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Alberta is a Canadian province with a high prevalence of multiple sclerosis (MS). In this ecological study, we examined group differences in health care utilization among persons with MS (pwMS) living within different regions of the province.
pwMS were identified from provincial administrative databases spanning 2002–2011. Utilization of health care services was determined for a 2-year period (April 2010–March 2012). Residential postal codes placed patients into their provincial health care zones. As data were provided to the investigators in an aggregated form, tests of statistical significance and confounding were not performed.
In total, 11,721 pwMS were identified. During the 2-year observation period, 96.2% of pwMS accessed a family physician and 57.1% accessed a neurologist. Nearly all (99.0%) pwMS who received neurologist care in Calgary visited an MS clinic, in contrast to Edmonton where a larger proportion (34.8%) received solely community neurologist care. More pwMS living in Edmonton accessed the ED (41.1%) compared to Calgary (35.7%), and the rate of visits per pwMS was higher in Edmonton (1.07/pwMS) than in Calgary (0.81/pwMS). The frequency of inpatient admissions was similar.
Over 2 years, most pwMS accessed primary care and over half saw a neurologist. Despite a similar frequency of inpatient admissions, the frequency of ED visits by pwMS was higher in Edmonton compared to Calgary, where more patients received MS clinic care. Although this exploratory study is subject to several limitations, our findings suggest that specialized MS clinics may reduce costly ED visits.
A 73-year-old male with a history of chronic ataxia presented with transient facial droop to the Emergency Department. A CT angiogram and MRI with diffusion weighted imaging (DWI) were negative for stroke. However, incidental note was made of numerous giant arachnoid granulation pits in the posterior fossa predominantly involving the left occipital bone (Figure 1). These arachnoid pits demonstrated multiple foci of herniation of the adjacent cerebellar parenchyma into the pits with gliosis of the herniated parenchyma and focal encephalomalacia of the subjacent cerebellar parenchyma. Review of bone windows on a remote CT brain performed almost 13 years earlier confirmed this to be a longstanding abnormality (Figure 2). The patient’s physical exam was suggestive of cerebellar ataxia with left-sided dysmetria on finger to nose testing and a wide-based unsteady gait.
The preconception, pregnancy and immediate postpartum and newborn periods are times for mothers and their offspring when they are especially vulnerable to major stressors – those that are sudden and unexpected and those that are chronic. Their adverse effects can transcend generations. Stressors can include natural disasters or political stressors such as conflict and/or migration. Considerable evidence has accumulated demonstrating the adverse effects of natural disasters on pregnancy outcomes and developmental trajectories. However, beyond tracking outcomes, the time has arrived for gathering more information related to identifying mechanisms, predicting risk and developing stress-reducing and resilience-building interventions to improve outcomes. Further, we need to learn how to encapsulate both the quantitative and qualitative information available and share it with communities and authorities to mitigate the adverse developmental effects of future disasters, conflicts and migrations. This article briefly reviews prenatal maternal stress and identifies three contemporary situations (wildfire in Fort McMurray, Alberta, Canada; hurricane Harvey in Houston, USA and transgenerational and migrant stress in Pforzheim, Germany) where current studies are being established by Canadian investigators to test an intervention. The experiences from these efforts are related along with attempts to involve communities in the studies and share the new knowledge to plan for future disasters or tragedies.
Carbon-14 (radiocarbon, 14C) is a long-lived radionuclide (5730 yr) of interest regarding the safety for the management of intermediate level wastes (ILW). The present study gives an overview of the release of 14C from irradiated Zircaloy cladding in alkaline media. 14C is found either in the alloy part of Zircaloy cladding due to the neutron activation of 14N impurities by 14N(n,p)14C reaction, or in the oxide layer (ZrO2) formed at the metal surface by the neutron activation of 17O from UO2 or (U-Pu)O2 fuel and water from the primary circuit in the reactor by 17O(n,α)14C reaction. Various irradiated and unirradiated Zircaloys have been studied. The total 14C inventory has been determined both experimentally and by calculations. The results seem to be in good agreement. Leaching experiments were conducted in alkaline media for several time durations. 14C was mainly released as carboxylic acids. Further, corrosion measurements were performed by using both hydrogen measurements and electrochemical measurements. The corrosion rate (CR) ranges from a few nm/yr to 100 nm/yr depending on the surface conditions and the method used for measurement. From a safety assessment point of view, the instant release fraction (IRF) was determined on irradiated Zircaloy-2. The results showed that the 14C inventory in the oxide was significantly below the 20% commonly used in safety case assessments.
OBJECTIVES/SPECIFIC AIMS: Patients with locally advanced pancreatic cancer typically have poor outcomes, with a median survival of ~16 months. Novel methods to improve local control are needed. Nab-paclitaxel (abraxane) has shown efficacy in pancreatic cancer and is FDA approved for metastatic disease in combination with gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on laboratory studies, but it has never been clinically tested with definitive radiotherapy for locally advanced disease. METHODS/STUDY POPULATION: We performed a phase 1 study using a 3+3 dose-escalation strategy to determine the safety and tolerability of dose escalated nab-paclitaxel with fractionated radiotherapy for patients with unresectable or borderline resectable pancreatic cancer. Following induction chemotherapy with 2 cycles of nab-paclitaxel and gemcitabine, patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was performed at day 65 after the start of radiotherapy. RESULTS/ANTICIPATED RESULTS: Nine patients received nab-paclitaxel at a dose level of either 100 mg/m2 (n=3) or 125 mg/m2 (n=6). One DLT (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab-paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%), and neutropenia (11%). No grade 4 toxicities were observed. With a median follow-up of 8 months (range 5–28 months), median survival was 19 months and median progression-free survival was 10 months. Following chemoradiation, 3 patients underwent surgical resection, all with negative margins and limited tumor viability. Of the 3 patients, 2 initially had borderline resectable tumors and 1 had an unresectable tumor. Tumor (SMAD-4, Caveolin-1) and peripheral (circulating tumor cells and microvesicles) biomarkers were collected and are being analyzed. DISCUSSION/SIGNIFICANCE OF IMPACT: The combination of fractionated radiation and weekly nab-paclitaxel was safe and well tolerated. This regimen represents a potentially promising therapy for patients with unresectable and borderline resectable pancreatic cancer and warrants further investigation.
Direct ink writing of silicone elastomers enables printing with precise control of porosity and mechanical properties of ordered cellular solids, suitable for shock absorption and stress mitigation applications. With the ability to manipulate structure and feedstock stiffness, the design space becomes challenging to parse to obtain a solution producing a desired mechanical response. Here, we derive an analytical design approach for a specific architecture. Results from finite element simulations and quasi-static mechanical tests of two different parallel strand architectures were analyzed to understand the structure-property relationships under uniaxial compression. Combining effective stiffness-density scaling with least squares optimization of the stress responses yielded general response curves parameterized by resin modulus and strand spacing. An analytical expression of these curves serves as a reduced order model, which, when optimized, provides a rapid design capability for filament-based 3D printed structures. As a demonstration, the optimal design of a face-centered tetragonal architecture is computed that satisfies prescribed minimum and maximum load constraints.
Although the importance and advantages of measurement-based care in mental healthcare are well established, implementation in daily practice is complex and far from optimal.
To accelerate the implementation of outcome measurement in routine clinical practice, a government-sponsored National Quality Improvement Collaborative was initiated in Dutch-specialised mental healthcare.
To investigate the effects of this initiative, we combined a matched-pair parallel group design (21 teams) with a cluster randomised controlled trial (RCT) (6 teams). At the beginning and end, the primary outcome ‘actual use and perceived clinical utility of outcome measurement’ was assessed.
In both designs, intervention teams demonstrated a significant higher level of implementation of outcome measurement than control teams. Overall effects were large (parallel group d=0.99; RCT d=1.25).
The National Collaborative successfully improved the use of outcome measurement in routine clinical practice.
Glucocorticoid treatment improves the speed of functional recovery of acute multiple sclerosis (MS) relapses but has not been shown to provide any long-term functional benefit. There is currently no convincing evidence that the clinical benefit is influenced by the route of administration or the dosage of glucocorticoid, or the particular glucocorticoid prescribed. Recent studies support similarities in the bioequivalence and in the clinical effect of high dose oral corticosteroids for MS relapses.
This survey aimed to determine the relapse treatment preferences of clinicians in Canadian MS clinics.
Members of the Canadian Network of MS Clinics are linked by an email server. A one page survey was distributed to the group to determine and report use of corticosteroids to manage MS relapses amongst Canadian MS specialists.
Fifty-one clinicians from 17 MS clinics were surveyed. 32 (63%) surveys were returned representing 16 clinics. Five doses are most commonly prescribed, usually without a taper. Three or four doses and the use of a corticosteroid taper, however, are not uncommon. Gastric cytoprotection and sedatives are often prescribed for use as needed.
This survey illustrates that when Canadian clinicians with expertise in managing MS treat MS relapses they choose high dose corticosteroids, either oral or IV. The results therefore represent Canadian practice as these clinicians provide direct patient care and influence care by community neurologists. Until evidence clearly identifies a superior practice all options should be available to clinicians and their patients.
Abundant tubular macrofossils occur in finely laminated siltstones and shales of the 548–542 Ma Schwarzrand Subgroup, Nama Group, Namibia. The Nama tubes occur in both the Vingerbreek and Feldschuhhorn members commonly in dense populations and always in fine-grained, lower shore-face lithologies deposited below fair-weather wave base. The tubes are preserved mostly as compressed casts and molds that range in width from 0.6 to 2.1 mm; apparently incomplete specimens reach lengths up to 10 cm. All specimens show sinuous bending and occasional brittle fracture, indicating an original construction of strong but flexible organic matter. Feldschuhhorn specimens preserve fine longitudinal pleats or folds that record pliant organic walls, but the older Vingerbreek populations do not. Similarly, some specimens in the Feldschuhhorn Member display branching, while Vingerbreek tubes do not. The abundant Feldschuhhorn tubes are assigned to the widespread Ediacaran problematicum Vendotaenia antiqua; however, the distinctive Vingerbreek population remains in open nomenclature. The most abundant fossils in Nama rocks, these tubes resemble populations in Ediacaran successions from Russia, China, Spain, and elsewhere. Beyond their local importance, then, such tubes may turn out to be the most abundant record of Ediacaran life.
Foreign accent syndrome is a speech disorder which leads listeners to perceive the patient as having a foreign accent. It has been recognized previously after stroke, brain injury or unknown causes.
A 52-year-old woman with clinically definite relapsing remitting multiple sclerosis (MS) presented with episodes of what was perceived as a Dutch accent along with other neurologic symptoms that would resolve simultaneously. She was assessed by a speech therapist both during an episode and after complete recovery. Speech and MRI changes (showing deep white matter lesions in the corpus callosum, left pariental lobe and left frontal lobe) were consistent with previous reports of foreign accent syndrome.
This patient's episodes of foreign accent are thought to be due to her MS. This is the first case reported of a patient with foreign accent syndrome secondary to MS.
Background: Many Canadians with multiple sclerosis (MS) have recently travelled internationally to have procedures for a putative condition called chronic cerebrospinal venous insufficiency (CCSVI). Here, we describe where and when they went and describe the baseline characteristics of persons with MS who participated in this non–evidence-based medical tourism for CCSVI procedures. Methods: We conducted a longitudinal observational study that used online questionnaires to collect patient-reported information about the safety, experiences, and outcomes following procedures for CCSVI. A convenience sample of all Albertans with MS was recruited between July 2011 and March 2013. Results: In total, 868 individuals enrolled; 704 were included in this cross-sectional, baseline analysis. Of these, 128 (18.2%) participants retrospectively reported having procedures for CCSVI between April 2010 and September 2012. The proportion of participants reporting CCSVI procedures declined from 80 (62.5%) in 2010, to 40 (31.1%) in 2011, and 8 (6.3%) in 2012. In multivariable logistic regression analysis, CCSVI procedures were independently associated with longer disease duration, secondary progressive clinical course, and greater disability status. Conclusions: Although all types of people with MS pursued procedures for CCSVI, a major driver of participation was greater disability. This highlights that those with the greatest disability are the most vulnerable to unproven experimental procedures. Participation in CCSVI procedures waned over time possibly reflecting unmet expectations of treated patients, decreased media attention, or that individuals who wanted procedures had them soon after the CCSVI hypothesis was widely publicized.
The long-term behavior of the UO2 fuel matrix under conditions of the Belgian “Supercontainer design” was investigated by dissolution tests of high burn-up spent nuclear fuel (SNF) in high alkaline solution under 40 bar of (Ar + 8%H2) atmosphere. Four fragments of SNF, obtained from a pellet previously leached during two years, were exposed to young cement water with Ca (YCWCa) under 3.2 bar H2 partial pressure in four single/independent autoclave experiments for a period of 59, 182, 252 and 341 days, respectively. After a decrease of the concentration of dissolved 238U, which is associated with a reduction of U(VI) to U(IV), the concentration of 238U in solution is constant in the experiments running for 252 and 341 days. These observations indicate an inhibition of the matrix dissolution due to the presence of H2. A slight increase in the concentration of 90Sr and 137Cs in the aqueous solution indicates that there is still dissolution of the grain boundaries. These findings are similar to those reported for spent nuclear fuel corrosion in synthetic near neutral pH solutions.
Listeria monocytogenes is a foodborne pathogen that can cause bacteraemia, meningitis, and complications during pregnancy. In July 2012, molecular subtyping identified indistinguishable L. monocytogenes isolates from six patients and two samples of different cut and repackaged cheeses. A multistate outbreak investigation was initiated. Initial analyses identified an association between eating soft cheese and outbreak-related illness (odds ratio 17·3, 95% confidence interval 2·0–825·7) but no common brand. Cheese inventory data from locations where patients bought cheese and an additional location where repackaged cheese yielded the outbreak strain were compared to identify cheeses for microbiological sampling. Intact packages of imported ricotta salata yielded the outbreak strain. Fourteen jurisdictions reported 22 cases from March–October 2012, including four deaths and a fetal loss. Six patients ultimately reported eating ricotta salata; another reported eating cheese likely cut with equipment also used for contaminated ricotta salata, and nine more reported eating other cheeses that might also have been cross-contaminated. An FDA import alert and US and international recalls followed. Epidemiology-directed microbiological testing of suspect cheeses helped identify the outbreak source. Cross-contamination of cheese highlights the importance of using validated disinfectant protocols and routine cleaning and sanitizing after cutting each block or wheel.
Background: A definitive diagnosis of multiple sclerosis (MS), as distinct from a clinically isolated syndrome, requires one of two conditions: a second clinical attack or particular magnetic resonance imaging (MRI) findings as defined by the McDonald criteria. MRI is also important after a diagnosis is made as a means of monitoring subclinical disease activity. While a standardized protocol for diagnostic and follow-up MRI has been developed by the Consortium of Multiple Sclerosis Centres, acceptance and implementation in Canada have been suboptimal. Methods: To improve diagnosis, monitoring, and management of a clinically isolated syndrome and MS, a Canadian expert panel created consensus recommendations about the appropriate application of the 2010 McDonald criteria in routine practice, strategies to improve adherence to the standardized Consortium of Multiple Sclerosis Centres MRI protocol, and methods for ensuring effective communication among health care practitioners, in particular referring physicians, neurologists, and radiologists. Results: This article presents eight consensus statements developed by the expert panel, along with the rationale underlying the recommendations and commentaries on how to prioritize resource use within the Canadian healthcare system. Conclusions: The expert panel calls on neurologists and radiologists in Canada to incorporate the McDonald criteria, the Consortium of Multiple Sclerosis Centres MRI protocol, and other guidance given in this consensus presentation into their practices. By improving communication and general awareness of best practices for MRI use in MS diagnosis and monitoring, we can improve patient care across Canada by providing timely diagnosis, informed management decisions, and better continuity of care.
Community-based studies can describe health status and related variables in people with Multiple Sclerosis (MS) while avoiding biases introduced by help-seeking in specific clinical settings.
To describe general health status, stress perceptions and life satisfaction in people with MS, in comparison to those with other types of disabilities.
Materials & Methods:
The Participation and Activity Limitation Survey (PALS) was a post-censual survey conducted by Statistics Canada in association with the 2006 Canadian Census. PALS collected data from a random sample of n = 22,513 respondents identified as having health-related impairments. Frequencies and quartiles as well as mean values, along with associated 95% confidence intervals, were calculated in the analysis.
PALS identified 245 individuals with MS. Health status, both perceived and when weighted for societal preference, was markedly lower than that of other disabled groups. No differences in self-perceived stress were seen. People with MS reported lower levels of satisfaction with their health but slightly higher levels of satisfaction with their family and friends.
People with MS report lower levels of general health status and more impairment than those with other disabling conditions. Higher levels of satisfaction with friends and family may reflect psychological adaptation to the illness.
Multiple Sclerosis (MS) is reported to be uncommon among North American aboriginals despite frequent intermarriage with people of European ancestry, but few population-based studies have been conducted. The purpose of this study was to determine the prevalence of MS among First Nations aboriginal people in Alberta, Canada compared to the general population.
All hospital in-patient and physician fee-for-service records between 1994 and 2002 where a diagnosis of MS was mentioned were extracted from government health databases in the province of Alberta. First Nations people can be identified since the federal government (Health Canada) pays health care insurance premiums on their behalf. Multiple Sclerosis prevalence per 100,000 population for both First Nations people and the general population of Alberta were calculated for each year during this time span.
Among First Nations in Alberta, MS prevalence was 56.3 per 100,000 in 1994 and 99.9 per 100,000 in 2002, an increase of 43.6%. In 2002 prevalence was 158.1 and 38.0 for females and males respectively, a female to male ratio of 4.2:1. Multiple Sclerosis prevalence among the general population of Alberta was 262.6 per 100,000 in 1994 and 335.0 per 100,000 in 2002, an increase of 21.6%. In 2002 prevalence was 481.5 and 187.5 for females and males respectively, a female to male ratio of 2.6:1. Peak prevalence for both First Nations and general population females in 2002 was age 50-59, also 50-59 for both First Nations and general population males.
While MS prevalence in First Nations people is lower than in the general population of Alberta, it is not rare by worldwide standards.
Current multiple sclerosis (MS) treatment is only partially effective and not all patients respond well. The goal in this study was to evaluate minocycline for its safety, tolerability, and MRI impact as a potential therapy over 36 months after a three month run-in in ten relapsing-remitting (RR) MS patients.
Clinical assessments were at three month intervals until six months, then at six month intervals. Three Tesla MRI was performed monthly during the run-in and first six months of treatment, then at 12, 24, and 36 months.
Treatment was safe and well tolerated. Annualized relapse rate was 1.2 during the run-in and 0.25 during treatment. The proportion of active scans was lower during the first six months of treatment (5.6%, p<0.001) and during the extension (8.7%, p= 0.002) than during the run-in (47.5%). Consistent with these outcomes, mean T2 lesion volume remained stable over three years and percent brain volume change was reduced during year three (-0.37%) of minocycline treatment.
This trial is limited by small sample and no control group but suggests that minocycline is safe and potentially beneficial in RRMS. This supports further investigation of its efficacy.
The corpus callosum (CC) is frequently compromised in patients with multiple sclerosis (MS). Structural and functional measurements of the CC may be useful to monitor the progression of the disease. The aim of this pilot study was to determine if bimanual tactile temporal thresholds correlates with CC volume. A tactile temporal threshold is the longest temporal interval that separates the onsets of two tactile stimuli when they are judged by the observer as simultaneous. Judgments to bimanual stimulations require interhemispheric transfer via the CC.
Thresholds were examined in MS patients and matched controls. Magnetic resonance (MR) images were acquired on a 3T MR system within 48 hours of clinical assessment and measurement of thresholds.
Corpus callosum volume was assessed by using a semiautomatic livewire algorithm. The CC volume was smaller (by 21% on average, p < 0.01) and thresholds were higher (by 49% on average, p < 0.03) in MS patients when compared to controls. A significant correlation (r = -0.66, p = 0.01) between CC volume and thresholds emerged for the MS patients.
Measuring treatment benefits of neuroprotective and repair therapies is a well recognized challenge in MS research. The overall findings of this study suggest that these measurements, which involve the transfer of information interhemispherically via the CC, may be promising outcome measures that warrant further scientific exploration to develop a model to measure recovery.