Personalised treatments for acute whiplash injuries: A pilot study of nested N-of-1 trials in a multiple baseline single-case experimental design.

BACKGROUND: Whiplash associated disorder (WAD), a common and disabling condition, incurs huge burden and costs to Australia. Yet, current treatments for whiplash are not very effective; improved outcomes are urgently needed. Clinical guidelines recommend simple analgesia (paracetamol and non-steroidal anti-inflammatory drugs) but there have been no trials of guideline-recommended drugs. This study will investigate the effectiveness of evidence-based advice (EBA), paracetamol, naproxen, and both paracetamol and naproxen, in reducing daily neck pain and preventing chronic neck pain after whiplash injury. METHODS: This study is a pilot series of multi-cycle, double-blinded, randomised N-of-1 trials, nested in a multiple baseline design. The design will comprise three baselines of 5, 8 or 11 days duration. Post enrolment, participants will be randomly assigned to one of the baselines. Fifteen participants with acute (<2 weeks) Grade II WAD, experiencing at least moderate pain (NRS: ≥ 5/10), and at risk of poor recovery will be recruited from hospitals in Queensland, Australia, and through local physiotherapists. Patients will receive EBA plus a randomised sequence of three cycles of ten day treatment triplets (paracetamol designated as a C phase, naproxen, designated as a D phase, and both paracetamol and naproxen, designated as an E phase). DISCUSSION: We will test the effects of different treatments on the primary outcome of average neck pain intensity collected daily and at 4 and 7 months post-injury. Secondary outcomes, including disability, depression, post-traumatic stress symptoms, pain catastrophizing, and feasibility of study procedures, will also be evaluated. The results of this study will inform a larger trial aiming to strengthen the evidence on EBA and simple analgesics for WAD. TRIAL REGISTRATION: Clinical Trials Primary Registry: Australian and New Zealand Clinical Trials Registry. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12618001291279. DATE OF REGISTRATION: 31/07/2018. PRIMARY TRIAL SPONSOR: The University of Queensland, Brisbane QLD 4072 Australia. FUNDING: The University of Queensland.

The efficacy of student-centered instruction in supporting science learning.

Transforming science learning through student-centered instruction that engages students in a variety of scientific practices is central to national science-teaching reform efforts. Our study employed a large-scale, randomized-cluster experimental design to compare the effects of student-centered and teacher-centered approaches on elementary school students' understanding of space-science concepts. Data included measures of student characteristics and learning and teacher characteristics and fidelity to the instructional approach. Results reveal that learning outcomes were higher for students enrolled in classrooms engaging in scientific practices through a student-centered approach; two moderators were identified. A statistical search for potential causal mechanisms for the observed outcomes uncovered two potential mediators: students' understanding of models and evidence and the self-efficacy of teachers.

Recognizing vocal expressions of emotion in patients with social skills deficits following traumatic brain injury.

Perception of emotion in voice is impaired following traumatic brain injury (TBI). This study examined whether an inability to concurrently process semantic information (the "what") and emotional prosody (the "how") of spoken speech contributes to impaired recognition of emotional prosody and whether impairment is ameliorated when little or no semantic information is provided. Eighteen individuals with moderate-to-severe TBI showing social skills deficits during inpatient rehabilitation were compared with 18 demographically matched controls. Participants completed two discrimination tasks using spoken sentences that varied in the amount of semantic information: that is, (1) well-formed English, (2) a nonsense language, and (3) low-pass filtered speech producing "muffled" voices. Reducing semantic processing demands did not improve perception of emotional prosody. The TBI group were significantly less accurate than controls. Impairment was greater within the TBI group when accessing semantic memory to label the emotion of sentences, compared with simply making "same/different" judgments. Findings suggest an impairment of processing emotional prosody itself rather than semantic processing demands which leads to an over-reliance on the "what" rather than the "how" in conversational remarks. Emotional recognition accuracy was significantly related to the ability to inhibit prepotent responses, consistent with neuroanatomical research suggesting similar ventrofrontal systems subserve both functions.

Measuring apathy after traumatic brain injury: Psychometric properties of the Apathy Evaluation Scale and the Frontal Systems Behavior Scale.

OBJECTIVES: To evaluate the reliability and validity of the Apathy Evaluation Scale (AES) and Apathy sub-scale of the Frontal Systems Behavior Scale (FrSBe-A) for people with traumatic brain injury (TBI). To identify an optimal cut-off score indicating presence of apathy according to the AES. METHODS AND PROCEDURES: A sample of 34 participants with severe TBI currently residing in the community underwent neuropsychological and psychosocial assessment to evaluate reliability, discriminant, convergent and divergent validity. Receiver Operating Characteristic (ROC) curve analysis was undertaken to identify an optimal cut-off score on the AES. RESULTS: AES and FrSBe-A correlated moderately with each other (r = 0.71). Both AES and FrSBe-A have good internal consistency and discriminant validity with measures of depression and fatigue. Support for hypothesized correlations with similar and dissimilar constructs was not shown. ROC analysis identified a cut-off score of 37 or higher on AES indicated presence of apathy. CONCLUSIONS: AES and FrSBe-A are reliable and valid measures of apathy following TBI. It is suggested that the two scales measure slightly differing aspects of the apathy construct, with AES addressing emotional-affective aspects of apathy more than FrSBe-A, which focuses more heavily on cognitive and behavioral elements of goal-directed behavior.

Apathy after acquired brain impairment: a systematic review of non-pharmacological interventions.

Apathy commonly occurs after acquired brain impairment. It is characterised by impaired initiative, diminished activity, and lack of concern; formally delineated as a decrease in cognitive, behavioural and emotional components of goal-directed activity. The impact is widespread, hampering rehabilitation and outcome. This systematic review identifies and assesses the efficacy of non-pharmacological treatments for apathy following four types of acquired brain impairment (traumatic brain injury, dementia, cerebrovascular accident, encephalitis). Nine databases were searched. Studies were reviewed according to the following criteria: age over 16 years, acquired brain impairment, non-pharmacological intervention for apathy, and data reported on treatment efficacy. The methodological quality of the studies was assessed. Searches yielded 1754 articles, with 28 meeting criteria. Methodological quality ranged greatly. The majority of trials involved the dementia population. Cognitive interventions were the most frequent mode of treatment. For those with severe impairments, the strongest evidence suggested music therapy and for milder impairment, the strongest evidence was for cognitive rehabilitation. This review reveals a need for more high quality, methodologically rigorous treatment studies for apathy, particularly within the milder ranges of impairment. Initially, however, a uniform operational definition needs to be utilised in all research studies to minimise variability. Additionally, employing a standardised outcome measure specific to apathy would greatly enhance comparison among treatments.

A multicentre, randomised trial examining the effect of test procedures measuring emergence from post-traumatic amnesia.

BACKGROUND: Post-traumatic amnesia (PTA) tests that record different PTA durations in the same patient, thereby raising measurement accuracy issues, have been reported previously. A major problem lies in determining the end point of PTA. AIMS: To delineate areas of discrepancy in PTA tests and to provide independent verification for a criterion signalling emergence from PTA. METHODS: In a randomised design, two related PTA procedures were compared, one purportedly more difficult (Westmead PTA Scale, WPTAS) than the other (Modified Oxford PTA Scale, MOPTAS). Eighty two patients in the early stages of PTA were examined daily until emergence, by using the Galveston Orientation and Amnesia Test (GOAT) and the WPTAS/MOPTAS. A short battery of cognitive and behavioural measurements was made on three occasions: at the early stage of PTA (time 1), towards the end of PTA when the maximum score (12/12) was first obtained (time 2) and at the traditional criterion for emergence (scoring 12/12 for 3 consecutive days; time 3). RESULTS: No significant difference was recorded in PTA duration between the MOPTAS and WPTAS. Both scales recorded longer PTA durations than the GOAT. By using Kaplan-Meier survival analyses, the WPTAS was found to show a more protracted pattern of emergence at the end stage of PTA than the MOPTAS. A time lag of > or = 1 week in the resolution of disorientation as compared with amnesia was observed in 59% cases. Significant improvements occurred on all independent measurements between time 1 and time 2, but on only 2 of 5 cognitive measurements between time 2 and time 3. CONCLUSIONS: Although no significant differences in the duration of PTA on the MOPTAS/WPTAS were recorded, emergence from the late stages of PTA occurred more promptly with the MOPTAS. The need for inclusion of both orientation and memory items in PTA tests is highlighted by the frequency of disorientation-amnesia dissociations. The patterns of results on the independent measures suggest that patients who are in PTA for > 4 weeks have probably emerged from PTA when they first score 12/12 on the MOPTAS/WPTAS, and this criterion can replace the traditional criterion.

Adjustment to chronic obstructive pulmonary disease: the importance of psychological factors.

Research has indicated a weak relationship between the degree of physical problems and quality of life in patients with chronic obstructive pulmonary disease (COPD). The importance of adaptive psychological functioning to maintain optimum quality of life has long been recognized, but there is a lack of empirical evidence concerning the nature of psychological factors involved in adjustment to COPD. Ninety-two males completed questionnaires to determine their coping strategies, levels of self-efficacy of symptom management and social support. Adjustment was measured in terms of depression, anxiety and quality of life. Symptom severity, socioeconomic status, duration of disease and age, which have been demonstrated to be of consequence in COPD, were used as control variables in hierarchical multiple regression analyses. Higher levels of catastrophic withdrawal coping strategies and lower levels of self-efficacy of symptom management were associated with higher levels of depression, anxiety and a reduced quality of life. Higher levels of positive social support were linked to lower levels of depression and anxiety, while higher levels of negative social support were linked to higher levels of depression and anxiety. To maximize quality of life in patients with chronic obstructive pulmonary disease, psychological factors need to be carefully assessed and addressed.

Predicting duration of posttraumatic amnesia (PTA) from early PTA measurements.

OBJECTIVES: To determine a set of variables that would reliably predict duration of posttraumatic amnesia (PTA) in patients with traumatic brain injury and to test the efficacy of the model. DESIGN: Simultaneous standard multiple regression analyses. PARTICIPANTS: Two independent samples of patients with traumatic brain injury who were in the early stages of PTA: a test sample (n = 61) and a cross-validation sample (n = 25). MAIN OUTCOME MEASURE: The Modified Oxford PTA Scale (MOPTAS) is a 12-item test measuring orientation (8 items) and anterograde memory (4 items). The Galveston Orientation and Amnesia Test (GOAT) was also used on a subset of the test sample. PROCEDURE: Patients were examined daily until they emerged from PTA. RESULTS: A statistically significant model, using three predictor variables, was derived that reliably predicted duration of PTA, accounting for 89% of the variance. A second model, using two predictor variables readily available to the clinician (day posttrauma on which PTA testing began and aggregate PTA scores over the first 5 days of testing) had comparable predictive accuracy. A third model, using GOAT data, was also statistically significant and successfully accounted for 72% of the variance. The MOPTAS model showed excellent application to an independent (validation) sample, with an intraclass correlation coefficient between observed and predicted durations of PTA of 0.95. Regression equations for all three models are provided to enable calculation of the predicted duration of PTA. CONCLUSIONS: These models can be readily applied in clinical practice and will provide clinically useful estimates of the duration of PTA within the first week of testing after admission to rehabilitation. This information will be important in terms of family counseling and planning of rehabilitation programs.

Resolution of disorientation and amnesia during post-traumatic amnesia.

OBJECTIVES: Despite the growing number of instruments for the prospective measurement of post-traumatic amnesia (PTA) after traumatic brain injury, fundamental issues about the natural history of its resolution and methods of examination remain unresolved. The aims of the present study were to: (1) examine the sequence of resolution of disorientation and amnesia, and (2) determine if the method of measuring the memory component affected the duration of PTA. METHODS: The sample comprised 31 severely injured patients admitted to a brain injury rehabilitation unit who were examined daily until they emerged from PTA. They were administered a composite PTA scale, covering orientation and memory items from standard PTA scales. Patients were consecutively allocated to one of two groups according to the method of measuring the memory component. Each group was administered identical materials with a different procedure. RESULTS: The most common sequence for resolution of disorientation in both groups was person, followed by place, then time. Overall, amnesia resolved before disorientation in 94% of cases. Correlation coefficients between return of components of orientation and memory were all highly significant, ranging from r=0. 81 to 0.93. Significant variability occurred in the number of days to emerge from PTA according to the scale used. There was evidence that the method of measuring memory influenced the patient's capacity to consistently sustain criterion scores on the scale. CONCLUSIONS: These results are contrary to findings in mildly injured patients, in whom orientation usually returns before memory. They also demonstrate that the duration of PTA will be dictated by the method used. These findings raise validity issues with respect to the prospective measurement of PTA, and in particular determining when an individual patient has emerged from PTA, which require further investigation.

Psychosocial adjustment after traumatic brain injury: what are the important variables?

BACKGROUND: The common legacy of severe degrees of traumatic brain injury is varying degrees and types of impairments, which impact significantly upon the individual's resumption of pre-morbid psychosocial roles. Yet there are few data to indicate the relative contribution of these and other non-injury related variables. METHODS: Seventy individuals with varying levels of disability after severe traumatic brain injury were examined neurologically and neuropsychologically, on average at 6 years post-trauma. A range of biographical, injury, impairment and psychological variables were examined with multiple regression analyses to identify those that contributed to successful psychosocial reintegration. RESULTS: Severity of injury and impairments, along with chronicity and level of self-esteem were significant predictors of psychosocial adjustment. Further analyses revealed that within the neuropsychological domain, the variable measuring behavioural regulation of abilities was the most significant. Examination of specific domains of psychosocial functioning (occupational activities, interpersonal relationships and independent living skills) revealed different patterns of significant predictor variables, in addition to indices of the severity of initial injury: neurophysical impairments and memory functioning predicted successful occupational activities; chronicity, cognitive speed and behavioural regulation predicted success in interpersonal relationships; and neurophysical impairments, behavioural regulation and memory functioning predicted independent living skills. CONCLUSIONS: These results reinforce the overriding importance of injury severity and neurological factors (both neurophysical as well as neuropsychological) in predicting psychosocial adjustment after traumatic brain injury. Support for the contribution of non-neurological factors was also found.

Executive dysfunction and characterological changes after traumatic brain injury: two sides of the same coin?

This study examined the capacity of neuropsychological variables indicative of dysfunction in the regulation of executive abilities (e.g. noncompliance with rules) to reflect changes in character associated with disturbances in regulatory abilities (e.g. impulsivity). A close relative of 30 participants with traumatic brain injury (TBI) was administered the Current Behaviour Scale (CBS) at admission (rating premorbid character) and six months posttrauma (rating current character). The TBI group was examined neuropsychologically at six months posttrauma, along with 30 nonbrain-damaged (NBD) participants. Significant increases in CBS factors, Loss of Emotional Control and Loss of Motivation, occurred in the TBI group posttrauma. Differences between TBI and NBD groups were found for most executive variables. Those TBI participants with impairments on the neuropsychological Rule Breaking variable showed significant posttrauma increases in Loss of Emotional Control. There was also a trend for individuals with frontal lesions to make rule-breaking and perseverative errors.

Incidence of hospital-treated traumatic brain injury in an Australian community.

This paper reports findings from an incidence study of head trauma in a defined population. In the North Coast Health Region of NSW, 1,259 subjects with head trauma were admitted to hospitals in a 12-month period in 1988. Direct examination of the medical records confirmed brain injury in only 413 of these cases, corresponding to an annual incidence of approximately 100/100,000 resident population. Although most injuries (62.2%) were mild, 38% were serious (either moderate, 20.3%, or severe, 13.6%; and 3.9% died after admission to hospital). Severe brain injury represented an annual incidence of 12/100,000 resident population. Road traffic accidents accounted for a higher proportion of injuries in the severe group in comparison with the other injury groups. Methodological issues involved in case ascertainment of brain injury are discussed.

Beyond one-bun, two-shoe: recent advances in the psychological rehabilitation of memory disorders after acquired brain injury.

Memory disorders are one of the most frequent types of cognitive impairment encountered in neurological populations. The more severe degrees of such impairment case major disability and handicap, and have a profound impact on a person's capacity to engage in independent living. To date, commonly used remediation strategies range from drills and practice, including computer-based tasks, to mnemonic techniques and memory notebooks. In general, these therapies have met with varying degrees of success. The last decade has seen exciting developments in remediation techniques for memory disorders, a number of which are based on implicit learning skills, as well as programmes tailored to an individual's unique pattern of deficits. The present paper provides an overview of this literature and discusses issues relating to their application in rehabilitation programmes.

Error types in ideomotor apraxia: a qualitative analysis.

Seventeen brain-damaged subjects with dominant hemisphere pathology and 24 matched control subjects were asked to perform simple familiar gestures under four conditions: (1) verbal command (pantomime), (2) imitation, (3) with the actual object, and (4) verbal command a second time. The subjects subsequently watched a video of an actor performing simple movements and decided whether or not these were performed accurately. The gestural production task was videoed and analyzed for error type. Error type remained consistent over the four task conditions, although subgroups of patients made different types of errors. One group of patients with Ideomotor Apraxia (IMA) made more errors but of the same type as the controls, i.e., movement-related errors and the use of "body part as object" (BPO). The second group made mainly substituted (i.e. unrelated) movements and perseverative errors. The second group of subjects was also poorer at discriminating incorrectly performed movements in the recognition task. BPO errors were commonly made by the control group and they were also chosen as correct in the recognition task. This indicated that use of BPO may reflect a convention in symbolising gestures rather than pathology. The performance of the IMA subjects was discussed in relation to current theories of the mechanisms underlying apraxia.

Analyzing individual status and change with hierarchical linear models: illustration with depression in college students.

A recently developed class of multilevel or hierarchical linear models (HLM) provides an intuitive and efficient way to estimate individual growth or change curves. The approach also models the between-subjects variation of the individual change curves with treatment factors and individual attributes. Unlike other repeated measures analysis methods common in the behavioral sciences, HLM allows the fit of data with unequal numbers of repeated observations for each subject, variable timing of observations, and missing data, features which are often characteristic of data from field studies. The application of HLM for the analysis of repeated psychological measures is discussed and illustrated here with depression data for college students. Strengths and limitations of the approach are discussed.

Patterns of neuropsychological impairment after severe blunt head injury.

A consecutive series of 100 subjects with severe blunt head injuries was followed up 6 years after trauma. Neuropsychological test performances of 82 subjects and of a noninjured control group were analyzed by two principal components analyses (PCAs). Each PCA extracted 15 factors relating to a range of cognitive impairments, as well as neuropsychological features consistent with posttraumatic personality changes. Measures identified by the PCAs were applied to 85 head-injured subjects in the series to examine the incidence of impairment in four neuropsychological areas: disorders of learning and memory, neuropsychological features consistent with posttraumatic personality change, slowness in rate of information processing, and a range of basic neuropsychological skills. Overall, impairments occurred in 70% of the series. Disorders of learning and memory were the most common type of deficit (56.5%), with disturbances in basic neuropsychological skills the least frequent (16.5%). Variability among subjects with respect to the types and combinations of neuropsychological impairments was a characteristic feature of this clinical group, but the largest proportion (one-third) demonstrated isolated impairments. The implications of the incidence and selectivity of neuropsychological impairments are discussed.

Sodium cholate-induced changes in the conformation and activity of rat pancreatic cholesterol esterase.

Pancreatic cholesterol esterase (CEase) regulates dietary cholesterol absorption and is activated in the presence of trihydroxy bile salts while remaining inactive monohydroxy bile salts. CEase from rat pancreas has been purified by ammonium sulfate precipitation, hydroxylapatite chromatography, and gel filtration on Sephacryl S-200/S-300 columns connected in series, and its homogeneity and Mr (55,418 +/- 288) have been determined by sedimentation equilibrium centrifugation. The effects of tri-, di-, and monohydroxy bile salts on the conformation of the purified enzyme in buffer solution and in an in vitro assay system were studied by circular dichroism spectropolarimetry. The CD spectrum of the enzyme in solution shows a curve shape suggestive of an alpha-helicity, but low mean residue ellipticity (MRE) values may indicate an important beta-turn contribution. Sodium cholate, a trihydroxy bile salt, induces a decrease in the negative MRE values of the enzyme in solution at bile salt concentrations of 70-100 nM, with no further spectral changes at concentrations as high as 1 mM. Sodium cholate concentrations higher than 1 microM also induce an increase in the enzyme's negative MRE values under activity assay conditions, which reverts toward its original value once the reaction reaches equilibrium. These latter changes are interpreted as induced by substrate binding to the enzyme followed by partial substrate depletion after the reaction reaches equilibrium. Sodium deoxycholate, a dihydroxy bile salt, induces unstable transient increases and decreases in the MRE values of CEase in buffer solution and under activity assay conditions. These changes are bile salt concentration-dependent and may reflect self-association of the protein. Sodium taurolithocholate, a monohydroxy bile salt, does not affect the CD spectrum of CEase, and neither the di- or the monohydroxy bile salt activates the enzyme.

Psychosocial outcome for the survivors of severe blunt head injury: the results from a consecutive series of 100 patients.

A consecutive series of 100 severely blunt head injured subjects was followed up six years after trauma and the level of psychosocial reintegration was determined for 87 subjects. Three-quarters of the series were classified as demonstrating major disability, having either a Poor Reintegration (33%) or a Substantially Limited Reintegration (43%); the remaining one-quarter of the series attained a Good Reintegration. The level of reintegration was related to the Glasgow Outcome Scale classification, although a one-to-one correspondence between the Glasgow Outcome Scale and the Psychosocial Disability Scale was not found: each of the Moderate Disability and Good Recovery groups was fairly evenly divided between a better and worse level of reintegration. Specific aspects of the subjects' psychosocial reintegration in employment, interpersonal relationships, functional independence, social contacts and leisure interests are described and the implications of the findings for the provision of extended care services to meet the long term needs are discussed.

DNA restriction patterns and DNA-DNA solution hybridization studies of Frankia isolates from Myrica pennsylvanica (bayberry).

Sixteen Frankia strains were isolated from Myrica pennsylvanica (bayberry) root nodules collected at diverse sites in New Jersey. Restriction pattern analysis of total genomic DNA was used to group the isolates into gel groups, and the genetic relatedness among the isolates was evaluated by DNA-DNA solution hybridization studies. Restriction pattern analysis provided a distinctive reproducible fingerprint for each isolate. Isolates fell into nine separate groups (strain types). More than one strain type was isolated from most sites. Isolates from two different gel groups were found in 3 of 10 nodules examined. Of the 16 isolates, 10 contained extrachromosomal DNA. Six different extrachromosomal DNA banding patterns were found. Genomically similar isolates carried related, but different, banding patterns. DNA hybridization studies indicated that isolates from a single plant species can be minimally related as determined by total genome homology. Homology ranged from 12 to 99%. Highly divergent strains were isolated from the same plant and found to cohabit the same nodule. Thus, this study demonstrated that Frankia strains which infect the same host plant are not only phenotypically different but also genetically diverse.

Physiological, chemical, morphological, and plant infectivity characteristics of Frankia isolates from Myrica pennsylvanica: correlation to DNA restriction patterns.

The filter exclusion method was used to isolate Frankia strains from Myrica pennsylvanica (bayberry) root nodules collected at diverse sites in New Jersey. A total of 16 isolates from five locations were cultured. The isolates were characterized by morphological, chemical, physiological, and plant infectivity criteria and compared with genomic DNA restriction pattern data, which were used to assign the isolates into gel groups (see accompanying paper). The isolates from M. pennsylvanica evaluated in this study were characteristic of Frankia physiological group B strains and were indistinguishable on the basis of whole-cell wall chemistry and diaminopimelic acid isomer analysis. Distinct differences in the spectrum of utilized organic acids and carbohydrates were observed among the isolates and were the only phenotypic criteria by which the isolates could be separated and assigned into separate groups. In general, isolates within a restriction pattern gel group had identical utilization patterns, whereas intragroup isolates had different utilization patterns. Correlation of these phenotypic characteristics with the results of molecular analysis revealed an exclusive carbohydrate and organic acid utilization pattern for each gel group as established by restriction pattern analysis.