Potentially advanced malignancies detected by screening for prostate carcinoma after an interval of 4 years

BACKGROUND: At the Rotterdam branch of the European Randomized Study of Screening for Prostate Cancer, a cohort of 19,970 men ages 55-75 years is screened at an interval of 4 years. Screening includes systematic sextant needle biopsy for men with elevated prostate-specific antigen (PSA) levels and/or positive findings on digital rectal examination or transrectal ultrasound. Detection during the second screening round of a large number of high-grade (Gleason Grade 4 or 5) malignancies and/or a large number of malignancies in general could be considered the result of a failure to identify these malignancies at an early stage, during prevalence screening. METHODS: Men diagnosed during the second screening round with potentially advanced carcinoma (PAC), characterized by a biopsy Gleason score of 7 (4 + 3, or 3 + 4 with > 30% malignant involvement) or a biopsy Gleason score of 8-10, were identified. Clinical data, including PSA values on prevalence screening, biopsy history, clinical stage, and follow-up data, were retrieved for these patients. Tumor features were further analyzed in radical prostatectomy specimens. RESULTS: During the second screening round, 503 malignancies, including 30 (6.0%) with features of PAC on diagnostic biopsy, were detected in 11,210 patients. Curative treatment was offered to 26 patients. Prostatectomy demonstrated the presence of organ-confined disease in 11 of 12 specimens, and tumor volume ranged from 0.11-7.93 cm3 (median, 1.05 cm3). PSA failure was noted in 6 of 22 patients who were offered curative therapy. CONCLUSIONS: PAC is a rare finding in the second round of screening after a 4-year interval, and a substantial proportion of PAC cases detected in the second screening round represent organ-confined disease. The findings of the current study suggest that the screening protocol used is sufficiently effective for detecting > 95% of malignancies before they develop features that would make them incurable.     

Gender differences in the management and experience of Chronic Obstructive Pulmonary Disease

Whether women receive the same medical care for COPD as men and if they are at risk of different outcomes as a result, is not known. The Confronting COPD International Survey was performed in the USA, Canada, France, Italy, Germany, The Netherlands, Spain and the UK in 2000 with 3265 COPD participants. Forty-one per cent were women; mean age in women and men was 61.2 (SD 10.5) and 64.4 (11.0) years, mean pack-years of smoking 36 (29) and 46 (35) years, respectively. After adjusting for age, pack-years, country and severe dyspnea (MRC scores 5 and 4), women were less likely to have had spirometry (OR 0.84, 95% C.I. 0.72-0.98) but more likely to get smoking cessation advice (OR 1.57, 1.33-1.86). Despite significantly lower pack-years of smoking, women were more likely to report severe dyspnea than men (OR 1.30, 1.10-1.54), with similar cough (OR 1.08, 0.92-1.27) and less sputum (OR 0.84, 0.72-0.98). There were no differences in the risk of hospitalisation or emergency room visit. This study indicates that gender differences in COPD care and outcomes exist.     

Cognitive performance in patients with COPD

BACKGROUND: Hypoxemic patients with Chronic Obstructive Pulmonary Disease (COPD) have impaired cognitive performance. These neuropsychological impairments are related to the degree of hypoxemia. So far, cognitive performance has not been tested in non-hypoxemic patients with COPD. METHODS: We recruited patients with stable COPD and PaO2 > 8.0 kPa (60 mmHg), as well as healthy subjects, who were matched for age, intelligence quotient (IQ), and level of education. Cognitive performance was studied by Stroop Colour Word Test, Trailmaking, digit-symbol of the Wechsler Adult Intelligence Scale, addition subtest of the Groningen Intelligence Test, and Story Recall. RESULTS: Thirty patients with COPD (FEV1 49.8% pred, mean age 64.8 yr) and 20 healthy volunteers (65.6 yr) were enrolled. COPD patients performed significantly worse on trailmaking B, the digit-symbol test, and on the addition subtest. There was no significant correlation between the tests of cognitive performance and disease specific health status (Chronic Respiratory Questionnaire). CONCLUSIONS: We conclude that even non-hypoxemic patients with COPD show significant impairments in cognitive performance. These impairments are not associated with deteriorations in health related quality of life. Prospective evaluation of the impact of treatment on cognitive performance in non-hypoxemic patients with COPD would be a logical subsequent study.     

Migration and fusion of tactile sensation--premorbid susceptibility to allochiria, neglect and extinction?

Migration of tactile sensation was found to occur very frequently in about 25% of normal people (High Error subjects) and very infrequently in others. When synchronous stimuli touched the two hands, if the unattended stimulus was modulated when the attended one was not (and was thus more salient) it "migrated" to the attended hand and fused with or replaced the attended stimulus. However, latencies reflecting congruence and incongruence of simultaneous stimuli showed that their identities on each hand had been (nonconsciously) registered veridically. Subsequent experiments, involving Focused and Divided Attention without speed pressure showed that mislocation errors in these subjects (i) were not due to confusion about location of otherwise perceptually distinct stimuli, (ii) nor to speed demand, (iii) nor to relative salience per se, (iv) were immune to attentional manipulation and practice in most subjects, (v) required a stimulus on the attended hand, and (vi) reflected a changed experience. Finally the same subjects rated similarity of the attended stimulus when accompanied by a distractor to each stimulus alone. Scaling distributions tested against a sampling model showed that most High Error subjects experienced a fusion of the stimuli, some experienced a replacement, and Low Error subjects experienced neither. The individual difference appears to be in attentional separability and spatial binding of tactile stimuli. Mislocation to the focus of spatial attention is common in healthy people, especially when binding is prevented. The present phenomenon appears equivalent to allochiria, but also accounts for phenomena in neglect and extinction, and suggests a premorbid susceptibility to spatial migration and integration that can be exaggerated by brain damage.     

Valuing prevention through economic evaluation: some considerations regarding the choice of discount model for health effects with focus on infectious diseases

In cost-effectiveness analysis, the valuing of costs and health effects over time remains a controversial issue. The debate mostly focuses on whether the discount rates for health and money should be equal and which discounting model and time preferences are most appropriate. In this paper we add to the debate by arguing that the assessment of effectiveness of a preventive intervention may influence the choice of the discounting procedure for health. Health effects in cost-effectiveness analysis are commonly expressed in life-years gained, QALYs gained or lives saved. These denominators are only indirect and partial measures of the effects of a preventive intervention. The actual effect of the intervention is a reduction of the risk of mortality and morbidity in a given period of time. This risk reduction will not always coincide with the moment at which the impact on (quality-adjusted) life-years gained is made (i.e. at risk exposure), for example when preventing chronic disease with an asymptomatic stage. In this paper we show that truly acknowledging the origin of health benefits could have implications for the discounting procedure. We present a discounting model that adequately focuses on the reduction of risk. This model recognises the potential interpretation of risk reduction for infection as an economic good to be acquired with associated mortality reductions as later indirect effects. This implies that our suggested discounting model focuses on the moment(s) of risk reduction. A numerical example illustrates our approach. We discuss the associated potential implications for public health policy and discuss how the effects of the intervention can be additionally corrected for societal preferences.     

Pharmacoeconomics of elderly vaccination against invasive pneumococcal infections: cost-effectiveness analyses and implications for The Netherlands

We performed a review of cost-effectiveness of elderly pneumococcal vaccination to prevent invasive disease. It concerns studies in the USA, Canada, Netherlands and Spain and a multinational study of five European countries. Cost-effectiveness of elderly vaccination against invasive pneumococcal infections varies from cost-saving to EUR 33,000 per life-year gained. The Dutch study estimates cost-effectiveness at EUR 10,100 per life-year gained (price level: 1995). This is below the level that has recently been defined for treatment of high cholesterol (EUR 20,000 per life-year gained) and may therefore be considered as favorable. Almost all studies base their estimate of vaccine efficacy on the same case-control study from the USA. We identify a need for a systematic review on the efficacy of the pneumococcal vaccine. Also, we suggest further analysis with respect to potential effects on cost-effectiveness of extended influenza vaccination for the Dutch elderly in recent years and inclusion of pneumococcal re-vaccination. Pending this additional information, we conclude that cost-effectiveness of vaccination against invasive pneumococcal infections for Dutch elderly is favorable (as in several other countries) and justifies implementation from a pharmacoeconomic point of view.     

Cardiac status in bone tumor survivors up to nearly 19 years after treatment with doxorubicin: a longitudinal study

BACKGROUND: Longitudinal assessment of cardiac toxicity in anthracycline-treated long-term bone tumor survivors. PROCEDURES: Cardiac status was assessed in 29 patients 14.1 (range 7-18.7) years after treatment with doxorubicin (DOXO) 360 mg/m(2) (median 225-550). The median age of the patients at the time of the study was 32.5 years (range 19.7-52). The evaluation consisted of an electrocardiogram (ECG), 24-hr ambulatory ECG with analysis of heart rate variability (HRV) and echocardiography. The results were compared to those of a study of the same patients that was performed 5 years earlier 8.9 years (range 2.3-14.1) after treatment. [Postma et al.: Med Pediatr Oncol 26:230-237, 1996] RESULTS: We found no progression of ECG abnormalities, arrhythmias, or echocardiographic abnormalities. Females were at risk for reduced contractility (P = 0.006). HRV was significantly reduced compared to age- and sex-matched controls and compared to the previous results. CONCLUSIONS: Anthracycline-related late echocardiographic abnormalities and arrhythmias detected 8.9 years after treatment, showed no further deterioration with ongoing follow-up. However, there was a significant reduction of HRV. This suggests that HRV might be a sensitive test for detection of anthracycline-induced cardiac toxicity.