To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Influenza vaccination remains the most effective primary prevention strategy for seasonal influenza. This research explores the percentage of emergency medical services (EMS) clinicians who received the seasonal flu vaccine in a given year, along with their reasons for vaccine acceptance and potential barriers.
A survey was distributed to all EMS clinicians in Virginia during the 2018-2019 influenza season. The primary outcome was vaccination status. Secondary outcomes were attitudes and perceptions toward influenza vaccination, along with patient care behaviors when treating an influenza patient.
Ultimately, 2796 EMS clinicians throughout Virginia completed the survey sufficiently for analysis. Participants were mean 43.5 y old, 60.7% male, and included the full range of certifications. Overall, 79.4% of surveyed EMS clinicians received a seasonal flu vaccine, 74% had previously had the flu, and 18% subjectively reported previous side effects from the flu vaccine. Overall, 54% of respondents believed their agency has influenza or respiratory specific plans or procedures.
In a large, state-wide survey of EMS clinicians, overall influenza vaccination coverage was 79.4%. Understanding the underlying beliefs of EMS clinicians remains a critical priority for protecting these frontline clinicians. Agencies should consider practical policies, such as on-duty vaccination, to increase uptake.
ABSTRACT IMPACT: Findings from this study will better characterize the role of hearing loss in falls risk among patients with vestibulopathy and identify groups that are most at risk for falls. OBJECTIVES/GOALS: Vestibular dysfunction and hearing loss are independent risk factors for experiencing falls. The purpose of this study is to determine the extent, if any, to which hearing loss contributes to falls in patients with concomitant vestibular dysfunction presenting to a specialty vestibular clinic. METHODS/STUDY POPULATION: A retrospective chart review of patients ≥18 years who underwent vestibular evaluation at our institution from June 1, 2015 to October 7, 2020 will be conducted. Patients who underwent vestibular evaluation also received audiologic evaluation and degree of hearing loss will be characterized by the 4-frequency pure-tone average (0.5, 1, 2, and 4 kHz) of the better hearing ear. Falls status will be determined by the response to the following question administered at clinic-check in, ‘Have you fallen in the last 90 days?’ Demographics, comorbidities, and falls-associated medications will also be collected. RESULTS/ANTICIPATED RESULTS: A total of 3,265 unique patients who underwent vestibular evaluation in the study time period were identified. Patients will be categorized into discrete groups (benign paroxysmal positional vertigo, unilateral hypofunction, bilateral hypofunction, central dysfunction, and normal) based on laboratory results. Regression models will be developed to evaluate the potential association between degree of hearing loss and falls in patients with different types of vestibular dysfunction, while adjusting for demographics, comorbidities, and falls-associated medications. DISCUSSION/SIGNIFICANCE OF FINDINGS: Findings from this study will better characterize the role of hearing loss in falls risk among patients with vestibulopathy and identify groups that are most at risk for falls. This study may potentially indicate the importance of hearing evaluation in the work-up of patients with vestibulopathy.
ABSTRACT IMPACT: This study characterizes interactions between human limbic circuitry and ventral temporal cortex using single pulse electrical stimulation, which may inform emerging stimulation therapies for epilepsy. OBJECTIVES/GOALS: The goal of electrical brain stimulation treatment is to modulate brain network function. However, stimulation inputs to different brain sites alter the network in a variety of ways. This study examines that variability by characterizing responses in a target region while stimulating multiple other brain sites. METHODS/STUDY POPULATION: We measured voltages in intracranial EEG in 6 patients who had electrodes implanted for epilepsy monitoring. We stimulated pairs of electrodes at multiple sites in the brain with a single pulse every 5 to 7 s and measured the resulting corticocortical evoked potential (CCEP) responses in the ventral temporal cortex (VTC). Using a novel clustering method, we uncovered sets of distinct canonical response shapes from the 20 to 500 ms post-stimulation period. This allowed us to group stimulation sites that evoked similar responses. We then related each group to high frequency, broadband, changes in spectral power as a reflection of local neuronal activity. RESULTS/ANTICIPATED RESULTS: We found that the VTC receives strong inputs specifically from the amygdala and hippocampus, both in terms of amplitude and broadband spectral power change. However, inputs from the hippocampus produced a different canonical shape than those from the amygdala. We also observed that VTC responses to inputs from the insula clustered in shape with those from the amygdala. These clustering patterns were consistent across subjects, although the actual shapes of the clusters showed variability. We further observed that some shapes were more associated with increases in overall neuronal activity than others, as reflected by broadband spectral power change. DISCUSSION/SIGNIFICANCE OF FINDINGS: Stimulation of connected sites may drive excitability at the target region in ways that are described by sets of full-time-course responses. By capturing their shapes, we can begin to decipher canonical input types at the circuit level. This approach might identify how stimulation inputs can be tailored to therapy while mitigating adverse effects.
Infection prevention and control (IPC) workflows are often retrospective and manual. New tools, however, have entered the field to facilitate rapid prospective monitoring of infections in hospitals. Although artificial intelligence (AI)–enabled platforms facilitate timely, on-demand integration of clinical data feeds with pathogen whole-genome sequencing (WGS), a standardized workflow to fully harness the power of such tools is lacking. We report a novel, evidence-based workflow that promotes quicker infection surveillance via AI-assisted clinical and WGS data analysis. The algorithm suggests clusters based on a combination of similar minimum inhibitory concentration (MIC) data, timing of sample collection, and shared location stays between patients. It helps to proactively guide IPC professionals during investigation of infectious outbreaks and surveillance of multidrug-resistant organisms and healthcare-acquired infections. Methods: Our team established a 1-year workgroup comprised of IPC practitioners, clinical experts, and scientists in the field. We held weekly roundtables to study lessons learned in an ongoing surveillance effort at a tertiary care hospital—utilizing Philips IntelliSpace Epidemiology (ISEpi), an AI-powered system—to understand how such a tool can enhance practice. Based on real-time case discussions and evidence from the literature, a workflow guidance tool and checklist were codified. Results: In our workflow, data-informed clusters posed by ISEpi underwent triage and expert follow-up analysis to assess: (1) likelihood of transmission(s); (2) potential vector(s) identity; (3) need to request WGS; and (4) intervention(s) to be pursued, if warranted. In a representative sample (spanning October 17, 2019, to November 7, 2019) of 67 total isolates suggested for inclusion in 19 unique cluster investigations, we determined that 9 investigations merited follow-up. Collectively, these 9 investigations involved 21 patients and required 115 minutes to review in ISEpi and an additional 70 minutes of review outside of ISEpi. After review, 6 investigations were deemed unlikely to represent a transmission; the other 3 had potential to represent transmission for which interventions would be performed. Conclusions: This study offers an important framework for adaptation of existing infection control workflow strategies to leverage the utility of rapidly integrated clinical and WGS data. This workflow can also facilitate time-sensitive decisions regarding sequencing of specific pathogens given the preponderance of available clinical data supporting investigations. In this regard, our work sets a new standard of practice: precision infection prevention (PIP). Ongoing effort is aimed at development of AI-powered capabilities for enterprise-level quality and safety improvement initiatives.
Funding: Philips Healthcare provided support for this study.
Disclosures: Alan Doty and Juan Jose Carmona report salary from Philips Healthcare.
Background: Due to limited therapeutic options and potential for spread, carbapenem-resistant Enterobacteriaceae (CRE)-producing New Delhi metallo-β-lactamases (NDMs) are a public health priority. We investigated the epidemiology of NDM-producing CRE reported to the CDC to clarify its distribution and relative prevalence. Methods: The CDC’s Antibiotic Resistance Laboratory Network supports molecular testing of CRE for 5 carbapenemases nationally. Although KPC is the most common carbapenemase in the United States, non-KPC carbapenemases are a growing concern. We analyzed CRE with any of 4 non-KPC plasmid-mediated carbapenemases (NDM, VIM, IMP, or OXA-48 type) isolated from specimens collected from January 1, 2017, through June 30, 2019; only a patient’s first isolate per organism–carbapenemase combination was included. We excluded isolates from specimen sources associated with colonization screening (eg, perirectal). We compared the proportion of NDM-producing CRE to all non-KPC–producing CP-CRE between period A (January to June 2018) and period B (January to June 2019). Health departments and the CDC collected additional exposure and molecular information in selected states to better describe current NDM-producing CRE epidemiology. Results: Overall, 47 states reported 1,013 non–KPC-producing CP-CRE (range/state, 1–109 isolates; median, 11 isolates); 46 states reported 631 NDM-producing CRE (range/state, 1–84; median, 6). NDM-producing CRE increased quarterly from the third quarter of 2018 through the second quarter of 2019; CP-CRE isolates with other non-KPC carbapenemases remained stable (Fig. 1). In period A, 124 of 216 emerging CP-CRE had NDM (57.1%), compared with 255 of 359 emerging CP-CRE (71.0%) during period B (P = .1179). Among NDM-producing CRE, the proportion of Enterobacter spp increased from 10.5% in 2018 to 18.4% in 2019 (P = .0467) (Fig. 2). In total, 18 states reported more NDM-producing CRE in the first 6 months of 2019 than in all of 2018. Connecticut, Ohio, and Oregon were among states that conducted detailed investigations; these 3 states identified 24 NDM-producing CRE isolates from 23 patients in period B. Overall, 5 (21.7%) of 22 patients with history available traveled internationally ≤12 months prior to culture; 17 (73.9%) acquired NDM-producing CRE domestically. Among 15 isolates sequenced, 8 (53.3%) carried NDM-5 (6 E. coli, 1 Enterobacter spp and 1 Klebsiella spp) and 7 (46.7%) carried NDM-1 (6 Enterobacter spp and 1 Klebsiella spp). Species were diverse; no single strain type was shared by >2 isolates. Conclusions: Detection of NDM-producing CRE has increased across the AR Lab Network. Among states with detailed information available, domestic acquisition was common, and no single variant or strain predominated. Aggressive public health response and further understanding of current US NDM-CRE epidemiology are needed to prevent further spread.
An examination of invasive procedure cancellations found that the lack of pre-procedural oral screening was a preventable cause, for children with congenital heart disease. The purpose of this study was to implement an oral screening tool within the paediatric cardiology clinic, with referral to paediatric dental providers for positive screens. The target population were children aged ≥6 months to <18 years old, being referred for cardiac procedures.
The quality implementation framework method was used for this study design. The multi-modal intervention included education, audit and feedback, screening guidelines, environmental support, and interdisciplinary collaboration. Baseline rates for oral screenings were determined by retrospective chart audit from January 2018 to January 2019 (n = 211). Provider adherence to the oral screening tool was the outcome measure. Positive oral screens, resulting in referral to the paediatric dental clinic, were measured as a secondary outcome. Provider adherence rates were used as a process measure.
Data collected over 14 weeks showed a 29% increase in documentation of oral screenings prior to referral, as compared to the retrospective chart audit. During the study period, 13% of completed screenings were positive (n = 5). Provider compliance for the period was averaged at 70% adherence.
A substantial increase in pre-procedural oral screenings by paediatric cardiologists was achieved using the quality implementation framework and targeted interventions.
To what extent does inadequate market regulation contribute to poor health outcomes? A series of prominent scandals involving harmful medical devices has made improving the regulation of these devices an urgent problem for the European Union (EU). This is, however, a specific example of a general phenomenon. The EU remains first and foremost a large and integrated market within which the EU institutions have considerable regulatory authority. Even if there is little EU commitment to a health or social policy agenda, its use of that regulatory authority shapes health care cost and quality and should be understood as health policy. We use data from EU-level and national policy documents to analyse the EU's current regulatory framework for medical devices and assess its likely future efficacy. Despite revising the medical devices directive to require more stringent pre-authorization requirements for high-risk medical devices and improvements in post-market surveillance, the key underlying problems of market fragmentation and patient safety persist. Without strong and consistent support for the implementation of the new directive, the likely result is the status quo, with significant consequences for health in Europe.
Fat metabolism is an important and complex biochemical reaction in vivo and is regulated by many factors. Recently, the findings on high expression of fibroblast growth factor-16 (FGF16) in brown adipose tissue have led to an interest in exploring its role in lipogenesis and lipid metabolism. The study cloned the goat’s FGF16 gene 624 bp long, including the complete open reading frame that encodes 207 amino acids. We found that FGF16 expression is highest in goat kidneys and hearts, followed by subcutaneous fat and triceps. Moreover, the expression of FGF16 reached its peak on the 2nd day of adipocyte differentiation (P < 0.01) and then decreased significantly. We used overexpression and interference to study the function of FGF16 gene in goat intramuscular preadipocytes. Silencing of FGF16 decreased adipocytes lipid droplet aggregation and triglyceride synthesis. This is in contrast to the situation where FGF16 is overexpressed. Furthermore, knockdown of FGF16 also caused down-regulated expression of genes associated with adipocyte differentiation including CCAAT enhancer-binding protein beta (P < 0.01), fatty acid-binding protein-2 (P < 0.01) and sterol regulatory element binding protein-1 (P < 0.05), but the preadipocyte factor-1 was up-regulated. At the same time, the genes adipose triglyceride lipase (P < 0.01) and hormone-sensitive lipase (P < 0.05) associated with triglyceride breakdown were highly expressed. Next, we locked the fibroblast growth factor receptor-4 (FGFR4) through the protein interaction network and interfering with FGF16 to significantly reduce FGFR4 expression. It was found that the expression profile of FGFR4 in adipocyte differentiation was highly similar to that of FGF16. Overexpression and interference methods confirmed that FGFR4 and FGF16 have the same promoting function in adipocyte differentiation. Finally, using co-transfection technology, pc-FGF16 and siRNA-FGFR4, siRNA2-FGF16 and siRNA-FGFR4 were combined to treat adipocytes separately. It was found that in the case of overexpression of FGF16, cell lipid secretion and triglyceride synthesis showed a trend of first increase and then decrease with increasing interference concentration. In the case of interference with FGF16, lipid secretion and triglyceride synthesis showed a downward trend with the increase of interference concentration. These findings illustrated that FGF16 mediates adipocyte differentiation via receptor FGFR4 expression and contributed to further study of the functional role of FGF16 in goat fat formation.
Within the scope of Design for Sustainable Behaviour, the connection between behavioural change strategies and design idea generation has received limited attention. This paper highlights metaphorical thinking in product design to stimulate sustainable behaviour. In particular, the current study proposes a metaphor-based design method to guide designers on how to associate product features with behavioural and experiential cues through metaphors. We next report two design cases to evaluate this method. In the end, the shortcomings of current research and future developments are also discussed.
From the prevention of natural disasters such as landslide and avalanches, to the enhancement of energy efficiencies in chemical and civil engineering industries, understanding the collective dynamics of granular materials is a fundamental question that are closely related to our daily lives. Using a recently developed multi-static radar system operating at 10 GHz (X-band), we explore the possibility of tracking a projectile moving inside a granular medium, focusing on possible sources of uncertainties in the detection and reconstruction processes. On the one hand, particle tracking with continuous-wave radar provides an extremely high temporal resolution. On the other hand, there are still challenges in obtaining tracer trajectories accurately. We show that some of the challenges can be resolved through a correction of the IQ mismatch in the raw signals obtained. Consequently, the tracer trajectories can be obtained with sub-millimeter spatial resolution. Such an advance can not only shed light on radar particle tracking, but also on a wide range of scenarios where issues relevant to IQ mismatch arise.
Surface waves called meniscus waves often appear in systems that are close to the capillary length scale. Since the meniscus shape determines the form of the meniscus waves, the resulting streaming circulation has features distinct from those caused by other capillary–gravity waves recently reported in the literature. In the present study, we produce symmetric and antisymmetric meniscus shapes by controlling boundary wettability and excite meniscus waves by oscillating the meniscus vertically. The symmetric and antisymmetric configurations produce different surface capillary–gravity wave modes and streaming flow structures. The root-mean-square speed of the streaming circulation increases with the second power of the forcing amplitude in both configurations. The flow symmetry of streaming circulation is retained under the symmetric meniscus, while it is lost under the antisymmetric meniscus. The streaming circulation pattern beneath the meniscus observed in our experiments is qualitatively explained using the method introduced by Nicolás & Vega (Fluid Dyn. Res., vol. 32 (4), 2003, pp. 119–139) and Gordillo & Mujica (J. Fluid Mech., vol. 754, 2014, pp. 590–604).
Introduction: Selecting appropriate patients for hospitalization following emergency department (ED) evaluation of syncope is critical for serious adverse event (SAE) identification. The primary objective of this study is to determine the association of hospitalization and SAE detection using propensity score (PS) matching. The secondary objective was to determine if SAE identification with hospitalization varied by the Canadian Syncope Risk Score (CSRS) risk-category. Methods: This was a secondary analysis of two large prospective cohort studies that enrolled adults (age ≥ 16 years) with syncope at 11 Canadian EDs. Patients with a serious condition identified during index ED evaluation were excluded. Outcome was a 30-day SAE identified either in-hospital for hospitalized patients or after ED disposition for discharged patients and included death, ventricular arrhythmia, non-lethal arrhythmia and non-arrhythmic SAE (myocardial infarction, structural heart disease, pulmonary embolism, hemorrhage). Patients were propensity matched using age, sex, blood pressure, prodrome, presumed ED diagnosis, ECG abnormalities, troponin, heart disease, hypertension, diabetes, arrival by ambulance and hospital site. Multivariable logistic regression assessed the interaction between CSRS and SAE detection and we report odds ratios (OR). Results: Of the 8183 patients enrolled, 743 (9.0%) patients were hospitalized and 658 (88.6%) were PS matched. The OR for SAE detection for hospitalized patients in comparison to those discharged from the ED was 5.0 (95%CI 3.3, 7.4), non-lethal arrhythmia 5.4 (95%CI 3.1, 9.6) and non-arrhythmic SAE 6.3 (95%CI 2.9, 13.5). Overall, the odds of any SAE identification, and specifically non-lethal arrhythmia and non-arrhythmia was significantly higher in-hospital among hospitalized patients than those discharged from the ED (p < 0.001). There were no significant differences in 30-day mortality (p = 1.00) or ventricular arrhythmia detection (p = 0.21). The interaction between ED disposition and CSRS was significant (p = 0.04) and the probability of 30-day SAEs while in-hospital was greater for medium and high risk CSRS patients. Conclusion: In this multicenter prospective cohort, 30-day SAE detection was greater for hospitalized compared with discharged patients. CSRS low-risk patients are least likely to have SAEs identified in-hospital; out-patient monitoring for moderate risk patients requires further study.
Introduction: Emergency department (ED) syncope management is extremely variable. We developed practice recommendations based on the validated Canadian Syncope Risk Score (CSRS) and outpatient cardiac monitoring strategy with physician input. Methods: We used a 2-step approach. Step-1: We pooled data from the derivation and validation prospective cohort studies (with adequate sample size) conducted at 11 Canadian sites (Sep 2010 to Apr 2018). Adults with syncope were enrolled excluding those with serious outcome identified during index ED evaluation. 30-day adjudicated serious outcomes were arrhythmic (arrhythmias, unknown cause of death) and non-arrhythmic (MI, structural heart disease, pulmonary embolism, hemorrhage)]. We compared the serious outcome proportion among risk categories using Cochran-Armitage test. Step-2: We conducted semi-structured interviews using observed risk to develop and refine the recommendations. We used purposive sampling of physicians involved in syncope care at 8 sites from Jun-Dec 2019 until theme saturation was reached. Two independent raters coded interviews using an inductive approach to identify themes; discrepancies were resolved by consensus. Results: Of the 8176 patients (mean age 54, 55% female), 293 (3.6%; 95%CI 3.2-4.0%) experienced 30-day serious outcomes; 0.4% deaths, 2.5% arrhythmic, 1.1% non-arrhythmic outcomes. The serious outcome proportion significantly increased from low to high-risk categories (p < 0.001; overall 0.6% to 27.7%; arrhythmic 0.2% to 17.3%; non-arrhythmic 0.4% to 5.9% respectively). C-statistic was 0.88 (95%CI0.86–0.90). Non-arrhythmia risk per day for the first 2 days was 0.5% for medium-risk, 2% for high-risk and very low thereafter. We recruited 31 physicians (14 ED, 7 cardiologists, 10 hospitalists/internists). 80% of physicians agreed that low risk patients can be discharged without specific follow-up with inconsistencies around length of ED observation. For cardiac monitoring of medium and high-risk, 64% indicated that they don't have access; 56% currently admit high-risk patients and an additional 20% agreed to this recommendation. A deeper exploration led to following refinement: discharge without specific follow-up for low-risk, a shared decision approach for medium-risk and short course of hospitalization for high-risk patients. Conclusion: The recommendations were developed (with online calculator) based on in-depth feedback from key stakeholders to improve uptake during implementation.
Background: Atrial fibrillation (AF) is a risk for stroke. The Canadian Cardiovascular Society advises patients who are CHADS65 positive should be started on oral anticoagulation (OAC). Our local emergency department (ED) review showed that only 16% of CHADS65 positive patients were started on OAC and that 2% of our patients were diagnosed with stroke within 90 days. We implemented a new pathway for initiation of OAC in the ED (the SAFE pathway). Aim Statement: We report the effectiveness and safety of the SAFE pathway for initiation of OAC in patients treated for AF in the ED. Measures & Design: A multidisciplinary group of physicians and pharmacist developed the SAFE pathway for patients who are discharged home from the ED with a diagnosis of AF. Step 1: contraindications to OAC, Step 2: CHADS65 score, Step 3: OAC dosing if indicated. The pathway triggers referral to AF clinic, family physician letter and follow up call from the ED pharmacist. Patients are followed for 90 days by a structured medical record review and a structured telephone interview. We record persistence with OAC, stroke, TIA, systemic arterial embolism and major bleeding (ISTH criteria). Patient outcomes are fed back to the treating ED physician. Evaluation/ Results: The SAFE pathway was introduced in two EDs in June 2018. In total, 177 patients have had the pathway applied. The median age was 70 (interquartile range (IQR) 61-78), 48% male, median CHADS2 score 2 (IQR 0-2). 19/177 patients (11%) had a contraindication to initiating OAC. 122 patients (69%) had no contraindication to OAC and were CHADS65 positive. Of these 122 patients, 109 were given a prescription for OAC (96 the correct dose, 9 too high a dose and 4 too low a dose). 6 patients declined OAC and the physician did not want to start OAC for 7 patients. 73/122 were contacted by phone at 90 days, 15 could not be reached and 34 have not completed 90 days of follow up since their ED visit. Of the 73 who were reached by phone after 90 days, 65 were still taking an anticoagulant. To date, 1 patient who declined OAC (CHADS2 score of 2) had a stroke within 90 days and one patient prescribed OAC had a gastrointestinal bleed. Discussion/Impact: The SAFE pathway appears safe and effective although we continue to evaluate and improve the process.
A variational framework for the identification and analysis of general nonlinear optimal disturbances in compressible flows is derived. The formulation is based on the compressible Navier–Stokes equations in conserved variables for an ideal gas with temperature-dependent viscosity. A discretely consistent implementation based on generalized coordinates allows the accurate analysis of a wide range of settings. An application in the identification of the optimal disturbances which experience the highest amplification in kinetic energy in pipe flow is presented. At low Mach numbers and moderate initial amplitude, the disturbances undergo a sequence of Orr mechanism, oblique nonlinear interaction and lift-up mechanism, and the energy amplification is consistent with results reported for incompressible flow (Pringle & Kerswell, Phys. Rev. Lett., vol. 105, 2010, 154502). When the Mach number is increased, the gain in perturbation kinetic energy grows appreciably, and the initial disturbance field becomes increasingly localized. Nonlinear optimal disturbances which are rescaled to higher initial kinetic energy than prescribed in the optimization procedure are demonstrated to evolve into a chaotic state. For a constant time horizon, the initial perturbation energy to reach a high-energy state decreases monotonically with Mach number.
This chapter argues that chronic pain (CP) represents an important and neglected type of disability. CP has important similarities to more familiar physical disabilities, but it cannot be regarded as a “mere difference,” and it fits uncomfortably under standard social models. The case of CP illustrates the need for flexibility in the definition of and social response to disability.
Efficacy of conventional repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder (MDD) is limited. The authors report here on an alternative treatment using low energy synchronized TMS (sTMS) at the intrinsic frequency of subjects’ alpha electroencephalogram (EEG).
Establish efficacy and safety profile of sTMS in MDD.
(1) Examine the clinical effectiveness of sTMS.
(2) Identify adverse effects associated with sTMS.
Fifty-two MDD subjects with 17-item Hamilton Depression Rating Scale (HAMD17) scores >17 were enrolled into a randomized, sham controlled, double-blind trial. Current medication remained unchanged during the trial. Depressive symptoms were evaluated by HAMD17 administered weekly.
EEGs were recorded at baseline to determine the stimulus frequency and at week 4 to evaluate the physiological effect. sTMS was delivered through three 6000-G cylindrical neodymium magnets synchronously rotating at a rate equal to the subject's intrinsic alpha frequency.
Forty-five subjects completed at least 1 week of treatment and were evaluable. Those who received active treatment had superior clinical response to sham (t = 2.54, P = 0.01), where 55.2% in the active treatment group were clinical responders versus 12.5% in sham (X2 = 7.82, P = 0.005). No significant side effects were reported. The clinical improvement was correlated with the degree of EEG improvement (r = .46, P = 0.009).
A therapeutic effect in MDD subjects can be achieved through administration of sTMS at the subject's alpha EEG frequency. Because of minimal side effects, this appears to be a safe and effective treatment option.
Despite strong evidence that the pathophysiology of tic disorders (TD) involves structural and functional disturbances of the basal ganglia, inconsistent findings from several TD imaging studies have supported contradictory conclusions.
To find brain structural differences between children with of TD and the health children and verify the pathogenesis hypothesis of that basal ganglia play an important role in this disorder.
The right handedness, first-episode TD children were chosen. Yale global tic severity scale (YGTSS) was used to assess the tic severity. MRI scan was performed on TD children and the controls. The volumes of caudate nucleus, putamen, globus pallidus and total intracranial volume were measured on high resolution MR images. We compared the volumes, relative volumes and asymmetry index, AI between groups.
Totally 11 patients finished this study with two excluded for the unclear image caused by tic and 18 subjects (9 TD patients and 9 controls) were finally analyzed. The right globus pallidus is significantly larger in TD patients. The volumes of left caudate increased significantly in both TD patients and controls. There was no significant difference in asymmetry index between two groups, relative volumes did not correlate significantly with the severity of tic and the course of disease.
The right globus pallidus may be the primary pathological change of TD. Asymmetry indexes between the two groups are not significantly different. The relative volume of any structure of basal ganglia has no significant correlation with the severity of tic and the course of disease.
We evaluated the efficacy of eszopiclone (ESZ) and concurrent escitalopram oxalate (EO) in patients with insomnia and co-morbid GAD.
Patients meeting DSM-IV-TR criteria for GAD and insomnia received 10 weeks of EO 10mg and co-therapy with ESZ 3mg or placebo (PBO) for 8 weeks. For the last 2 weeks, ESZ was replaced with single-blind PBO to evaluate discontinuation effects. Sleep, daytime functioning and anxiety measures were captured during the study.
ESZ+EO improved sleep and daytime functioning at each week and the double-blind period average (p<0.05). At Week 8, significantly more ESZ+EO patients had no clinically meaningful insomnia based on ISI</=7. Significant improvements with ESZ+EO (relative to PBO+EO) were observed in HAM-A total scores each week, and Weeks 4-10 excluding the insomnia item. ESZ+EO was significantly better at every timepoint on CGI-I (p<0.02); CGI-S was not different between treatments after Week 1. Median time to anxiolytic response was reduced with ESZ+EO based on HAM-A and CGI-I. HAM-A response and remission rates at Week 8 were higher with ESZ+EO, and HAM-D17 scores were improved at all timepoints (p<0.004). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and no treatment differences in sleep or daytime function. Significant treatment differences in anxiety and mood were maintained after discontinuation.
In this study, ESZ+EO was well tolerated and associated with improved sleep and daytime function without evidence of tolerance. Improvements in anxiety and mood were observed with ESZ+EO.
Support for this study provided by Sepracor Inc., Marlborough, MA.
Patients with chronic kidney disease (CKD) have more cognitive impairments. However, the etiologies are not fully clear. Plasma homocysteine levels and vascular burden rise in CKD; meanwhile, high homocysteine levels and vascular factors are known risk factors of dementia in non-CKD patients. Thus, we aimed to investigate the association between homocysteine, vascular burden and cognitive impairment in CKD and to see if the effect of elevated homocysteine on cognitive impairment mediated by vascular factor.
146 patients with CKD and 69 normal comparisons were recruited. Cognitive function was evaluated by comprehensive neuropsychological tests assessing processing speed, executive function, language, visuospatial function, memory, and attention domains. Vascular burden was assessed by Framinghan cardiovascular risk scale (FCRS) which indicates risk of atherosclerotic diseases including stroke.
In controlled analysis, patients with CKD had lower scores in all cognitive domains, and had higher homocysteine levels (18.5±6.4 vs. 9.8±2.9, p< 0.0001) and FCRS(17.0±4.7 vs. 14.0±4.7, p< 0.0001). Among patients with CKD, higher homocysteine levels (p=0.026) were associated with lower score on digit symbol task which is related to processing speed and executive function with controlling for age, sex, education and stage of CKD. The association persisted (p=0.047) after controlling for vascular risks.
Patients with CKD had extensive cognitive impairments. Elevated homocysteine levels may be an risk factor, which is independent of vascular burden, of cognitive impairment on processing speed and executive function. Further studies to investigate if normalization of homocysteine can improve cognitive function will be suggested.