Middle-aged children of persons with Alzheimer's disease: APOE genotypes and cognitive function in the Wisconsin Registry for Alzheimer's Prevention

Adult children of persons with Alzheimer's disease are at increased risk of developing Alzheimer's disease because of hereditary, environmental, and health risk factors shared with affected parents. The Wisconsin Registry for Alzheimer's Prevention (WRAP) has completed baseline assessments on 452 middle-aged persons (mean = 53 years) who have at least 1 parent with AD. Forty-five percent had 1 or more apolipoprotein (APOE) epsilon4 alleles. There were few significant differences between epsilon4 carriers and noncarriers in demographics, health, and lifestyle measures or in neuropsychological performance. The high percentage of WRAP participants who are carriers of APOE epsilon4 underscores their increased risk for developing Alzheimer's disease, but the absence of differences related to APOE status and high mean scores on cognitive tests suggests that the APOE epsilon4 gene has yet to have a clinical impact on cognitive functioning. The WRAP cohort may be a valuable group to follow prospectively to characterize the nature of cognitive change in relation to risk factors and to identify underlying preclinical neurobiological changes.     

Follow-up and final results of the Oslo I Study comparing screen-film mammography and full-field digital mammography with soft-copy reading

Purpose: To compare cancer detection rates of screen-film (SFM) and full-field digital mammography (FFDM) with soft-copy reading in a screening program including the initial positive scores for interval cancers and cancers in the subsequent screening round, and to analyze the false-negative FFDM interpretations.

Material and Methods: Using a paired study design, 3683 women underwent SFM and FFDM in a population-based screening program. Two standard views of each breast were acquired. The images were interpreted without previous films for comparison. Independent double reading using a 5-point rating scale for probability of cancer was used for each modality. An examination was defined as positive if at least one of the two independent readers scored 2 or higher on the 5-point rating scale. SFM-positive cases were discussed in a SFM consensus meeting and FFDM-positive cases in a separate FFDM consensus meeting before recall. The study population was followed for more than 2 years so that interval cancers and screen-detected cancers in the subsequent screening round could be included. Cancer detection rates were compared using the McNemar test for paired proportions. The kappa statistic and Wilcoxon signed-rank test for matched pairs were used for comparing rating scores. The reading time was recorded for all FFDM interpretations.

Results: A total of 31 cancers (detection rate 0.84%) were diagnosed initially, of which SFM detected 28 and FFDM 23 (McNemar test P = 0.23, discordant pair 8 and 3). Two cancers with a positive score at initial SFM reading and three with a positive score at initial FFDM reading were dismissed at SFM and FFDM consensus meetings, respectively. The difference in cancer detection after recall (discordant pair 11 and 5) was not significant (McNemar test, P = 0.21). Of the 10 interval cancers and 16 screen-detected cancers in the subsequent round, 3 had true-positive SFM scores while 4 had true-positive FFDM scores in the initial reading session. A total of 38 cancers therefore had a positive result at double reading at one or both modalities, 31 at SFM and 27 at FFDM (McNemar test, P = 0.48). Comparison of SFM and FFDM interpretations using the mean score for each case revealed no statistically significant difference between the two modalities (Wilcoxon signed-rank test for matched pairs; P-value = 0.228). Two initial round cancers (one tumor found incidentally at work-up for a mass proved to be a simple cyst with a positive score at FFDM but a negative score at SFM, and one tumor with positive score at SFM but negative score at FFDM due to positioning failure) were excluded from the further analysis. Excluding these two cancers from comparison, there were 31% (22 of 72) false-negative SFM and 47% (34 of 72) false-negative FFDM individual interpretations. The overall mean interpretation time for normal FFDM examinations was 45 s. For most false-negative FFDM results, the reading time was shorter or longer than for normal examinations. The recorded FFDM interpretation time was noticeably short for several overlooked cancers manifesting as microcalcifications (ductal carcinoma in situ).

Conclusion: There is no statistically significant difference in cancer detection rate between SFM and FFDM with soft-copy reading in a mammography screening program. Analysis of cancers missed at FFDM with soft-copy reading indicates that close attention has to be paid to systematic use of image display protocols.     

Stimulant and relaxant drugs combined with stimulant and relaxant information: a study of active placebo

Rationale The active placebo hypothesis states that placebo effects are potentiated when an active drug is administered.Objective This hypothesis was tested in an experiment where information about the effect of a drug was combined with administration of an active drug or placebo.Methods Information that a drug acted as a relaxant, a stimulant, or as a placebo was crossed with oral administration of a relaxant drug (700 mg carisoprodol), a stimulant drug (400 mg caffeine) or placebo (lactose) in healthy volunteers (n=94). Dependent variables were subjective and physiological measures of arousal, as well as serum carisoprodol and caffeine levels. Data were collected from 15 to 280 min after administration of drug or placebo.Results Caffeine increased alertness, systolic and diastolic blood pressure, startle blink reflexes, and skin conductance responses. Subjects were calmer after carisoprodol, and heart rate was increased. There was a positive correlation between increased arousal and carisoprodol levels when stimulant information had been provided. However, this was only seen when carisoprodol levels were very low. There was no evidence that caffeine modulated the placebo response.Conclusions Active placebo responses were seen only transiently when carisoprodol levels were low, and only in the subjective arousal data. Caffeine did not support active placebo responses. The overall findings did not favour the active placebo hypothesis.     

New paradigms for cancer drug discovery

Discovering drugs has never been an easy task. Traditionally, this task has exclusively been undertaken by large pharmaceutical companies that recovered their high research and development costs by selling expensive medications. Despite the huge amount of time and effort devoted towards drug discovery over the last decade, the successful therapy of cancer has been limited. There are signs that the approach of how to discover drugs might change, especially in the field of cancer. Recently, several academic institutions have started to develop their own drug discovery programs. By pointing out the critical elements of the cancer drug discovery process, we examine why it would not be a surprise if some future cancer drugs will come out of academic research institutions and complement the ones developed by big pharma.     

New methods and data sources for measuring economic consequences of workplace injuries

BACKGROUND: Evaluation of programs and policies to reduce the incidence of workplace injuries require that the consequences of injury are estimated correctly. Because workplace injuries are complex events, the availability of data that reflects this complexity is the largest obstacle to this estimation. METHODS: We review the literature on the consequences of workplace injuries for both workers and employers, focusing on data sources, particularly linked administrative data from different public agencies. We also review other approaches to obtaining data to examine workplace injuries, including public-use longitudinal survey data, primary data collection, and linked employee-employer databases. We make suggestions for future research. RESULTS: Recent advances in the literature on the economic consequences of workplace injuries for workers have been driven to a great extent by the availability of new data sources. Much remains unexplored. We find longitudinal survey databases including the National Longitudinal Survey of Youth, and the Health and Retirement Survey, to be very promising though largely untapped sources of data on workplace injuries. We also find that linked employee-employer databases are well suited for the study of consequences for employers. CONCLUSIONS: We expect that new data sources should lead to rapid advances in our understanding of the economic consequences of workplace injuries for both workers and employers.