at any partial sum reduces to the unique quotient of two polynomials, which is the FPT. In this Green function as a Maclaurin series in powers of the harmonic variable, the expansion coefficients are the time signal values as damped complex-exponentials with stationary and non-stationary amplitudes for non-degenerate (Lorentzian) and degenerate (non-Lorentzian) spectra. This is automatically shared by the FPT to represent an enormous advantage over the Hankel-Lanczos singular value decomposition (HLSVD) which works only for Lorentzian spectra. Moreover, the resonance amplitudes in the FPT are obtained analytically, rather than solving a system of linear equations as done in the HLSVD. We use two variants of the FPT, initially defined inside and outside the unit circle, but extended automatically to the whole complex frequency plane by the Cauchy analytical continuation. The converged spectra from these two variants of the FPT are found to give the same results, within the experimental background noise level, and this represents an intrinsic cross-validation of the findings and the error analysis.

Signal processing in magnetic resonance spectroscopy with biomedical applications

Basic Tasks of Signal Processing in Spectroscopy Challenges with quantification of time signals The quantum-mechanical concept of resonances in scattering and spectroscopy Resonance profiles Why is this topic relevant to biomedical researchers and clinical practitioners? The Role of Quantum Mechanics in Signal Processing Direct link of quantum-mechanical spectral analysis with rational response functions Expansion methods for signal processing Recurrent time signals and their generating fractions as spectra with no recourse to Fourier integrals Fast Pade transform (FPT) for quantum-mechanical spectral analysis and signal processing Pade acceleration and analytical continuation of time series Description of the background contribution by the off-diagonal FPT Diagonal and para-diagonal FPT Froissart doublets and the exact number of resonances Harmonic Transients in Time Signals Rational response function to generic external perturbations The exact solution for the general harmonic inversion problem General time series Response or Green function The key prior knowledge: internal structure of time signals The Rutishauser quotient-difference recursive algorithm The Gordon product-difference recursive algorithm The Lanczos continued fractions The Pade-Lanczos approximant FPT(-) outside the unit circle FPT(+) inside the unit circle Signal-Noise Separation via Froissart Doublets Critical importance of poles and zeros in generic spectra Spectral representations via Pade poles and zeros: pFPT(+-) and zFPT(+-) Pade canonical spectra Signal-noise separation: exclusive reliance upon resonant frequencies Model reduction problem via Pade canonical spectra Denoising Froissart filter Signal-noise separation: exclusive reliance upon resonant amplitudes Pade partial fraction spectra Model reduction problem via Pade partial fraction spectra Disentangling genuine from spurious resonances Pade Processing for Magnetic Resonance (MR) Total Shape Spectra from in vivo Free Induction Decays (FIDs) Comparison of the performances of the FPT and fast Fourier transform (FFT) for total shape spectra The FIDs, convergence regions, and absorption spectra at full signal length for 4T and 7T Convergence patterns of the FPT(-) and FFT for absorption spectra at 4T and 7T Error analysis Prospects for comprehensive applications of the FPT to in vivo MR time signals for brain tumor diagnostics Exact Reconstructions of Spectral Parameters by FPT Tabular data Absorption total shape spectra Residual spectra and consecutive difference spectra Absorption component shape spectra of individual resonances Distributions of reconstructed spectral parameters in the complex plane Discussion Relevance of exact quantification in brain tumor diagnostics Machine Accurate Pade Quantification and Exact Signal-Noise Separation Numerical presentation of the spectral parameters Direct comparison of the performance of the FFT and the FPT Convergence of total shape spectra versus component spectra in the FPT Signal-noise separation through the concept of Froissart doublets/pole-zero cancellation Diagnostic significance of the Froissart filter for exact signal-noise separation Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) in Neuro-Oncology: Achievements and Challenges MRS and MRSI as a key non-invasive diagnostic modality for neuro-oncology Major limitations and dilemmas with MRS and MRSI in neuro-oncology related to reliance upon conventional Fourier-based data analysis Accurate extraction of clinically relevant metabolite concentrations for neurodiagnostics via MRS Pade Quantification of Malignant and Benign Ovarian MRS Data Studies to date using in vivo proton MRS to evaluate benign and malignant ovarian lesions Insights for ovarian cancer diagnostics from in vitro MRS Performance of the FPT for in vitro MRS data derived from benign and malignant ovarian cyst fluid, and comparisons with the FFT Prospects for Pade-optimized MRS for ovarian cancer diagnostics Breast Cancer and Non-Malignant Breast Data: Quantification by FPT Current challenges in breast cancer diagnostics In vivo MR-based modalities for breast cancer diagnostics and clinical assessment Insights for breast cancer diagnostics from in vitro MRS Performance of the FPT for MRS data from breast tissue Prospects for Pade-optimized MRS for breast cancer diagnostics Multiplet Resonances in MRS Data from Normal and Cancerous Prostate Dilemmas in prostate cancer diagnostics and screening Insights for prostate cancer diagnostics by means of 2D in vivo MRS and in vitro MRS Performance of the FPT for MRS data from prostate tissue Prospects for Pade-optimized MRSI within prostate cancer diagnostics General Discussion Why the FPT for signal processing? The two variants of the FPT converging inside and outside the unit circle Computation of the complex frequencies and amplitudes by FPT Interpolation and extrapolation by the FPT Determination of the exact number of metabolites Lorentzian and non-Lorentzian spectra both computed by FPT Validity assessment of the FPT Error analysis Clinical ramifications of implementing Pade-based in vivo MRS: special importance for cancer diagnostics Conclusions and Outlooks Prediction and extrapolation for resolution improvement

Workplace Stressors and Lifestyle-Related Cancer Risk Factors among Female Physicians: Assessment Using the Occupational Stress Index

Workplace Stressors and Lifestyle‐Related Cancer Risk Factors among Female Physicians: Assessment Using the Occupational Stress Index: Karen Belkić, et al. Department of Oncology and Pathology, Karolinska Institute, Sweden—This study examined the relationship between work stressors and lifestyle‐related cancer risk factors (LRCRF): smoking, obesity, sedentariness and alcohol consumption, among 112 female physicians in Novi Sad, a region of high LRCRF prevalence. The participation rate was 92.6%. Participants completed the physician‐specific version of the Occupational Stress Index (OSI). Self‐reported data concerning LRCRF and working conditions were cross‐validated with medical records, as well as with worksite measurements and expert observations. A total of 35 (31.3%) of the physicians were current smokers and 10 (8.9%) were heavy smokers (>20 cigarettes/day); 23 (20.5%) had a body mass index (BMI) of 28 or more, and 11 (9.8%) were obese (BMI≥30). Only 27 (24.1%) regularly engaged in recreational physical activity (PA). Slightly over 5% consumed alcohol daily. Altogether 15 (13.4%) had a low lifestyle‐related cancer risk profile (not a current smoker, BMI<28, regular recreational PA and no daily alcohol consumption). Total OSI and several OSI aspects, particularly threat avoidance alone or in combination, showed significant multivariate associations with LRCRF, as did individual OSI elements. The latter included long work hours, restricted problem‐solving strategy, insufficient help with clinical difficulties and supervisory responsibility (obesity and/or sedentariness) and problems hampering patient care (smoking). There is an urgent need to lower the LRCRF among female physicians in this high risk region. Our findings suggest that diminishing the work stressor burden should be considered when developing intervention strategies aimed at these risk factors.

Survival in 1,431 Pacemaker Patients: Prognostic Factors and Comparison With the General Population

A total of 1,431 patients (mean age 63.4 ± 14.1) with pacemakers (96.2% VVI) primoimplanled between 1967 and 1985 were followed for a mean duration of 78.2 ± 40 pacing months, with 0.6% loss to follow‐up. Cumulative survival for 1, 3, and 10 years was 0.9427, 0.9136, and 0.7536, respectively. There was no significant difference in survival between atrioventricular block (AVB) and sick sinus syndrome (SSS) patients. In addition to age and gender, factors existent prior to implantation that independently affected prognosis included manifest coronary heart disease (CHD), congenital/acquired heart lesions, heart failure, noncardiac internal disease, syncope, and generalized fatigue. After implantation, the most important factor was generalized fatigue, [hen age, stroke, myocardial infarct (Ml), gender (male), heart failure, and syncope. Patients with no underlying disease showed an extremely high cumulative survival (0.9173 at 10 years). Compared to the general population of Yugoslavia, the pacemaker patients showed a similar yearly mortality rate until 1981. After that, elderly males (70+) had a significantly lower yearly mortality than the matched population. Thus, in this large series of pacemaker patients followed into (he most recent period with an extremely low loss to follow‐up, short‐and long‐term survival was very high. Pacemaker patients of any age who are otherwise in good health have an excellent prognosis.

Work Environment and Recent Suicidal Thoughts Among Male University Hospital Physicians in Sweden and Italy: The Health and Organization Among University Hospital Physicians in Europe (HOUPE) Study

BACKGROUND Male and female physicians are at elevated suicide risk. The work environment has become a focus of attention as a possible contributor to this risk. The potential association between work environment and suicidal thoughts has been examined among female physicians in several countries, and significant findings have been reported. OBJECTIVE The purpose of this study was to examine the role of the work environment in relation to suicidal thoughts among male university hospital physicians in 2 European countries. METHODS Cross-sectional multivariate analysis was performed to identify significant associations between work-related factors and suicide risk among male physicians from the Health and Organization among University Hospital Physicians in Europe (HOUPE) study. The dependent variable was termed recent suicidal thoughts, which includes having thought about suicide and/or having thought about specific ways to commit suicide within the previous year. Adjusted odds ratios (ORs) and CIs are reported. RESULTS Of the 456 Swedish (56%) and 241 Italian (39%) male physicians who participated, 12% of the physicians from each country reported affirmatively regarding recent suicidal thoughts. Degrading work experiences were associated with recent suicidal thoughts for the Swedish and Italian physicians (OR = 2.1; 95% CI, 1.01-4.5; OR = 3.3; 95% CI, 1.3-8.0, respectively). Role conflict was associated with recent suicidal thoughts among the Swedish physicians (OR = 1.6; 95% CI, 1.1-2.2). Support at work when difficulties arose appeared to be protective for the Swedish physicians (OR = 0.7; 95% CI, 0.5-0.96). Italian physicians with little control over working conditions had an increased risk of recent suicidal thoughts, whereas confidential discussions about work experiences appeared to be protective (OR = 0.6; 95% CI, 0.4-0.9). CONCLUSION Attention should be paid to the work environment as it relates to suicide risk among male university hospital physicians, particularly to bolstering social support and preventing harassment.