Krista L Lanctôt

Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Are you Krista L Lanctôt?

Claim your profile

Publications (233)962.99 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Reports of elevated inflammatory markers in mild cognitive impairment (MCI) suggest that inflammation may be a potential early marker of the neurodegenerative cascade associated with Alzheimer's disease (AD). The aim of this study was to quantitatively summarize the data on peripheral blood concentrations of inflammatory factors in patients with MCI compared to controls. Mean (±SD) blood concentrations of inflammatory factors for MCI and control subjects were extracted from original English language peer-reviewed studies for meta-analysis. Twenty-two studies measuring concentrations of cytokines, chemokines, acute phase reactant proteins, immunoglobulins, intercellular adhesion molecules, and fibrinogen were included. No significant differences in inflammatory factors studied were found between subjects with MCI and healthy controls. These findings do not support the involvement of inflammatory markers at the MCI stage of cognitive decline although significant heterogeneity was observed in some comparisons. It remains to be established whether inflammation may predict increased rate of conversion to dementia.
    Journal of Alzheimer's disease: JAD 09/2015; 47(3):669-679. DOI:10.3233/JAD-150042 · 4.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Depression is a frequent complication of coronary artery disease (CAD) with an unknown etiology. Platelet activating factor (PAF) lipids, which are associated with CAD, have recently been linked with novel proposed etiopathological mechanisms for depression such as inflammation, oxidative/nitrosative stress, and vascular endothelial dysfunction. Methods and results This hypothesis-generating study investigated the relationships between various PAF species and depressive symptoms in 26 CAD patients (age: 60.6±9.2 years, 69% male, mean Hamilton Depression Rating Scale [HAM-D] score: 11.8±5.2, HAM-D range: 3–20). Plasma PAF analyses were performed using high performance liquid chromatography electrospray ionization mass spectrometry in precursor ion scan. Significant associations between depressive symptom severity (HAM-D score) and a greater plasma abundance of the PAFs phosphocholine (PC) PC(O-12:0/2:0) (r=0.49, P=0.01), PC(O-14:1/2:0) (r=0.43, P=0.03), PC(O-17:3/2:0) (r=0.44, P=0.04), and PC(O-18:3/2:0) (r=0.50, P=0.01) were observed. Associations between those PAFs and HAM-D score persisted after adjusting for age and sex. Conclusion These preliminary findings support the exploration of the PAF lipidome for depressive symptom biomarkers in CAD patients. Patients were recruited as part of the following clinical trial: NCT00981383.
    Neuropsychiatric Disease and Treatment 09/2015; 11:2309. DOI:10.2147/NDT.S87111 · 1.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is frequently associated with neuropsychiatric symptoms (NPS) such as agitation and aggression, especially in the moderate to severe stages of the illness. The limited efficacy and high-risk profiles of current pharmacotherapies for the management of agitation and aggression in AD have driven the search for safer pharmacological alternatives. Over the past few years, there has been a growing interest in the therapeutic potential of medications that target the endocannabinoid system (ECS). The behavioural effects of ECS medications, as well as their ability to modulate neuroinflammation and oxidative stress, make targeting this system potentially relevant in AD. This article summarizes the literature to date supporting this rationale and evaluates clinical studies investigating cannabinoids for agitation and aggression in AD. Letters, case studies, and controlled trials from four electronic databases were included. While findings from six studies showed significant benefits from synthetic cannabinoids-dronabinol or nabilone-on agitation and aggression, definitive conclusions were limited by small sample sizes, short trial duration, and lack of placebo control in some of these studies. Given the relevance and findings to date, methodologically rigorous prospective clinical trials are recommended to determine the safety and efficacy of cannabinoids for the treatment of agitation and aggression in dementia and AD.
    CNS Drugs 08/2015; DOI:10.1007/s40263-015-0270-y · 5.11 Impact Factor
  • Jinghan Jenny Chen · Parco Chan · Bosco Paes · Ian Mitchell · Abby Li · Krista L. Lanctôt
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To evaluate the safety and tolerability of palivizumab for RSV prophylaxis in high-risk children in everyday practice. Methods: High-risk children prophylaxed against RSV infection were recruited into a prospective, observational, Canadian RSV Evaluation Study of Palivizumab (CARESS) registry with active, serious adverse event (SAE) monitoring from 2008 to 2013. SAE reports were systematically collected and assessed for severity and relationship to palivizumab. Data were analyzed by Chi-square or Fisher Exact Tests to examine group differences in proportions. Results: 13025 infants received 57392 injections. Hospitalizations for respiratory-related illness (RIH) were reported in 915 patients, and SAEs other than RIH were reported in 52 patients. Of these, 6 (0.05%) patients had a total of 14 hypersensitivity reactions that were deemed possibly or probably related to palivizumab (incidence: 2.8 per 10,000 patient-months). The SAEs of 42 patients were assessed as not related to palivizumab. SAEs in the remaining 4 patients were not classifiable as their records were incomplete. There were no significant demographic predictors of SAE occurrence. Conclusions: Under active surveillance, a small proportion of infants in the CARESS registry experienced SAEs that had a potential relationship with palivizumab and these appeared to be unpredictable in terms of onset. Palivizumab appears to be a safe and well-tolerated antibody for RSV prophylaxis in high-risk children in routine practice.
    PLoS ONE 08/2015; 10(8):e0134711. DOI:10.1371/journal.pone.0134711 · 3.23 Impact Factor
  • W Swardfager · P Yang · N Herrmann · K L Lanctôt · B R Shah · A Kiss · P I Oh
    [Show abstract] [Hide abstract]
    ABSTRACT: To quantify the impact of depressive symptoms on completion of exercise-based rehabilitation for Type 2 diabetes management. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale in a prospective cohort of consecutive patients with Type 2 diabetes entering a 6-month hybrid (home- and clinic-based) exercise rehabilitation programme. Attendance at exercise sessions was monitored and programme completion/non-completion was ascertained. Of the programme participants (n=624, mean age 55.6±10.5 years, 47% male), 26.8% endorsed significant depressive symptoms (depression score ≥16) and 68.1% completed the intervention, attending 54.6±30.0% of supervised exercise sessions. Baseline depressive symptoms (depression scale score ≥16) increased the risk of non-completion [hazard ratio 1.49 (95% CI 1.10-2.03); P = 0.010], and predicted fewer sessions attended (β=-2.1, P= 0.002) in adjusted models. A depression score threshold of ≥10 (48.4% of participants) predicted non-completion [hazard ratio 1.60 (95% CI 1.19-2.17); P= 0.002) with optimum accuracy. Non-completions resulting from lack of interest (18.9 vs. 11.0%; P= 0.026) and medical complications (14.6 vs. 6.6%; P= 0.006) were more common among participants with depression scores ≥10. Greater hazard ratios for depression scores ≥10 were observed in subgroups not currently using insulin [hazard ratio 1.70 (95% CI 1.24-2.33); P= 0.001), or an antidepressant [hazard ratio 1.83 (95% CI 1.32-2.54); P<0.001]. Depressive symptoms were highly prevalent among participants with Type 2 diabetes entering exercise-based rehabilitation, and even mild depressive symptoms posed a significant barrier to completion. Depression screening may help target additional supports to facilitate completion of exercise interventions for people with Type 2 diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Diabetic Medicine 07/2015; DOI:10.1111/dme.12872 · 3.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Every year, approximately 62 000 people with stroke and transient ischemic attack are treated in Canadian hospitals, and the evidence suggests one-third or more will experience vascular-cognitive impairment, and/or intractable fatigue, either alone or in combination. The 2015 update of the Canadian Stroke Best Practice Recommendations: Mood, Cognition and Fatigue Module guideline is a comprehensive summary of current evidence-based recommendations for clinicians in a range of settings, who provide care to patients following stroke. The three consequences of stroke that are the focus of the this guideline (poststroke depression, vascular cognitive impairment, and fatigue) have high incidence rates and significant impact on the lives of people who have had a stroke, impede recovery, and result in worse long-term outcomes. Significant practice variations and gaps in the research evidence have been reported for initial screening and in-depth assessment of stroke patients for these conditions. Also of concern, an increased number of family members and informal caregivers may also experience depressive symptoms in the poststroke recovery phase which further impact patient recovery. These factors emphasize the need for a system of care that ensures screening occurs as a standard and consistent component of clinical practice across settings as stroke patients transition from acute care to active rehabilitation and reintegration into their community. Additionally, building system capacity to ensure access to appropriate specialists for treatment and ongoing management of stroke survivors with these conditions is another great challenge. © 2015 World Stroke Organization.
    International Journal of Stroke 06/2015; DOI:10.1111/ijs.12557 · 3.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Exercise is a promising strategy to prevent dementia, but no clinically supervised exercise program is widely available to people with mild cognitive impairment (MCI). The objective was to survey health professionals to assess the feasibility of using cardiac rehabilitation exercise programs for MCI populations. We distributed surveys to: 1) health professionals working in cardiac rehabilitation exercise programs (36/72 responded); and 2) physicians who treat MCI (22/32 responded). Questions addressed clinician and clinic characteristics and feasibility of referring and accommodating people with MCI. Most cardiac rehabilitation exercise programs currently treat people with MCI (61.1%). Nearly all were willing and able to accept people with MCI and comorbid vascular risk (91.7%), though only a minority could accept MCI without vascular risk (16.7%). Although most physicians recommend exercise to people with MCI (63.6%), few referred patients with MCI to programs or people to guide exercise (27.3%). However, all physicians (100%) would refer patients with MCI to a cardiac rehabilitation exercise program. Our study supports cardiac rehabilitation exercise programs as a feasible model of exercise for patients with MCI with vascular risk. Patients with and without vascular risk could likely be accommodated if program mandates were expanded.
    06/2015; 18(2):65-72. DOI:10.5770/cgj.18.166
  • P. Chan · J. Chen · B. Paes · I. Mitchell · A. Li · K. Lanctôt
    Value in Health 05/2015; 18(3):A228-A229. DOI:10.1016/j.jval.2015.03.1329 · 3.28 Impact Factor
  • A. Li · B. Paes · I. Mitchell · K. Lanctôt
    Value in Health 05/2015; 18(3):A232-A233. DOI:10.1016/j.jval.2015.03.1353 · 3.28 Impact Factor
  • H.Y. Abraha · A. Li · B. Paes · I. Mitchell · K. Lanctôt
    Value in Health 05/2015; 18(3):A231. DOI:10.1016/j.jval.2015.03.1343 · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Current treatments for Alzheimer's disease (AD) provide modest symptomatic relief but do not slow the progression of the disease. Latrepirdine may modulate several targets involved in AD pathology, including lipid peroxidation, mitochondrial permeability, voltage-gated calcium ion channels as well as neurotransmitter receptor activity, and thus potentially represents both a symptomatic and disease-modifying intervention. Several randomized, placebo-controlled trials have sought to evaluate the effect of latrepirdine on cognition, function and behaviour in patients with AD. To evaluate the efficacy and safety of latrepirdine for the treatment of AD. We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 4 June 2014 using the terms: latrepirdine OR dimebon OR dimebolin OR 2,3,4,5-tetrahydro-2,8-dimethyl-5- (2-(6-methyl-3-pyridyl)ethyl)-1H-pyrido(4,3-b)indole. We included all randomized, double-blind, placebo-controlled trials where latrepirdine was administered to patients with mild, moderate or severe AD. We assessed the quality of studies and two authors extracted data. We calculated mean difference (MD), risk ratio (RR) and 95% confidence interval (CI) on an intention-to-treat (ITT) basis for all relevant outcome measures. Seven trials involving a total of 1697 participants were found and six were included in the quantitative analyses. No data were available from the seventh trial. Three trials involving 1243 patients were included in analyses of efficacy outcomes, and four trials involving 1034 patients were included in analyses of safety and tolerability outcomes. We judged five trials to be at high risk of bias due to selective outcome reporting and three to be at high risk of attrition bias. There was low quality evidence favouring latrepirdine on the Clinician's Interview - Based Impression of Change Plus Caregiver Input after 26 weeks (CIBIC-Plus) (MD -0.60, 95% CI -0.89 to -0.31, 1 study, P < 0.001). Due to imprecision in the results, it was not possible to determine whether latrepirdine had any effect on cognition measured with the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) (MD -1.49, 95% CI -3.47 to 0.49, 3 studies, P = 0.14) or the Mini-Mental State Examination (MMSE) (MD 0.59, 95% CI -0.94 to 2.11, 3 studies, P = 0.45), or on function measured with the Alzheimer's Disease Co-operative Study - Activities of Daily Living scale (ADCS-ADL) (MD 1.00, 95% CI -1.15 to 3.15, 3 studies, P = 0.36) at study endpoint (26 or 52 weeks). We considered the evidence provided on these outcomes to be of overall low quality. However, there was some high quality evidence showing a very small benefit of latrepirdine on the Neuropsychiatric Inventory (NPI) (MD -1.77, 95% CI -3.09 to -0.45, 3 studies, P = 0.009) at study endpoint (26 or 52 weeks). Additionally, moderate quality evidence suggested that latrepirdine and placebo were comparable in adverse events (RR 1.03, 95% CI 0.93 to 1.14, P = 0.51), serious adverse events (RR 0.86, 95% CI 0.55 to 1.35, P = 0.52), dropouts (RR 0.91, 95% CI 0.65 to 1.27, P = 0.57) and dropouts due to adverse events (RR 0.98, 95% CI 0.57 to 1.67, P = 0.93). Our meta-analysis is limited by the small number of studies, imprecision, inconsistencies between studies and likelihood of bias. Nevertheless, the evidence to date suggests that while not associated with an increased risk of adverse events compared with placebo, there is no effect of latrepirdine on cognition and function in mild-to-moderate AD patients, though there appears to be a modest benefit for behaviour. Further studies should investigate the potential benefit of latrepirdine on neuropsychiatric symptoms in AD.
    Cochrane database of systematic reviews (Online) 04/2015; 4:CD009524. DOI:10.1002/14651858.CD009524.pub2 · 6.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine risk factors for clinically significant progression during 12 months in patients with mild-to-moderate Alzheimer disease. Community-dwelling patients with mild-to-moderate Alzheimer disease were enrolled in a 3-year prospective study, the Canadian Outcomes Study in Dementia (commonly referred to as COSID), at 32 Canadian sites. Assessments included the Global Deterioration Scale (GDS) for disease severity, the Mini-Mental State Examination (MMSE) for cognition, the Functional Autonomy Measurement System (SMAF) for daily functioning, and the NeuroPsychiatric Inventory (NPI) for behaviour, measured at baseline and at 12 months. Logistic regression identified factors associated with GDS decline, and subsequent stepwise regression identified key independent predictors. Area under the curve (AUC) was then calculated for the model. Among 488 patients (mean age 76.5 years [SD 6.4], MMSE 22.1 [SD4.6], 44.1% male), 225 (46%) showed GDS decline. After adjusting for age, baseline risk factors for deterioration included the following: poorer cognition (lower MMSE score, OR 0.55; 95% CI 0.4 to 0.72 per 5 points, P ≤ 0.001), greater dependence (lower SMAF, OR 0.72; 95% CI 0.63 to 0.83 per 5 points, P ≤ 0.001), and more neuropsychiatric symptoms (higher NPI, OR 1.11; 95% CI 1.02 to 1.2 per 5 points, P = 0.02), with a protective effect of male sex (OR 0.59; 95% CI 0.39 to 0.9, P = 0.02), and higher (worse) GDS score (very mild, compared with mild OR 0.25; 95% CI 0.09 to 0.70, P ≤ 0.01; compared with moderate, OR 0.08; 95% CI 0.03 to 0.23, P < 0.001; compared with moderately severe, OR 0.03; 95% CI 0.01 to 0.11, P < 0.001). The AUC was 73% (P < 0.001) (sensitivity 90% and specificity 33%). The progression of Alzheimer disease in Canada can be predicted using readily available clinical information.
    Canadian journal of psychiatry. Revue canadienne de psychiatrie 04/2015; 60(4):189-99. · 2.55 Impact Factor
  • American Journal of Geriatric Psychiatry 03/2015; 23(3):S172-S173. DOI:10.1016/j.jagp.2014.12.181 · 4.24 Impact Factor
  • Source
    Ka Sing Paris Lai · Nathan Herrmann · Mahwesh Saleem · Krista L. Lanctôt
    [Show abstract] [Hide abstract]
    ABSTRACT: Severe aortic stenosis is the most common valvular heart disease in the elderly in the Western world and contributes to a large proportion of all deaths over the age of 70. Severe aortic stenosis is conventionally treated with surgical aortic valve replacement; however, the less invasive transcatheter aortic valve implantation (TAVI) is suggested for those at high surgical risk. While TAVI has been associated with improved survival and favourable outcomes, there is a higher incidence of cerebral microembolisms in TAVI patients. This finding is of concern given mechanistic links with cognitive decline, a symptom highly prevalent in those with cardiovascular disease. This paper reviews the literature assessing the possible link between TAVI and cognitive changes. Studies to date have shown that global cognition improves or remains unchanged over 3 months following TAVI while individual cognitive domains remain preserved over time. However, the association between TAVI and cognition remains unclear due to methodological limitations. Furthermore, while these studies have largely focused on memory, cognitive impairment in this population may be predominantly of vascular origin. Therefore, cognitive assessment focusing on domains important in vascular cognitive impairment, such as executive dysfunction, may be more helpful in elucidating the association between TAVI and cognition in the long term.
    Cardiovascular Psychiatry and Neurology 02/2015; 2015:1-8. DOI:10.1155/2015/209569
  • Biological Psychiatry 12/2014; 77(3). DOI:10.1016/j.biopsych.2014.06.006 · 10.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs. Methods: The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process. Results: Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as "strongly agree" or "somewhat agree" (68-88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications. Conclusions: A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.
    International Psychogeriatrics 10/2014; 27(1):1-11. DOI:10.1017/S1041610214001963 · 1.93 Impact Factor
  • Canadian Journal of Diabetes 10/2014; 38(5):S64. DOI:10.1016/j.jcjd.2014.07.180 · 2.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives Coronary artery disease (CAD) is associated with an increased risk of cognitive decline. While cerebral white matter (WM) damage predicts cognitive function in CAD, conventional neuroimaging measures only partially explain the effect of CAD on cognition. The purpose of this study is to determine if white matter microstructural integrity and CAD using diffusion tensor imaging (DTI) correlates with cognitive function in older adults with CAD. Methods 49 CAD patients (66±7 years, 86% male) underwent neurocognitive assessments using the cognitive battery recommended by the National Institute of Neurological Disorders and Stroke–Canadian Stroke Network for the study of vascular cognitive impairment. Composite scores for each cognitive domain were calculated. Microstructural integrity in normal appearing WM was quantified as fractional anisotropy (FA) using DTI in 9 bilateral and 2 inter-hemispheric WM tracts from the Johns Hopkins University WM Tractography Atlas. Linear regression models examined associations between FA and cognitive performance, controlling for age, sex, and education, with correction for multiple comparisons using a false discovery rate of 5%. Results Executive function was most significantly associated with FA in the left parahippocampal cingulum (β=.471, t=3.381, df=44, p=.002) and left inferior fronto-occipital fasciculus (β=.430, t=2.984, df=44, p=.005). FA was not associated with memory in any of the WM tracts examined. Conclusions These results suggest that WM microstructural integrity may be an important neural correlate of executive function even in cognitively intact CAD patients. This study suggests WM damage may be relevant to subtle cognitive decline in a population that may have early neural risk for dementia.
    American Journal of Geriatric Psychiatry 09/2014; 23(7). DOI:10.1016/j.jagp.2014.09.008 · 4.24 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Depression is a commonly occurring and persistent sequel of stroke affecting approximately 29% of patients. An immunological hypothesis has been put forward, and synthesis of kynurenine from tryptophan has been proposed to link inflammatory activity with neurotoxicity and neurotransmitter dysfunction. This study assessed the relationship between peripheral blood kynurenine and poststroke depressive symptoms.
    Neuropsychiatric Disease and Treatment 09/2014; 10:1827-35. DOI:10.2147/NDT.S65740 · 1.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose: Arterial transit time is the time needed for blood to travel from large arteries to capillaries, as estimated from arterial spin-labeling MR imaging. The purpose of this study was to determine whether vascular risk factors and cognitive performance are related to regional differences in cerebral arterial transit time in patients with coronary artery disease who are at risk for cognitive decline. Materials and methods: Arterial transit time was estimated from multiple postlabel delay pseudocontinuous arterial spin-labeling images obtained from 29 men with coronary artery disease. Tests of memory, attention, processing speed, and executive function were administered. Principal component analysis was used to create separate models of cognition and vascular risk, which were related to brain regions through voxelwise analyses of arterial transit time maps. Results: Principal component analysis identified 2 components of vascular risk: 1) "pressor" (age, systolic blood pressure, and pulse pressure) and 2) "obesity" (body fat percentage and body mass index). Obesity was inversely related to arterial transit time in the posterior cingulate, precuneus, lateral occipital cortices, middle temporal gyrus, and frontal pole (P corrected < .05), whereas pressor was not significant. Cognitive scores were factored into a single component. Poor performance was inversely related to precuneus arterial transit time (P corrected < .05). The average arterial transit time in regions identified by obesity was associated with poorer cognitive function (r(2) = 0.21, t = -2.65, P = .01). Conclusions: Altered cerebral hemodynamics, notably in nodal structures of the default mode network, may be one way that vascular risk factors impact cognition in patients with coronary artery disease.
    American Journal of Neuroradiology 08/2014; 36(2). DOI:10.3174/ajnr.A4094 · 3.59 Impact Factor

Publication Stats

5k Citations
962.99 Total Impact Points


  • 1994–2015
    • Sunnybrook Health Sciences Centre
      • Department of Psychiatry
      Toronto, Ontario, Canada
  • 1990–2015
    • University of Toronto
      • • Department of Psychiatry
      • • Department of Pharmacology and Toxicology
      • • Faculty of Medicine
      • • Sunnybrook Health Sciences Centre
      Toronto, Ontario, Canada
  • 2010
    • The University of Western Ontario
      • Department of Medicine
      London, Ontario, Canada
  • 1989
    • Instituto de Investigación Clínica de Occidente
      Zapopan, Jalisco, Mexico