Postmarketing Analysis of Misuse, Abuse, and Diversion of Xtampza ER.

OBJECTIVE: To evaluate abuse, misuse, and diversion of Xtampza ER, an extended-release (ER) abuse-deterrent formulation (ADF) of oxycodone. METHODS: Abuse, misuse, and diversion of Xtampza ER were assessed using Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System data sources. Xtampza ER was compared with immediate-release (IR) oxycodone, other ADF ER products combined, and non-ADF ER products combined. RESULTS: Xtampza ER prescriptions increased 50-fold during the study period. In contrast, cases from poison centers, substance abuse treatment centers, and diversion were infrequent and did not increase. Adjusted for prescriptions dispensed, poison center exposures were greater for IR oxycodone (rate ratio [RR] = 2.3, P = 0.008), other ADF ER opioids (RR = 5.2, P < 0.001), and non-ADF ER opioids (RR = 2.5, P = 0.004) than for Xtampza ER. In Treatment Center Programs Combined, past-month abuse prevalence for other ADF ER opioids (odds ratio [OR] = 7.4, P < 0.001) and non-ADF ER opioids (OR = 2.0, P = 0.002) was greater than Xtampza ER; IR oxycodone was not significantly different (OR = 1.2, P = 0.349). In the Drug Diversion Program, rates for IR oxycodone (RR = 3.7, P = 0.003), other ADF ER opioids (RR = 4.2, P = 0.002), and non-ADF ER opioids (RR = 3.4, P = 0.007) were greater than Xtampza ER. Adjustment using morphine equivalents provided similar results, except that IR oxycodone in Treatment Center Programs Combined became higher than Xtampza ER. Nonoral abuse cases involving Xtampza ER were infrequent; Web monitoring data support findings that Xtampza ER is difficult to abuse nonorally. CONCLUSION: Xtampza ER abuse, misuse, and diversion and tampering are low relative to other prescription opioid analgesics. Abuse and diversion did not increase over the study period.

Mortality after surviving traumatic brain injury: risks based on age groups.

OBJECTIVE: To assess mortality, life expectancy, risk factors, and causes of death by age groups among persons who received inpatient traumatic brain injury (TBI) rehabilitation. DESIGN: Prospective cohort study. SETTING: The TBI Model Systems. PARTICIPANTS: 8573 individuals injured between 1988 and 2009, with survival status per December 31, 2009, determined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Standardized mortality ratio, life expectancy, and cause of death. RESULTS: Moderate-severe TBI increases risk of mortality compared with the general population in all age groups, with the exception of those 85 years or older at the time of injury. Teenagers to middle-aged adults are at particular risk. Risk factors for death varied by age group and included gender, marital and employment status, year and cause of injury, and level of disability. External causes of death predominate in younger groups. For the youngest male participants in the sample, longevity was reduced up to 16 years. CONCLUSION: Risk factors and causes of death varied considerably by age group for individuals with moderate-severe TBI who were receiving acute care rehabilitation. Moderate-severe TBI is a chronic health condition.

Life expectancy following rehabilitation: a NIDRR Traumatic Brain Injury Model Systems study.

OBJECTIVE: To characterize overall and cause-specific mortality and life expectancy among persons who have completed inpatient traumatic brain injury rehabilitation and to assess risk factors for mortality. DESIGN: Prospective cohort study. SETTING: The Traumatic Brain Injury Model Systems. PARTICIPANTS: A total of 8573 individuals injured between 1988 and 2009, with survival status per December 31, 2009, determined. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Standardized mortality ratio (SMR), life expectancy, cause of death. RESULTS: SMR was 2.25 overall and was significantly elevated for all age groups, both sexes, all race/ethnic groups (except Native Americans), and all injury severity groups. SMR decreased as survival time increased but remained elevated even after 10 years postinjury. SMR was elevated for all cause-of-death categories but especially so for seizures, aspiration pneumonia, sepsis, accidental poisonings, and falls. Life expectancy was shortened an average of 6.7 years. Multivariate Cox regression showed age at injury, sex, race/ethnic group, marital status and employment status at the time of injury year of injury, preinjury drug use, days unconscious, functional independence and disability on rehabilitation discharge, and comorbid spinal cord injury to be independent risk factors for death. CONCLUSION: There is an increased risk of death after moderate or severe traumatic brain injury. Risk factors and causes of death have been identified that may be amenable to intervention.

Relationship of patient characteristics and rehabilitation services to outcomes following spinal cord injury: the SCIRehab project.

BACKGROUND/OBJECTIVE: To examine associations of patient characteristics along with treatment quantity delivered by seven clinical disciplines during inpatient spinal cord injury (SCI) rehabilitation with outcomes at rehabilitation discharge and 1-year post-injury. METHODS: Six inpatient SCI rehabilitation centers enrolled 1376 patients during the 5-year SCIRehab study. Clinicians delivering standard care documented details of treatment. Outcome data were derived from SCI Model Systems Form I and II and a project-specific interview conducted at approximately 1-year post-injury. Regression modeling was used to predict outcomes; models were cross-validated by examining relative shrinkage of the original model R(2) using 75% of the dataset to the R(2) for the same outcome using a validation subsample. RESULTS: Patient characteristics are strong predictors of outcome; treatment duration adds slightly more predictive power. More time in physical therapy was associated positively with motor Functional Independence Measure at discharge and the 1-year anniversary, CHART Physical Independence, Social Integration, and Mobility dimensions, and smaller likelihood of rehospitalization after discharge and reporting of pressure ulcer at the interview. More time in therapeutic recreation also had multiple similar positive associations. Time spent in other disciplines had fewer and mixed relationships. Seven models validated well, two validated moderately well, and four validated poorly. CONCLUSION: Patient characteristics explain a large proportion of variation in multiple outcomes after inpatient rehabilitation. The total amount of treatment received during rehabilitation from each of seven disciplines explains little additional variance. Reasons for this and the phenomenon that sometimes more hours of service predict poorer outcome, need additional study. Note: This is the first of nine articles in the SCIRehab series.

Relationship of physical therapy inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: the SCIRehab project.

BACKGROUND/OBJECTIVE: Examine associations of type and quantity of physical therapy (PT) interventions delivered during inpatient spinal cord injury (SCI) rehabilitation and patient characteristics with outcomes at the time of discharge and at 1 year post-injury. METHODS: Physical therapists delivering routine care documented details of PT interventions provided. Regression modeling was used to predict outcomes at discharge and 1 year post-injury for a 75% subset; models were validated with the remaining 25%. Injury subgroups also were examined: motor complete low tetraplegia, motor complete paraplegia, and American Spinal Injury Association (ASIA) Impairment Scale (AIS) D motor incomplete tetra-/paraplegia. RESULTS: PT treatment variables explain more variation in three functionally homogeneous subgroups than in the total sample. Among patients with motor complete low tetraplegia, higher scores for the transfer component of the discharge motor Functional Independence Measure () are strongly associated with more time spent working on manual wheelchair skills. Being male is the most predictive variable for the motor FIM score at discharge for patients with motor complete paraplegia. Admission ASIA lower extremity motor score (LEMS) and change in LEMS were the factors most predictive for having the primary locomotion mode of "walk" or "both (walk and wheelchair)" on the discharge motor FIM for patients with AIS D injuries. CONCLUSION: Injury classification influences type and quantity of PT interventions during inpatient SCI rehabilitation and is a strong predictor of outcomes at discharge and 1 year post-injury. The impact of PT treatment increases when patient groupings become more homogeneous and outcomes become specific to the groupings. Note: This is the second of nine articles in the SCIRehab series.

Relationship of occupational therapy inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: the SCIRehab project.

BACKGROUND/OBJECTIVE: Describe associations of occupational therapy (OT) interventions delivered during inpatient spinal cord injury (SCI) rehabilitation and patient characteristics with outcomes at the time of discharge and 1-year post-injury. METHODS: Occupational therapists at six inpatient rehabilitation centers documented detailed information about treatment provided. Least squares regression modeling was used to predict outcomes at discharge and 1-year injury anniversary for a 75% subset; models were validated with the remaining 25%. Functional outcomes for injury subgroups (motor complete low tetraplegia and motor complete paraplegia) also were examined. RESULTS: OT treatment variables explain a small amount of variation in Functional Independence Measure (FIM) outcomes for the full sample and significantly more in two functionally homogeneous subgroups. For patients with motor complete paraplegia, more time spent in clothing management and hygiene related to toileting was a strong predictor of higher scores on the lower body items of the self-care component of the discharge motor FIM. Among patients with motor complete low tetraplegia, higher scores for the FIM lower body self-care items were associated with more time spent on lower body dressing, manual wheelchair mobility training, and bathing training. Active patient participation during OT treatment sessions also was predictive of FIM and other outcomes. CONCLUSION: OT treatments add to explained variance (in addition to patient characteristics) for multiple outcomes. The impact of OT treatment on functional outcomes is more evident when examining more homogeneous patient groupings and outcomes specific to the groupings. Note: This is the third of nine articles in the SCIRehab series.

Relationship of therapeutic recreation inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: the SCIRehab project.

OBJECTIVE: To investigate associations of therapeutic recreation (TR) interventions during inpatient rehabilitation for patients with traumatic spinal cord injury (SCI) with functional, participation, and quality of life outcomes. METHODS: In this prospective observational study, data were obtained from systematic recording of TR services by certified TR specialists, chart review, and patient interview. RESULTS: TR interventions, including exposure to community settings and leisure activities, add to the variance explained (in addition to the strong predictors of injury classification, admission motor Functional Independence Measure (FIM), and other patient characteristics) in outcomes at the time of rehabilitation discharge (FIM, discharge to home) and at the 1-year injury anniversary (FIM, working or being in school, residing at home, and societal participation as measured by the Craig Handicap Assessment and Reporting Technique (CHART)). They also are associated with less rehospitalization and less pressure development after discharge. In addition, more time spent in specific TR activities during rehabilitation is associated with more participation in the same type of activities at the 1-year injury anniversary. CONCLUSION(S): Greater participation in TR-led leisure skill and community activities during rehabilitation is a positive predictor of multiple outcomes at rehabilitation discharge and the 1-year injury anniversary demonstrating that TR activities are associated with a return to a productive and healthy life after SCI. Further research should focus on the impact of TR on longer-term outcomes to determine whether relationships continue or change as persons continue to adapt to their life after SCI. Note: This is the fourth of nine articles in the SCIRehab series.

Relationship of speech-language pathology inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: the SCIRehab project.

BACKGROUND/OBJECTIVE: Describe associations of patient characteristics and speech-language pathology (SLP) interventions provided during impatient rehabilitation for spinal cord injury (SCI) to outcomes at discharge and 1-year post-injury. METHODS: Speech-language pathologists at six inpatient rehabilitation centers documented details of treatment provided. Least squares regression modeling was used to predict outcomes at discharge and 1-year injury anniversary. Cognitive, participation, and mood outcomes for a subsample of patients with traumatic brain injury (TBI) and cognitive-communication limitations (CCLs) were examined. RESULTS: SLP treatment factors explain a small amount of variation in cognitive Functional Independence Measure (FIM), participation, and mood. Variation explained by treatment factors for cognitive outcomes at the time of discharge increased when the patient group was more homogeneous (patients with TBI and CCLs). More time in SLP cognitive-communication interventions had a negative relationship, while longer length of stay was positive. The added explanatory power was not seen for similar outcomes at 1-year post-injury. CONCLUSION: Patients with SCI who have the greatest need for interventions to address cognitive limitations due to TBI receive the most SLP cognitive-communication treatment and show the greatest amount of improvement during rehabilitation. Their cognitive functioning remained impaired at discharge; this likely accounts for the consistent finding that more hours of SLP cognitive-communication treatment is associated with lower cognitive FIM scores at discharge. Future research on individuals with dual SCI and TBI should include more comprehensive assessment of individual differences in cognitive performance in order to better examine the complex relationships between SLP treatments and outcomes. Note: This is the fifth of nine articles in this SCIRehab series.

Relationship of psychology inpatient rehabilitation services and patient characteristics to outcomes following spinal cord injury: the SCIRehab project.

CONTEXT AND OBJECTIVE: To evaluate the effects of psychological interventions on rehabilitation outcomes, including residence and functional status at discharge, and residence, school attendance, or employment, and physical, social, occupational, and mobility aspects of participation 1 year after spinal cord injury (SCI). DESIGN: Prospective observational cohort study. SETTING: Six inpatient rehabilitation facilities in the United States. PARTICIPANTS: Inpatients with SCI 12 years of age and older. INTERVENTIONS: Usual rehabilitation care. OUTCOME MEASURES: Functional Independence Measure at rehabilitation discharge and 1-year injury anniversary; discharge destination and residence at 1-year anniversary; Craig Handicap Assessment and Reporting Technique, Diener Satisfaction with Life Scale, Patient Health Questionnaire, employment or school attendance, rehospitalization, and occurrence of a pressure ulcer at 1-year anniversary. RESULTS: More time in psycho-educational interventions was associated with better function, discharge to home, home residence at 1 year, and the absence of pressure ulcers at 1 year. More psychotherapeutic sessions focusing on processing emotions and/or locus of control were associated with poorer function at discharge and 1 year, less physical independence and community mobility, lower satisfaction with life, and the presence of pressure sores at 1 year. CONCLUSIONS: Psychological services are an important component of comprehensive medical rehabilitation and tailored to patient needs and readiness to benefit from rehabilitation. Services focused on remediating deficits tend to be associated with negative outcomes, while services intended to foster adjustment and growth tend to be associated with favorable outcomes. Further research is needed to determine the optimal type and timing of psychological services during inpatient rehabilitation based on individuals' strengths and vulnerabilities. Note: This is the sixth in this third series of SCIRehab articles.

Outcomes of social work and case management services during inpatient spinal cord injury rehabilitation: the SCIRehab project.

OBJECTIVE: To investigate associations of social work/case management (SW/CM) services during inpatient rehabilitation following spinal cord injury (SCI) and patient characteristics with outcomes. DESIGN: Prospective observational cohort of individuals with SCI receiving inpatient rehabilitation. SETTING: Six inpatient rehabilitation centers. PARTICIPANTS: 1032 individuals with traumatic SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): Type of residence at the time of rehabilitation discharge. Employment/school status, presence of a pressure ulcer, Patient History Questionnaire, Satisfaction with Life Scale, Craig Handicap Assessment and Reporting Technique (CHART) subscales, and rehospitalization at 1-year post-injury. RESULTS: The intensity of specific SW/CM services is associated with multiple outcomes examined. More sessions dedicated to discharge planning for a home discharge and financial planning were associated positively with more discharge to home, while more sessions focused on planning for discharge to a location other than home, e.g. nursing home or long-term acute care facilities, have negative associations with societal participation outcomes (CHART Social Integration, Occupation, and Mobility scores) as well as with residing at home at the time of the 1-year injury anniversary. CONCLUSION(S): The intensity and type of SW/CM services are associated with outcomes at rehabilitation discharge and at 1-year post-injury. Discharge to home may require assistance from SW/CM in the area of discharge planning and financial planning, while discharge to non-home residence demands directed SW/CM services for such placement. Note: This is the eighth of nine articles of this SCIRehab series.

Relationship of nursing education and care management inpatient rehabilitation interventions and patient characteristics to outcomes following spinal cord injury: the SCIRehab project.

OBJECTIVE: To investigate associations of nursing bedside education and care management activities during inpatient rehabilitation with functional, participation, and quality-of-life outcomes for patients with traumatic spinal cord injury (SCI). METHODS: In a prospective observational study, data were obtained by means of systematic recording of nursing activities by registered nurses (RNs), chart review and patient interview. RESULTS: Greater patient participation in nursing activities is associated with better outcomes. More time spent by RNs in coordination with other members of the care team, consultants and specialists, along with participation in physician rounds (team process) is associated with patient report of higher life satisfaction and higher CHART mobility at the one-year injury anniversary; more time providing psychosocial support is associated with higher CHART mobility and occupation scores and with greater likelihood of working or being in school at the anniversary. More time spent providing education about specific care needs is associated with several outcomes but not as consistently as might be expected. CONCLUSION(S): Higher levels of patient participation in nursing care activities is associated with multiple better outcomes, and hence, nurses should promote active patient participation during all aspects of care and interactions between themselves and patients with SCI. Time spent providing psychosocial support of patients and their families should be evaluated to ensure that other necessary education or care management interventions are not minimized. Note: This is the seventh of nine articles in the SCIRehab series.

Demonstration of the presence of cyclic inositol phosphohydrolase in human urine.

Cyclic inositol phosphohydrolase (cIPH), cleaves the cyclic bond of cyclic inositol monophosphate (cIP) to yield inositol monophosphate. In this communication, we demonstrate the presence of cIPH in human urine. cIPH was measured in the 24-h urine samples of both male and female hospital patients. cIPH released per day ranged from 0 to 243 units in men (n = 16) and from 15 to 346 units in women (n = 18). Release of cIPH activity was not related to renal function as measured by creatinine clearance. HPLC ion-exchange chromatography or HPLC gel filtration of ammonium sulfate precipitate yielded a distinct cIPH peak with an apparent molecular weight of 40 kDa on gel filtration. This is the first demonstration of the presence of this enzyme in human urine. The large variation (over 20-fold) in the excretion of this protein suggests that it may have physiological and/or pathological significance.

High salt lysates: a simple method to store blood samples without refrigeration for subsequent use with DNA probes.

Blood specimens to be tested for the presence of Plasmodium falciparum using specific DNA probes can be stored as high salt lysates (HSL) without refrigeration. The lysates are prepared from 100 microliter blood samples by a simple 3-step procedure using 2 volumes of H2O to lyse the erythrocytes (step I), 1 volume of a detergent/EDTA mix to lyse the parasites (step II), followed by the addition of 1 volume cesium trifluoroacetate (CsTFA) (step III). The parasite DNA was found to be undegraded, as shown by the unaltered pattern of repetitive sequences obtained after storage of up to 1 month at 37 degrees C, due to the inhibition of DNA degrading enzymes by the cesium salt. The bulk of protein can be removed from the samples by a 1-step precipitation. The addition of 0.3 volumes of a mixture of ethanol: chloroform: isoamyl alcohol (2.5:1:0.04 v/v) precipitates greater than 90% of the proteins from the lysates, leaving greater than 86% of the parasite DNA in the supernatant. The reduced protein content of the samples, when applied to solid supports, results in an increased signal: background ratio on autoradiograms.

Detection of Plasmodium falciparum DNA using repetitive DNA clones as species specific probes.

Repetitive sequences were identified in genomic libraries of Plasmodium falciparum and analyzed for their potential use as specific DNA probes. Nucleotide sequencing revealed inserts composed of 21 base pair tandem repeats. Clone 26 containing an insert of 147 base pairs in M13mp18 was used in three different approaches as a probe to detect P. falciparum DNA: the replicative form of clone 26 was labeled by nick translation; the single strand DNA of clone 26 was labeled by primer extension and a two step sandwich assay was employed hybridizing single strand unlabeled clone 26 DNA to the target DNA (first step) and using nick translated M13 DNA in a second step to detect the vector part of clone 26. The most sensitive probes detected 25 pg of P. falciparum DNA after 2 h of film exposure, 3 pg after 14 h and 0.78 pg after 40 h. Hybridization to genomic blots of Plasmodium vivax and human DNA using clone 26 as a probe revealed that the 21 base pair repeats specifically hybridized with P. falciparum DNA while failing to react with either human or P. vivax DNA.