Christine Leong

Staphylococcus aureus harbouring Enterotoxin A as a possible risk factor for multiple sclerosis exacerbations

Background: Staphylococcus aureus may produce superantigens that can non-specifically activate CD4+ cells to potentially target the myelin basic protein. Objective: This study examined the association between individuals with multiple sclerosis (MS) and colonization with S. aureus harbouring superantigens. Methods: Nasal swabs were collected from non-MS subjects and patients with MS who had not experienced a relapse in the past six months (MS stable group) and who had suffered a relapse within 30 days of study recruitment (MS exacerbation group). S. aureus was isolated from the anterior nares of participants following standard procedures and staphylococcal superantigen genes (sea, seb, and tsst-1) were detected using standard laboratory PCR techniques. Results: The study enrolled 204 patients, 80 in the non-MS and MS stable groups and 44 patients in the MS exacerbation group. Overall, 27.0% of patients were colonized with S. aureus with no significant differences identified between study groups. Amongst individuals colonized with S. aureus, the prevalence of sea was significantly greater in the MS exacerbation versus non-MS study group (p < 0.05; odds ratio 7.9; 95% confidence interval 1.2–49.5). Conclusions: The ability to rapidly screen patients for the presence of S. aureus producing sea may serve as a useful marker of a potential MS exacerbation.

Fatigue and Cognition in Patients with Relapsing Multiple Sclerosis Treated with Interferon Beta

ABSTRACT Introduction: Fatigue and cognitive deficits are common symptoms affecting patients with multiple sclerosis. Methods: The effects of interferon beta on fatigue and cognitive deficits were assessed in 50 patients with relapsing multiple sclerosis (recruited at a single center). The pre-treatment assessments were performed on visits 1 and 2 (Months 0 and 3). Patients started treatment with subcutaneous interferon beta-1a or beta-1b, or intramuscular interferon beta-1a at Month 3, with reassessment at visits 3 and 4 (6 and 12 months, respectively). Co-primary endpoints were change in fatigue (Modified Fatigue Impact Scale) and change in cognition (Brief Repeatable Battery of Neuropsychological Tests) from pre-treatment to visits 3 and 4. Follow-up data were obtained for 40 patients. Results: The pre-treatment demographic and disease characteristics did not differ between groups. Improvements in fatigue levels were reported for patients receiving subcutaneous interferon beta-1a versus patients in the intramuscular interferon beta-1a group (p = .04) and in the interferon beta-1b group (p = .09). Improvements were also reported in five out of 17 cognitive indices for all the treatment groups. Conclusion: The data suggest that interferon beta may reduce fatigue and cognitive deficits in patients with relapsing multiple sclerosis. Larger, randomized, and controlled studies are required to confirm our findings.

Axotomy-induced up-regulation of tumor necrosis factor-alpha in the dorsal root ganglia.

Abstract Objectives: Neuropathic pain is a chronic pain syndrome associated with drug, injury or disease-induced damage or destruction of sensory afferent fibers of the dorsal root ganglia (DRG). Although the exact underlying pathologic mechanisms are not known, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) are recognized as potential modulators of peripheral and central nervous system inflammatory responses. They play a crucial role in injury and the pathologic development of chronic pain syndromes such as neuropathic pain. Methods: Twenty-four rats were divided into a naive control (n=6), sham (surgery exposing sciatic nerve, n=6), and peripheral nerve lesion group (unilateral axotomy of sciatic nerve, n=12). Results: The results of this study demonstrate a transient up-regulation of TNF-α expression within ipsi- and contralateral DRG following complete unilateral sciatic nerve axotomy as confirmed by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR. Elevated expression of TNF-α was noted to occur within the first 7 days post-axotomy, which subsequently normalized to baseline levels by day 14. This transient up-regulation was also associated with a switch in cellular source from predominant satellite cell expression at baseline to that involving satellite cells and abundant numbers of sensory neurons. Discussion: These results support the role of TNF-α in the upstream cascade of cellular events involved in the underlying pathogenesis of neuropathic pain. Strategies targeting the early attenuation of TNF-α within the DRG during the first week post-injury may have significant clinical impact in preventing the downstream cascade of events involved in the underlying cellular pathology of neuropathic pain.

Psychotropic Drug Use before, during, and after Pregnancy: A Population-Based Study in a Canadian Cohort (2001-2013):

Objective: To describe the extent of increase in use and the rate of continuation versus discontinuation of psychotropic agents before, during, and after pregnancy. Methods: Rates of psychotropic use (antidepressants, anxiolytic/sedative-hypnotics, antiepileptics, antipsychotics, lithium, stimulants) among women with a hospital-recorded pregnancy outcome were assessed using databases at the Manitoba Centre for Health Policy. Rate of use was defined as ≥1 prescription over the total number of pregnancies in the 3-12 months before pregnancy, 0-3 months before pregnancy, during pregnancy, or 3 months after pregnancy. Continued use was defined as ≥2 prescriptions with gap ≤14 days. Poisson regression was used to analyze trends. Results: Over the study period, a psychotropic drug was used before, during, or after pregnancy in 41,923 of 224,762 pregnancies. From 2001 to 2013, psychotropic use increased 1.5-fold from 11.1% to 16.2% (p < 0.0001) in the 3-12 months before pregnancy, 1.6-fold from 6.4% to 10.5% (p < 0.0001) in the 3 months before pregnancy, 1.8-fold from 3.3% to 6.0% (p < 0.0001) during pregnancy, and 1.5-fold from 6.2% to 9.5% (p < 0.0001) in the 3 months postpartum. Among the 13,579 women who received at least 1 psychotropic agent in the 3 months prior to pregnancy, 38.5% stopped the agent prior to pregnancy and only 10.3% continued use throughout pregnancy. Continued use throughout pregnancy was higher (56.9%) among the 6693 women who received at least 2 prescriptions for a psychotropic agent and were at least 80% adherent in the 3 months prior to pregnancy. Conclusion: The use of psychotropic agents increased over 12 years. The safety of continuing versus discontinuing these agents during pregnancy remains uncertain, but we observed a decrease in psychotropic drug use during the pregnancy period.

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research

Various adverse events resulting from, or associated with, benzodiazepine and/or Z-drug use have been extensively reported on and discussed in great detail within the biomedical literature. It is widely accepted that motor vehicle accidents and falls leading to fractures in older adults are major adverse events that have been shown to occur more frequently in users of sedative-hypnotic medication, especially of the benzodiazepine and related Z-drug variety. However, the last few years have seen increasing reports in the literature raising the issue of benzodiazepine and Z-drug exposure in the development of other serious medical issues including dementia, infections, respiratory disease exacerbation, pancreatitis, and cancer. This article provides an overview and interpretation on the current state of evidence regarding each of these associations and proposes what gaps in the evidence for drug-exposure–harm associations need to be addressed in the future for the purpose of evaluating causality of harm as it relates to these drugs.

Student perspectives of an online module for teaching physical assessment skills for dentistry, dental hygiene, and pharmacy students

Abstract The integration of web-based learning into the curriculum of healthcare education has significantly increased over the past decade. This article aims to describe the student perspectives of an online module to teach physical assessment skills for pharmacy, dentistry, and dental hygiene students. A total of 103 students completed the online module: 48 third-year pharmacy students, 29 first-year dentistry students, and 26 first-year dental hygiene students. Students were asked to rate a list of 10 statements on a 5-point Likert scale on the relevance, impact, and overall satisfaction of the online module. Eighty-four of the 103 students (81.6% response rate) completed the questionnaire. While most students responded positively to the online content, pharmacy students responded more favorably compared with students from Dentistry and Dental Hygiene. These findings provide useful information to identify areas in which the web-based module can be improved for teaching skills in physical assessment across multiple healthcare programs.

A physical assessment skills module on vital signs.

Objectives. To implement and evaluate a physical assessment module for pharmacy students. Design. A physical assessment module focusing on vital signs was incorporated into the curriculum for third-year pharmacy students. This module consisted of an online component, a practical skills workshop, and a clinical practice site. Assessment. The mean score on the in-class quiz, which evaluated students’ knowledge of physical assessment after completion of the online module, was 94%. During the practical skills laboratory, 48% of student-measured systolic blood pressure (BP) readings and 60% of student-measured diastolic BP readings were within 5 mmHg of the machine reading. In the assessment of blood pressure technique, areas of difficulty included detection of Korotkoff sounds; steady deflation of cuff; and hand-eye coordination. Conclusion. Students more frequently underestimated systolic BP than the diastolic BP when compared to the automated machine readings. Findings from this study will be used to improve existing modules and evaluation methods on the physical assessment of vital signs.

Emerging Therapies for the Management of Multiple Sclerosis

Objective: To provide a comprehensive overview on the emerging treatments used for the treatment management of multiple sclerosis (MS). Data Sources: PubMed, MEDLINE, Cochrane, and Toxnet databases were used to conduct all comprehensive literature searches over the time period of 1989 to 2009. Search terms such as: multiple sclerosis and oral treatment, monoclonal antibodies, hormonal therapy, and stem cell transplant were used as key word search indicators. Study Selection: A total of 48 studies were reviewed and selected based on Level 1, 2, and 3 search strategies. Data Extraction: Level 1 search strategies were initially aimed at evidence-based trials of large sample size (N > 100) with a randomized, double-blind, placebo-controlled design in the area of specialized interest. A level 2 search was conducted for additional trials that had many but not all of the desirable traits of evidence-based trials. In addition, a level 3 search strategy was conducted to compare key findings stated in anecdotal reports of very small (N < 15), poorly designed trials with the results of well-designed, evidence-based trials identified in level 1 and/or level 2 searches. Data Synthesis and Conclusion: Despite the wide array of recent treatment advances in the field of MS, the cure still remains elusive. At present, current available treatments at best are only able to slow disease progression by reducing the incidence severity and duration of MS attacks. Recent treatment advances involving the use of newly designed orally administered drugs, monoclonal antibodies with the introduction of stem cell transplantation have revolutionized clinical outcomes for MS patients. Despite great strides made toward disease attenuation, the risks associated with the new treatments are real and have to be weighed against the projected benefits of drug treatment for a disease which has no cure.

New antidepressant use in older adults: a Canadian population-based study (1997–2013)

ABSTRACT Objective: There has been much attention on appropriate prescribing in older adults in recent years. Recent guidelines favor the use of newer antidepressants over older agents based on their safety profile in this population. This study aimed to examine whether there has been a decline in older antidepressants and an increase in newer antidepressants used by older adults. Method: A retrospective cross-sectional study using administrative databases examined the annual incidence of antidepressant use (per 1000) of community-dwelling adults ≥60 years old between 1997/1998 and 2012/2013 in Manitoba, Canada. Results: The population of Manitoba ≥60 years increased by 25.6% from 188,296 to 236,569 from 1997/1998 to 2012/2013. New antidepressant use peaked to 45.9 per 1000 in 1999/2000, and then decreased steadily to 30.5 per 1000 in 2012/2013 (p < 0.0001). Incident amitriptyline use was high but declined from 15.5 to 7.4 per 1000 (p < 0.001). An increase in incident trazodone, mirtazapine, and venlafaxine use was observed (p < 0.001). Conclusions: There has been an overall decrease in the annual incidence of antidepressant users in older adults over the last 16 years, with a marked decline in new amitriptyline use and an increase in the incidence of newer agents.

Treating recurrent postmenopausal vasomotor symptoms in a patient with a positive family history for breast cancer.

OBJECTIVE To report a case of recurrent hot flashes unresponsive to gabapentin in a postmenopausal patient with a positive family history of breast cancer. CASE SUMMARY A 69-year-old Caucasian female experienced a recurrence of debilitating hot flashes for the past eight months. More recently, she failed a two-month trial of gabapentin 600 mg by mouth at bedtime after she previously received effective hormone replacement therapy (HRT) seven years ago with near-complete resolution of her symptoms. The patient had a sister and a niece who developed breast cancer in their 40s. DISCUSSION The treatment of postmenopausal hot flashes in a patient with a positive family history of breast cancer represents a clinical challenge for many clinicians. This case is an example in which gabapentin was ineffective in the treatment of severe hot flashes in a postmenopausal woman. The risks and benefits of HRT compared with nonhormonal alternatives were assessed. CONCLUSION In this case, a two-month trial of gabapentin 600 mg/day failed to demonstrate efficacy in reducing the severity, frequency, and duration of hot flashes. Controlled trials are necessary to evaluate the safety and efficacy of other therapeutic alternatives.