Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related ...to these agents, which are renally cleared, but data regarding the risk thereof are lacking.
From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0-100, >100-200, >200-300, and >300 mg) and pregabalin (>0-100 and >100 mg).
In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%-41%) and fall (26%-30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively.
Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.
Patients on hemodialysis frequently experience pain and may be particularly vulnerable to opioid-related complications. However, data evaluating the risks of opioid use in patients on hemodialysis ...are limited.
Using the US Renal Data System, we conducted a cohort study evaluating the association between opioid use (modeled as a time-varying exposure and expressed in standardized oral morphine equivalents) and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture among 140,899 Medicare-covered adults receiving hemodialysis in 2011. We evaluated risk according to average daily total opioid dose (>60 mg, ≤60 mg, and per 60-mg dose increment) and specific agents (per 60-mg dose increment).
The median age was 61 years old, 52% were men, and 50% were white. Sixty-four percent received opioids, and 17% had an episode of altered mental status (15,658 events), fall (7646 events), or fracture (4151 events) in 2011. Opioid use was associated with risk for all outcomes in a dose-dependent manner: altered mental status (lower dose: hazard ratio, 1.28; 95% confidence interval, 1.23 to 1.34; higher dose: hazard ratio, 1.67; 95% confidence interval, 1.56 to 1.78; hazard ratio, 1.29 per 60 mg; 95% confidence interval, 1.26 to 1.33), fall (lower dose: hazard ratio, 1.28; 95% confidence interval, 1.21 to 1.36; higher dose: hazard ratio, 1.45; 95% confidence interval, 1.31 to 1.61; hazard ratio, 1.04 per 60 mg; 95% confidence interval, 1.03 to 1.05), and fracture (lower dose: hazard ratio, 1.44; 95% confidence interval, 1.33 to 1.56; higher dose: hazard ratio, 1.65; 95% confidence interval, 1.44 to 1.89; hazard ratio, 1.04 per 60 mg; 95% confidence interval, 1.04 to 1.05). All agents were associated with a significantly higher hazard of altered mental status, and several agents were associated with a significantly higher hazard of fall and fracture.
Opioids were associated with adverse outcomes in patients on hemodialysis, and this risk was present even at lower dosing and for agents that guidelines have recommended for use.
BACKGROUND
Guidelines recommend avoidance of several psychoactive medications such as hypnotics in older adults due to their adverse effects. Older patients on hemodialysis may be particularly ...vulnerable to complications related to use of these agents, but only limited data are available about the risks in this population.
OBJECTIVES
To evaluate the association between the use of psychoactive medications and time to first emergency department visit or hospitalization for altered mental status, fall, and fracture among older patients receiving hemodialysis.
DESIGN
Observational cohort study.
SETTING
National registry of patients receiving hemodialysis (US Renal Data System).
PARTICIPANTS
A total of 60 007 adults 65 years or older receiving hemodialysis with Medicare Part D coverage in 2011.
MEASUREMENTS
The predictors were use of sedative‐hypnotics and anticholinergic antidepressants (modeled as separate time‐varying exposures). The outcomes were time to first emergency department visit or hospitalization for altered mental status, fall, and fracture (modeled separately).
RESULTS
Overall, 17% and 6% used sedative‐hypnotics and anticholinergic antidepressants, respectively, in 2011. In multivariable‐adjusted Cox regression, anticholinergic antidepressant use was associated with a 25%, 27%, and 39% higher hazard of altered mental status, fall, and fracture, respectively, compared with no use. Use of sedative‐hypnotics was not associated with adverse outcomes.
CONCLUSION
Anticholinergic antidepressants were associated with adverse outcomes in older hemodialysis patients, and alternative treatments should be considered. Sedative‐hypnotics were not associated with the risks evaluated in this study, but further investigation of the harms of this class of agents is warranted before their recommendation as a treatment option for insomnia in this population. J Am Geriatr Soc 67:449–454, 2019.
See related Editorial by Rasheeda Hall in this issue.
Muscle relaxants are often used to treat musculoskeletal pain or cramping, which are commonly experienced by hemodialysis patients. However, the extent to which muscle relaxants are prescribed in ...this population and the risks associated with their use have not been characterized.
Observational cohort study.
140,899 Medicare-covered adults receiving hemodialysis in 2011, identified in the US Renal Data System.
Time-varying muscle relaxant exposure.
Primary outcomes were time to first emergency department visit or hospitalization for altered mental status, fall, or fracture. Secondary outcomes were death and composites of death with each of the primary outcomes.
Multivariable Cox regression analysis.
10% of patients received muscle relaxants in 2011. 11%, 6%, 3%, and 13% had an episode of altered mental status, fall, fracture, and death, respectively. Muscle relaxant use was associated with higher risk for altered mental status (HR, 1.39; 95% CI, 1.29-1.51) and fall (HR, 1.18; 95% CI, 1.05-1.33) compared to no use. Muscle relaxant use was not statistically significantly associated with higher risk for fracture (HR, 1.17; 95% CI, 0.98-1.39). Muscle relaxant use was associated with lower hazard of death (HR, 0.85; 95% CI, 0.76-0.94). However, hazards were higher for altered mental status or death (HR, 1.17; 95% CI, 1.10-1.25), fall or death (HR, 1.14; 95% CI, 1.06-1.22), and fracture or death (HR, 1.10; 95% CI, 1.01-1.20).
A causal association between muscle relaxant use and outcomes cannot be inferred, and residual confounding cannot be excluded. Exposure and outcomes were ascertained using administrative claims.
Muscle relaxant use was common in hemodialysis patients and associated with altered mental status and falls. We could not rule out a clinically meaningful association between muscle relaxant use and fracture. The lower risk for death with muscle relaxants may have been the result of residual confounding. Future research to define the appropriate use of muscle relaxants in this population is warranted.
The sudden onset of a cue triggers visual attention, which then enhances visual processing in the zone near the cue. This enhancement causes a motion illusion in subsequent stimuli presented near the ...cue. At greater separations from the cue, the illusory motion reverses direction, indicating prolonged processing speed. Measurements of the strength and direction of illusory motion at increasing separations from the cue reveal an attentional ‘perceptive field’ with an excitatory center at the locus cued and an inhibitory surround subtending the remaining visual field. These findings help explain the traditional attentional ‘benefits’ and ‘costs’ of attention.
Authors’ Reply Ishida, Julie H.; McCulloch, Charles E.; Steinman, Michael A. ...
Journal of the American Society of Nephrology,
11/2018, Volume:
29, Issue:
11
Journal Article
Authors’ Reply Ishida, Julie H.; McCulloch, Charles E.; Steinman, Michael A. ...
Journal of the American Society of Nephrology,
09/2018, Volume:
29, Issue:
11
Journal Article
This study examined how different measures of individual perceptions of community social dynamics relate to each other and how these measures relate to self-reported general health and depressive ...symptoms. Results of a principal components analysis conducted to investigate the interrelationships between these individual measures suggest that these measures measure separate phenomena. In addition, in results of multiple-regression analyses conducted to examine associations between the various measures of individual perceptions of community social dynamics and the dependent variables of self-reported general health and depressive symptoms, sense of community, perceived neighborhood control, and neighborhood participation were all associated with the outcome variables in separate regression models. In a regression model with these three variables added to control variables, only sense of community was significantly, albeit modestly, associated with depressive symptoms and self-reported general health.
Robust visual attentional responses are produced by the sudden onset of a visual cue, but the properties of cues that best elicit an attentional response are not fully known. We used the line-motion ...illusion (Hikosaka et al., 1991) to investigate the optimal cue properties that evoke visual attention. We found that visual attention is driven primarily by the luminance contrast of the cue. Furthermore, by manipulating the spatial, chromatic, and contrast properties of cues, we found that magnocellular (M) stream biased cues always override the response to parvocellular (P) stream biased cues, even when the P stream biased cues are presented first. Our data suggest that cues that preferentially excite the M pathway predominantly capture visual attention.
Visual attention has been defined by different researchers and clinicians in a variety of ways that are sometimes conflicting or confusing. This paper will provide a unified definition of visual ...attention, as well as a putative neurophysiological mechanism that is consistent with this unified definition. In addition, recent data on the mechanisms of visual attention will be presented, including its spatial organization and temporal dependencies, as well as the role of parallel visual pathways in its activation.
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