Dose patterns in commercially insured subjects chronically exposed to opioids: a large cohort study in the United States

<p>Abstract</p> <p>Background</p> <p>Little data exist on how opioid doses vary with the length of exposure among chronic opioid users.</p> <p>Methods</p> <p>To characterize the change in the dosage of opioids over time, a retrospective cohort study using the PharMetrics database for the years 1999 through 2008 was conducted. Individuals exposed to opioids in 2000 who had 2 opioid dispensings at least 6 months apart and were opioid naive (did not receive any opioid 6 month before their exposure in 2000) were included. The date of the first dispensing in 2000 was defined as the index date and the dispensing had to be for a strong and full agonist opioid. All opioid doses were converted to oral morphine equivalent doses. Exposure was classified as continuous or intermittent. Mean, median, interquartile range, and 95^thpercentile of opioid dose over 6-month periods, as well as the percentage of subjects who ever received a high or very high opioid dose, were calculated.</p> <p>Results</p> <p>Among the 48,986 subjects, the mean age was 44.5 years and 54.5% were women. Intermittent exposure was observed in 99% of subjects; continuous exposure was observed in 1% of subjects. The mean duration of exposure for the subjects who were continuously exposed to opioids was 477 days. In subjects with no cancer diagnosis who were continuously exposed to opioids, the mean, 25^th, 50^th, and 75^thpercentile of dose was stable during the first 2 years of use, but the 95^thpercentile increased. Seven percent of them were exposed to doses of 180 mg or more of morphine at some point.</p> <p>Conclusions</p> <p>Dose escalation is uncommon in subjects with intermittent exposure to opioids. For subjects with continuous exposure to opioids who have cancer, doses rise substantially with time. For those without cancer, doses remain relatively stable for the first 2 years of use, but subsequently increase. Seven percent of subjects with no cancer diagnosis will be exposed to daily doses of 180 mg or more of morphine equivalent at some point.</p

Rescuing the Corticostriatal Synaptic Disconnection in the R6/2 Mouse Model of Huntington's Disease: Exercise, Adenosine Receptors and Ampakines.

In the R6/2 mouse model of Huntington's disease (HD) we examined the effects of a number of behavioral and pharmacological manipulations aimed at rescuing the progressive loss of synaptic communication between cerebral cortex and striatum. Two cohorts of transgenic mice with ~110 and 210 CAG repeats were utilized. Exercise prevented the reduction in striatal medium-sized spiny neuron membrane capacitance but did not reestablish synaptic communication. Activation of adenosine A2A type receptors renormalized postsynaptic activity to some extent. Finally, the ampakine Cx614, which has been shown to prevent α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor desensitization, slow deactivation, and facilitate glutamate release, induced significant increases in synaptic activity, albeit the effect was somewhat reduced in fully symptomatic, compared to control mice. With some limitations, each of these strategies can be used to delay and partially rescue phenotypic progression of HD in this model

Complex regional pain syndrome type I: efficacy of stellate ganglion blockade

PubMed ID: 19888550Background: This study was performed to evaluate the treatment of complex regional pain syndrome (CRPS) type I with stellate ganglion blockade. Materials and methods: We performed three blockades at weekly intervals in 22 patients with CRPS type I in one hand. The patients were divided into two groups depending on the time between symptom onset and treatment initiation. Group 1and 2 patients had short and long symptom-onset-to-treatment intervals, respectively. Pain intensity, using a visual analog score (VAS), and range of motion (ROM) for the wrist joint were assessed before and 2 weeks after treatment and were compared using nonparametric statistical analysis. Results: Treatment produced a statistically significant difference in wrist ROM for all patients (P < 0.001). VAS values showed an overall decrease from 8 ± 1 to 1 ± 1 following treatment, and there was a significant difference in VAS value between groups 1 and 2 (P < 0.05). Conclusions: We concluded that stellate ganglion blockade successfully decreased VAS and increased ROM of wrist joints in patients with CRPS type I. Further, the duration between symptom onset and therapy initiation was a major factor affecting blockade success. © 2009 Springer-Verlag

Propensity scores in the presence of effect modification: A case study using the comparison of mortality on hemodialysis versus peritoneal dialysis

Purpose. To control for confounding bias from non-random treatment assignment in observational data, both traditional multivariable models and more recently propensity score approaches have been applied. Our aim was to compare a propensity score-stratified model with a traditional multivariable-adjusted model, specifically in estimating survival of hemodialysis (HD) versus peritoneal dialysis (PD) patients. Methods. Using the Dutch End-Stage Renal Disease Registry, we constructed a propensity score, predicting PD assignment from age, gender, primary renal disease, center of dialysis, and year of first renal replacement therapy. We developed two Cox proportional hazards regression models to estimate survival on PD relative to HD, a propensity score-stratified model stratifying on the propensity score and a multivariable-adjusted model, and tested several interaction terms in both models. Results. The propensity score performed well: it showed a reasonable fit, had a good c-statistic, calibrated well and balanced the covariates. The main-effects multivariable-adjusted model and the propensity score-stratified univariable Cox model resulted in similar relative mortality risk estimates of PD compared with HD (0.99 and 0.97, respectively) with fewer significant covariates in the propensity model. After introducing the missing interaction variables for effect modification in both models, the mortality risk estimates for both main effects and interactions remained comparable, but the propensity score model had nearly as many covariates because of the additional interaction variables. Conclusion. Although the propensity score performed well, it did not alter the treatment effect in the outcome model and lost its advantage of parsimony in the presence of effect modification

The empirical analysis of non-problematic video gaming and cognitive skills: a systematic review

Videogames have become one of the most popular leisure activities worldwide, including multiple game genres with different characteristics and levels of involvement required. Although a small minority of excessive players suffer detrimental consequences including impairment of several cognitive skills (e.g., inhibition, decision-making), it has also been demonstrated that playing videogames can improve different cognitive skills. Therefore, the current paper systematically reviewed the empirical studies experimentally investigating the positive impact of videogames on cognitive skills. Following a number of inclusion and exclusion criteria, a total of 32 papers were identified as empirically investigating three specific skills: taskswitching (eight studies), attentional control (22 studies), and sub-second time perception (two studies). Results demonstrated that compared to control groups, non-problematic use of videogames can lead to improved task-switching, more effective top-down attentional control and processing speed and increased sub-second time perception. Two studies highlighted the impact of gaming on cognitive skills differs depends upon game genre. The studies reviewed suggest that videogame play can have a positive impact on cognitive processes for players

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO