Modelling the consequences of a reduction in alcohol consumption among patients with alcohol dependence based on real-life observational data.

BACKGROUND: Most available pharmacotherapies for alcohol-dependent patients target abstinence; however, reduced alcohol consumption may be a more realistic goal. Using randomized clinical trial (RCT) data, a previous microsimulation model evaluated the clinical relevance of reduced consumption in terms of avoided alcohol-attributable events. Using real-life observational data, the current analysis aimed to adapt the model and confirm previous findings about the clinical relevance of reduced alcohol consumption. METHODS: Based on the prospective observational CONTROL study, evaluating daily alcohol consumption among alcohol-dependent patients, the model predicted the probability of drinking any alcohol during a given day. Predicted daily alcohol consumption was simulated in a hypothetical sample of 200,000 patients observed over a year. Individual total alcohol consumption (TAC) and number of heavy drinking days (HDD) were derived. Using published risk equations, probabilities of alcohol-attributable adverse health events (e.g., hospitalizations or death) corresponding to simulated consumptions were computed, and aggregated for categories of patients defined by HDDs and TAC (expressed per 100,000 patient-years). Sensitivity analyses tested model robustness. RESULTS: Shifting from >220 HDDs per year to 120-140 HDDs and shifting from 36,000-39,000 g TAC per year (120-130 g/day) to 15,000-18,000 g TAC per year (50-60 g/day) impacted substantially on the incidence of events (14,588 and 6148 events avoided per 100,000 patient-years, respectively). Results were robust to sensitivity analyses. CONCLUSIONS: This study corroborates the previous microsimulation modeling approach and, using real-life data, confirms RCT-based findings that reduced alcohol consumption is a relevant objective for consideration in alcohol dependence management to improve public health.

Development and validation of a visual grading scale for assessing image quality of AP pelvis radiographic images.

OBJECTIVE: The aim of this article was to apply psychometric theory to develop and validate a visual grading scale for assessing the visual perception of digital image quality anteroposterior (AP) pelvis. METHODS: Psychometric theory was used to guide scale development. Seven phantom and seven cadaver images of visually and objectively predetermined quality were used to help assess scale reliability and validity. 151 volunteers scored phantom images, and 184 volunteers scored cadaver images. Factor analysis and Cronbach's alpha were used to assess scale validity and reliability. RESULTS: A 24-item scale was produced. Aggregated mean volunteer scores for each image correlated with the rank order of the visually and objectively predetermined image qualities. Scale items had good interitem correlation (≥0.2) and high factor loadings (≥0.3). Cronbach's alpha (reliability) revealed that the scale has acceptable levels of internal reliability for both phantom and cadaver images (α = 0.8 and 0.9, respectively). Factor analysis suggested that the scale is multidimensional (assessing multiple quality themes). CONCLUSION: This study represents the first full development and validation of a visual image quality scale using psychometric theory. It is likely that this scale will have clinical, training and research applications. ADVANCES IN KNOWLEDGE: This article presents data to create and validate visual grading scales for radiographic examinations. The visual grading scale, for AP pelvis examinations, can act as a validated tool for future research, teaching and clinical evaluations of image quality.

Mechanisms of protein homeostasis in health, aging and disease.

When emerging from the ribosomes, new polypeptides need to fold properly, eventually translocate, and then assemble into stable, yet functionally flexible complexes. During their lifetime, native proteins are often exposed to stresses that can partially unfold and convert them into stably misfolded and aggregated species, which can in turn cause cellular damage and propagate to other cells. In animal cells, especially in aged neurons, toxic aggregates may accumulate, induce cell death and lead to tissue degeneration via different mechanisms, such as apoptosis as in Parkinson's and Alzheimer's diseases and aging in general. The main cellular mechanisms effectively controlling protein homeostasis in youth and healthy adulthood are: (1) the molecular chaperones, acting as aggregate unfolding and refolding enzymes, (2) the chaperone-gated proteases, acting as aggregate unfolding and degrading enzymes, (3) the aggresomes, acting as aggregate compacting machineries, and (4) the autophagosomes, acting as aggregate degrading organelles. For unclear reasons, these cellular defences become gradually incapacitated with age, leading to the onset of degenerative diseases. Understanding these mechanisms and the reasons for their incapacitation in late adulthood is key to the design of new therapies against the progression of aging, degenerative diseases and cancers.