Austin Lee

Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis

Objective To investigate whether angiotensin receptor blockers protect against Alzheimer’s disease and dementia or reduce the progression of both diseases. Design Prospective cohort analysis. Setting Administrative database of the US Veteran Affairs, 2002-6. Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease. Main outcome measures Time to incident Alzheimer’s disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the “cardiovascular comparator”) over a four year period (fiscal years 2003-6) using Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer’s disease or dementia. Results Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 (95% confidence interval 0.69 to 0.84) compared with the cardiovascular comparator and 0.81 (0.73 to 0.90) compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer’s disease were associated with a significantly lower risk of admission to a nursing home (0.51, 0.36 to 0.72) and death (0.83, 0.71 to 0.97). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54, 0.51 to 0.57) and admission to a nursing home (0.33, 0.22 to 0.49). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer’s disease. Conclusions Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer’s disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population.

The development, validation, and testing of a health outcomes burn questionnaire for infants and children 5 years of age and younger: American Burn Association/Shriners Hospitals for Children.

The 12-member American Burn Association/Shriners Hospitals for Children Outcomes Task Force was charged with developing a health outcomes questionnaire for use in children 5 years of age and younger that was clinically based and valid. A 55-item form was tested using a cross-sectional design on the basis of a range of 184 infants and children between 0 and 5 years of age at 8 burn centers, nationally. A total of 131 subjects completed a follow-up health outcomes questionnaire 6 months after the baseline assessment. A comparison group of 285 normal nonburn children was also obtained. Internal consistency reliability of the scales ranged from 0.74 to 0.94. Tests of clinical validity were significant in the hypothesized direction for the majority of scales for length of hospital stay, duration since the burn, percent of body surface area burned, overall clinician assessment of severity of burn injury, and number of comorbidities. The criterion validity of the instrument was supported using the Child Developmental Inventories for Burn Children in early childhood and preschool stages of development comparing normal vs abnormal children. The instrument was sensitive to changes over time following a clinical course observed by physicians in practice. The Health Outcomes Burn Questionnaire for Infants and Children 5 years of age and younger is a clinically based reliable and valid assessment tool that is sensitive to change over time for assessing burn outcomes in this age group.

Benchmarks for multidimensional recovery after burn injury in young adults: The development, validation, and testing of the american burn association/shriners hospitals for children young adult burn outcome questionnaire

Although data exist on burn survival, there are little data on long-term burn recovery. Patient-centered health outcomes are useful in monitoring and predicting recovery and evaluating treatments. An outcome questionnaire for young adult burn survivors was developed and tested. This 5-year (2003–2008) prospective, controlled, multicenter study included burned and nonburned adults ages 19 to 30 years. The Young Adult Burn Outcome Questionnaires were completed at initial contact, 10 days, and 6 and 12 months. Factor analysis established construct validity. Reliability assessments used Cronbach &agr; and test-retest. Recovery patterns were investigated using generalized linear models, with generalized estimating equations using mixed models and random effects. Burned (n = 153) and nonburned subjects (n = 112) completed 620 questionnaires (47 items). Time from injury to first questionnaire administration was 157 ± 36 days (mean ± SEM). Factor analysis included 15 factors: Physical Function, Fine Motor Function, Pain, Itch, Social Function Limited by Physical Function, Perceived Appearance, Social Function Limited by Appearance, Sexual Function, Emotion, Family Function, Family Concern, Satisfaction With Symptom Relief, Satisfaction With Role, Work Reintegration, and Religion. Cronbach &agr; ranged from 0.72 to 0.92, with 11 scales >0.8. Test-retest reliability ranged from 0.29 to 0.94, suggesting changes in underlying health status after burns. Recovery curves in five domains, Itch, Perceived Appearance, Social Function Limited by Appearance, Family Concern, and Satisfaction with Symptom Relief, remained below the reference group at 24 months. The Young Adult Burn Outcome Questionnaire is a reliable and valid instrument for multidimensional functional outcomes assessment. Recovery in some domains was incomplete.

Long-term posttraumatic stress symptoms vary inversely with early opiate dosing in children recovering from serious burns: effects durable at 4 years.

BACKGROUND Children surviving serious burns are at risk for developing posttraumatic stress disorder (PTSD) as a function both of the injury and of its treatment. Short-term studies in such children have demonstrated reduced PTSD symptoms with intensive early pain control. However, the long-term impact of early pain control strategies on posttraumatic stress symptoms in children recovering from serious burn injuries has not been examined. METHODS This was a retrospective review of a multiple time point data collection involving a cohort of 147 infants, children, and teenagers with 4 years of follow-up after serious burns conducted at 4 pediatric burn centers to examine the impact of early opiate dosing on long-term posttraumatic stress symptoms. The main outcome measure was the nine-item Short Form Child Stress Disorders Checklist, which is an established and validated assessment. The impact of total opiate dosing during the first 7 days on these scores was assessed. RESULTS Subjects had an average age of 11 years and average injury size of 22% total body surface area burned (%TBS). The correlation between opiate units (OUs) and %TBS was 0.46 at baseline, OU increasing with increasing %TBS. OUs were strongly predictive of Child Stress Disorders Checklist scores up to 4 years, with higher OU (10 units vs. 6 and 2 units) remaining constantly different up to 4 years in predicting lower stress scores for both smaller and larger burns. CONCLUSION Early opiate management of pain associated with acute burn wounds and burn treatment predicts the development and resolution rate of PTSD symptoms in a large multicenter sample of children hospitalized for serious burns. The effect seems to be dose related and durable at least up to 4 years in a range of burn sizes. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level II.

Off‐label use of second generation antipsychotics for post‐traumatic stress disorder in the Department of Veterans Affairs: time trends and sociodemographic, comorbidity, and regional correlates

Second generation antipsychotics (SGAs) are widely used for post‐traumatic stress disorder (PTSD), although without strong evidence base. With substantial numbers of veterans returning from Iraq/Afghanistan conflicts with PTSD, it is important to characterize the extent of SGA use and identify associated factors.

The American Burn Association/Shriners Hospitals for Children Burn Outcomes Program: a progress report at 15 years.

Abstract The American Burn Association and the Shriners Hospitals for Children Outcomes Program has been in development for more than 15 years. Many of the tools and important findings are described in this special issue of The Journal of Trauma. This unique program in outcomes research introduces a model for outcome assessments from the patient-centered perspective with a cohort of 1,140 children with burn injury after hospitalization for up to 4 years. The findings represent a fundamental contribution to the field of burn care for monitoring outcomes from the perspective of the parent or child/adolescent. The Multi-Center Benchmarking Study of four burn centers serve as a model for collecting empiric scientific data on the variation and the expected trajectories of recovery in the most important domains of patient outcomes and can inform clinical decisions and the conduct of health service research. The dramatic progress in survival of children with severe burn injury and other advances in burn management can now move into a new phase of understanding the most cost-effective components of this care.

Recovery trajectories after burn injury in young adults: Does burn size matter?

The impact of burn size on mortality is well known, but the association of burn size with the trajectories of long-term functional outcomes remains poorly studied. This prospective multi-center study included burned adults ages 19 to 30 years who completed the Young Adult Burn Outcome Questionnaire at initial baseline contact, 2 weeks, and at 6 and 12 months after initial questionnaire administration. Non-burned adults of comparable ages also completed the questionnaire as a reference group. The association between functional recovery and TBSA burned was analyzed longitudinally using generalized linear models with the generalized estimation equation technique. Functional status was characterized in 15 domains: physical function, fine motor function, pain, itch, social function limited by physical function, perceived appearance, social function limited by appearance, sexual function, emotion, family function, family concern, satisfaction with symptom relief, satisfaction with role, work reintegration, and religion. Scores were standardized to a mean of 50 and a SD of 10 based on non-burned controls. There were 153 burned and 112 non-burned subjects with a total of 620 questionnaires. TBSA burned was 11 ± 14% (mean ± SD); 31% had face involvement and 57% had hand involvement. The lag time from burn injury to questionnaire administration was on average 7 ± 7.7 months, with a maximum of 36 months. Lower recovery levels were associated with increasing burn size for physical function, pain, itch, work reintegration, emotion, satisfaction with symptom relief, satisfaction with role, family function, and family concern (P value ranged from .04–<.0001). No significant differences in recovery levels were found with increasing burn size for fine motor function, social function limited by physical function, sexual function, and religion; these areas tracked toward the age-matched non-burned group regardless of burn size. Perceived appearance and social function limited by appearance remained below the non-burn levels throughout the 3-year period regardless of burn size. Three-year recovery trajectories of survivors with larger burn size showed improvements in most areas, but these improvements lagged behind those with smaller burns. Poor perceived appearance was persistent and prevalent regardless of burn size and was found to limit social function in these young adult burn survivors. Expectations for multidimensional recovery from burns in young adults can be benchmarked based on burn size with important implications for patient monitoring and intervening in clinical care.

Recovery curves for pediatric burn survivors advances in patient-oriented outcomes

IMPORTANCE Patient-reported outcomes serving as benchmarks for recovery of pediatric burn survivors are lacking, and new approaches using longitudinal cohorts for monitoring their expected recovery based on statistical models are needed for patient management during the early years following the burn. OBJECTIVE To describe multidimensional patient-reported outcomes among pediatric burn survivors younger than 5 years to establish benchmarks using recovery curve methods. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of pediatric burn survivors younger than 5 years at 12 burn centers. Age-matched nonburned reference groups were studied to define expected results in normal growth and development. The Burn Outcomes Questionnaire for children aged 0 to 5 years (BOQ0-5) was administered to parents of children who had burns and were younger than 5 years. Mixed models were used to generate 48-month recovery curves for each of the 10 BOQ0-5 domains. The study was conducted between January 1999 and December 2008. MAIN OUTCOMES AND MEASURES The 10 BOQ0-5 domains including play, language, fine motor skills, gross motor skills, emotional behavior, family functioning, pain/itching, appearance, satisfaction with care, and worry/concern up to 48 months after burn injury. RESULTS A total of 336 pediatric burn survivors younger than 5 years (mean [SD] age, 2.0 [1.2] years; 58.4% male; 60.2% white, 18.6% black, and 12.0% Hispanic) and 285 age-matched nonburned controls (mean [SD] age, 2.4 [1.3] years; 51.1% male; 67.1% white, 8.9% black, and 15.0% Hispanic) completed the study. Predicted scores improved exponentially over time for 5 of the BOQ0-5 domains (predicted scores at 1 month vs 24 months: play, 48.6 vs 52.1 [P = .03]; language, 49.2 vs 54.4 [P < .001]; gross motor skills, 48.7 vs 53.0 [P = .002]; pain/itching, 15.8 vs 33.5 [P < .001]; and worry/concern, 31.6 vs 44.9 [P < .001]). Pediatric burn survivors had higher scores in language, emotional behavior, and family functioning domains compared with healthy children in later months. CONCLUSIONS AND RELEVANCE This study demonstrates significant deficits in multiple functional domains across pediatric burn survivors compared with controls. Recovery curves can be used to recognize deviation from the expected course and tailor care to patient needs.

Effects of diagnostic inclusion criteria on prevalence and population characteristics in database research

OBJECTIVES Studies of serious mental illnesses that use administrative databases have employed various criteria to establish diagnoses of interest. Several studies have assessed the validity of diagnostic inclusion criteria against research diagnoses. However, no studies have examined the effect of diagnostic inclusion criteria on prevalence and population characteristics across such groups. METHODS Administrative data for 2003-2010 from the Department of Veterans Affairs were used to calculate prevalence rates and assess effects of varying the diagnostic inclusion criteria on population composition for bipolar disorder, schizophrenia, and posttraumatic stress disorder (PTSD). Specifically, for each diagnosis, mutually exclusive subpopulations were compared on the basis of the following inclusion criteria for a given diagnosis: one treatment encounter, two outpatient encounters or one inpatient encounter, and any two encounters. For bipolar disorder and schizophrenia, effects of excluding individuals who had a competing diagnosis of, respectively, schizophrenia or bipolar disorder in the prior 12 months and since 2002 were also determined. RESULTS In 2010, moving from the broadest definitions of bipolar disorder (N=120,382), schizophrenia (N=91,977), and PTSD (N=554,028) to the most restrictive definitions reduced prevalence rates by, respectively, 28.7%, 34.9%, and 25.7%, with temporal trends for 2003-2010 paralleling results in 2010. Population composition changes with changing diagnostic inclusion criteria were variable, with predominantly small odds ratios. CONCLUSIONS Population composition was relatively robust across common diagnostic inclusion criteria for each condition. Thus choice of criteria can focus on considerations of diagnostic validity and case-finding needs. Three mechanisms for the impact of diagnostic criteria on population composition in administrative data sets are discussed.

The Ascendancy of Second-Generation Antipsychotics as Frontline Antimanic Agents.

IntroductionKnowledge of the factors affecting the adoption of new medications can enhance mental health care and guide quality improvement and policy development. Food and Drug Administration indications for treating bipolar disorder with several second-generation antipsychotics (SGAs) in the 2000s represent an opportunity to identify factors that impact the spread of a then-innovative treatment through a new population. MethodsAnalysis of Department of Veterans Affairs administrative data identified the population of 170,811 veterans diagnosed with bipolar disorder from 2003 to 2010. We analyzed time trends and predictors of antimanic choice (SGA vs other) among the 40,512 outpatients with bipolar disorder who initiated their first VA outpatient antimanic prescription, using multinomial logistic regression in month-by-month analyses. We conducted classwise analyses and investigated prespecified predictors among specific agents. ResultsIn classwise analyses, SGAs supplanted lithium, valproate, and carbamazepine/oxcarbazepine as the most commonly initiated antimanics by 2007. Psychosis, but not other indices of severity, predicted SGA initiation. Demographic analyses did not identify substantial disparities in initiation of SGAs. Drug-specific analyses revealed some consideration of medical comorbidities in choosing among specific antimanic agents, although effect sizes were small. Most patients initiating an antimanic had received an antidepressant in the previous year. DiscussionSecond-generation antipsychotics quickly became the frontline antimanic treatment for bipolar disorder, although antidepressants most commonly predated antimanic prescriptions. Second-generation antipsychotics were used for a broad range of patients rather than being restricted to a severely ill subpopulation. The modest association of antimanic choice with relevant medical comorbidities suggests that continued attention to quality prescribing practices is warranted.