CARD9 in the pathogenesis of axial spondyloarthritis.

Axial spondyloarthritis (axSpA) has been long classified as an autoimmune disease caused by a breakdown in the ability of the immune system to delineate self from foreign, resulting in self-reactive T cells. The strong genetic association of HLA-B27 supports this role for T cells. More recently, genetic and clinical studies indicate a prominent role of the environment in triggering axSpA, including an important role for microbes and the innate immune response. As an example, mutations in genes associated with innate immunity, including the anti-fungal signaling molecule Caspase recruitment domain-containing protein 9 (CARD9), have been linked to axSpA susceptibility. Thus, current thought classifies axSpA as a "mixed pattern condition" caused by both autoimmune and autoinflammatory mechanisms. The goal of this review is to convey.

Post-traumatic stress disorder and serum cytokine and chemokine concentrations in patients with rheumatoid arthritis✰.

OBJECTIVE: Although post-traumatic stress disorder (PTSD) is identified as a risk factor in the development of rheumatoid arthritis (RA), associations of PTSD with disease progression are less clear. To explore whether PTSD might influence disease-related measures of systemic inflammation in RA, we compared serum cytokine/chemokine (cytokine) concentrations in RA patients with and without PTSD. METHODS: Participants were U.S. Veterans with RA and were categorized as having PTSD, other forms of depression/anxiety, or neither based on administrative diagnostic codes. Multiplex cytokines were measured using banked serum. Associations of PTSD with cytokine parameters (including a weighted cytokine score) were assessed using multivariable regression, stratified by anti-CCP status and adjusted for age, sex, race, and smoking status. RESULTS: Among 1,460 RA subjects with mean (SD) age of 64 (11) years and disease duration of 11 (11) years, 91% were male, 77% anti-CCP positive, and 80% ever smokers. Of these, 11.6% had PTSD, 23.7% other depression/anxiety, and 64.7% had neither. PTSD, but not depression/anxiety, was associated with a higher cytokine score and number of high-concentration analytes in adjusted models, though this was limited to anti-CCP positive subjects. PTSD was associated with heightened expression of several individual cytokines including IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-17, IFN-γ, GM-CSF, MCP-1, and TNF-α. CONCLUSION: Anti-CCP positive RA patients with PTSD have higher serum cytokine concentrations than those without PTSD, demonstrating that systemic inflammation characteristic of RA is heightened in the context of this relatively common psychiatric comorbidity.

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015: recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis

OBJECTIVE: To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). METHODS: A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. RESULTS: In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. CONCLUSION: These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.(AU)

Folic acid pathway single nucleotide polymorphisms associated with methotrexate significant adverse events in United States veterans with rheumatoid arthritis.

OBJECTIVES: Methotrexate (MTX) is the cornerstone medication in the treatment of rheumatoid arthritis (RA). We examined whether single nucleotide polymorphisms (SNPs) in enzymes of the folic acid pathway (folylpoly-gamma-glutamate synthetase [FPGS], gamma-glutamyl hydrolase [GGH], and methylenetetrahydrofolate reductase [MTHFR]) associate with significant adverse events (SigAE). METHODS: Patients (n=319) enrolled in the Veterans Affairs RA (VARA) registry taking MTX were genotyped for HLA-DRB1-SE and the following SNPs: FPGS (rs7033913, rs10760503, rs10106), GGH (12548933, rs7010484, rs4617146, rs719235, rs11988534), MTHFR (rs1801131, rs1801133). AE were abstracted from the medical record using a structured instrument. SigAE were defined as an AE leading to MTX discontinuation. Covariates included: age, gender, race, RA antibody status, tobacco, RA disease duration between diagnosis and MTX course, Charlson-Deyo comorbidity index, glucocorticoids, use of prior RA medications, and mean 4-variable disease activity score. Cox regression was performed to determine factors associated with time-to-SigAE. A p-value ≤ 0.005 established significance in the final model. RESULTS: The presence of ≥ 1 copy of the minor allele in MTHFR rs1801131 was associated with an increased hazard ratio (HR) of SigAE (HR 3.05, 95% CI 1.48-6.29, p-value 0.003 and HR 3.88, 95% CI 1.62-9.28, p-value 0.002 for heterozygotes and homozygotes for the minor allele, respectively). An interaction term, between FPGS rs7033913 heterozygotes and GGH rs11988534 homozygotes for the minor allele, had a p-value <0.0001. CONCLUSIONS: RA subjects taking MTX may have decreased time-to-SigAE with ≥ 1 copy of the minor allele in MTHFR rs1801131. Further investigation is warranted, as these SNPs may indicate susceptibility to MTX toxicity.

The ASCOD phenotyping of ischemic stroke (Updated ASCO Phenotyping).

ASCO phenotyping (A: atherosclerosis; S: small-vessel disease; C: cardiac pathology; O: other causes) assigns a degree of likelihood of causal relationship to every potential disease (1 for potentially causal, 2 for causality is uncertain, 3 for unlikely causal but the disease is present, 0 for absence of disease, and 9 for insufficient workup to rule out the disease) commonly encountered in ischemic stroke describing all underlying diseases in every patient. In this new evolution of ASCO called ASCOD, we have added a 'D' for dissection, recognizing that dissection is a very frequent disease in young stroke patients. We have also simplified the system by leaving out the 'levels of diagnostic evidence', which has been integrated into grades 9 and 0. Moreover, we have also changed the cutoff for significant carotid or intracranial stenosis from 70% to more commonly used 50% luminal stenosis, and added a cardiogenic stroke pattern using neuroimaging. ASCOD captures and weights the overlap between all underlying diseases present in ischemic stroke patients.

Factors affecting the prevalence of chronic diseases in Palestinian people: an analysis of data from the Palestinian Central Bureau of Statistics.

This study determined whether there are significant differences in the prevalence of diabetes, hypertension, cardiovascular disease (CVD) and cancer among Palestinians with respect to different demographic variables using secondary data from the Palestinian Central Bureau of Statistics. Living in the Gaza Strip was a protective factor, with this group being 21% less likely to have diabetes, 35% less likely to have hypertension, and 48% less likely to have CVD than those living in the West Bank. No significant difference was found for cancer. Being a refugee was a significant risk factor for diabetes and CVD while being married/engaged or divorced/ separated/widowed was a risk factor for diabetes and hypertension. Gender was a risk factor for hypertension with females being 60% more likely to have hypertension than males. Living in a rural setting was protective against hypertension. As expected, age was a risk factor for diabetes, hypertension and CVD; the magnitude of this increased risk was alarming, 36 to 434 times greater in those aged 40-65 years compared with those aged 0-19 years.

Factors affecting the prevalence of chronic diseases in Palestinian people: an analysis of data from the Palestinian Central Bureau of Statistics

This study determined whether there are significant differences in the prevalence of diabetes, hypertension, cardiovascular disease [CVD] and cancer among Palestinians with respect to different demographic variables using secondary data from the Palestinian Central Bureau of Statistics. Living in the Gaza Strip was a protective factor, with this group being 21% less likely to have diabetes, 35% less likely to have hypertension, and 48% less likely to have CVD than those living in the West Bank. No significant difference was found for cancer. Being a refugee was a significant risk factor for diabetes and CVD while being married/engaged or divorced/ separated/widowed was a risk factor for diabetes and hypertension. Gender was a risk factor for hypertension with females being 60% more likely to have hypertension than males. Living in a rural setting was protective against hypertension. As expected, age was a risk factor for diabetes, hypertension and CVD; the magnitude of this increased risk was alarming, 36 to 434 times greater in those aged 40-65 years compared with those aged 0-19 years

An observational study of glucocorticoid-induced osteoporosis prophylaxis in a national cohort of male veterans with rheumatoid arthritis.

UNLABELLED: We applied regression techniques to a large cohort of patients to understand why certain patients are prescribed medications to prevent glucocorticoid-induced osteoporosis (GIO). Rates of prescriptions to prevent osteoporosis were low. The presence of drugs and disorders associated with osteoporosis and gastrointestinal conditions actually are associated with a decreased likelihood of receiving osteoporosis-preventing medications. INTRODUCTION: To understand why some patients are prescribed medications to prevent GIO while other patients are not, we examined whether there is an association among osteoporosis-inducing medical conditions or medications and prescriptions for osteoporosis prophylaxis in a large cohort of rheumatoid arthritis patients on chronic glucocorticoids. METHODS: Department of Veterans' Affairs national administrative databases were used to construct a cohort (n = 9,605) and provide the data for this study. Multivariate logistic regression was performed to determine medical conditions and medications associated with dispensing of GIO-preventive medications, controlling for sociodemographic variables, comorbidities, glucocorticoid dosage, prior fractures, and rheumatoid arthritis severity. A subanalysis examined predictors of early GIO prevention. RESULTS: Subjects were more likely to receive GIO prophylaxis if they were older, African American, treated with multiple antirheumatic disease-modifying drugs, or received greater glucocorticoid exposure. The prescription of certain drug classes (loop diuretics and anticonvulsants) and conditions (malignancy, renal insufficiency, alcohol abuse, and hepatic disease) were associated with lower likelihood of GIO prophylaxis, despite putative links between these agents/conditions and osteoporosis. The presence of gastrointestinal disorders dramatically decreased likelihood of GIO prophylaxis. Few characteristics predicted the dispensing of GIO-preventing medications within 7 days of the initial glucocorticoid start date. CONCLUSIONS: Rates of prescriptions to prevent osteoporosis in a cohort of older men with rheumatoid arthritis on chronic glucocorticoids were low. Gastrointestinal disorders and drugs and disorders potentially linked to osteoporosis are associated with diminished odds of being prescribed GIO-preventing medications.

Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke. METHODS: We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI. RESULTS AND RECOMMENDATIONS: DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U).

Atraumatic convexal subarachnoid hemorrhage: clinical presentation, imaging patterns, and etiologies.

OBJECTIVE: To identify patterns of clinical presentation, imaging findings, and etiologies in a cohort of hospitalized patients with localized nontraumatic convexal subarachnoid hemorrhage. METHODS: Twenty-nine consecutive patients with atraumatic convexal subarachnoid hemorrhage were identified using International Classification of Diseases-9 code from 460 patients with subarachnoid hemorrhage evaluated at our institution over a course of 5 years. Retrospective review of patient medical records, neuroimaging studies, and follow-up data was performed. RESULTS: There were 16 women and 13 men between the ages of 29 and 87 years. Two common patterns of presentations were observed. The most frequent presenting symptom in patients < or =60 years (n = 16) was a severe headache (n = 12; 75%) of abrupt onset (n = 9; 56%) with arterial narrowing on conventional angiograms in 4 patients; 10 (p = 0.003) were presumptively diagnosed with a primary vasoconstriction syndrome. Patients >60 years (n = 13) usually had temporary sensory or motor symptoms (n = 7; 54%); brain MRI scans in these patients showed evidence of leukoaraiosis and/or hemispheric microbleeds and superficial siderosis (n = 9; 69%), compatible with amyloid angiopathy (n = 10; p < 0.0001). In a small group of patients, the presentation was more varied and included lethargy, fever, and confusion. Four patients older than 60 years had recurrent intracerebral hemorrhages in the follow-up period with 2 fatalities. CONCLUSION: Convexal subarachnoid hemorrhage is an important subtype of nonaneurysmal subarachnoid bleeding with diverse etiologies, though a reversible vasoconstriction syndrome appears to be a common cause in patients 60 years or younger whereas amyloid angiopathy is frequent in patients over 60. These observations require confirmation in future studies.

Poor to modest agreement between rheumatoid arthritis response measures in clinical practice.

OBJECTIVE: To evaluate the agreement among several rheumatoid arthritis (RA) response measures in a clinical setting. METHODS: 529 patients with RA were seen at 2 regular visits where the following response measures were determined: ACR-20, EULAR good or moderate (EULAR-GM), Simplified Disease Activity Index moderate (SDAI-M), Clinical DAI moderate (CDAI-M), and Patient Reported Outcomes Index-M 20 (PRO-IM-20). Each measure was modified to include a "worse" response, i.e. the inverse of the respective guidelines for a positive improvement response.Introduced for comparison was the Real-time Assessment of Disease Activity in Rheumatoid Arthritis (RADARA), a response measure that registers improvement if the patient's tender and swollen joint counts and HAQ score all improve and worsening if all three increase. Contingency tables comparing the three responses (worse, no change, and improvement) along with Cohen's kappa were calculated. RESULTS: The mean (SD) baseline characteristics of the patients included: age 66.5 (10.7) years, RA duration 12.9 (11.0) years, 91.3% male, 84.1% rheumatoid factor positive, and a Disease Activity Score-28 of 3.5 (1.3). The percentage of patients who improved/worsened were as follows: ACR-20 4.7/9.1, EULAR-GM 23.4/26.3, SDAI-M 16.1/20.6, CDAI-M 16.3/20.0, PRO-IM-20 22.5/34.4, and RADARA 7.0/11.5. Agreement (kappa) was poor to slight (

Classification of stroke subtypes.

This article reviews published stroke subtype classification systems and offers rules and a basis for a new way to subtype stroke patients. Stroke subtyping can have different purposes, e.g. describing patients' characteristics in a clinical trial, grouping patients in an epidemiological study, careful phenotyping of patients in a genetic study, and classifying patients for therapeutic decision-making in daily practice. The classification should distinguish between ischemic and hemorrhagic stroke, subarachnoid hemorrhage, cerebral venous thrombosis, and spinal cord stroke. Regarding the 4 main categories of etiologies of ischemic stroke (i.e. atherothrombotic, small vessel disease, cardioembolic, and other causes), the classification should reflect the most likely etiology without neglecting the vascular conditions that are also found (e.g. evidence of small vessel disease in the presence of severe large vessel obstructions). Phenotypes of large cohorts can also be characterized by surrogate markers or intermediate phenotypes (e.g. presence of internal carotid artery plaque, intima-media thickness of the common carotid artery, leukoaraiosis, microbleeds, or multiple lacunae). Parallel classifications (i.e. surrogate markers) may serve as within-study abnormalities to support research findings.

New approach to stroke subtyping: the A-S-C-O (phenotypic) classification of stroke.

We now propose a new approach to stroke subtyping. The concept is to introduce a complete 'stroke phenotyping' classification (i.e. stroke etiology and the presence of all underlying diseases, divided by grade of severity) as distinguished from past classifications that subtype strokes by characterizing only the most likely cause(s) of stroke. In this phenotype-based classification, every patient is characterized by A-S-C-O: A for atherosclerosis, S for small vessel disease, C for cardiac source, O for other cause. Each of the 4 phenotypes is graded 1, 2, or 3. One for 'definitely a potential cause of the index stroke', 2 for 'causality uncertain', 3 for 'unlikely a direct cause of the index stroke (but disease is present)'. When the disease is completely absent, the grade is 0; when grading is not possible due to insufficient work-up, the grade is 9. For example, a patient with a 70% ipsilateral symptomatic stenosis, leukoaraiosis, atrial fibrillation, and platelet count of 700,000/mm(3) would be classified as A1-S3-C1-O3. The same patient with a 70% ipsilateral stenosis, no brain imaging, normal ECG, and normal cardiac imaging would be identified as A1-S9-C0-O3. By introducing the 'level of diagnostic evidence', this classification recognizes the completeness, the quality, and the timing of the evaluation to grade the underlying diseases. Diagnostic evidence is graded in levels A, B, or C: A for direct demonstration by gold-standard diagnostic tests or criteria, B for indirect evidence or less sensitive or specific tests or criteria, and C for weak evidence in the absence of specific tests or criteria. With this new way of classifying patients, no information is neglected when the diagnosis is made, treatment can be adapted to the observed phenotypes and the most likely etiology (e.g. grade 1 in 1 of the 4 A-S-C-O phenotypes), and analyses in clinical research can be based on 1 of the 4 phenotypes (e.g. for genetic analysis purpose), while clinical trials can focus on 1 or several of these 4 phenotypes (e.g. focus on patients A1-A2-A3).

Vasoreactivity and peri-infarct hyperintensities in stroke.

OBJECTIVE: It is unknown if impaired cerebral vasoreactivity recovers after ischemic stroke, and whether it compromises perfusion in regions surrounding infarct and other vascular territories. We investigated the regional differences in CO2 vasoreactivity (CO2 VR) and their relationships to peri-infarct T2 hyperintensities (PIHs), chronic infarct volumes, and clinical outcomes. METHODS: We studied 39 subjects with chronic large middle cerebral artery territory infarcts and 48 matched controls. Anatomic and three-dimensional continuous arterial spin labeling imaging at 3-Tesla MRI were used to measure regional cerebral blood flow (CBF) and CO2 VR during normocapnia, hypercapnia, and hypocapnia in main arteries distributions. RESULTS: Stroke patients showed a significantly lower augmentation of blood flow at increased CO2 but greater reduction of blood flow with decreased CO2 than the control group. This altered vasoregulatory response was observed both ipsilateral and contralateral to the stroke. Lower CO2 VR on the stroke side was associated with PIHs, greater infarct volume, and worse outcomes. The cases with PIHs (n = 27) had lower CBF during all conditions bilaterally (p < 0.0001) compared to cases with infarct only. CONCLUSIONS: Perfusion augmentation is inadequate in multiple vascular territories in patients with large artery ischemic infarcts, but vasoconstriction is preserved. Peri-infarct T2 hyperintensities are associated with lower blood flow. Strategies aimed to preserve vasoreactivity after an ischemic stroke should be tested for their effect on long-term outcomes.

The HAT Score: a simple grading scale for predicting hemorrhage after thrombolysis.

OBJECTIVE: To develop a grading scale to predict the risk of intracerebral hemorrhage (ICH) and prognosis after treatment with IV tissue-plasminogen activator (t-PA) in patients with ischemic stroke. METHODS: We constructed a five-point scale based on NIH Stroke Scale score, extent of hypodensity on CT scan, serum glucose at baseline, and history of diabetes to predict the risk of hemorrhage after thrombolysis (HAT score). We evaluated the predictive ability of this scale, using c-statistics, in two independent cohorts: the t-PA treated group in the National Institute of Neurological Disorders and Stroke study, and consecutive patients treated with IV t-PA at our institution. RESULTS: The percentage of patients who developed any ICH after t-PA increased with higher scores in both cohorts. Collectively, the rate of any symptomatic ICH was 2% (0 point), 5% (1 point), 10% (2 points), 15% (3 points), and 44% (>3 points). The c-statistic was 0.72 (95% CI 0.65-0.79; p < 0.001) for all hemorrhages; 0.74 (0.63-0.84; p < 0.001) for symptomatic hemorrhages; and 0.79 (0.70-0.88; p < 0.001) for hemorrhages with final fatal outcome. Similar results were obtained when each cohort was analyzed separately. The score also reasonably predicted good (mRS < or = 2) (c-statistic 0.75; 0.69-0.80; p < 0.001) and catastrophic (mRS > or = 5) (0.78; 0.72-0.84; p < 0.001) functional outcomes on day 90 in the National Institute of Neurological Disorders and Stroke t-PA-treated patients. CONCLUSIONS: The hemorrhage after thrombolysis (HAT) score is a practical, quick, and easy-to-perform scale that allows reasonable risk stratification of intracerebral hemorrhage after IV tissue-plasminogen activator (t-PA). However, the prognostic value of this scale and its use to predict the net benefit from t-PA needs to be refined and prospectively confirmed in a larger cohort of patients before it can be used in clinical decision-making.

Rheumatoid arthritis treatment and the risk of severe interstitial lung disease.

OBJECTIVES: Interstitial lung disease (ILD) is an important complication of rheumatoid arthritis (RA) or its treatment, and is associated with substantially increased mortality. Reports have suggested that infliximab with or without azathioprine might lead to rapidly progressive or fatal ILD. We used an RA data bank to assess the associations of treatments for RA and severe ILD. METHODS: ILD was identified in hospitalisations and death records in 100 of 17,598 RA patients and studied in relation to RA therapy with Cox regression analyses. RESULTS: The incidence of hospitalisation for ILD (HILD) was 260 per 100,000 patient years. Among those hospitalised for ILD, 27.0% died. In multivariable models of current and past RA treatment, the only current treatment associated with HILD was prednisone: hazard ratio (HR) 2.5 [95% confidence interval (CI) 1.5-4.1]. Among past therapies, prednisone (HR 3.0, 95% CI 1.0-8.9), infliximab (HR 2.1, 95% CI 1.1-3.8), etanercept (HR 1.7, 95% CI 1.0-3.0), and cyclophosphamide (HR 3.7, 95% CI 0.9-15.5) were associated with HILD. Pre-existing lung problems were identified in 67% of HILD. Only one case of HILD in the 100 hospitalisations suggested a possible temporal relationship between infliximab and HILD. CONCLUSIONS: Associations between RA treatment and HILD are confounded by the prescription of treatments for ILD such as prednisone, infliximab, etanercept, and cyclophosphamide. There is no clear pattern of causal association of treatment and ILD, and there is no clear evidence to support a causal relationship between infliximab, azathioprine, and HILD.

Antiplatelets, ACE inhibitors, and statins combination reduces stroke severity and tissue at risk.

BACKGROUND: Antiplatelets (APL), angiotensin-converting enzyme (ACE) inhibitors (ACEI), and statins (STAT) are commonly used for stroke prevention. The authors examined whether combination therapy with these agents has additive protective effects in reducing ischemic stroke severity. METHODS: The authors retrospectively analyzed data from 210 consecutive patients presenting within 24 hours of stroke onset. Baseline NIH Stroke Scale (NIHSS) score and diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI), and PWI-DWI mismatch lesion volumes as clinical and radiologic measures of stroke severity were measured among patients who were not taking APL, ACEI, or STAT before stroke onset vs those who were taking APL alone or in combination with either ACEI, STAT, or both. RESULTS: Sixty-nine patients were not on APL, ACEI, or STAT at stroke onset; 47 were on APL alone, 43 on dual (14 APL + STAT, 29 APL + ACEI), and 20 on triple combination therapy. Patients on triple therapy had lower NIHSS score (p = 0.001) and smaller mean PWI-DWI mismatch lesion volumes (p = 0.03) than those on two agents, APL alone, or no prestroke therapy. Higher percentages of patients on triple therapy had shorter length of hospitalization and better functional status upon discharge. Age, risk factor profile, blood pressure, glucose levels, onset to evaluation time, stroke subtypes, and DWI lesion volumes were comparable among all groups. CONCLUSIONS: Prestroke use of available drugs for stroke prevention, in combination, may result in additive reduction in stroke severity, as measured by NIH Stroke Scale, and the volume of ischemic tissue at risk, as assessed by perfusion-weighted imaging-diffusion-weighted imaging mismatch. These findings require further validation in larger-scale, randomized, prospective studies.