Effect of acute inflammatory brain injury on accumulation of morphine and morphine 3- and 6-glucuronide in the human brain.

OBJECTIVE: In animals, central nervous system inflammation increases drug accumulation in the brain partly due to a loss of central nervous system drug efflux transporter function at the blood-brain barrier. To determine whether a similar loss of active drug efflux occurs in humans after acute inflammatory brain injury. DESIGN: Observational human pharmacokinetic study. SETTING: Medical-surgical-neurosurgical intensive care unit at a university-affiliated, Canadian tertiary care center. PATIENTS: Patients with acute inflammatory brain injury, including subarachnoid hemorrhage (n = 10), intracerebral and/or intraventricular hemorrhage (n = 4), or closed head trauma (n = 2) who received morphine intravenously after being fitted with cerebrospinal fluid ventriculostomy and peripheral arterial catheters. INTERVENTIONS: We correlated the cerebrospinal fluid distribution of morphine, morphine-3-glucuronide, and morphine-6-glucuronide with the cerebrospinal fluid and plasma concentration of the proinflammatory cytokine interleukin-6 and the passive marker of blood-brain barrier permeability, albumin. MEASUREMENTS AND MAIN RESULTS: Acute brain injury produced a robust inflammatory response in the central nervous system as reflected by the elevated concentration of interleukin-6 in cerebrospinal fluid. Penetration of morphine metabolites into the central nervous system increased in proportion to the neuroinflammatory response as demonstrated by the positive correlation between cerebrospinal fluid interleukin-6 exposure and the area under the curve cerebrospinal fluid/plasma ratio for morphine-3-glucuronide (r = .49, p < .001) and morphine-6-glucuronide (r = .51, p < .001). In contrast, distribution of morphine into the brain was not linked with cerebrospinal fluid interleukin-6 exposure (r = .073, p = .54). Albumin concentrations in plasma and cerebrospinal fluid were consistently in the normal range, indicating that the physical integrity of the blood-brain barrier was likely undisturbed. CONCLUSIONS: Our results suggest that central nervous system inflammation following acute brain injury may selectively inhibit the activity of specific drug efflux transporters within the blood-brain barrier. This finding may have significant implications for patients with neuroinflammatory conditions when administered centrally acting drugs normally excluded from the brain by such transporters.

More daytime sleeping predicts less functional recovery among older people undergoing inpatient post-acute rehabilitation.

STUDY OBJECTIVES: To study the association between sleep/wake patterns among older adults during inpatient post-acute rehabilitation and their immediate and long-term functional recovery DESIGN: Prospective, observational cohort study. SETTING: Two inpatient post-acute rehabilitation sites (one community and one Veterans Administration). PARTICIPANTS: Older patients (aged > or = 65 years, N = 245) admitted for inpatient post-acute rehabilitation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Based on 7-day wrist actigraphy during the rehabilitation stay, mean nighttime percent sleep was only 52.2% and mean daytime percent sleep was 15.8% (16.3% based on structured behavioral observations). Using the Pittsburgh Sleep Quality Index (PSQI), participants reported their sleep was worse during rehabilitation compared to their premorbid sleep. Functional recovery between admission and discharge from rehabilitation (measured by the motor component of the Functional Independence Measure) was not significantly associated with reported sleep quality (PSQI scores) or actigraphically measured nighttime sleep. However, more daytime percent sleep (estimated by actigraphy and observations) during the rehabilitation stay was associated with less functional recovery from admission to discharge, even after adjusting for other significant predictors of functional recovery (mental status, hours of rehabilitation therapy received, rehospitalization, and reason for admission; adjusted R2= 0.267, P < 0.0001). More daytime sleeping during rehabilitation remained a significant predictor of less functional recovery in adjusted analyses at 3-month follow-up. CONCLUSIONS: Sleep disturbance is common among older people undergoing inpatient post-acute rehabilitation. These data suggest that more daytime sleeping during the rehabilitation stay is associated with less functional recovery for up to three months after admission for rehabilitation.

Comparison between a tilt-in-space wheelchair and a manual wheelchair equipped with a new rear anti-tip device from the perspective of the caregiver.

OBJECTIVE: To test the hypothesis that, in comparison with a commercially available tilt-in-space wheelchair, a lightweight manual wheelchair equipped with a new, rear anti-tip device (Arc-RAD) provides caregivers with improved wheelchair-handling performance, less exertion, and greater satisfaction. DESIGN: Within-participant comparisons. SETTING: Rehabilitation center. PARTICIPANTS: Able-bodied participants (n=19) simulating caregivers and simulating wheelchair users (n=7). INTERVENTION: Caregiver participants were trained (50-75 min) in wheelchair-handling skills. MAIN OUTCOME MEASURES: Each participant was tested in both wheelchairs, in random order. To evaluate wheelchair-handling skills, we used the total percentage score on the Wheelchair Skills Test (WST), version 3.2. For exertion, we used a visual analog scale (in percent). For satisfaction, we used the Quebec Users' Evaluation of Satisfaction with assistive Technology (QUEST; range of values, 8-40), version 2. RESULTS: Mean percentage WST scores +/- SD for the Arc-RAD and tilt-in-space wheelchairs were 95.9%+/-4.2%, and 91.9%+/-4.8%, respectively (P=.008). The mean perceived exertions during Arc-RAD and tilt-in-space wheelchair use were 26.1%+/-20.4% and 46.6%+/-23.2% (P=.003). The mean total QUEST satisfaction scores for the Arc-RAD and tilt-in-space wheelchairs were 35.1+/-3.8 and 28.4+/-4.7 (P=.002). CONCLUSIONS: In comparison with the larger and heavier tilt-in-space wheelchair, a lightweight manual wheelchair equipped with a new rear anti-tip design allows 4.4% better wheelchair-handling performance, 44% less exertion, and 23.6% greater wheelchair satisfaction.

Comparing performance of manual wheelchair skills using new and conventional rear anti-tip devices: randomized controlled trial.

OBJECTIVE: To test the hypotheses that, compared with participants using manual wheelchairs equipped with conventional rear anti-tip devices (C-RADs), those using a new RAD design that deploys through an arc (Arc-RAD) perform RAD-relevant wheelchair skills better and as safely. DESIGN: A randomized controlled study. SETTING: A rehabilitation center. PARTICIPANTS: Participants (N=30) including 16 able-bodied and 14 wheelchair users. INTERVENTION: Participants were provided with wheelchair skills training (up to 2.4h). MAIN OUTCOME MEASURES: Total percentage score on a set of 23 RAD-relevant skills of the Wheelchair Skills Test (WST, version 3.2) administered a minimum of 3 days after training. RESULTS: For the C-RAD and Arc-RAD groups, the mean +/- standard deviation RAD-relevant WST scores were 32.3%+/-8.5% and 85.1%+/-18.9% (Kruskal-Wallis, P<.001). Of the 23 RAD-relevant individual skills, the success rates for the Arc-RAD group were at least 20% higher (the criterion we set for clinical significance) in 17 (74%). For the C-RAD group, the success rate was 0% for the 12 wheelie-dependent skills, the 13-cm-high obstacle, and the 15-cm level change ascent. There were no serious adverse effects in either group. CONCLUSIONS: The new RAD design allows much better performance on relevant wheelchair skills than the conventional design without compromising safety.

Randomized, controlled trial of a nonpharmacological intervention to improve abnormal sleep/wake patterns in nursing home residents.

OBJECTIVES: Abnormal sleep/wake patterns are common in nursing home residents. Lifestyle and environmental factors likely contribute to these poor sleep patterns. The objective of this study was to test a multidimensional, nonpharmacological intervention to improve abnormal sleep/wake patterns in nursing home residents. DESIGN: Randomized, controlled trial. SETTING: Four nursing homes in the Los Angeles area. PARTICIPANTS: Residents were screened for excessive daytime sleeping (asleep > or = 15% of daytime observations) and nighttime sleep disruption (asleep < 80% of nighttime hours, according to wrist actigraphy). Four hundred ninety-two residents were screened; 339 had excessive daytime sleeping. Of these, 133 had nighttime sleep disruption and consented to participate; 120 completed baseline assessments, and 118 (77% female, mean age 86.9, 90% non-Hispanic white) were randomized to intervention versus usual care. INTERVENTION: Five consecutive days and nights of efforts to decrease daytime in-bed time, 30 minutes or more of daily sunlight exposure, increased physical activity, structured bedtime routine, and efforts to decrease nighttime noise and light. MEASUREMENTS: Seventy-two consecutive hours of wrist actigraphy (nighttime sleep) and structured behavioral observations (daytime sleep and participation in social and physical activities and social conversation) at baseline and repeated at follow-up while the intervention or usual care condition was in place. RESULTS: The only effect on nighttime sleep was a modest decrease in mean duration of nighttime awakenings in intervention participants (10.6 minutes at baseline, 9.8 minutes at follow-up) versus an increase in controls (9.8 minutes at baseline, 13.8 minutes at follow-up) (F=4.27, P=.04). There were no significant effects on percentage of nighttime sleep or number of nighttime awakenings. There was a significant decrease in daytime sleeping in intervention participants (32% of daytime observations asleep at baseline, 21% at follow-up), with no change in controls (32% at baseline, 30% at follow-up; F=20.68, P<.001). Intervention participants had increased participation in social (F=22.42, P<.001) and physical (F=12.65, P=.001) activities and social conversation (F=5.04, P=.03). CONCLUSION: A multidimensional, nonpharmacological intervention into lifestyle and environmental factors that likely contribute to abnormal sleep/wake patterns in nursing home residents resulted in decreased daytime sleeping and increased participation in social and physical activities and social conversation. Nonpharmacological interventions should be considered in the management of abnormal sleep/wake patterns in nursing home residents. The main effect may be a significant decrease in daytime sleeping, which may translate to an improvement in quality of life.

Depression in older patients admitted for postacute nursing home rehabilitation.

OBJECTIVES: To describe the prevalence, recognition, and persistence of depression in older adults undergoing postacute rehabilitation in a nursing home (NH) setting and to explore the effect of depression on rehabilitation outcomes. DESIGN: Prospective cohort study. SETTING: One rehabilitative NH in the Los Angeles area. PARTICIPANTS: One hundred fifty-eight patients (aged >/=65) admitted for postacute rehabilitation over a 9-month recruitment period. MEASUREMENTS: Depression was assessed using the 15-item Geriatric Depression Scale (GDS-15) or the Cornell Scale for Depression (in participants with dementia). Medical records were reviewed for documentation of depression and antidepressant use before and during the rehabilitative NH stay. Rehabilitation process was assessed using total amount of successfully completed therapy (minutes). Rehabilitation outcome was assessed using the motor component of the Functional Independence Measure (mFIM). Measures were performed at admission and 2 months later. RESULTS: Of the 646 potentially eligible patients admitted during the study, 158 consented, and 151 were screened for depression. Forty-two (27.8%) had depressive symptoms (GDS=6 or Cornell=5). Of these, only 15 had a documented diagnosis of depression, and 12 were receiving antidepressants. Depression was associated with longer NH stay but not with discharge mFIM score. Two months later, depression persisted in 24 participants and was associated with worse mFIM (55.5+/-22.7 vs 67.0+/-23.7, depressed vs nondepressed; P=.03). CONCLUSION: Depression was common, underrecognized, and undertreated in these postacute rehabilitation patients. Depression generally persisted and was associated with worse functional status at 2-month follow-up.

Do age and comorbidity impact treatment allocation and outcomes in limited stage small-cell lung cancer? a community-based population analysis.

PURPOSE: The effects of age and comorbidity on treatment and outcomes for patients with limited stage small-cell lung cancer (L-SCLC) are unclear. This study analyzes relapse and survival in a community-based population with L-SCLC according to age and comorbidity. METHODS: A retrospective review was performed on 174 patients with L-SCLC referred to the British Columbia Cancer Agency, Vancouver Island Centre, between January 1991 and December 1999. Patient and treatment characteristics, disease response, relapse, and survival were compared among three age cohorts: <65 years (n = 55, 32%), 65-74 years (n = 76, 44%), and > or =75 years (n = 43, 25%); and according to Charlson comorbidity scores 0, 1, and > or =2. Multivariate analysis was performed to identify independent prognostic factors associated with treatment response and survival. RESULTS: Patient factors that significantly differed with age were functional status classified by Eastern Cooperative Oncology Group performance status and number of comorbidities. Increasing age was significantly associated with fewer diagnostic scans. Combined modality chemoradiotherapy (CRT) was given in 86%, 66%, and 40% of patients ages <65, 65-74, and > or =75 years, respectively, (p <0.0001). Thoracic irradiation use was comparable among the age cohorts (p >0.05), but chemotherapy use varied significantly with less intensive regimens, fewer cycles, and lower total doses with advancing age (p <0.05). Prophylactic cranial irradiation (PCI) was used in 41 patients, only 3 of whom were age >70 years. Overall response rates to primary treatment significantly decreased with advancing age: 91%, 79%, and 74% in patients ages <65, 65-74, and > or =75 years, respectively (p = 0.014). Treatment toxicity and relapse patterns were similar across the age cohorts. Overall 2-year survival rates were significantly lower with advancing age: 37%, 22%, and 19% (p = 0.003), with corresponding median survivals of 17, 12, and 7 months among patients ages <65, 65-74, and > or =75 years, respectively. On multivariate analysis, age and Charlson comorbidity scores were not significantly associated with treatment response and survival. Independent prognostic factors favorably associated with survival were good performance status, normal lactate dehydrogenase, absence of pleural effusion, and > or =four cycles of chemotherapy. CONCLUSION: Increasing age was associated with decreased performance status and increased comorbidity. Older patients with L-SCLC were less likely to be treated with CRT, intensive chemotherapy, and PCI. Treatment response and survival rates were lower with advancing age, but this may be attributed to poor performance status and suboptimal treatment rather than age.

Determining the efficacy of auricular acupuncture for reducing anxiety in patients withdrawing from psychoactive drugs.

Auricular acupuncture (AA) is a widely accepted treatment option for substance abuse that is used in more than 700 treatment centers worldwide. Despite claims of perceived clinical benefits by patients and treatment staff, research efforts have failed to substantiate purported benefits, and the mechanism(s) by which AA serves in the treatment of addiction remain inconclusive. Numerous studies have shown AA to be an effective treatment for perioperative anxiety. In this study, we hypothesize that AA reduces the anxiety associated with withdrawal from psychoactive drugs. The study used a randomized, controlled design and included a sample of 101 patients recruited from an addiction treatment service. Subjects were assigned to one of three treatment groups (National Acupuncture Detoxification Association [NADA] AA, AA at sham points, or treatment setting control) and were instructed to attend treatment sessions for 3 days. The primary outcome measure state anxiety was assessed using a pretest-posttest treatment design. The study hypothesis was not confirmed. The NADA protocol was not more effective than sham or treatment setting control in reducing anxiety. The widespread acceptance of AA in the treatment of addiction remains controversial.

Chair massage for treating anxiety in patients withdrawing from psychoactive drugs.

CONTEXT: Therapeutic massage has been proven to be an effective, nonpharmacologic, alternative for managing state and trait anxiety in a variety of clinical situations. However, no controlled study has investigated this effect in an addiction treatment setting. AIM: The aim of this study was to investigate the effectiveness of chair massage for reducing anxiety in persons participating in an inpatient withdrawal management program for psychoactive drugs. DESIGN: The design was a randomized, controlled clinical trial conducted from June 2008 to January 2009. SUBJECTS: Eighty-two (82) adult patients received inpatient treatment for psychoactive drug withdrawal (alcohol, cocaine, and opiates). SETTING: This study was conducted at the Withdrawal Management Services at the Capital District Health Authority, Halifax, Nova Scotia. INTERVENTIONS: Subjects were randomly assigned to receive chair massage (n = 40) or a relaxation control condition (n = 42). Treatments were offered for 3 consecutive days. Standard counseling and pharmacologic management were also offered concurrently to patients in all conditions. MEASUREMENTS: The primary outcome measure was anxiety assessed using the Spielberger State-Trait Anxiety Inventory (STAI). State and trait anxiety scores were determined immediately prior to and following each treatment intervention. RESULTS: Analysis of STAI scores showed a significant reduction in state and trait anxiety for both interventions (p < 0.001). The magnitude in the reduction in state (p = 0.001) and trait (p = 0.045) anxiety was significantly greater in the chair massage group where the effect on state anxiety was sustained, at least in part, for 24 hours. CONCLUSIONS: Within the clinical context of this study, chair massage was more effective that relaxation control in reducing anxiety. Further investigation of chair massage as a potential nonpharmacologic adjunct in the management of withdrawal related anxiety is warranted.

Analysis of hospital discharge data to characterize obstructive sleep apnea and its management in adult patients hospitalized in Canada: 2006 to 2007.

BACKGROUND: Diagnosed obstructive sleep apnea (OSA) affects 2% to 7% of middle-age persons worldwide and represents a substantial health care burden. The gold standard for treating OSA in adults is continuous positive airway pressure (CPAP) therapy. Compliance with this treatment is especially important in OSA patients experiencing concomitant acute and chronic disease or illness, and those undergoing procedures associated with sedation, analgesia and anesthesia. OBJECTIVE: To describe the clinical characteristics and management of hospitalized OSA patients in Canada. METHODS: Using the Canadian Institute for Health Information's hospital Discharge Abstract Database (fiscal year 2006/2007), a retrospective cohort study of all acute care patients discharged with a diagnosis that included OSA was performed. RESULTS: An examination of the discharge data of 2,400,245 acute care hospital abstracts identified 8823 cases of OSA. The mean age of OSA patients was 45.7 years and 66.5% were men. The most common comorbidities in the adult OSA population were obesity, cardiovascular disease, type 2 diabetes mellitus and chronic obstructive pulmonary disease. In adult OSA patients, the reported surgical intervention rate using uvulopalatopharyngoplasty (9.6%) was much higher than interventional CPAP therapy (4.8%). CONCLUSIONS: Only a small percentage of hospitalized OSA patients were documented as having received CPAP therapy during their stay. Issues relating to the accuracy, specificity and completeness of the Canadian Institute for Health Information's hospital Discharge Abstract Database specific to OSA and its management were identified. Practices pertaining to the reporting, coding and management of hospitalized adult OSA patients warrant further investigation and research.

Sitting pressure in the tilted position: manual tilt-in-space wheelchair vs. manual wheelchair with a new rear antitip device.

To test the hypothesis that, in comparison with a heavier, larger and more expensive manual tilt-in-space wheelchair, a lightweight manual wheelchair equipped with new rear antitip devices provides comparable mean sitting pressures in the tilted position, each of eight able-bodied participants sat for 8 mins in each wheelchair, upright, and tilted back (38-39 degrees). The mean (+/-SD) sitting pressures (of all active sensors in a force-sensing array) at the eighth minute in the upright and tilted positions with the new rear antitip device wheelchair were 58.6 (+/-14.0) and 45.8 (+/-9.3) mm Hg (a 20.7% reduction) (P = 0.005). For the tilt-in-space wheelchair, the mean values were 55.7 (+/-13.9) and 47.2 (+/-10.8) mm Hg (a 26.3% reduction) (P = 0.008). There were no significant differences between the wheelchairs in the upright (P = 0.843) or tilted (P = 0.624) positions. A lightweight manual wheelchair equipped with a new rear antitip device provides equivalent reductions of sitting pressures in the tilted position to a comparably tilted tilt-in-space wheelchair.

Effect of a high-rolling-resistance training method on the success rate and time required to learn the wheelchair wheelie skill: a randomized controlled trial.

OBJECTIVE: The primary objective of this study was to test the hypotheses that a wheelie training method that begins in a high-rolling-resistance (RR) setting (1) improves the success rate and (2) reduces the training time. Our secondary objectives were to assess the effects of other factors (e.g., age, gender) on training time and to acquire data on the perceptions of the participants that would assist us in refining our training methods. DESIGN: Randomized controlled study including 48 able-bodied participants with no significant wheelchair experience. Each participant was taught the wheelie skill, using up to five training sessions. Participants in the conventional group did all of their training on a smooth, level, tile surface. The RR group began training in a high-RR setting (rear wheels initially prevented from moving at all, progressing to being on 12-cm-thick foam that permitted some movement) before moving to the tile surface. Outcome measures were success rate (%), training time (mins) to achieve wheelie competence (defined as the ability to perform two consecutive 30-sec wheelies within a 1.5-m-diameter circle, assessed at least 2 days after training), and a questionnaire. RESULTS: The success rates for those in the conventional and RR groups were 96% and 100%, respectively (P = 1.000). The mean (+/-SD) training times for the conventional and RR groups were 55.9 mins (+/-27.1) and 51.8 mins (+/-18.7) (P = 0.549). Training time was not significantly affected by trainer or age, but it was affected by sex, with women requiring an average of 21.4 mins more than men (P = 0.002). Perceptions of participants in both groups about the training were positive. Of the participants in the RR group, 14 (74%) perceived the RR technique as "very effective," and five (26%) perceived it as "moderately effective." CONCLUSIONS: Neither success rate nor training time for wheelie skill acquisition by able-bodied learners are improved by a training method using high RR. Women require more time to learn than men. Learners using the RR technique perceive it to be effective. These results have implications for training practices.

Publication bias in the medical literature: a review by a Canadian Research Ethics Board.

BACKGROUND: We reviewed the publication record of all protocols submitted to the Capital District Health Authority Research Ethics Board (REB) in Halifax, Nova Scotia, for the period 1995-1996. Because of a heightened awareness of the issue, we hypothesized that there would be less publication bias (a failure to report negative results) and a higher publication rate from completed studies, than previously reported. METHODS: Closed studies were identified from the REB database. Publications were identified by the investigators, requests from sponsors, and a literature review. For each publication, we identified authors, title, journal, number of subjects enrolled, and whether or not the publication was a report of a randomized clinical trial. Comparisons were done using a Student's t test, the Chi-square statistic, or Fisher's exact test as appropriate. RESULTS: From the database of closed studies, 106 remained unpublished, while completed investigations resulted in 84 publications (44% publication rate). The median time to publication was 32.5 months. Publication of statistically significant results occurred in 71/84 trials. Publication of protocols submitted by departments ranged from 91% (anesthesia; 10/11) to 25% [nursing; 2/8 (P<0.05)]. Trials investigating new drugs in Phase 3 or 4 studies were more likely to be published than trials investigating agents in Phase 1 or 2 (P<0.05), and were less likely to be published if sponsored by a pharmaceutical company (P<0.05). CONCLUSIONS: Publication bias continues to be a problem, particularly for early phase investigative studies. Our results suggest that a different approach is required to reduce publication bias. The role that REBs and peer-reviewed journals might play requires further exploration.

Daytime sleeping, sleep disturbance, and circadian rhythms in the nursing home.

OBJECTIVE: This study reports the frequency of abnormal daytime sleeping and identifies factors related to daytime sleeping, nighttime sleep disturbance, and circadian rhythm abnormalities among nursing home residents. METHODS: The authors conducted secondary analysis of data collected under usual care conditions within a nonpharmacologic sleep intervention trial. All residents from four Los Angeles nursing homes were screened for daytime sleeping (asleep>or=15% of observations, 9:00 am-5:00 pm). Consenting residents with daytime sleeping had two nights of wrist actigraphy to assess nighttime sleep disturbance (asleep<80%, 10:00 pm-6:00 am). Residents with nighttime sleep disturbance completed an additional 72-hour wrist actigraphy recording to assess circadian activity rhythms and light exposure. RESULTS: Sixty-nine percent of 492 observed residents had daytime sleeping, of whom 60% also had disturbed nighttime sleep. Sleep disturbance and daytime sleeping were rarely documented in medical records. Residents spent one-third of the day in their rooms, typically in bed, and were seldom outdoors or exposed to bright light. More time in bed and less social activity were significant predictors of daytime sleepiness. Ninety-seven percent of residents assessed had abnormal circadian rhythms. More daytime sleeping and less nighttime sleep were associated with weaker circadian activity rhythms. Later circadian rhythm acrophase (peak) was associated with more bright light exposure. CONCLUSION: Daytime sleepiness, nighttime sleep disturbance, and abnormal circadian rhythms were common in nursing home residents. Modifiable factors (e.g., time in bed) are associated with sleep/wake abnormalities. Mental health specialists should consider the complexity of factors causing sleep problems in nursing home residents.