While a network of cortical regions contribute to face processing, the lesions in acquired prosopagnosia are highly variable, and likely result in different combinations of spared and affected regions of this network. To assess the residual functional sensitivities of spared regions in prosopagnosia, we designed a rapid event-related functional magnetic resonance imaging (fMRI) experiment that included pairs of faces with same or different identities and same or different expressions. By measuring the release from adaptation to these facial changes we determined the residual sensitivity of face-selective regions-of-interest. We tested three patients with acquired prosopagnosia, and all three of these patients demonstrated residual sensitivity for facial identity changes in surviving fusiform and occipital face areas of either the right or left hemisphere, but not in the right posterior superior temporal sulcus. The patients also showed some residual capabilities for facial discrimination with normal performance on the Benton Facial Recognition Test, but impaired performance on more complex tasks of facial discrimination. We conclude that fMRI can demonstrate residual processing of facial identity in acquired prosopagnosia, that this adaptation can occur in the same structures that show similar processing in healthy subjects, and further, that this adaptation may be related to behavioral indices of face perception.
face perception; identity; expression; fMRI; adaptation; sensitivity; prosopagnosia
To estimate recent age- and sex-specific changes in long-term opioid prescription among patients with chronic pain in two large American Health Systems.
Analysis of administrative pharmacy data to calculate changes in prevalence of long-term opioid prescription (90 days or more during a calendar year) from 2000 to 2005, within groups based on sex and age (18–44, 45–64, and 65 years and older). Separate analyses were conducted for patients with and without a diagnosis of a mood disorder or anxiety disorder. Changes in mean dose between 2000 and 2005 were estimated, as were changes in the rate of prescription for different opioid types (short-acting, long-acting, and non-Schedule 2).
Enrollees in HealthCore (N = 2,716,163 in 2000) and Arkansas Medicaid (N = 115,914 in 2000).
Within each of the age and sex groups, less than 10% of patients with a chronic pain diagnosis in HealthCore, and less than 33% in Arkansas Medicaid, received long-term opioid prescriptions. All age, sex, and anxiety/depression groups showed similar and statistically significant increases in long-term opioid prescription between 2000 and 2005 (35–50% increase). Per-patient daily doses did not increase.
No one group showed especially large increases in long-term opioid prescriptions between 2000 and 2005. These results argue against a recent epidemic of opioid prescribing. These trends may result from increased attention to pain in clinical settings, policy or economic changes, or provider and patient openness to opioid therapy. The risks and benefits to patients of these changes are not yet established.
Opioids; Prescriptions; Chronic Pain; Disparities—Gender; Aged; Mood; Anxiety
Variations in serum markers of collagen production (CICP) and degradation (ICTP), insulin-like growth factor I (IGF-I) and anterior knee laxity (AKL) were measured in 20 women [10 with spontaneous cycles (eumenorrheic), 10 using oral contraceptives] over 5 consecutive days at menses (M1-M5, 1st pill week), the initial estrogen rise near ovulation (O1-O5, 2nd pill week), the initial progesterone rise of the early luteal phase (EL1-EL5, 3rd pill week) and post progesterone peak of the late luteal phase (LL1-LL5, 4th pill week). ICTP was higher in oral contraceptive women (5.3±1.7 vs. 3.7±1.3µg/L; P=.030), primarily during days near ovulation and the early luteal phase when concentrations decreased in eumenorrheic women (P=.04). IGF-I concentrations increased during menses then decreased and remained lower during the early and late luteal phase in oral contraceptive women, resulting in lower concentrations compared to eumenorrheic women at EL2 and LL1 (P=.03). CICP decreased in early and late luteal days (P<.01), and there was a trend toward lower concentrations in eumenorrheic vs. oral contraceptive women (85.7±35.7 vs. 123.2±49.8 ng/mL; P=.07). Lower CICP and greater IGF-I concentrations predicted greater AKL across the 20 cycle days in both groups (R2=.310 and .400). Sex hormone concentration changes across the menstrual cycle are of sufficient magnitude to influence collagen metabolism, and may indirectly influence knee structure and function.
collagen markers; growth factors; menstrual cycle; sex hormones; knee laxity; ACL
This study examined the effect of clopidogrel and proton pump inhibitors (PPIs) interaction on subsequent acute coronary syndrome (ACS)-related inpatient and emergency room (ER) visits.
Population based, retrospective cohort study.
IMS LifeLink Health Plan administrative claims database containing a large nationally dispersed group of commercially insured subjects between 2001 and 2008.
Subjects age ≥18 years with a diagnosis of ACS and at least one clopidogrel prescription within 90 days after the diagnosis were included. Exposed group was defined as having overlapping clopidogrel-PPI prescriptions. Subjects were followed from their first clopidogrel prescription until they experienced an adverse cardiovascular event (re-hospitalization or errors visit due to ACS), were disenrolled or reached the end of study period.
Measurements and Main Results
The clopidogrel plus PPIs group was matched 1:1 with the clopidogrel alone group using the propensity scoring method. Exposure to overlapping clopidogrel-PPI prescriptions was modeled as a time dependent covariate. Cox hazards regression was used to estimate the risk of an adverse cardiovascular event for those having overlapping clopidogrel-PPI prescriptions versus those having clopidogrel alone. Propensity score matching resulted in 2,674 patient pairs. The mean age was 61.30 years with a mean follow-up of 268 days and 70.04% were male. Clopidogrel use co-medicated with PPIs was associated with a significantly increased risk of cardiovascular adverse events (HR=1.438; 95% CI, 1.237-1.671), as compared to clopidogrel use not co-medicated with PPIs.
Concurrent use of clopidogrel plus PPIs was associated with a significant increase in risk of adverse cardiovascular events for ACS patients.
Clopidogrel; Proton; Pump; Inhibitors; Interaction; Cardiovascular; Adverse; Events; Outcomes; Acute; Coronary; Syndrome
Training in action video games can increase the speed of perceptual processing. However, it is unknown whether video-game training can lead to broad-based changes in higher-level competencies such as cognitive flexibility, a core and neurally distributed component of cognition. To determine whether video gaming can enhance cognitive flexibility and, if so, why these changes occur, the current study compares two versions of a real-time strategy (RTS) game. Using a meta-analytic Bayes factor approach, we found that the gaming condition that emphasized maintenance and rapid switching between multiple information and action sources led to a large increase in cognitive flexibility as measured by a wide array of non-video gaming tasks. Theoretically, the results suggest that the distributed brain networks supporting cognitive flexibility can be tuned by engrossing video game experience that stresses maintenance and rapid manipulation of multiple information sources. Practically, these results suggest avenues for increasing cognitive function.
There has been an increase in over dose deaths and emergency department visits (EDVs) involving use of prescription opioids, but the association between opioid prescribing and adverse outcomes is unclear.
Data were obtained from administrative claim records from Arkansas Medicaid and HealthCore commercially insured enrollees, 18 years and older, who used prescription opioids for at least 90 continuous days within a 6-month period between 2000 and 2005 and had no cancer diagnoses. Regression analysis was used to examine risk factors for EDVs and alcohol- or drug-related encounters (ADEs) in the 12 months following 90 days or more of prescribed opioids.
Headache, back pain, and preexisting substance use disorders were significantly associated with EDVs and ADEs. Mental health disorders were associated with EDVs in HealthCore enrollees and with ADEs in both samples. Opioid dose per day was not consistently associated with EDVs but doubled the risk of ADEs at morphine-equivalent doses over 120 mg/d. Use of short-acting Drug Enforcement Agency Schedule II opioids was associated with EDVs compared with use of non–Schedule II opioids alone (relative risk range, 1.09–1.74). Use of Schedule II long-acting opioids was strongly associated with ADEs (relative risk range, 1.64–4.00).
Use of Schedule II opioids, headache, back pain, and substance use disorders are associated with EDVs and ADEs among adults prescribed opioids for 90 days or more. It may be possible to increase the safety of chronic opioid therapy by minimizing the prescription of Schedule II opioids in these higher-risk recipients.
Category learning is a complex phenomenon that engages multiple cognitive processes, many of which occur simultaneously and unfold dynamically over time. For example, as people encounter objects in the world, they simultaneously engage processes to determine their fit with current knowledge structures, gather new information about the objects, and adjust their representations to support behavior in future encounters. Many techniques that are available to understand the neural basis of category learning assume that the multiple processes that subserve it can be neatly separated between different trials of an experiment. Model-based functional magnetic resonance imaging offers a promising tool to separate multiple, simultaneously occurring processes and bring the analysis of neuroimaging data more in line with category learning’s dynamic and multifaceted nature. We use model-based imaging to explore the neural basis of recognition and entropy signals in the medial temporal lobe and striatum that are engaged while participants learn to categorize novel stimuli. Consistent with theories suggesting a role for the anterior hippocampus and ventral striatum in motivated learning in response to uncertainty, we find that activation in both regions correlates with a model-based measure of entropy. Simultaneously, separate subregions of the hippocampus and striatum exhibit activation correlated with a model-based recognition strength measure. Our results suggest that model-based analyses are exceptionally useful for extracting information about cognitive processes from neuroimaging data. Models provide a basis for identifying the multiple neural processes that contribute to behavior, and neuroimaging data can provide a powerful test bed for constraining and testing model predictions.
category learning; model-based imaging; medial temporal lobe; entropy; recognition
Systematic reviews and meta-analyses of randomized trials that include patient-reported outcomes (PROs) often provide crucial information for patients and clinicians facing challenging health care decisions. Based on emerging methods, guidance on combining PROs in meta-analysis is likely to enhance their usefulness.
The objectives of this paper are: i) to describe PROs and why they are important for health care decision-making, ii) illustrate the key risk of bias issues that systematic reviewers should consider and, iii) address outcome characteristics of PROs and provide guidance for combining outcomes.
We suggest a step-by-step approach to addressing issues of PROs in meta-analyses. Systematic reviewers should begin by asking themselves if trials have addressed all the important effects of treatment on patients’ quality of life. If the trials have addressed PROs, have investigators chosen the appropriate instruments? In particular, does evidence suggest the PROs used are valid and responsive, and is the review free of outcome reporting bias? Systematic reviewers must then decide how to categorize PROs and when to pool results.
Patient-reported outcomes; Health-related quality of life; Meta-analysis; Systematic review; Health care decision-making
The objective was to study the effect of colpocleisis on pelvic support, symptoms, and quality of life and report-associated morbidity and postoperative satisfaction. Women undergoing colpocleisis for treatment of pelvic organ prolapse (POP) were recruited at six centers. Baseline measures included physical examination, responses to the Pelvic Floor Distress Inventory, and Pelvic Floor Impact Questionnaire. Three and 12 months after surgery we repeated baseline measures. Of 152 patients with mean age 79 (±6) years, 132 (87%) completed 1 year follow-up. Three and 12 months after surgery, 90/110 (82%) and 75/103 (73%) patients following up had POP stage ≤1. All pelvic symptom scores and related bother significantly improved at 3 and 12 months, and 125 (95%) patients said they were either ‘very satisfied’ or ‘satisfied’ with the outcome of their surgery. Colpocleisis was effective in resolving prolapse and pelvic symptoms and was associated with high patient satisfaction.
Pelvic organ prolapse; Urinary incontinence; Pelvic floor disorders; Colpocleisis; Quality of life; Surgical outcomes
To estimate the effect of two separate policy changes in the North Carolina Medicaid program: (1) reduced prescription lengths from 100 to 34 days' supply, and (2) increased copayments for brand name medications.
Data Sources/Study Setting
Medicaid claims data were obtained from the Centers for Medicare and Medicaid Services for January 1, 2000–December 31, 2002.
We used a pre–post controlled partial difference-in-difference-in-differences design to examine the effect of the policy change on adults in North Carolina; adult Medicaid recipients from Georgia served as controls. Outcomes examined include medication adherence and Medicaid expenditures.
Data Collection/Extraction Methods
Data were aggregated to the person-quarter level. Individuals in HMOs, nursing homes, pregnant, or deceased in the quarter were excluded.
Both policies decreased medication adherence. The days' supply policy had a much larger effect on adherence than did the copayment increase. Total Medicaid spending declined from the days' supply policy, but the copayment policy resulted in a net increase in Medicaid expenditures.
Although Medicaid costs decreased with the change in days supply policy, these savings were due to reduced adherence to these chronic medications. Additional research should examine the effect of these policy changes from the perspective of Medicaid enrollees.
Medicaid; prescription drugs; chronic medications; days' supply
The purpose of this study was to examine the association between mental health disorders and subsequent risk for chronic opioid use among adolescents and young adults presenting with common chronic pain complaints (back pain, neck pain, headache and arthritis/joint pain).
Using claims data from January 1, 2001 to June 30, 2008, we conducted a longitudinal analysis of opioid use patterns among 13–24 year-olds presenting with a new episode of chronic pain. Chronic opioid use was defined as receiving >90 days of opioids within a 6-month period with no gap in use of >30 days in the 18 months following the fist qualifying pain diagnosis. Mental health disorders were identified from claims in the 6 months prior to the first qualifying pain diagnosis.
59,077 youth met criteria for a new episode of chronic pain. Among these youth, 321 (0.5%) met criteria for chronic opioid use and 16,172 (27.4%) had some opioid use. After controlling for demographic and clinical factors, youth with pre-existing mental health diagnoses had a 2.4-fold increased risk of subsequently receiving chronic opioids versus no opioids (OR: 2.36, 95% CI = 1.73–3.23) and a 1.8-fold increased likelihood of receiving chronic opioids versus some opioids (OR: 1.83, 95% CI= 1.34–2.50).
Mental health disorders are associated with increased risk for chronic opioid use among adolescents and emerging young adults. Further study is warranted to examine risks and benefits of chronic opioid use in this population.
The use of a multidisciplinary approach is becoming increasingly important when developing management strategies that mitigate the economic and biological costs associated with invasive pests. A framework of simulated dispersal is combined with life-history information and analyses of population genetic structure to investigate the invasion dynamics of a plant disease vector, the island sugarcane planthopper (Eumetopina flavipes), through an archipelago of significant Australian quarantine concern. Analysis of eight microsatellite loci from 648 individuals suggests that frequent, wind-assisted immigration from multiple sources in Papua New Guinea contributes significantly to repeated colonization of far northern islands. However, intermittent wind-assisted immigration better explains patterns of genetic diversity and structure in the southern islands and on the tip of mainland Australia. Significant population structuring associated with the presence of clusters of highly related individuals results from breeding in-situ following colonization, with little postestablishment movement. Results also suggest that less important secondary movements occur between islands; these appear to be human mediated and restricted by quarantine zones. Control of the planthopper may be very difficult on islands close to Papua New Guinea given the apparent propensity for multiple invasion, but may be achievable further south where local populations appear highly independent and isolated.
colonization; invasion pathway; isolation by distance; long-distance dispersal; microsatellites; pest management; planthopper
To determine the effect of contact with a podiatrist on the occurrence of Lower Extremity Amputation (LEA) in people with diabetes.
Design and data sources
We conducted a systematic review of available literature on the effect of contact with a podiatrist on the risk of LEA in people with diabetes. Eligible studies, published in English, were identified through searches of PubMed, CINAHL, EMBASE and Cochrane databases. The key terms, ‘podiatry’, ‘amputation’ and ‘diabetes’, were searched as Medical Subject Heading terms. Reference lists of selected papers were hand-searched for additional articles. No date restrictions were imposed.
Published randomised and analytical observational studies of the effect of contact with a podiatrist on the risk of LEA in people with diabetes were included. Cross-sectional studies, review articles, chart reviews and case series were excluded. Two reviewers independently assessed titles, abstracts and full articles to identify eligible studies and extracted data related to the study design, characteristics of participants, interventions, outcomes, control for confounding factors and risk estimates.
Meta-analysis was performed separately for randomised and non-randomised studies. Relative risks (RRs) with 95% CIs were estimated with fixed and random effects models as appropriate.
Six studies met the inclusion criteria and five provided data included in meta-analysis. The identified studies were heterogenous in design and included people with diabetes at both low and high risk of amputation. Contact with a podiatrist did not significantly affect the RR of LEA in a meta-analysis of available data from randomised controlled trials (RCTs); (1.41, 95% CI 0.20 to 9.78, 2 RCTs) or from cohort studies; (0.73, 95% CI 0.39 to 1.33, 3 Cohort studies with four substudies in one cohort).
There are very limited data available on the effect of contact with a podiatrist on the risk of LEA in people with diabetes.
Renal parenchymal volume can be used clinically to estimate differential renal function. Unfortunately, conventional methods to determine renal volume from computed tomography (CT) are time-consuming or difficult due to software limitations. We evaluated the accuracy of simple renal measurements to estimate renal volume as compared with estimates made using specialized CT volumetric software.
We reviewed 28 patients with contrast-enhanced abdominal CT. Using a standardized technique, one urologist and one urology resident independently measured renal length, lateral diameter and anterior-posterior diameter. Using the ellipsoid method, the products of the linear measurements were compared to 3D volume measurements made by a radiologist using specialized volumetric software.
Linear kidney measurements were highly consistent between the urologist and the urology resident (intraclass correlation coefficients: 0.97 for length, 0.96 for lateral diameter, and 0.90 for anterior-posterior diameter). Average renal volume was 170 (SD: 36) cm3 using the ellipsoid method compared with 186 (SD 37) cm3 using volumetric software, for a mean absolute bias of −15.2 (SD 15.0) cm3 and a relative volume bias of −8.2% (p < 0.001). Thirty-one of 56 (55.3%) estimated volumes were within 10% of the 3D measured volume and 54 of 56 (96.4%) were within 30%.
Renal volume can be easily approximated from contrast-enhanced CT scans using the ellipsoid method. These findings may obviate the need for 3D volumetric software analysis in certain cases. Prospective validation is warranted.
Dietary phosphorus intake is usually restricted in dialysis patients but the associations of dietary phosphorus intake with mortality in moderate chronic kidney disease (CKD) are unknown. Therefore, we examined these associations in National Health and Nutrition Examination Survey III.
Dietary phosphorus intake was estimated from 24-h dietary recalls administered by trained personnel. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Time to mortality was examined by Cox regression models taking into account the complex survey design.
1105 adults with CKD were studied. Phosphorus intake was 1033 ± 482 mg/day (mean ± SD), eGFR was 49.3 ± 9.5 mL/min/1.73 m2 and serum phosphorus was 3.5 ± 0.5 mg/dL. Compared to those in the lowest tertile of phosphorus intake (mean 532 ± 161 mg/day), those in the highest third (1478 ± 378 mg/day) had similar serum phosphorus levels (3.6 ± 0.5 versus 3.5 ± 0.6 mg/dL, P = 0.113) and modestly higher eGFR (50.0 ± 8.1 versus 47.5 ± 12.0 mL/min/1.73 m2, P = 0.014). After adjustment for demographics, comorbidity, eGFR, physical activity, energy intake and nutritional variables, phosphorus intake was not associated with mortality [hazard ratio (HR) 0.98 per 100 mg/dL increase, 0.93–1.03].
High dietary phosphorus intake is not associated with increased mortality in moderate CKD, presumably because serum phosphorus levels are maintained in the normal range at this level of GFR. Interventional trials are needed to define optimal phosphorus intake in moderate CKD.
dietary phosphorus intake; mortality; moderate chronic kidney disease
Systematic reviewer authors intending to include all randomized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data.
The objective of this paper is to provide systematic reviewer authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of randomized trials.
This guide is based on a review of the Cochrane handbook and published methodological research. The guide deals with participants excluded from the analysis who were considered ‘non-adherent to the protocol’ but for whom data are available, and participants with missing data.
Systematic reviewer authors should include data from ‘non-adherent’ participants excluded from the primary study authors' analysis but for whom data are available. For missing, unavailable participant data, authors may conduct a complete case analysis (excluding those with missing data) as the primary analysis. Alternatively, they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data. When the primary analysis suggests important benefit, sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis. The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta-analysis. The proposed guide does not take into account the uncertainty associated with assumed events.
This guide proposes methods for handling participants excluded from analyses of randomized trials. These methods can help in establishing the extent to which risk of bias impacts meta-analysis results.
FDA advisory-committees recently made some recommendations to address acetaminophen (APAP)-related toxicity.
To study the proportion of APAP-users potentially consuming APAP over the currently recommended dose (4gm/day) and a toxic dose (10gm/day). To explore the impact of substituting the APAP-strength in combination-prescriptions to 325mg on potential APAP-overuse patterns.
Using the 2001-2008 pharmacy claims from IMS LifeLink Health Plans, APAP potential maximum daily dose (PMDD), potential cumulative dose and potential average daily dose (PADD) were calculated annually for APAP-users. The proportion of users with potential APAP-use above 4gm/day and 10gm/day are reported. Analyses were repeated by substituting the maximum APAP-strength in combination-prescriptions to 325mg. Ordinary least squares regression was used to detect linear trends in APAP-use/overuse.
790,188 of 2,656,161 study subjects were prescribed acetaminophen in one or more years from 2001-2008. The proportions of adult APAP-users with PMDD >4gm/day and PADD >4gm/day significantly decreased (p=0.0020 and p=0.0024 respectively). If the maximum APAP-strength in combination-prescriptions was 325mg, the proportion of APAP-users with PMDD >4gm would be 14.08% in 2001 and 13.67% in 2008 while the proportion of those with PMDD >10gm would be 0.21% and 2.30%.
About 1 in 4 APAP-users have a PMDD >4gm/day while 2-3% have a PMDD >10gm based exclusively on prescription data which is concerning. These proportions could reduce by over half if the maximum APAP-strength in combination-prescriptions is 325mg. Additional monitoring of opioid prescription-patterns, physician and pharmacist cognizance in prescribing APAP-containing combination products and dose reduction strategies should be considered to reduce APAP-overuse.
Background and Aims
Cognitive impairment is a risk factor for death in dialysis patients and the general population. We sought to determine if cognitive impairment is associated with death in people with non-dialysis-dependent chronic kidney disease (CKD), and if so, whether this relationship is greater in the CKD population compared to the general population.
National Health and Nutrition Examination Survey-III participants older than 60 years were asked to subtract 3 from 20 five times and to perform immediate and delayed recall of three items. A cognitive score of 0–11 was assigned based on the number of correct responses. Participants were categorized according to cognitive score (11, 9–10, 6–9, and 0–5) and CKD status. Survival analyses were conducted using Cox models.
Within the CKD subpopulation, those in the lowest cognitive score group had a twofold increased hazard of death compared to those with maximum score. Within the non-CKD subpopulation, those in the lowest cognitive score group had a 46% increased hazard of death compared to those with maximum score. However, the difference in the hazards of death in the CKD and non-CKD subpopulations with the lowest cognitive score was not significant (p = 0.99).
Low cognitive score is associated with an increased risk of death in elderly individuals with and without CKD; however, there was no interaction of CKD and low cognitive score in this analysis.
Cognitive function; Cognitive score; Chronic kidney disease; Mortality
Swimming Escherichia coli cells are propelled by the rotary motion of their flagellar filaments. In the normal swimming pattern, filaments positioned randomly over the cell form a bundle at the posterior pole. It has long been assumed that the hook functions as a universal joint, transmitting rotation on the motor axis through up to ∼90° to the filament in the bundle. Structural models of the hook have revealed how its flexibility is expected to arise from dynamic changes in the distance between monomers in the helical lattice. In particular, each of the 11 protofilaments that comprise the hook is predicted to cycle between short and long forms, corresponding to the inside and outside of the curved hook, once each revolution of the motor when the hook is acting as a universal joint. To test this, we genetically modified the hook so that it could be stiffened by binding streptavidin to biotinylated monomers, impeding their motion relative to each other. We found that impeding the action of the universal joint resulted in atypical swimming behavior as a consequence of disrupted bundle formation, in agreement with the universal joint model.
We report methodological advances that extend the current capabilities of ion-abrasion scanning electron microscopy (IA–SEM), also known as focused ion beam scanning electron microscopy, a newly emerging technology for high resolution imaging of large biological specimens in 3D. We establish protocols that enable the routine generation of 3D image stacks of entire plastic-embedded mammalian cells by IA-SEM at resolutions of ~10 to 20 nm at high contrast and with minimal artifacts from the focused ion beam. We build on these advances by describing a detailed approach for carrying out correlative live confocal microscopy and IA–SEM on the same cells. Finally, we demonstrate that by combining correlative imaging with newly developed tools for automated image processing, small 100 nm-sized entities such as HIV-1 or gold beads can be localized in SEM image stacks of whole mammalian cells. We anticipate that these methods will add to the arsenal of tools available for investigating mechanisms underlying host-pathogen interactions, and more generally, the 3D subcellular architecture of mammalian cells and tissues.
Ion-Abrasion Scanning Electron Microscopy; Focused Ion Beam Scanning Electron Microscopy; Correlative Light Electron Microscopy; T cells; HIV
To report chronic opioid therapy discontinuation rates after five years and identify factors associated with discontinuation.
Medical and pharmacy claims records from January 2000 through December 2005 from a national private health network (HealthCore), and Arkansas (AR) Medicaid were used to identify ambulatory adult enrollees who had 90 days of opioids supplied. Recipients were followed until they discontinued opioid prescription fills or disenrolled. Kaplan Meier survival models and Cox proportional hazards models were estimated to identify factors associated with time until opioid discontinuation.
There were 23,419 and 6,848 chronic opioid recipients followed for a mean of 1.9 and 2.3 years in the HealthCore and AR Medicaid samples. Over a maximum follow up of 4.8 years, 67.0% of HealthCore and 64.9% AR Medicaid recipients remained on opioids. Recipients on high daily opioid dose (greater than 120 milligrams morphine equivalent (MED)) were less likely to discontinue than recipients taking lower doses: HealthCore hazard ratio (HR) = 0.66 (95%CI: 0.57–0.76), AR Medicaid HR = 0.66 (95%CI: 0.50–0.82). Recipients with possible opioid misuse were also less likely to discontinue: HealthCore HR = 0.83 (95%CI: 0.78–0.89), AR Medicaid HR = 0.78 (95%CI: 0.67–0.90).
Over half of persons receiving 90 days of continuous opioid therapy remain on opioids years later. Factors most strongly associated with continuation were intermittent prior opioid exposure, daily opioid dose ≥ 120 mg MED, and possible opioid misuse. Since high dose and opioid misuse have been shown to increase the risk of adverse outcomes special caution is warranted when prescribing more than 90 days of opioid therapy in these patients.
opioids; opioid misuse; persistence; discontinuation
Accumulated evidence from animal studies implicates the ventral striatum in the processing of reward information. Recently, deep brain stimulation (DBS) surgery has enabled researchers to analyze neurophysiological recordings from humans engaged in reward tasks. We present data recorded from the human ventral striatum during DBS surgery as a participant played a video game coupled to the receipt of visual reward images. To our knowledge, we identify the first instances of reward-sensitive single unit activity in the human ventral striatum. Local field potential data suggests that alpha oscillations are sensitive to positive feedback, while beta oscillations exhibit significantly higher power during unrewarded trials. We report evidence of alpha–gamma cross-frequency coupling that differentiates between positive and negative feedback.
ventral striatum; deep brain stimulation; nucleus accumbens; reward
Opioids are among the most commonly abused drugs among adolescents and the prescription of these drugs has increased over the last decade. The goal of the current study is to examine trends and factors associated with prescription opioid use among adolescents with common non-cancer pain (NCP) conditions, sampled from two contrasting populations.
We conducted a secondary data analysis examining time trends from 2001 to 2005 in opioid use in two dissimilar populations: a national, commercially-insured population and a state Medicaid plan. We examined trends in mean dose prescribed, mean number of prescriptions, and types of medications given, as well as clinical and demographic features of adolescents receiving opioids.
In 2005, 21% of adolescents with common NCP conditions in HealthCore and 40.2% of adolescents with NCP in Arkansas Medicaid had received prescription opioids. The majority of opioid prescriptions in both 2001 and 2005 were for DEA Schedule II and III short acting opioids. In both samples, rates of prescription were higher for adolescents with comorbid mental health diagnoses compared to those without and for adolescents with multiple pain conditions compared to a single pain condition.
Prescription of opioids among adolescents with NCP is common and the prescription rate is higher among adolescents with multiple pain conditions and comorbid mental health disorders. Further research is necessary to determine risk factors for abuse and misuse of opioids in adolescents to help develop guidelines for use in this age group.
Pain; Adolescents; Opioids