Postural Changes in Spinal Cord Stimulation Thresholds: Current and Voltage Sources.

OBJECTIVE: Spinal cord stimulation (SCS) thresholds are known to change with body position; however, these changes have not been fully characterized for both "constant-voltage" and "constant-current" pulse generators. This study aimed to evaluate and quantify changes in psychophysical thresholds resulting from postural changes that may affect both conventional paresthesia-based SCS and novel paresthesia-free SCS technologies. MATERIALS AND METHODS: We measured perceptual, usage, and discomfort thresholds in four body positions (prone, supine, sitting, standing) in 149 consecutive patients, with temporary lower thoracic percutaneous epidural electrodes placed for treating persistent low back and leg pain. We trialed 119 patients with constant-voltage stimulators and 30 patients with constant-current stimulators. RESULTS: Moving from supine to the sitting, standing, or prone positions caused all three thresholds (perceptual, usage, and discomfort) to increase by 22% to 34% for constant-voltage stimulators and by 44% to 82% for constant-current stimulators. Changing from a seated to a supine position caused stimulation to exceed discomfort threshold significantly more often for constant-current (87%) than for constant-voltage (63%) stimulators (p = 0.01). CONCLUSIONS: Posture-induced changes in SCS thresholds occurred consistently as patients moved from lying (supine or prone) to upright (standing or sitting) positions. These changes were more pronounced for constant-current than for constant-voltage pulse generators and more often led to stimulation-evoked discomfort. These observations are consistent with postural changes in spinal cord position measured in imaging studies, and with computer model predictions of neural recruitment for these different spinal cord positions. These observations have implications for the design, implantation, and clinical application of spinal cord stimulators, not only for conventional paresthesia-based SCS but also for paresthesia-free SCS.

Streptococcus agalactiae infective endocarditis in Canada: a multicenter retrospective nested case control analysis.

BACKGROUND: Infective endocarditis (IE) caused by Streptococcus agalactiae (GBS) is increasingly reported and associated with an aggressive course and high mortality rate. Existing literature on GBS IE is limited to case series; we compared the characteristics of patients with GBS IE to patients with GBS bacteremia without IE to identify risk factors for development of IE. METHODS: A nested case-control study in a cohort of adult patients with GBS bacteremia over a 18-year period was conducted across seven centres in three Canadian cities. A chart review identified patients with possible or definite IE (per Modified Duke Criteria) and patients with IE were matched to those without endocarditis in a 1:3 fashion. Multivariate analyses were completed using logistic regression. RESULTS: Of 520 patients with GBS bacteremia, 28 cases of possible or definite IE were identified (5.4%). 68% (19/28) met criteria for definite IE, surgery was performed in 29% (8/28), and the overall in-hospital mortality rate was 29% (8/28). Multivariate analysis demonstrated that IE was associated with injection drug use (OR = 19.6, 95% CI = 3.39-111.11, p = 0.001), prosthetic valve (OR = 11.5, 95% CI = 1.73-76.92, p = 0.011) and lack of identified source of bacteremia (OR = 3.81, 95% CI = 1.24-11.65, p = 0.019). CONCLUSIONS: GBS bacteremia, especially amongst people who inject drugs, those with prosthetic valves, and those with no apparent source of infection, should increase clinical suspicion for IE.

Systemic immune activation leads to neuroinflammation and sickness behavior in mice.

Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS) is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and depressive-like behavior in mice. We report that systemic administration of LPS induced astrocyte activation in transgenic GFAP-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice. Furthermore, LPS treatment caused a strong but transient increase in cytokine levels in the serum and brain. In addition to studying LPS-induced neuroinflammation, we tested whether sickness could be separated from depressive-like behavior by evaluating LPS-treated mice in a panel of behavioral paradigms. Our behavioral data indicate that systemic LPS administration caused sickness and mild depressive-like behavior. However, due to the overlapping time course and mild effects on depression-related behavior per se, it was not possible to separate sickness from depressive-like behavior in the present rodent model.

Cannabis education needs assessment among Canadian physicians-in-training.

BACKGROUND: Since 1999, the Canadian courts have recognized the rights of patients to access cannabis for therapeutic purposes (CTP). Due to the increasing interest in the use of CTP, competency with the topic among health care providers is essential. As concerns mount around the role of industry involvement in cannabis education, it has become increasingly important for medical schools to provide physicians-in-training balanced evidence regarding the harms and benefits of CTP. In the present study, we surveyed Canadian physicians-in-training regarding their knowledge, experience, attitudes, and barriers surrounding CTP. METHODS: Survey questions were adapted from extant physician and nurse practitioner education needs assessments. We invited representatives from all 17 Canadian universities with a Faculty of Medicine to electronically distribute the survey to physicians-in-training. RESULTS: The survey was accessed by 93 physicians-in-training of whom 76 provided responses (46 % female; Mage = 28, SD = 3.03). Physicians-in-training reported receiving significantly less instruction on CTP than they desired. Responses demonstrated differences between current and desired knowledge across all domains queried. More education was the factor identified as most likely to increase comfort authorizing and discussing CTP with patients. CONCLUSIONS: Findings from this study demonstrate an expressed desire for more education surrounding CTP among a self-selected sample of Canadian physicians-in-training. There was a substantial divergence between current and desired levels of knowledge, and the largest gaps related to creating effective treatment plans and understanding the risks and benefits of CTP. Improving the educational opportunities of students will improve standard-of-care for patients.

Systematic Analysis of the Cytokine and Anhedonia Response to Peripheral Lipopolysaccharide Administration in Rats.

Inflammatory processes may cause depression in subsets of vulnerable individuals. Inflammation-associated behavioral changes are commonly modelled in rodents by administration of bacterial lipopolysaccharide (LPS). However, the time frame in which immune activation and depressive-like behavior occur is not very clear. In this study, we showed that systemic administration of LPS robustly increased circulating levels of corticosterone, leptin, pro- and anti-inflammatory cytokines, and chemokines. Serum concentrations of most analytes peaked within the first 6 h after LPS injection and returned to baseline values by 24 h. Chemokine levels, however, remained elevated for up to 96 h. Using an optimized sucrose preference test (SPT) we showed that sickness behavior was present from 2 to 24 h. LPS-induced anhedonia, as measured by decreased sucrose preference, lasted up to 96 h. To mimic the human situation, where depression develops after chronic inflammation, rats were preexposed to repeated LPS administration or subchronic restraint stress and subsequently challenged with LPS. While these procedures did not increase the duration of anhedonia, our results do indicate that inflammation may cause depressive symptoms such as anhedonia. Using our SPT protocol, more elaborate rodent models can be developed to study the mechanisms underlying inflammation-associated depression in humans.