Automated Assessment of the DWI-FLAIR Mismatch in Patients with Acute Ischemic Stroke: Added Value to Routine Clinical Practice.

BACKGROUND AND PURPOSE: The DWI-FLAIR mismatch is used to determine thrombolytic eligibility in patients with acute ischemic stroke when the time since stroke onset is unknown. Commercial software packages have been developed for automated DWI-FLAIR classification. We aimed to use e-Stroke software for automated classification of the DWI-FLAIR mismatch in a cohort of patients with acute ischemic stroke and in a comparative analysis with 2 expert neuroradiologists. MATERIALS AND METHODS: In this retrospective study, patients with acute ischemic stroke who had MR imaging and known time since stroke onset were included. The DWI-FLAIR mismatch was evaluated by 2 neuroradiologists blinded to the time since stroke onset and automatically by the e-Stroke software. After 4 weeks, the neuroradiologists re-evaluated the MR images, this time equipped with automated predicted e-Stroke results as a computer-assisted tool. Diagnostic performances of e-Stroke software and the neuroradiologists were evaluated for prediction of DWI-FLAIR mismatch status. RESULTS: A total of 157 patients met the inclusion criteria. A total of 82 patients (52%) had a time since stroke onset of ≤4.5 hours. By means of consensus reads, 81 patients (51.5%) had a DWI-FLAIR mismatch. The diagnostic accuracy (area under the curve/sensitivity/specificity) of e-Stroke software for the determination of the DWI-FLAIR mismatch was 0.72/90.0/53.9. The diagnostic accuracy (area under the curve/sensitivity/specificity) for neuroradiologists 1 and 2 was 0.76/69.1/84.2 and 0.82/91.4/73.7, respectively; both significantly (P < .05) improved to 0.83/79.0/86.8 and 0.89/92.6/85.5, respectively, following the use of e-Stroke predictions as a computer-assisted tool. The interrater agreement (κ) for determination of DWI-FLAIR status was improved from 0.49 to 0.57 following the use of the computer-assisted tool. CONCLUSIONS: This automated quantitative approach for DWI-FLAIR mismatch provides results comparable with those of human experts and can improve the diagnostic accuracies of expert neuroradiologists in the determination of DWI-FLAIR status.

Overestimation of ischemic core on baseline MRI in acute stroke.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke (AIS), overestimation of ischemic core on MRI-DWI has been described primarily in regions with milder reduced diffusion. We aimed to assess the possibility of ischemic core overestimation on pretreatment MRI despite using more restricted reduced diffusion (apparent diffusion coefficient (ADC) ≤620 × 10-6 mm2/s) in AIS patients with successful reperfusion. MATERIALS AND METHODS: In this retrospective single institutional study, AIS patients who had pretreatment MRI underwent successful reperfusion and had follow-up MRI to determine the final infarct volume were reviewed. Pretreatment ischemic core and final infarction volumes were calculated. Ghost core was defined as overestimation of final infarct volume by baseline MRI of >10 mL. Baseline clinical, demographic, and treatment-related factors in this cohort were reviewed. RESULTS: A total of 6/156 (3.8%) patients had overestimated ischemic core volume on baseline MRI, with mean overestimation of 65.6 mL. Three out of six patients had pretreatment ischemic core estimation of >70 mL, while the final infarct volume was <70 mL. All six patients had last known well-to-imaging <120 min, median (IQR): 65 (53-81) minutes. CONCLUSIONS: Overestimation of ischemic core, known as ghost core, is rare using severe ADC threshold (≤620 × 10-6 mm2/s), but it does occur in nearly 1 of every 25 patients, confined to hyperacute patients imaged within 120 min of symptom onset. Awareness of this phenomenon carries implications for treatment and trial enrollment.

CTP-based estimated ischemic core: A comparative multicenter study between Olea and RAPID software.

BACKGROUND AND PURPOSE: CTP is increasingly used to assess eligibility for endovascular therapy (EVT) in patients with large vessel occlusions (LVO). There remain variability and inconsistencies between software packages for estimation of ischemic core. We aimed to use heterogenous data from four stroke centers to perform a comparative analysis for CTP-estimated ischemic core between RAPID (iSchemaView) and Olea (Olea Medical). METHODS: In this retrospective multicenter study, patients with anterior circulation LVO who underwent pretreatment CTP, successful EVT (defined TICI ≥ 2b), and follow-up MRI included. Automated CTP analysis was performed using Olea platform [rCBF < 25% and differential time-to-peak (dTTP)>5s] and RAPID (rCBF < 30%). The CTP estimated core volumes were compared against the final infarct volume (FIV) on post treatment MRI-DWI. RESULTS: A total of 151 patients included. The CTP-estimated ischemic core volumes (mean ± SD) were 18.7 ± 18.9 mL on Olea and 10.5 ± 17.9 mL on RAPID significantly different (p < 0.01). The correlation between CTP estimated core and MRI final infarct volume was r = 0.38, p < 0.01 for RAPID and r = 0.39, p < 0.01 for Olea. Both software platforms demonstrated a strong correlation with each other (r = 0.864, p < 0.001). Both software overestimated the ischemic core volume above 70 mL in 4 patients (2.6%). CONCLUSIONS: Substantial variation between Olea and RAPID CTP-estimated core volumes exists, though rates of overcalling of large core were low and identical. Both showed comparable core volume correlation to MRI infarct volume.

Risk factors associated with veterinary attrition from clinical practice: a descriptive study.

A sustainable workforce is important for the veterinary profession to meet the demands of society. To maintain a sustainable workforce, it has been recommended to retain veterinary clinicians. However, there seems to be an increasing issue with retention of veterinarians in clinical practice. In the following study, the researchers sought to understand the associations between demographic and work-related factors and attrition of veterinarians from clinical practice. Responses to an online cross-sectional survey of 881 current and former Australian veterinary clinicians were analysed. A logistic regression model was used to identify and describe associations between attrition from veterinary clinical practice and salary, working hours, role in practice, years of experience, field of work, interaction with regulatory authorities, region of work and on-call duties. Lower salary, longer working hours, having on-call duties and having worked in both rural and metropolitan regions were found to significantly (P < 0.05) increase the likelihood of leaving clinical practice. The results may inform intervention strategies to assist the industry to retain veterinarians in clinical practice.

A pilot mixed methods investigation of the use of Oswestry standing frames in the homes of nine people with severe multiple sclerosis.

PURPOSE: People with multiple sclerosis (MS) commonly experience muscle weakness which limits their ability to stand. Supported standing may minimise the secondary complications of prolonged sitting but evidence for this is scarce. This study investigated the effects of regular standing in an Oswestry frame on some secondary complications of immobility and explored the lived experience of standing. METHODS: Nine people with MS participated in a mixed-methods study over 48 weeks. Single-case experiments were used. Outcomes included: Amended Motor Club Assessment, Canadian Occupational Performance Measure, Penn Spasm Scale, bowel frequency and a numerical pain-scale. The qualitative strand used a case-study approach with a phenomenological perspective. RESULTS: Significant improvements (p < 0.05) were demonstrated for individuals in strength, ADL and spasms but not in bowel frequency or pain. Subjective improvements occurred in continence, clonus and fall-rate. Being upright or strengthened by standing enabled participants to re-engage with activities and re-establish themselves within relationship roles. This engendered a sense of achievement and increased optimism. CONCLUSION: This study provides preliminary evidence of the effectiveness of regular frame-standing in improving strength, function, spasms, continence and fall-rate in people with severe MS. Standing reinstated a sense of belonging and optimism by restoring important life-roles and feelings of normality as participants regained previously valued activities. Implications for Rehabilitation Regular standing in an Oswestry frame may improve functional ability in people with severe MS. Regular frame standing may have a positive psychological effect on people with severe MS. Self-management of a standing regime may be feasible.

Herding the U.S. cattle industry toward a paradigm shift in parasite control.

Contemporary management of nematode parasitism in cattle relies heavily on a single class of drugs, the macrocyclic lactones (MLs). The potency and convenience of the MLs, along with the low cost of generic formulations, have largely supplanted the need for critical thinking about parasite control, and rote treatment has become the default 'strategy'. This approach to parasite control has exerted substantial pressure to select populations of nematodes that can survive recommended dosages of ML products. Although macrocyclic lactones have been available for over 30 years, putative ML resistance in U.S. cattle was not reported until fairly recently. This pattern begs the question, "Is this a new, emergent problem, or an old issue that is finally commanding some attention?" The implications of bovine anthelmintic resistance should stimulate a paradigm shift for U.S. cattle producers and their advisors. However, there are significant obstacles to changes in current thinking. It is anticipated that cattle producers will be extremely reluctant to abandon historical practices unless they can be convinced of the value of alternatives that are communicated through targeted education, practical demonstrations, economic analyses, and scientific evidence. Historically, the management advice of practitioners has not relied strongly on parasite epidemiology, and practitioners may not have the knowledge to implement evidence-based recommendations. Pharmaceutical companies could play a significant role in helping to shape and shift the thinking about sustainable use of anthelmintics. However, their primary responsibility is to stockholders, and they have strong economic incentives for maintaining the status quo. It is complicated and difficult to change attitudes and practices, and it will take more than logic or fear to shift the parasite control paradigm in the U.S. cattle industry. Achieving that goal will require collaboration among stakeholders, a consistent, straightforward and understandable message about resistance, and recommendations that are practical as well as effective. But if we hope to ultimately influence producers and their advisors, we need to be conscious of how individuals and groups change their minds.

Companion animal veterinarians' use of clinical communication skills.

OBJECTIVE: To describe the communication techniques used by clients and veterinarians during companion animal visits in Australia. DESIGN: A cross-sectional descriptive study. METHODS: A total of 64 veterinary consultations were audiotaped and analysed with the Roter Interaction Analysis System (RIAS); clients completed appointment level measures, including their satisfaction and perceptions of relational communication. RESULTS: Participants were 24 veterinarians and 64 clients. Statements intended to reassure clients were expressed frequently in the consultations, but in 59% of appointments empathy statements were not expressed towards either the client or the patient. In 10% of appointments, veterinarians did not used any open-ended questions. Overall client satisfaction was high and veterinarians' expressions of empathy directed to the client resulted in higher levels of client satisfaction. Clients' perceptions of relational communication were related to several veterinarian and client nonverbal scales. CONCLUSIONS: A focus on developing evidence-based clinical communication skills is expected to further enhance the veterinarian-client-patient relationship and associated clinical outcomes. Particular recommendations include the development of a broader emotion-handling repertoire, increased emphasis on the use of open-ended enquiry, including assessment of the client's perspective, as well as attention to aspects of nonverbal communication. The study provides preliminary evidence for the importance of verbal expressions of empathy during the companion animal consultation.

Spontaneous high-grade glial intramedullary tumor of the spine in a rhesus macaque (Macaca mulatta).

BACKGROUND: A 4-year-old rhesus macaque presented with acute, progressive paresis of the extremities. METHODS: A complete blood count, serum biochemical analysis, neurologic exam and necropsy were performed. RESULTS: The clinical, histopathological, and immunohistochemical findings confirmed a high-grade intramedullary glial tumor of the spinal cord that was most consistent with an ependymoma. CONCLUSIONS: We describe a case of a naturally occurring spontaneous spinal cord neoplasia in a non-human primate.

An in situ study of protein adsorption on combinatorial Cu-Al films using spectroscopic ellipsometry.

An approach to quantifying adsorbed protein layers at the protein/metal interface through spectroscopic ellipsometry using an in situ technique is described. A combinatorial binary Cu(1-x)Al(x) (0

Surface characteristics and protein adsorption on combinatorial binary Ti-M (Cr, Al, Ni) and Al-M (Ta, Zr) library films.

Systematic studies of protein adsorption onto metallic biomaterial surfaces are generally lacking. Here, combinatorial binary library films with compositional gradients of Ti(1-x)Cr(x), Ti(1-x)Al(x), Ti(1-x)Ni(x) and Al(1-x)Ta(x), (0

Resistance to a triple combination of broad-spectrum anthelmintics in naturally-acquired Ostertagia circumcincta infections in sheep.

AIM: To measure the efficacy of two macrocyclic lactone-levamisole-benzimidazole combination drenches against naturally-acquired abomasal nematode infections on a sheep farm in the North Island, New Zealand. METHODS: Eighteen lambs carrying naturally-acquired worm burdens were removed from pasture and randomly allocated to one of three equal-sized groups, consisting of an untreated control group and two treatment groups. One treatment group was given a single oral dose of a triple-combination anthelmintic administered at the manufacturer's recommended dose rate of 0.2 mg/kg ivermectin, 7.5 mg/kg levamisole and 5.0 mg/kg albendazole. The other treatment group received a similar dose of another triple-combination drench consisting of 0.2 mg/kg abamectin, 8.0 mg/kg levamisole and 4.5 mg/kg oxfendazole. Worm counts were carried out post mortem on the abomasa of all animals in all groups, 10 days after treatment. RESULTS: While the abamectin-levamisole-oxfendazole combination was highly effective against all three abomasal nematode species present, the ivermectin-levamisole-albendazole combination was not. In the latter instance, a reduction of only 78% was achieved against infections of Ostertagia (=Teladorsagia) circumcincta. CONCLUSIONS: These results provide evidence of resistance to an ivermectin-levamisole-albendazole combination drench by O. circumcincta. CLINICAL RELEVANCE: Besides representing the first confirmed report of resistance to a combination drench consisting of three broad-spectrum anthelmintics, the present results provide further evidence of the continuing escalation of multiple anthelmintic resistance in sheep nematodes in New Zealand.

Hospital-acquired invasive group a streptococcal infections in Ontario, Canada, 1992-2000.

BACKGROUND: A significant proportion of invasive group A streptococcal infections are hospital acquired. No large, prospective studies have characterized this subgroup of cases and evaluated the risk of transmission in hospitals. METHODS: We conducted prospective, population-based surveillance of invasive group A streptococcal infections in Ontario, Canada, from 1992 to 2000. Epidemiologic and microbiologic investigations were conducted to identify cross-transmission. RESULTS: We identified 291 hospital-acquired cases (12.4%) among 2351 cases of invasive group A streptococcal disease. Hospital-acquired invasive group A streptococcal infections are heterogeneous, including surgical site (96 cases), postpartum (86 cases), and nonsurgical, nonobstetrical infections (109 cases). Surgical site infections affected 1 of 100,000 surgical procedures and involved all organ systems. Postpartum infections occurred at a rate of 0.7 cases per 10,000 live births and exhibited an excellent prognosis. Nonsurgical, nonobstetrical infections encompassed a broad range of infectious syndromes (case-fatality rate, 37%). Nine percent of cases were associated with in-hospital transmission. Transmission occurred from 3 of 142 patients with community-acquired cases of necrotizing fasciitis requiring intensive care unit (ICU) admission, compared with 1 of 367 patients with community-acquired cases without necrotizing fasciitis admitted to the ICU and 1 of 1551 patients with other cases (P<.001). Fifteen outbreaks were identified; 9 (60%) involved only 2 cases. Hospital staff were infected in 1 of 15 outbreaks, but colonized staff were identified in 6 (60%) of 10 investigations in which staff were screened. CONCLUSIONS: Presentation of hospital-associated invasive group A streptococcal infections is diverse. Cross-transmission is common; illness occurs in patients but rarely in staff. Isolation of new cases of necrotizing fasciitis and intervention after a single nosocomial case may also prevent transmission.

Metabolic adaptations to chronic glucose infusion in rats.

AIMS/HYPOTHESIS: Several studies have employed the chronic glucose infusion protocol to quantify the metabolic adaptations associated with a prolonged glucose challenge. However, the limited number of indices and time points reported by these studies has generated an incomplete picture of this process. In this study we aimed to generate an integrative and dynamic picture of the physiological adaptations that occur during chronic glucose infusion. METHODS: Sprague-Dawley rats were infused with either 50% dextrose or saline (2 ml/h) for a period of between 0 and 6 days. Glucose, insulin and NEFA dynamics were determined from daily blood samples. Subsets of animals were killed daily for histological determination of beta cell mass, size and replication rates. The mathematical model of coupled beta cell mass, insulin and glucose (the betaIG model) was used to estimate insulin sensitivity, beta cell function and net neogenesis from this data. RESULTS: Glucose-infused rats displayed transient hyperglycaemia, persistent hyperinsulinaemia and unchanged NEFA levels. Insulin sensitivity decreased by approximately 80% during the first day of glucose infusion, but had returned to pre-infusion levels by Day 3. Beta cell function was four to six times higher than in control rats throughout the experiment. Beta cell mass doubled over the 6 days of glucose infusion due to three phases of adaptation: (i) neogenesis; (ii) hypertrophy and hyperplasia; and (iii) continued hyperplasia coupled to a second wave of neogenesis. CONCLUSIONS/INTERPRETATION: Contrary to the results reported for perfused pancreas and in vitro experiments, we found that chronic glucose infusion elevated beta cell function. The prediction of a second wave of beta cell neogenesis, coupled with our previous report of "focal areas" on Day 3, suggests the existence of delayed acinar-to-islet transdifferentiation.

Probable multigeneric resistance to macrocyclic lactone anthelmintics in cattle in New Zealand.

AIM: To establish the efficacy of topical formulations of eprinomectin and abamectin against naturally acquired abomasal and small intestinal nematode infections in cattle purchased from a North Island bull-beef property. METHODS: A controlled slaughter trial, involving eighteen 6-8-month-old mixed breed calves, was conducted in May 2002.The animals were randomly allocated on the basis of faecal egg count to one of three equal-sized groups (n=6), consisting of an untreated control group and two treatment groups. One of the treatment groups was treated with a topical formulation of eprinomectin, the other with abamectin. Both anthelmintics were administered as a single topical treatment on an individual liveweight basis, at the manufacturer's recommended dose rates of 0.5 mg/kg. All calves were housed in separate groups with no access to pasture throughout the entire trial and were slaughtered 7-10 days after treatment. RESULTS: Both anthelmintic treatments were highly effective(worm count reduction >98%) against Ostertagia ostertagi, Trichostrongylus axei and Cooperia punctata, but were not effective at reducing worm counts significantly of either Cooperia oncophora or Trichostrongylus longispicularis. Against these latter two parasites, worm count reductions of only 72% and 79%, and 81% and 76%, respectively, were recorded following treatment with eprinomectin or abamectin, respectively (all p>0.05). CONCLUSIONS: These results demonstrate evidence of resistance to macrocyclic lactone anthelmintics by C. oncophora and probably T. longispicularis also. CLINICAL RELEVANCE: As well as perhaps providing the first record of resistance to any anthelmintic by T. longispicularis, the present findings may also represent the first case of resistance to macrocyclic lactone anthelmintics exhibited by more than one parasite species at a time in cattle in New Zealand.

Quantification of DNaseI-sensitivity by real-time PCR: quantitative analysis of DNaseI-hypersensitivity of the mouse beta-globin LCR.

We employ real-time PCR to allow us to quantify the sensitivity of chromatin to digestion by DNaseI. This approach has three clear advantages over the more conventional use of the Southern hybridization assay: the accuracy of quantification is improved; the resolution of the assay is enhanced, by designing primers to amplify small amplicons it is possible to analyze sequences both co-incident and proximal to sites of DNaseI-hypersensitivity; less material is needed, as little as 5 ng of treated genomic DNA. We applied this method in an analysis of the chromatin structure of the previously described mouse beta-globin locus control region (LCR) using fetal liver cells. The four hypersensitive sites of the canonical mouse LCR, HS1 to HS4, are shown to have kinetics of digestion consistent with these sequences being nucleosome-free in vivo. A different pattern was seen for HS6, a recently described "weak" hypersensitive site. The site was also rapidly lost but more of the sites proved resistant, we interpreted this to show that this hypersensitive was only forming in a portion of the erythroid cells. This finding implies that in vivo the LCR is structurally heterogeneous. Sequences proximal to the hypersensitive sites show a third pattern of intermediate sensitivity, consistent with the chromatin being unfolded but the sites still bound by a continual nucleosomal array. Our results demonstrate that this method has the potential to achieve accurate and detailed mapping of chromatin structure from small amounts of tissue samples.

The 5'HS4 core element of the human beta-globin locus control region is required for high-level globin gene expression in definitive but not in primitive erythropoiesis.

To assess the contribution of DNase I-hypersensitive site 4 (HS4) of the beta-globin locus control region (LCR) to overall LCR function we deleted a 280 bp fragment encompassing the core element of 5'HS4 from a 248 kb beta-globin locus yeast artificial chromosome (beta-YAC) and analyzed globin gene expression during development in beta-YAC transgenic mice. Four transgenic lines were established; each contained at least one intact copy of the beta-globin locus. The deletion of the 5'HS4 core element had no effect on globin gene expression during embryonic erythropoiesis. In contrast, deletion of the 5'HS4 core resulted in a significant decrease of gamma and beta-globin gene expression during definitive erythropoiesis in the fetal liver and a decrease of beta-globin gene expression in adult blood. We conclude that the core element of 5'HS4 is required for globin gene expression only in definitive erythropoiesis. Absence of the core element of HS4 may limit the ability of the LCR to provide an open chromatin domain and/or enhance gamma and beta-globin gene expression in the adult erythroid cells.

Prevention of influenza and pneumococcal pneumonia in Canadian long-term care facilities: how are we doing?

BACKGROUND: Influenza and pneumococcal pneumonia are serious health problems among elderly people and a major cause of death in long-term care facilities. We describe the results of serial surveys of vaccination coverage and influenza outbreak management in Canadian long-term care facilities over the last decade. METHODS: Cross-sectional surveys consisting of questionnaires mailed to all Canadian residential long-term care facilities for elderly people in 1991 and to a random sample of respondents in 1995 and 1999. RESULTS: The response rates were 83% (430/515) in 1995 and 75% (380/506) in 1999. In 1999 the mean reported rates of influenza vaccination were 83% among residents and 35% among staff, and the mean rate of pneumococcal vaccination among residents was 71%; all 3 rates were significantly higher than those in 1991. The rates were also higher in facilities with an infection control practitioner than in those without such an individual (88% v. 82% for influenza vaccination among residents [p < 0.001], 42% v. 35% for influenza vaccination among staff [p = 0.008] and 75% v. 63% for pneumococcal vaccination among residents [p < 0.001]). Obtaining consent for vaccination on admission to the facility was associated with higher influenza and pneumococcal vaccination rates among residents (p = 0.04 and p < 0.001 respectively). Facilities with higher influenza vaccination rates among residents and staff reported lower rates of influenza outbreaks (p = 0.08 and 0.03 respectively). Despite recommendations from the National Advisory Committee on Immunization, only 50% of the facilities had policies for amantadine prophylaxis during influenza A outbreaks. Amantadine was judged effective in controlling 76% of the influenza A outbreaks and was discontinued because of side effects in 3% of the residents. INTERPRETATION: Influenza and pneumococcal vaccination rates among residents and staff in Canadian long-term care facilities have increased over the last decade but remain suboptimal. Vaccination of residents and staff against influenza is associated with a reduced risk of influenza outbreaks. Amantadine is effective in controlling influenza outbreaks in long-term care facilities.

Antibiotic use in Ontario facilities that provide chronic care.

OBJECTIVE: To determine the incidence and variability of antibiotic use in facilities which provide chronic care and to determine how often clinical criteria for infection are met when antibiotics are prescribed in these facilities. DESIGN: A prospective, 12-month, observational cohort study. SETTING: Twenty-two facilities which provide chronic care in southwestern Ontario. PARTICIPANTS: Patients who were treated with systemic antibiotics over the study period. MEASUREMENTS: Characteristics of antibiotic prescriptions (name, dose, duration, and indication) and clinical features of randomly selected patients who were treated with antibiotics. RESULTS: A total of 9,373 courses of antibiotics were prescribed for 2,408 patients (66% of all patients in study facilities). The incidence of antibiotic prescriptions in the facilities ranged from 2.9 to 13.9 antibiotic courses per 1,000 patient-days. Thirty-six percent of antibiotics were prescribed for respiratory tract infections, 33% for urinary infections, and 13% for skin and soft tissue infections. Standardized surveillance definitions of infection were met in 49% of the 1,602 randomly selected patients who were prescribed antibiotics. Diagnostic criteria for respiratory, urinary, and skin infection were met in 58%, 28%, and 65% of prescriptions, respectively. One third of antibiotic prescriptions for a urinary indication were for asymptomatic bacteriuria. Adverse reactions were noted in 6% of prescriptions for respiratory and urinary infections and 4% of prescriptions for skin infection. CONCLUSIONS: Antibiotic use is frequent and highly variable amongst patients who receive chronic care. Reducing antibiotic prescriptions for asymptomatic bacteriuria represents an important way to optimize antibiotic use in this population.