Pryseley Nkouibert Assam

Association between white matter hyperintensity and medial temporal atrophy at various stages of Alzheimer's disease

Whilst there is evidence implicating small vessel cerebrovascular disease in the pathogenesis of Alzheimers disease (AD), its specific contribution to the pathophysiology of AD remains unclear. The burden of small vessel cerebrovascular disease visualized as white matter hyperintensity (WMH) and its association with medial temporal atrophy (MTA) at different stages of AD was studied.

Rationale, Methodology, and Implementation of a Dispatcher-assisted Cardiopulmonary Resuscitation Trial in the Asia-Pacific (Pan-Asian Resuscitation Outcomes Study Phase 2)

Abstract Background. Survival outcomes from out-of-hospital cardiac arrest (OHCA) in Asia are poor (2–11%). Bystander cardiopulmonary resuscitation (CPR) rates are relatively low in Asia. Dispatcher-assisted CPR (DA-CPR) has recently emerged as a potentially cost-effective intervention to increase bystander CPR and survival from OHCA. The Pan-Asian Resuscitation Outcomes Study (PAROS), an Asia-Pacific cardiac arrest registry, was set up in 2009, with the aim of understanding OHCA as a disease in Asia and improving OHCA survival. The network has adopted DA-CPR as part of its strategy to improve OHCA survival. Objective. This article aims to describe the conceptualization, study design, potential benefits, and difficulties for implementation of DA-CPR trial in the Asia-Pacific. Methods. Two levels of intervention, basic and comprehensive, will be offered to PAROS participating sites. The basic level consists of implementation of a DA-CPR protocol and training program, while the comprehensive level consists of implementation of the basic level, with the addition of a dispatch quality measurement tool, quality improvement program, and community education program. Sites that are not able to implement the package will contribute control data. The primary outcome of the study is survival to hospital discharge or survival to 30 days post cardiac arrest. DA-CPR and bystander CPR are secondary outcomes. Conclusion. Implementation of DA-CPR requires concerted efforts by EMS leaders and supervisors, dispatchers, hospital stakeholders, policy makers, and the general public. The DA-CPR trial implemented by the PAROS sites, if successful, can serve as a model for other countries considering such an intervention in their EMS systems.

Assessment of an updated double‐vasopressor automated system using Nexfin™ for the maintenance of haemodynamic stability to improve peri‐operative outcome during spinal anaesthesia for caesarean section

Hypotension occurs commonly during spinal anaesthesia for caesarean section, associated with maternal and fetal adverse effects. We developed a double‐vasopressor automated system with a two‐step algorithm and continuous non‐invasive haemodynamic monitoring using the Nexfin™ device. The system delivered 25 μg phenylephrine every 30 s when systolic blood pressure was between 90% and 100% of baseline, or 2 mg ephedrine at this blood pressure range and heart rate < 60 beats.min−1; and 50 μg phenylephrine or 4 mg ephedrine when systolic blood pressure was < 90% of baseline with the same heart rate criterion. Fifty‐seven women received standardised spinal anaesthesia. Twenty‐seven (47.4%) had at least one reading of hypotension defined as systolic blood pressure < 80% baseline. Systolic blood pressure was within 20% of the baseline in a mean (SD) of 79.8 (20.9)% of measurements. Fifty‐three (93.0%) women required phenylephrine before delivery while 10 (17.5%) required ephedrine. Six women (10.5%) experienced nausea and three (5.3%) vomited. The system was able to achieve a low incidence of maternal hypotension with good maternal and fetal outcomes.

A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial

We sought to determine if vitamin D supplementation, to target 25(OH)D concentrations of 30–40 ng/mL, improves endothelial function in Singapore’s multi-ethnic type 2 diabetes mellitus population. We randomised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [baseline 25(OH)D < 20 ng/mL] or cholecalciferol 2000 International Unit/matching placebo [baseline 25(OH)D: 20–30 ng/mL] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry (reactive hyperaemia index–endothelial peripheral arterial tonometry) and vascular biomarkers: E-selectin, von-Willebrand factor and high-sensitivity C-reactive protein. We compared the change from baseline parameters in the two groups using Student’s t-test or Kruskal–Wallis test. A log-normal multivariate regression analysis was used to adjust for relevant baseline variables. The median reactive hyperaemia index in the vitamin D group increased from 0.65 (interquartile range: 0.42) to 0.73 (interquartile range: 0.36), whereas it decreased from 0.73 (interquartile range: 0.65) to 0.65 (interquartile range: 0.38) (p = 0.02) in the placebo group. After adjustment for baseline variables, the change was not statistically significant for reactive hyperaemia index (p = 0.07) and for other vascular biomarkers (p > 0.05). Targeted vitamin D supplementation for 16 weeks resulted in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort.

Modifiable Factors Associated With Survival After Out-of-Hospital Cardiac Arrest in the Pan-Asian Resuscitation Outcomes Study

Study objective The study aims to identify modifiable factors associated with improved out‐of‐hospital cardiac arrest survival among communities in the Pan‐Asian Resuscitation Outcomes Study (PAROS) Clinical Research Network: Japan, Singapore, South Korea, Malaysia, Taiwan, Thailand, and the United Arab Emirates (Dubai). Methods This was a prospective, international, multicenter cohort study of out‐of‐hospital cardiac arrest in the Asia‐Pacific. Arrests caused by trauma, patients who were not transported by emergency medical services (EMS), and pediatric out‐of‐hospital cardiac arrest cases (<18 years) were excluded from the analysis. Modifiable out‐of‐hospital factors (bystander cardiopulmonary resuscitation [CPR] and defibrillation, out‐of‐hospital defibrillation, advanced airway, and drug administration) were compared for all out‐of‐hospital cardiac arrest patients presenting to EMS and participating hospitals. The primary outcome measure was survival to hospital discharge or 30 days of hospitalization (if not discharged). We used multilevel mixed‐effects logistic regression models to identify factors independently associated with out‐of‐hospital cardiac arrest survival, accounting for clustering within each community. Results Of 66,780 out‐of‐hospital cardiac arrest cases reported between January 2009 and December 2012, we included 56,765 in the analysis. In the adjusted model, modifiable factors associated with improved out‐of‐hospital cardiac arrest outcomes included bystander CPR (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.31 to 1.55), response time less than or equal to 8 minutes (OR 1.52; 95% CI 1.35 to 1.71), and out‐of‐hospital defibrillation (OR 2.31; 95% CI 1.96 to 2.72). Out‐of‐hospital advanced airway (OR 0.73; 95% CI 0.67 to 0.80) was negatively associated with out‐of‐hospital cardiac arrest survival. Conclusion In the PAROS cohort, bystander CPR, out‐of‐hospital defibrillation, and response time less than or equal to 8 minutes were positively associated with increased out‐of‐hospital cardiac arrest survival, whereas out‐of‐hospital advanced airway was associated with decreased out‐of‐hospital cardiac arrest survival. Developing EMS systems should focus on basic life support interventions in out‐of‐hospital cardiac arrest resuscitation.

Cognitive Impairment after Mild Stroke: Development and Validation of the SIGNAL2 Risk Score.

BACKGROUND Post stroke cognitive impairment (PSCI), an important complication of strokes, has numerous risk factors. A scale adequately classifying risk of cognitive impairment 3-6 months after mild stroke will be useful for clinicians. OBJECTIVE To develop a risk score based on clinical and neuroimaging variables that will be useful in identifying mild ischemic stroke patients at high risk for PSCI. METHODS The risk score development cohort comprised of a retrospective dataset of 209 mild stroke patients with MRI confirmed infarcts, without pre-stroke cognitive impairment, and evaluated within 6 months post-stroke for PSCI. Logistic regression identified factors predictive of PSCI and a risk score was developed based on regression coefficients. The risk score was checked for stability using 10-fold cross-validation and validated in an independent prospective cohort of 185 ischemic mild stroke patients. RESULTS Within 6 months post-stroke, 37.32% developed PSCI in the retrospective dataset. A 15-point risk score based on age, education, acute cortical infarcts, white matter hyperintensity, chronic lacunes, global cortical atrophy, and intracranial large vessel stenosis was highly predictive of PSCI with an AUC of 0.829. 10.11% with low scores, 52.69% with moderate scores, and 74.07% with high scores developed PSCI. In the prospective validation cohort, the model had an AUC of 0.776, and exhibited similar accuracy and stability statistics at both 6 and 12 months. CONCLUSION The seven item risk score adequately identified mild stroke patients who are at an increased risk of developing PSCI.

Investigating analgesic and psychological factors associated with risk of postpartum depression development: a case–control study

Aim The aim of this study was to investigate the role of peripartum analgesic and psychological factors that may be related to postpartum depression (PPD). Methods This case–control study was conducted in pregnant females who delivered at KK Women’s and Children’s Hospital from November 2010 to October 2013 and had postpartum psychological assessment. Demographic, medical, and postpartum psychological status assessments, intrapartum data including method of induction of labor, mode of labor analgesia, duration of first and second stages of labor, mode of delivery, and pain intensity on hospital admission and after delivery were collected. PPD was assessed using the Edinburgh Postnatal Depression Scale and clinical assessment by the psychiatrist. Results There were 62 cases of PPD and 417 controls after childbirth within 4–8 weeks. The odds of PPD was significantly lower (33 of 329 [10.0%]) in females who received epidural analgesia for labor compared with those who chose nonepidural analgesia (29 of 150 [19.3%]) ([odds ratio] 0.47 (0.27–0.8), P=0.0078). The multivariate analysis showed that absence of labor epidural analgesia, increasing age, family history of depression, history of depression, and previous history of PPD were independent risk factors for development of PPD. Conclusion The absence of labor epidural analgesia remained as an independent risk factor for development of PPD when adjusted for psychiatric predictors of PPD such as history of depression or PPD and family history of depression.

Uncontrolled diabetes mellitus: Prevalence and risk factors among people with type 2 diabetes mellitus in an Urban District of Karachi, Pakistan.

AIMS This study aimed to explore the prevalence of, and factors associated with, uncontrolled diabetes mellitus (UDM) in a community setting in Pakistan. METHODOLOGY A single-center, cross-sectional study, conducted in a community-based specialized care center (SCC) for diabetes in District Central Karachi, in 2003, registered 452 type 2 DM participants, tested for HbA1c and interviewed face-to-face for other information. Logistic regression analysis was conducted to identify factors associated with UDM. RESULTS Prevalence of UDM among diabetes patients was found to be 38.9% (95% CI: 34.4-43.4%). Multivariable logistic regression model analysis indicated that age <50 years (OR: 1.9; 95% CI: 1.2-2.9), being diagnosed in a hospital (vs. a clinic) (OR: 1.8; 95% CI: 1.1-2.8), diabetes information from a doctor or nurse only (vs. multiple sources) (OR: 1.8; 95% CI: 1.2-2.9), higher monthly treatment cost (OR: 1.3; 95% CI: 1.1-1.6; for every extra 500 PKR), and higher consumption of tea (OR: 1.5; 95% CI: 1.0-2.2; for every 2 extra cups) were independently associated with UDM. CONCLUSION The prevalence of UDM was approximately 39% among persons with type 2 diabetes visiting a community based SCC for diabetes. Modifiable risk factors such as sources of diabetes information and black tea consumption can be considered as potential targets of interventions in Karachi.

Early detection of dementia in multilingual populations: Visual Cognitive Assessment Test (VCAT)

Background Early diagnosis of cognitive impairment allows timely intervention with pharmacological and non-pharmacological measures. However, current cognitive evaluation tools do not cater for multilingual populations. Objective To develop and validate a visual-based cognitive evaluation tool, the Visual Cognitive Assessment Test (VCAT), which can be administered to multilingual populations without the need for translation or adaptation. Method We designed a battery of tests to evaluate the domains of memory, executive function, visuospatial function, language and attention. Pilot testing of individual test items, followed by test refinement and development of a field version was performed. We subsequently validated VCAT for the diagnosis of mild cognitive impairment (MCI) and mild Alzheimers disease (AD). Diagnostic performance was assessed by the area under the curve (AUC), sensitivity (Se) and specificity (Sp). Results VCAT was validated in a sample of 206 participants. The sample comprised 53.9% males; mean age (SD) was 67.8 (8.86) years; mean years of education was 10.5(6.0). AUC of VCAT for detection of cognitive impairment was found to be 93.3 (95% CI 90.1 to 96.4). Also, the Se and Sp of VCAT for the diagnosis of cognitive impairment (MCI and mild AD) were 85.6% and 81.1%, respectively. VCATs diagnostic Se and Sp comparable to those of the Montreal Cognitive Assessment in the same cohort. Mean time-to-complete VCAT was 15.7±7.3 min. Conclusions The VCAT has good Se and Sp for the diagnosis of MCI and mild AD. The visual-based test paradigm allows easy application to multilingual populations without the need for translation or adaptation.

Estimating Information Processing in a Memory System: The Utility of Meta-analytic Methods for Genetics

Genetic studies in Drosophila reveal that olfactory memory relies on a brain structure called the mushroom body. The mainstream view is that each of the three lobes of the mushroom body play specialized roles in short-term aversive olfactory memory, but a number of studies have made divergent conclusions based on their varying experimental findings. Like many fields, neurogenetics uses null hypothesis significance testing for data analysis. Critics of significance testing claim that this method promotes discrepancies by using arbitrary thresholds (α) to apply reject/accept dichotomies to continuous data, which is not reflective of the biological reality of quantitative phenotypes. We explored using estimation statistics, an alternative data analysis framework, to examine published fly short-term memory data. Systematic review was used to identify behavioral experiments examining the physiological basis of olfactory memory and meta-analytic approaches were applied to assess the role of lobular specialization. Multivariate meta-regression models revealed that short-term memory lobular specialization is not supported by the data; it identified the cellular extent of a transgenic driver as the major predictor of its effect on short-term memory. These findings demonstrate that effect sizes, meta-analysis, meta-regression, hierarchical models and estimation methods in general can be successfully harnessed to identify knowledge gaps, synthesize divergent results, accommodate heterogeneous experimental design and quantify genetic mechanisms.