Association between statin-associated myopathy and skeletal muscle damage

BACKGROUND: Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. METHODS: We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. RESULTS: Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10x the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). INTERPRETATION: Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.

The significance of at-risk symptoms for psychosis in children and adolescents

The early detection and treatment of people at risk for psychosis is currently regarded as a promising strategy in fighting the devastating consequences of psychotic disorders. Currently, the 2 most broadly used sets of at-risk criteria, that is, ultra-high risk (UHR) and basic symptom criteria, were developed mainly in adult samples. We review the data regarding the presence and relevance of at-risk symptoms for psychosis in children and adolescents. The few existing studies suggest that attenuated psychotic symptoms (APS) and brief limited intermittent psychotic symptoms (BLIPS) do have some clinical relevance in young adolescents from the general population. Nevertheless, their differentiation from atypical psychotic symptoms or an emerging schizotypal personality disorder, as well as their stability and predictive accuracy for psychosis, are still unclear. Further, standard interviews for UHR criteria do not define a minimum age for the assessment of APS and BLIPS or guidelines as to when and how to include information from parents. APS and basic symptoms may be predictive of conversion to psychosis in help-seeking young adolescents. Nevertheless, the rate and timing, and thus the required observation time, need further study. Moreover, no study has yet addressed the issue of how to treat children and adolescents presenting with at-risk symptoms and criteria. Further research is urgently needed to examine if current at-risk criteria and approaches have to be tailored to the special needs of children and adolescents. A preliminary rationale for how to deal with at-risk symptoms for psychosis in clinical practice is provided.

Efficacy pneumococcal vaccination in adults: a meta-analysis

Background: Clinical trials and meta-analyses have produced conflicting results of the efficacy of unconjugated pneumococcal polysaccharide vaccine in adults. We sought to evaluate the vaccine’s efficacy on clinical outcomes as well as the methodologic quality of the trials. Methods: We searched several databases and all bibliographies of reviews and meta-analyses for clinical trials that compared pneumococcal polysaccharide vaccine with a control. We examined rates of pneumonia and death, taking the methodologic quality of the trials into consideration. Results: We included 22 trials involving 101 507 participants: 11 trials reported on presumptive pneumococcal pneumonia, 19 on all-cause pneumonia and 12 on allcause mortality. The current 23-valent vaccine was used in 8 trials. The relative risk (RR) was 0.64 (95% confidence interval [CI] 0.43–0.96) for presumptive pneumococcal pneumonia and 0.73 (95% CI 0.56–0.94) for all-cause pneumonia. There was significant heterogeneity between the trials reporting on presumptive pneumonia (I2 = 74%, p < 0.001) and between those reporting on all-cause pneumonia (I2 = 90%, p < 0.001). The RR for all-cause mortality was 0.97 (95% CI 0.87–1.09), with moderate heterogeneity between trials (I2 = 44%, p = 0.053). Trial quality, especially regarding double blinding, explained a substantial proportion of the heterogeneity in the trials reporting on presumptive pneumonia and all-cause pneumonia. There was little evidence of vaccine protection in trials of higher methodologic quality (RR 1.20, 95% CI 0.75–1.92, for presumptive pneumonia; and 1.19, 95% CI 0.95–1.49, for allcause pneumonia in double-blind trials; p for heterogeneity > 0.05). The results for all-cause mortality in double-blind trials were similar to those in all trials combined. There was little evidence of vaccine protection among elderly patients or adults with chronic illness in analyses of all trials (RR 1.04, 95% CI 0.78–1.38, for presumptive pneumococcal pneumonia; 0.89, 95% CI 0.69–1.14, for all-cause pneumonia; and 1.00, 95% CI 0.87–1.14, for all-cause mortality). Interpretation: Pneumococcal vaccination does not appear to be effective in preventing pneumonia, even in populations for whom the vaccine is currently recommended.

Variation of a test's sensitivity and specificity with disease prevalence

BACKGROUND Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. METHODS We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. RESULTS Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. INTERPRETATION The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation.

Lifshitz holographic renormalization from anti-de Sitter 1

Lifshitz space–times with critical exponent z = 2 can be obtained by dimensional reduction of Schrödinger space–times with critical exponent z = 0. The latter space–times are asymptotically anti-de Sitter (AdS) solutions of AdS gravity coupled to an axion–dilaton system (or even just a massless scalar field). This basic observation is used to perform holographic renormalization for four-dimensional asymptotically locally Lifshitz space–times by dimensional reduction of the corresponding problem of holographic renormalization for five-dimensional asymptotically AdS space–times coupled to an axion–dilaton system. In this setup the four-dimensional structure of the Lifshitz – Fefferman-Graham expansion and the structure of the counterterm action, including the scale anomaly, will be summarized.

The bivalency effect in task switching: General and enduring

The purpose of this study was to investigate the generality and temporal endurance of the bivalency effect in task switching. This effect refers to the slowing on univalent stimuli that occurs when bivalent stimuli appear occasionally. We used a paradigm involving predictable switches between 3 simple tasks, with bivalent stimuli occasionally occurring on one of the tasks. The generality of the bivalency effect was investigated by using different tasks and different types of bivalent stimuli, and the endurance of this effect was investigated across different intertrial intervals (ITIs) and across the univalent trials that followed trials with bivalent stimuli. In 3 experiments, the results showed a general, robust, and enduring bivalency effect for all ITI conditions. Although the effect declined across trials, it remained significant for about 4 trials following one with a bivalent stimulus. Our findings emphasise the importance of top–down processes in task-switching performance. (PsycINFO Database Record (c) 2012 APA, all rights reserved)