Can We Miniaturize CT Technology for a Successful Mobile Stroke Unit Roll-Out?

Mortality from stroke remains high in Australia, especially for patients located outside the metropolitan cities. This is because they have limited access to specialized stroke facilities for optimal stroke treatment. Mobile stroke units have the capability to take CT scanners out to the patient however current CT commercial scanner designs are large and heavy. As such, this paper aims to design and develop a lightweight CT scanner for use in a mobile stroke unit (either road-based or air-based ambulance) to bring healthcare solution to patients in the rural and remote areas. We used the engineering design optimization approach to redesign and reduce the weight of the existing CT scanner with without compromised it structural performance. We managed to reduce the weight the CT scanner by three-fold while reducing design costs by allowing numerous simulations to be performed using computer software to achieve our design goals. The results are not only useful to optimize CT scanner structure to retrofit on a mobile stroke unit, but also bring the medical device solution to the market and support scalable solution to the larger community. Such an advance will allow for improved equity in healthcare whereby patients can be treated irrespective of location.

Extinction and survival in two-species annihilation.

We study diffusion-controlled two-species annihilation with a finite number of particles. In this stochastic process, particles move diffusively, and when two particles of opposite type come into contact, the two annihilate. We focus on the behavior in three spatial dimensions and for initial conditions where particles are confined to a compact domain. Generally, one species outnumbers the other, and we find that the difference between the number of majority and minority species, which is a conserved quantity, controls the behavior. When the number difference exceeds a critical value, the minority becomes extinct and a finite number of majority particles survive, while below this critical difference, a finite number of particles of both species survive. The critical difference Δ_{c} grows algebraically with the total initial number of particles N, and when N≫1, the critical difference scales as Δ_{c}∼N^{1/3}. Furthermore, when the initial concentrations of the two species are equal, the average number of surviving majority and minority particles, M_{+} and M_{-}, exhibit two distinct scaling behaviors, M_{+}∼N^{1/2} and M_{-}∼N^{1/6}. In contrast, when the initial populations are equal, these two quantities are comparable M_{+}∼M_{-}∼N^{1/3}.

FBXO10 deficiency and BTK activation upregulate BCL2 expression in mantle cell lymphoma.

Targeting Bruton tyrosine kinase (BTK) by ibrutinib is an effective treatment for patients with relapsed/refractory mantle cell lymphoma (MCL). However, both primary and acquired resistance to ibrutinib have developed in a significant number of these patients. A combinatory strategy targeting multiple oncogenic pathways is critical to enhance the efficacy of ibrutinib. Here, we focus on the BCL2 anti-apoptotic pathway. In a tissue microarray of 62 MCL samples, BCL2 expression positively correlated with BTK expression. Increased levels of BCL2 were shown to be due to a defect in protein degradation because of no or little expression of the E3 ubiquitin ligase FBXO10, as well as transcriptional upregulation through BTK-mediated canonical nuclear factor-κB activation. RNA-seq analysis confirmed that a set of anti-apoptotic genes (for example, BCL2, BCL-XL and DAD1) was downregulated by BTK short hairpin RNA. The downregulated genes also included those that are critical for B-cell growth and proliferation, such as BCL6, MYC, PIK3CA and BAFF-R. Targeting BCL2 by the specific inhibitor ABT-199 synergized with ibrutinib in inhibiting growth of both ibrutinib-sensitive and -resistant cancer cells in vitro and in vivo. These results suggest co-targeting of BTK and BCL2 as a new therapeutic strategy in MCL, especially for patients with primary resistance to ibrutinib.

Transport of ice into the stratosphere and the humidification of the stratosphere over the 21st century.

Climate models predict that tropical lower-stratospheric humidity will increase as the climate warms. We examine this trend in two state-of-the-art chemistry-climate models. Under high greenhouse gas emissions scenarios, the stratospheric entry value of water vapor increases by ~1 part per million by volume (ppmv) over this century in both models. We show with trajectory runs driven by model meteorological fields that the warming tropical tropopause layer (TTL) explains 50-80% of this increase. The remainder is a consequence of trends in evaporation of ice convectively lofted into the TTL and lower stratosphere. Our results further show that, within the models we examined, ice lofting is primarily important on long time scales - on interannual time scales, TTL temperature variations explain most of the variations in lower stratospheric humidity. Assessing the ability of models to realistically represent ice-lofting processes should be a high priority in the modeling community.

ICARUSS, the Integrated Care for the Reduction of Secondary Stroke trial: rationale and design of a randomized controlled trial of a multimodal intervention to prevent recurrent stroke in patients with a recent cerebrovascular event, ACTRN = 12611000264987.

BACKGROUND: The majority of strokes, both ischaemic and haemorrhagic, are attributable to a relatively small number of risk factors which are readily manageable in primary care setting. Implementation of best-practice recommendations for risk factor management is calculated to reduce stroke recurrence by around 80%. However, risk factor management in stroke survivors has generally been poor at primary care level. A model of care that supports long-term effective risk factor management is needed. AIM: To determine whether the model of Integrated Care for the Reduction of Recurrent Stroke (ICARUSS) will, through promotion of implementation of best-practice recommendations for risk factor management reduce the combined incidence of stroke, myocardial infarction and vascular death in patients with recent stroke or transient ischaemic attack (TIA) of the brain or eye. DESIGN: A prospective, Australian, multicentre, randomized controlled trial. SETTING: Academic stroke units in Melbourne, Perth and the John Hunter Hospital, New South Wales. SUBJECTS: 1000 stroke survivors recruited as from March 2007 with a recent (<3 months) stroke (ischaemic or haemorrhagic) or a TIA (brain or eye). RANDOMIZATION: Randomization and data collection are performed by means of a central computer generated telephone system (IVRS). INTERVENTION: Exposure to the ICARUSS model of integrated care or usual care. PRIMARY OUTCOME: The composite of stroke, MI or death from any vascular cause, whichever occurs first. SECONDARY OUTCOMES: Risk factor management in the community, depression, quality of life, disability and dementia. STATISTICAL POWER: With 1000 patients followed up for a median of one-year, with a recurrence rate of 7-10% per year in patients exposed to usual care, the study will have at least 80% power to detect a significant reduction in primary end-points CONCLUSION: The ICARUSS study aims to recruit and follow up patients between 2007 and 2013 and demonstrate the effectiveness of exposure to the ICARUSS model in stroke survivors to reduce recurrent stroke or vascular events and promote the implementation of best practice risk factor management at primary care level.

Names of infamy: tainted eponyms.

The use of eponyms is controversial. A distinction must be made between those doctors and scientists after whom disorders and syndromes are named in honour of their discoveries, and those whose discoveries were made as a result of maltreatment of defenceless prisoners, utilizing specimens from victims of Nazi extermination policies, and euthanasia victims of racial policies. The second group of scientists should have their names expunged from the historical record, and their deeds brought to the attention of their colleagues. We are not however advocating the abolition of eponyms in general, only tainted ones.

Self-reported and accelerometer-measured physical activity by body mass index in US Hispanic/Latino adults: HCHS/SOL.

The association between obesity and physical activity has not been widely examined in an ethnically diverse sample of Hispanic/Latino adults in the US. A cross-sectional analysis of 16,094 Hispanic/Latino adults 18-74 years was conducted from the multi-site Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Body mass index (BMI) was measured and categorized into normal, overweight, and obese; underweight participants were excluded from analyses. Physical activity was measured using the 16-item Global Physical Activity Questionnaire and by an Actical accelerometer. Minutes/day of physical activity and prevalence of engaging in ≥ 150 moderate-vigorous physical activity (MVPA) minutes/week were estimated by BMI group and sex adjusting for covariates. No adjusted differences were observed in self-reported moderate (MPA), vigorous (VPA), or MVPA across BMI groups. Accelerometry-measured MPA, VPA, and MVPA were significantly higher for the normal weight (females: 18.9, 3.8, 22.6 min/day; males: 28.2, 6.1, 34.3 min/day, respectively) compared to the obese group (females: 15.3, 1.5, 16.8 min/day; males: 23.5, 3.6, 27.1 min/day, respectively). The prevalence of engaging in ≥ 150 MVPA minutes/week using accelerometers was lower compared to the self-reported measures. Efforts are needed to reach the Hispanic/Latino population to increase opportunities for an active lifestyle that could reduce obesity in this population at high risk for metabolic disorders.

Salvage of the PWI/DWI mismatch up to 48 h from stroke onset leads to favorable clinical outcome.

BACKGROUND AND PURPOSE: In acute ischemic stroke perfusion/diffusion-weighted image, mismatch using magnetic resonance imaging approximates the ischemic penumbra. For early time windows, mismatch salvage improves clinical outcomes, but uncertainty exists at later time epochs. We hypothesized that (a) mismatch may exist up to 48 h; (b) the proportion of mismatch salvage is time independent; and (c) when salvaged, it improves clinical outcomes. METHODS: Magnetic resonance imaging was performed within 48 h of ischemic stroke. Perfusion-weighted image was defined by relative Tmax two-second delay. Perfusion/diffusion-weighted image mismatch was the perfusion-weighted image not overlapped by the diffusion-weighted image when coregistered. Infarct volume and disability (modified Rankin Score) were assessed at three-months. Mismatch salvage was the region not overlapped by final infarction. Favorable outcome was defined as modified Rankin Score 0-1. RESULTS: Sixty-six patients were studied [mean age 69.9 years (standard deviation 13.1), initial median National Institute of Health Stroke Scale 9.0 (interquartile range 6.0, 18.3)]. There was no relationship between time of stroke onset and the proportion of mismatch salvaged (P = 0.73). Age (adjusted odds ratio = 0.92, 95% confidence interval 0.86-0.98, P = 0.01), initial National Institute of Health Stroke Scale (adjusted odds ratio = 0.80, 95% confidence interval 0.70-0.92, P < 0.01), mismatch volume (adjusted odds ratio = 0.98, 95% confidence interval 0.968-0.1, P = 0.05), and percentage of mismatch salvage (adjusted odds ratio = 1.04, 95% confidence interval 0.99-1.07, P = 0.05) were independently associated with favorable outcome. CONCLUSION: Using coregistered perfusion/diffusion-weighted image criteria, mismatch persists up to 48 h post stroke. For the whole group, the proportion of mismatch salvage remains independent of time and, although the effect is small, its salvage is independently associated with improved clinical outcomes at three-months. Larger sample sizes are needed to determine the time limit for mismatch salvage.

Twenty-eight day Holter monitoring is poorly tolerated and insensitive for paroxysmal atrial fibrillation detection in cryptogenic stroke.

This pilot study in a prospective cohort of 20 cryptogenic stroke patients showed that a significant proportion has paroxysmal atrial fibrillation undetected by 24-h Holter monitoring. However, longer monitoring with 28-day Holter was poorly tolerated and still insufficiently sensitive for paroxysmal atrial fibrillation detection. Further studies are urgently needed to elucidate the optimal timing, method and duration of cardiac rhythm monitoring following ischaemic stroke.

Relative filling time delay based on CT perfusion source imaging: a simple method to predict outcome in acute ischemic stroke.

BACKGROUND AND PURPOSE: Collateral vessel status is strongly associated with clinical outcome in ischemic stroke but can be challenging to assess. The aim of this study was to develop a tomography perfusion source imaging-based assessment of collateral vessel status. MATERIALS AND METHODS: Consecutive patients with ischemic stroke who received intravenous thrombolysis or intra-arterial reperfusion therapy after CTP were retrospectively analyzed. In those with middle cerebral artery or internal carotid artery occlusion, CT perfusion source imaging was used to identify the relative filling time delay between the normal MCA Sylvian branches and those in the affected hemisphere. Receiver operating characteristic analysis and logistic regression were used to assess the association of the relative filling time delay with the 24-hour Alberta Stroke Program Early CT Score based on noncontrast CT and the 90-day modified Rankin Scale score. RESULTS: There were 217 patients treated in 2009-2011 who had CTP data, of whom 60 had MCA or ICA occlusion and 55 had 90-day mRS data. The intraclass correlation coefficient for relative filling time delay was 0.95. Relative filling time delay was correlated with 24-hour ASPECTS (Spearman ρ=-0.674; P<.001) and 90-day mRS score (ρ=0.516, P<.01). Increased relative filling time delay was associated with poor radiologic outcome (ASPECTS, 0-7) (area under the curve=0.79, P<.001) and poor functional outcome (mRS score, 3-6) (area under the curve=0.77, P=.001). In multivariate logistic regression, the association of longer relative filling time delay with poor outcome remained significant, independent of age, sex, and baseline National Institutes of Health Stroke Scale score. CONCLUSIONS: Relative filling time delay is a useful independent predictor of clinical outcome after ischemic stroke.

Stratospheric water vapor feedback.

We show here that stratospheric water vapor variations play an important role in the evolution of our climate. This comes from analysis of observations showing that stratospheric water vapor increases with tropospheric temperature, implying the existence of a stratospheric water vapor feedback. We estimate the strength of this feedback in a chemistry-climate model to be +0.3 W/(m(2)⋅K), which would be a significant contributor to the overall climate sensitivity. One-third of this feedback comes from increases in water vapor entering the stratosphere through the tropical tropopause layer, with the rest coming from increases in water vapor entering through the extratropical tropopause.

Quantitative CT densitometry for predicting intracerebral hemorrhage growth.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage growth independently predicts disability and death. We hypothesized that noncontrast quantitative CT densitometry reflects active bleeding and improves predictive models of growth. MATERIALS AND METHODS: We analyzed 81 of the 96 available baseline CT scans obtained <3 hours post-ICH from the placebo arm of the phase IIb trial of recombinant factor VIIa. Fifteen scans could not be analyzed for technical reasons, but baseline characteristics were not statistically significantly different. Hounsfield unit histograms for each ICH were generated. Analyzed qCTD parameters included the following: mean, SD, coefficient of variation, skewness (distribution asymmetry), and kurtosis ("peakedness" versus "flatness"). These densitometry parameters were examined in statistical models accounting for baseline volume and time-to-scan. RESULTS: The coefficient of variation of the ICH attenuation was the most significant individual predictor of hematoma growth (adjusted R(2) = 0.107, P = .002), superior to BV (adjusted R(2) = 0.08, P = .006) or TTS (adjusted R(2) = 0.03, P = .05). The most significant combined model incorporated coefficient of variation, BV, and TTS (adjusted R(2) = 0.202, P = .009 for coefficient of variation) compared with BV and TTS alone (adjusted R(2) = 0.115, P < .05). qCTD increased the number of growth predictions within ±1 mL of actual 24-hour growth by up to 47%. CONCLUSIONS: Heterogeneous ICH attenuation on hyperacute (<3 hours) CT imaging is predictive of subsequent hematoma expansion and may reflect an active bleeding process. Further studies are required to determine whether qCTD can be incorporated into standard imaging protocols for predicting ICH growth.

Does the cognitive measure Cog-4 show improvement among patients treated with thrombolysis after acute stroke?

BACKGROUND: Although the established measure of disability post stroke, the modified Rankin Scale emphasizes motor function and may underestimate the importance of cognitive impairment in more disabled patients. A subset of four items from the National Institutes of Health Stroke Scale has been proposed to assess cognitive function after stroke (Cog-4), and to correlate with modified Rankin Scale. Items correspond to orientation, executive function, language, and inattention. We investigated responsiveness of Cog-4 to treatment with thrombolysis and whether it offers information that supplements modified Rankin Scale. METHODS: We included 6268 patients from the Virtual International Stroke Trials Archive: 2734 received intravenous thrombolysis and 3534 were treated conservatively. We compared day 90 outcomes between treated and untreated groups, by modified Rankin Scale (illustrative) and by Cog-4 (primary measure) adjusting for age, baseline National Institutes of Health stroke scale, hemispheric lateralisation as well as baseline Cog-4 and baseline National Institutes of Health Stroke Scale excluding baseline Cog-4 separately. Analysis of Cog-4 was repeated within strata of 90 day modified Rankin Scale. Statistical analyses included proportional odds logistic regression and Cochran-Mantel-Haenszel test. RESULTS: Modified Rankin Scale showed a difference between treatment groups of expected magnitude (odds ratio 1·56; 95% confidence interval 1·43-1·72; P < 0·001). After adjustment for imbalance in baseline prognostic factors, the distribution of Cog-4 scores at 90 days was better in thrombolysed patients compared with nonthrombolysed patients (odds ratio 1·31; 95% confidence interval 1·18-1·47; P = 0·006). However, Cog-4 analysis stratified by 90-day modified Rankin Scale was neutral between treatment groups (OR 1·01; 95% CI 0·90-1·14), and Cog-4 was not responsive to treatment group even within modified Rankin Scale categories 4 and 5 despite substantial cognitive deficits in these patients. CONCLUSION: Although Cog-4 may be responsive to treatment effects, it does not provide additional information beyond modified Rankin Scale assessment.

Age over 80 years is not associated with increased hemorrhagic transformation after stroke thrombolysis.

Thrombolysis trials have recruited few patients aged ≥80 years, which has led to uncertainty about the likely risk-to-benefit profile in the elderly. Leukoaraiosis (LA) has been associated with hemorrhagic transformation (HT) and increases with advanced age. We tested whether there were any independent associations between age, LA and HT. Consecutive patients treated with intravenous (IV) tissue plasminogen activator (tPA) were identified from a prospective database. LA on baseline CT scans was assessed by two independent raters using the modified Van Swieten Score (mVSS) (maximum score 8, severe >4). HT was assessed on routine 24 hour to 48 hour CT /MRI scans using the European Cooperative Acute Stroke Study criteria for hemorrhagic infarct (HI) or parenchymal hematoma (PH) and judged symptomatic by the treating neurologist as per Safe Implementation of Thrombolysis in Stroke criteria. There were 206 patients treated with IV tPA (mean age: 71.0 years; range: 24-92 years), of whom 65/206 (32%) were aged ≥80 years. Overall, HT occurred in 41/206 patients (20%), HI in 31, PH1 in four (one symptomatic) and PH2 in six (three symptomatic). Age was not associated with HT (any HT: odds ratio [OR]=1.01; 95% confidence interval [CI]=0.5-2.08; p=0.99; PH: OR=0.53; 95% CI=0.12-2.3; p=0.51). There was one patient with PH1 and one patient with PH2 in 65 patients ≥80 years, both asymptomatic. LA was present in 112/208 (54%), and severe in 16.5%. LA increased with age (p<0.001) but was not associated with PH (any LA: OR=0.83; 95% CI=0.25-2.8; p=0.99; severe LA: OR=0.54, 95% CI=0.09-3.5; p=0.99). Age ≥80 years or LA did not increase the risk of HT (including PH) after thrombolysis, although LA increased with age. Neither factor should exclude otherwise eligible patients from tPA treatment.

Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch.

OBJECTIVE: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. METHODS: EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. RESULTS: In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. CONCLUSIONS: True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.

Baseline diabetic status and admission blood glucose were poor prognostic factors in the EPITHET trial.

BACKGROUND: Previous data have suggested that diabetes and hyperglycemia predict poor outcome following stroke. We studied the prognostic impact of diabetes and admission blood glucose in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). METHODS: EPITHET was a prospective randomized placebo-controlled trial of intravenous tissue plasminogen activator (tPA) in the 3- to 6-hour time window. A preexisting diagnosis of diabetes was noted and baseline serum glucose was measured. RESULTS: Intravenous tPA attenuated infarct growth in non-diabetics, but not in diabetics (p = 0.029). In the tPA treatment group, admission blood glucose was higher among patients with poor functional outcome (p = 0.002). CONCLUSIONS: Diabetes and hyperglycemia attenuate the effects of tPA on infarct evolution. Future thrombolytic trials should consider randomizing patients by subgroups based on diabetic status and serum glucose levels.

Penumbral mismatch is underestimated using standard volumetric methods and this is exacerbated with time.

BACKGROUND AND AIMS: The mismatch between perfusion weighted images (PWI) and diffusion weighted images (DWI) using MR is increasingly being applied in patient selection for therapeutic trials. Two approaches to the calculation of the mismatch volume exist--the commonly used volumetric and the more precise co-registration method, the latter of which considers lesion topography. That there are differences in the mismatch volume analysed by each method and that these are time dependent was hypothesised. METHODS: Patients within 48 h of ischaemic stroke onset had baseline MR PWI/DWI mismatch and T2 outcome volumes at 3 months. Volumetric mismatch volume was defined as PWI minus DWI lesion. Co-registration mismatch volume was defined as the PWI defect lesion not overlapped by the co-registered DWI lesion. RESULTS: 72 patients of median age 74.0 years were studied. Median baseline MR was at 5.9 h (IQR 3.0, 20.4 h) after stroke onset. Consistent underestimation of the mismatch volume occurred using the volumetric method (volumetric median 9.3 ml, IQR 0, 63 ml; co-registration median 20.1 ml, IQR 3.2, 69.8 ml; p<0.0001). This difference increased with time from stroke onset (p = 0.006). CONCLUSIONS: Volumetric analysis consistently underestimates the PWI/DWI mismatch volume compared with the more precise co-registration method. This effect increases with time.

Gender issues in acute stroke thrombolysis.

We systematically reviewed the literature to explore gender issues in acute stroke thrombolysis. The literature is inconsistent regarding the influence of gender on the timing of presentation to hospital, decision-making and utilization of acute thrombolysis among ischemic stroke patients, and hence any reported gender bias may be site-specific. Without treatment with thrombolysis, female stroke patients have a poorer clinical outcome compared to their male counterparts. Although some studies show that women have better clinical outcomes than men following intravenous thrombolysis, no gender difference is seen in others. Post-hoc analyses of relatively small studies show higher recanalisation rates in women than men following intravenous thrombolysis, and no gender difference in recanalisation rates following intra-arterial thrombolysis. Future thrombolytic trials should consider the effects of gender on both surrogate and clinical outcomes.

Imaging the penumbra - strategies to detect tissue at risk after ischemic stroke.

The aim of thrombolytic therapy after acute ischemic stroke is salvage of the ischemic penumbra. Several imaging techniques have been used to identify the penumbra in patients who may benefit from reperfusion beyond the currently narrow 3-hour time-window for thrombolysis. We discuss the advantages and disadvantages of positron emission tomography (PET), single photon emission computed tomography (SPECT), MRI and CT scans. We comment on concepts of clinical-imaging mismatch models and we explore the implications for clinical trials.

Unhealthy behaviours for self-management of HIV-related peripheral neuropathy.

The prevalence of peripheral neuropathy is frequent in HIV disease and is often associated with antiretroviral therapy. Unhealthy behaviours, particularly substance-use behaviours, are utilized by many HIV-positive individuals to manage neuropathic symptoms. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of unhealthy behaviours to self-manage peripheral neuropathy in HIV disease. Sociodemographic and disease-related correlates and unhealthy behaviours were examined in a convenience sample of 1,217 respondents who were recruited from data collection sites in several US cities, Puerto Rico, Colombia, and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n=450) identified a variety of unhealthy self-care behaviours including injection drug use, oral drug use, smoking cigarettes and alcohol ingestion. Specific unhealthy behaviours that participants reported to alleviate peripheral neuropathy included use of marijuana (n=67), smoking cigarettes (n=139), drinking alcohol (n=81) and street drugs (n=30). A subset of those individuals (n=160), who identified high levels of neuropathy (greater than five on a scale of 1-10), indicated significantly higher use of amphetamines and injection drug use in addition to alcohol use and cigarette smoking. For participants from Norway, substance use (using alcohol: 56%) was one of the most frequent self-management strategies. Implications for clinical practice include assessment and education of persons with HIV for self-care management of the complex symptom of peripheral neuropathy.