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.

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.

Measuring psychological adjustment to HIV infection.

AIMS: A modified version of the Mental Adjustment to Cancer Scale (The Mental Adjustment to HIV Scale--MAHIVS) was used to evaluate patterns of psychological adjustment in response to HIV infection. METHODS: A sample of 164 HIV positive homosexual/bisexual men were recruited across three Australian centers (79 asymptomatic (CDC II/III) and 85 symptomatic HIV infection (CDC IV)). Factor analysis of the MAHIVS was conducted and the predictive validity of the MAHIVS was investigated using the General Health Questionnaire, while The Diagnostic Interview Schedule was used to assess current and lifetime psychiatric disorder. Other measures of adjustment/coping were used to investigate the construct validity of the MAHIVS (neuroticism, locus of control, defense style). RESULTS: Factor analysis of the MAHIVS detected four factors: Hopelessness, Fighting Spirit/Self Efficacy, Personal Control, and Minimization. Hopelessness and Fighting Spirit factors exhibited acceptable levels of internal consistency and validity, with significant correlations detected with psychological symptoms and significant association with other measures of psychological adjustment and personality. Fighting Spirit emerged as a potential indicator of psychological resilience, whereas Hopelessness was significantly associated with psychological symptoms and current major depression (but not past depression). CONCLUSIONS: The findings indicate the validity of the MAHIVS and support the presence of common themes in the psychological adaptation to life-threatening illness that can be detected across disease categories and groups.

Posttraumatic stress disorder in response to HIV infection.

This study investigated the psychological impact of HIV infection through assessment of posttraumatic stress disorder in response to HIV infection. Sixty-one HIV-positive homosexual/bisexual men were assessed for posttraumatic stress disorder in response to HIV infection (PTSD-HIV) using a modified PTSD module of the DIS-III-R. Thirty percent met criteria for a syndrome of posttraumatic stress disorder in response to HIV diagnosis (PTSD-HIV). In over one-third of the PTSD cases, the disorder had an onset greater than 6 months after initial HIV infection diagnosis. PTSD-HIV was associated with other psychiatric diagnoses, particularly the development of first episodes of major depression after HIV infection diagnosis. PTSD-HIV was significantly associated with a pre-HIV history of PTSD from other causes, and other pre-HIV psychiatric disorders and neuroticism scores, indicating a similarity with findings in studies of PTSD from other causes. The findings from this preliminary study suggest that a PTSD response to HIV diagnosis has clinical validity and requires further investigation in this population and other medically ill groups. The results support the inclusion of the diagnosis of life-threatening illness as a traumatic incident that may lead to a posttraumatic stress disorder, which is consistent with the DSM-IV criteria.

Suicidal ideation, suicide attempts, and HIV infection.

A cross-sectional study was performed to investigate the prevalence and predictors of suicidal ideation and past suicide attempt in an Australian sample of human immunodeficiency virus (HIV)-positive and HIV-negative homosexual and bisexual men. Sixty-five HIV-negative and 164 HIV-positive men participated. A suicidal ideation score was derived from using five items selected from the Beck Depression Inventory and the General Health Questionnaire (28-item version). Lifetime and current prevalence rates of psychiatric disorder were evaluated with the Diagnostic Interview Schedule Version-III-R. The HIV-positive (Centers for Disease Control and Prevention [CDC] Stage IV) men (n = 85) had significantly higher total suicidal ideation scores than the asymptomatic HIV-positive men (CDC Stage II/III) (n = 79) and the HIV-negative men. High rates of past suicide attempt were detected in the HIV-negative (29%) and HIV-positive men (21%). Factors associated with suicidal ideation included being HIV-positive, the presence of current psychiatric disorder, higher neuroticism scores, external locus of control, and current unemployment. In the HIV-positive group analyzed separately, higher suicidal ideation was discriminated by the adjustment to HIV diagnosis (greater hopelessness and lower fighting spirit), disease factors (greater number of current acquired immunodeficiency syndrome [AIDS]-related conditions), and background variables (neuroticism). Significant predictors of a past attempted suicide were a positive lifetime history of psychiatric disorder (particularly depression diagnoses), a lifetime history of infection drug use, and a family history of suicide attempts. The findings indicate increased levels of suicidal ideation in symptomatic HIV-positive men and highlight the role that multiple psychosocial factors associated with suicidal ideation and attempted suicide play in this population.

Psychiatric disorder in HIV infection.

OBJECTIVE: This study aimed to investigate rates of psychiatric disorder in human immunodeficiency virus (HIV) infection, in an Australian sample of homosexual and bisexual men. METHOD: A cross-sectional study of a total of 65 HIV sero-negative (HIV-) and 164 HIV sero-positive men (HIV+) (79 CDC stage II/III and 85 CDC stage IV) was conducted in three centres. Lifetime and current prevalence rates of psychiatric disorder were evaluated using the Diagnostic Interview Schedule Version IIIR (DIS-IIIR). RESULTS: Elevated current and lifetime rates of major depression were detected in both HIV negative and HIV positive homosexual/bisexual men. Lifetime rates of alcohol abuse/dependence were significantly elevated in HIV positive men (CDC group IV) when compared with HIV negative men. Among the HIV positive group the majority of psychiatric disorders detected were preceded by a pre-HIV diagnosis of psychiatric disorder. Major depression represented the disorder most likely to have first onset after HIV infection diagnosis. CONCLUSIONS: Lifetime rates of major depression were elevated in this sample of HIV-negative and HIV-positive men. In the HIV-positive men, psychiatric disorder was significantly associated with the presence of lifetime psychiatric disorder prior to HIV infection diagnosis. The findings indicate the importance of evaluation of psychiatric history prior to HIV infection and the clinical significance of depressive syndromes in this population.

Clinical Markers of the Presence of Dementia and Neuropsychological Impairment in HIV Infection.

OBJECTIVE: To identify clinical, laboratory and demographic markers which are associated with the presence of dementia and neuropsychological impairment in severely immunodeficient patients. METHOD: Fifty-nine HIV+ patients participated in the study. Patients were assessed neurologically and neuropsychologically, and a subset of patients underwent lumbar punctures. Logistic regression was used to determine which variables from a set including age, education, IQ, depression, anxiety, CD4 cell counts, haemoglobin, serum and CSF â2 microglobulin and neopterin, constitutional symptoms, past opportunistic infections and use of antiretroviral therapy was associated with the occurrence of dementia and neuropsychological impairment. RESULTS: An increased likelihood of neurological and neuropsychological dysfunction was associated with diarrhoea at some time in the recent past, elevated serum neopterin at the time of assessment, and increased age. A decreased likelihood of impairment was associated with a higher estimated IQ, more years of education, and the presence of an AIDS-defining illness at the time of assessment. CONCLUSION: Recent diarrhoea, elevated serum neopterin, advanced age and low education and IQ can serve as ''signals'' for the presence of neurological and neuropsychological dysfunction.

Neuropsychological function in asymptomatic HIV-1 infection: methodological issues.

There have been conflicting reports as to whether significant neuropsychological deterioration occurs in asymptomatic HIV-1 infection. Comparisons among studies have been hindered by substantial variations in sample size, statistical methods, definitions of neuropsychological abnormality, and attention to potential confounding factors. In this study, the neuropsychological performance of 44 subjects with asymptomatic HIV-1 infection and 41 seronegative (SN) controls was compared using analysis of variance models. Rates of abnormality were also determined using commonly employed impairment criteria. The seropositive (SP) subjects performed comparably to SN controls once differences in full scale IQ were taken into account. Rates of abnormality for HIV-1 SP subjects were estimated at 10%, 17.5%, and 67.5% by three different criteria, and were not significantly different from the rates of the control group. The findings indicated that both premorbid characteristics, and the validity and biases of definitions of impairment should be examined and incorporated into the interpretation of study findings.

Anxiety, depression and HIV related symptomatology across the spectrum of HIV disease.

Levels of anxiety and depression were assessed for 207 HIV seropositive homosexual/bisexual men (AIDS = 34, ARC = 72, asymptomatic HIV infection = 101), and 36 seronegative controls. Lymphocyte subset enumeration, history of opportunistic infections, and occurrence of HIV-related symptoms were recorded at the time of assessment. No differences between groups were found on age, educational level, state/trait anxiety or depression scores. Neither the number of symptoms reported, their duration, severity, frequency of occurrence, nor the proportion of patients who reported a specific symptom was different between the three HIV seropositive groups. Severity of anxiety and depression was related to the magnitude of symptomatology, but not associated with either degree of immunodeficiency, number of opportunistic infections or diagnostic group. Principal component analysis extracted five symptom factors (cognitive, affective, psychosocial, neurological and physical), none of which predicted state anxiety scores. However, affective and psychosocial symptom factors predicted trait anxiety and depression scores. The results indicate that ratings of anxiety and depression are independent of stage of HIV infection, may be in part mediated by constitutional and physical symptoms of HIV disease, but are primarily associated with the presence of psychological and psychosocial symptoms.

Changes in neuropsychological performance of AIDS-related complex patients who progress to AIDS.

OBJECTIVE: To investigate the changes in neuropsychological performance associated with progression from AIDS-related complex (ARC) to AIDS. DESIGN: A repeated measures design was used to compare three groups: ARC patients who progressed to AIDS (n = 15), those who did not (n = 19) and seronegative controls (n = 16). METHODS: The three groups were compared on tests of memory, information processing, motor performance, attention and conceptual flexibility. Clinical and immunological characteristics were recorded. Rates of neuropsychological impairment among the three groups were calculated and compared. RESULTS: The only significant difference between the groups at baseline was for one measure of motor performance. Repeated measures analysis indicated that there was a differential rate of change for the three subject groups for tasks of motor performance and attention. ARC patients who progressed to AIDS did not differ significantly from the non-progressors, although both groups showed significant deterioration over time compared with seronegative controls. Although there was a tendency for the progressors to have a higher rate of impairment, there were no consistent significant differences between visits. CONCLUSION: There were no significant changes in performance exclusively associated with progression to AIDS.

Neuropsychological investigation of patients with AIDS and ARC.

A group of 34 homosexual men with acquired immune deficiency syndrome (AIDS) spectrum disorders were assessed for cognitive impairment on a range of neuropsychological tests. There were 17 patients with AIDS, and 17 with AIDS-related complex (ARC). Although none of the patients showed signs of the severe dementing syndrome that has been described in persons with HIV infection, they demonstrated signs of cognitive impairment consistent with organic brain dysfunction. The profile of deficits shown by AIDS and ARC patients could be broadly grouped into disorders of recent and delayed memory and learning, generalized cognitive slowing, and reduced mental flexibility. Considerations of the clinical and neuropathological similarities between subcortical dementing syndromes and HIV-related cognitive impairment suggest that in both processes the pathogenesis of the observed deficits may involve disruption of frontodiencephalic projections.

[High-resolution eye movement recording in the assessment of neurologic complications in HIV-1 infection]. / Hochauflösende Augenmotilitätsmessungen bei der Untersuchung neurologischer Komplikationen der HIV-1-Infektion.

HIV-1 related brain disease gives rise to widespread eye movement abnormalities that include impairment of fixation, saccadic speed and accuracy, antisaccadic generation and smooth pursuit function. Quantitative high resolution recording of eye movements is a valuable, non-invasive technique both for measuring the severity and progression of the AIDS dementia complex and the early detection of neurologic dysfunction in asymptomatic HIV-seropositive subjects or in patients with AIDS. In particular, it may be of use in neurologically at-risk patients requiring antiviral therapy and in monitoring the neurologic responses to such treatment.

The neurological features of early and 'latent' human immunodeficiency virus infection.

Neurological manifestations of unknown cause occurring in patients who become or are HIV antibody positive with presumed normal immune function have been described recently. This report adds a further six cases, all of whom had normal CD4+ cell counts either throughout the period of observation or after the episode of seroconversion. Three had an acute presentation, two in the context of documented seroconversion consisting of one of the following: an encephalitis, an ataxia, and confusion with neuralgic amyotrophy. Three had a subacute disorder occurring at a later phase of HIV infection but before opportunistic infections or neoplasms, and marked by a static mild cognitive deficit. This report extends the range of abnormalities that may be seen at seroconversion and documents the presence of a non-progressive cognitive deficit occurring in the latent phase of HIV infection.

Simple and choice reaction time in patients with human immunodeficiency virus infection.

The performance of 56 homosexual men infected with human immunodeficiency virus (HIV) was compared to that of 23 HIV antibody-seronegative controls on simple (SRT) and choice (CRT) reaction time tasks. Patients were classified into 3 groups according to Centers for Disease Control clinical criteria. There were 18 patients who had acquired immunodeficiency syndrome (AIDS), 18 who had AIDS-related complex (ARC), and 20 who were HIV antibody-seropositive but otherwise asymptomatic (HIV-Ab+). The SRT task consisted of 5 trials, each containing 10 target stimuli. The CRT task consisted of 10 trials, each containing 5 target stimuli randomly interspersed with 5 nontarget stimuli. The mean response latency of each of the patient groups on the SRT task was not significantly different from that of controls. However, the performance of patients with AIDS or ARC on the CRT task was significantly lower than that of controls, whereas that of HIV-Ab+ patients was not. Analysis of the quality of RT task performance also indicated that the impairment of processing efficiency at higher levels of task difficulty reflected a disruption of processing prior to the response selection stage.

The prevalence of the Wernicke-Korsakoff syndrome in Sydney, Australia: a prospective necropsy study.

In a prospective necropsy study, the prevalence of the Wernicke-Korsakoff syndrome (WKS) in Sydney, Australia was 2.1% of adults over the age of 15 years. The population studied encompassed a wide spectrum of socio-economic and cultural backgrounds. Abuse of alcohol appeared to be the major predisposing factor to the development of the WKS in cases which were adequately documented. This high prevalence rate is in line with other clinical and pathological Australian studies and provides additional support for the idea of prevention of the WKS by the use of thiamin supplements in the Australian diet in flour, bread and perhaps alcoholic beverages.

Eye movement abnormalities as a predictor of the acquired immunodeficiency syndrome dementia complex.

Using infrared oculography, we recorded the eye movements in a group of patients with acquired immunodeficiency syndrome (AIDS), with or without the AIDS dementia complex (ADC). Our aim was to determine whether the severity of dementia could be correlated with abnormalities of eye movement and whether eye movement abnormalities could be detected prior to the onset of clinical dementia. Abnormalities of eye movement were present in seven of seven patients with mild, moderate, or severe ADC and in six of seven AIDS or asymptomatic human immunodeficiency virus-seropositive patients without clinical dementia, but at risk for ADC. The eye movement abnormalities detected included disturbances of both saccadic and smooth-pursuit function, and their severity correlated strongly with the severity of dementia. The abnormalities were qualitatively similar to those that occur in Alzheimer's disease but quantitatively less severe. Recording of eye movements may be a valuable, noninvasive technique for the early detection of neurologic dysfunction in asymptomatic patients who are seropositive for human immunodeficiency virus or in patients with AIDS, even prior to other clinical evidence of ADC. In particular, it may be of use in selecting high-risk patients requiring antiviral therapy and in monitoring the neurologic response to such treatment.