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Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.
Background: Saskatchewan’s Rural and Remote Memory Clinic (RRMC) has provided post-diagnostic virtual dementia care for approximately 19 years. In response to the COVID-19 pandemic and a new need for remote dementia diagnosis, we developed a virtual, team-based, interdisciplinary (neurology, neuropsychology, nursing), diagnostic memory clinic (vRRMC). We evaluated patient and caregiver satisfaction with the new virtual clinic. Methods: Semi-structured telephone interviews were conducted with rural vRRMC patients (n=7), caregivers (n= 13), and one patient/caregiver dyad. Ages of respondents ranged from 40 to 70 years old (60% female). Level of diagnosed cognitive dysfunction ranged from subjective cognitive impairment to major neurocognitive disorder. Respondents saved an average of 460 km of travel compared to a trip to Saskatoon. Results: Thematic analysis of responses revealed universal satisfaction with the virtual model. The technology training sessions, offered prior to the first vRRMC visit, was described as important for satisfaction. Analysis of preference for future visits revealed more nuance; some preferred in-person visits and planned to travel for future appointments post-pandemic, while others preferred to maintain the virtual model due to perceived travel burden (cost, time, and inconvenience). Conclusions: When clinically appropriate, virtual diagnostic memory clinics should persist as an option post pandemic for families who experience high travel burden.
Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.
Background: Objective markers of disease progression are needed for patients with multiple sclerosis (MS). Increased randomness in neural networks is hypothesized to be an important cause of morbidity that can be objectified using graph theory. Methods: We use voxel-based structural similarity determined from T1-weighted MRI scans of 23 patients with MS receiving autologous stem cell transplant (ASCT) to compute cortical covariance network parameters. We examine associations between measures of cortical integration or segregation and biochemical/clinical measures of cortical health or function using Spearman correlation coefficients. P<0.05 was considered significant. Results: Path length increase was associated with markers of greater inflammation (ρ=0.56,P<.046) at baseline and reduced Naa/Cr ratio (P<.041) at 12 months. Reduced lambda was associated with markers of greater grey matter atrophy (ρ=0.55,P<.019) after 12 months and lower cognition (ρ=0.56,P<.008) at 12 months. Reduced clustering was associated with higher neurofilament (ρ=-0.68,P<.010) at baseline, greater white matter atrophy (ρ=0.62,P<.006) after 12 months, lower 2-second PASAT performance (ρ=0.56,P<.011) at baseline, and reduced Naa/Cr ratio (P<.001) at 12 months. Conclusions: Reduced cortical integration and segregation (random network features) co-occur with unfavourable markers of cortical health and function in patients with MS receiving ASCT. Network features show promise as important longitudinal markers of patient status and progression.
Background: Prognostic biomarkers are badly needed to direct MS treatment intensity early in the condition Levels of serum neurofilament light chains (sNfL) result from the destruction of central nervous system axons in MS and correlate with the aggressiveness of the disease. Methods: In this prospective cohort study, we identified patients with serum collected within 5 years of first MS symptom onset with more than 15 years of clinical follow-up. Levels of sNfL were quantified in patients and matched controls using digital immunoassay. Results: Sixty-seven patients had a median follow-up period of 17.4 years (range:15.1-26.1). Median serum NfL levels in baseline samples of MS patients was 10.1 pg/ml, 38.5% higher than median levels in 37 controls (7.26pg/ml, p=0.004). Baseline NfL level was most helpful as a predictive marker to rule out progression; patients with levels less 7.62pg/ml were 4.3 times less likely to develop an EDSS score of 34 (p=0.001) and 7.1 times less likely to develop progressive MS (p=0.054). Patients with the highest NfL levels (3rd-tertile, >13.2 pg/ml) progressed most rapidly with an EDSS annual rate of 0.16 (p=0.004), remaining significant after adjustment for sex, age, and disease-modifying treatment (p=0.022). Conclusions: This study demonstrates that baseline sNfL is associated with long term disease progression.
Mr. C, a 75-year-old man, noticed difficulty remembering names and adding numbers after wakening while on vacation. Although these problems were quite subtle, his wife was puzzled because he seemed to have no difficulty the day before. One week later, he noted that “something was wrong” but could not describe the changes in detail. He felt that his balance was “not right” and experienced difficulty keeping track of his golf scores. Over the next few months, he developed word-finding problems and had difficulty expressing himself. He was very forgetful, had trouble problem solving, was distractible, and was unable to do simple calculations. Whereas he had previously been very reserved, he started talking with others in a more open way than he would normally have done. He continued to complain of balance problems and started to notice changes in his handwriting.
Prenatal choline is a key nutrient, like folic acid and vitamin D, for fetal brain development and subsequent mental function. We sought to determine whether effects of higher maternal plasma choline concentrations on childhood attention and social problems, found in an initial clinical trial of choline supplementation, are observed in a second cohort.
Of 183 mothers enrolled from an urban safety net hospital clinic, 162 complied with gestational assessments and brought their newborns for study at 1 month of age; 83 continued assessments through 4 years of age. Effects of maternal 16 weeks of gestation plasma choline concentrations ⩾7.07 μM, 1 s.d. below the mean level obtained with supplementation in the previous trial, were compared to lower levels. The Attention Problems and Withdrawn Syndrome scales on Child Behavior Checklist 1½–5 were the principal outcomes.
Higher maternal plasma choline was associated with lower mean Attention Problems percentiles in children, and for male children, with lower Withdrawn percentiles. Higher plasma choline concentrations also reduced Attention Problems percentiles for children of mothers who used cannabis during gestation as well as children of mothers who had gestational infection.
Prenatal choline's positive associations with early childhood behaviors are found in a second, more diverse cohort. Increases in attention problems and social withdrawal in early childhood are associated with later mental illnesses including attention deficit disorder and schizophrenia. Choline concentrations in the pregnant women in this study replicate other research findings suggesting that most pregnant women do not have adequate choline in their diets.
Introduction: Acute bloody diarrhea obligates rapid and accurate diagnostic evaluation; few studies have described such cohorts of children. Methods: We conducted a planned secondary analysis employing the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) acute gastroenteritis study cohort to describe the characteristics of children with acute bloody diarrhea, compared to a cohort of children without hematochezia. Children <18 years of age presenting to 2 pediatric tertiary care emergency departments (EDs) in Alberta, with ≥3 episodes of diarrhea and/or vomiting in the preceding 24 hours and <7 days of symptoms were consecutively recruited. Stools were tested for 17 viruses, bacteria and parasites. Primary outcomes were clinical characteristics and pathogens identified. Secondary outcomes included interventions and resource utilization. Results: Of 2257 children enrolled between October 2015 and August 2018, hematochezia before or at the index ED visit was reported in 122 (5.4%). Compared to children with nonbloody diarrhea, children with hematochezia had longer illness duration [59.5 vs. 41.5 hrs, difference 10.6, 95% CI 3.5, 19.9], more diarrheal episodes in a 24-hour period [8 vs. 5, difference 3, 95% CI 2, 4], and less vomiting [55.7% vs. 91.1%; difference -35.3%; 95% CI -44.7, -26.3]. They received more intravenous fluids [32.0% vs. 18.3%; difference 13.7%, 95% CI 5.5, 23.0], underwent non-study stool testing [53.7% vs. 4.8%; difference 49.0%, 95% CI 39.6, 58.0], experienced longer ED visits [4.1 vs. 3.3 hours, difference 0.9, 95% CI 0.3, 1.0] and were more likely to have repeat healthcare visits within 14 days [54.8% vs. 34.2%; difference 20.6%, 95% CI 10.8, 30.1]. A bacterial enteric pathogen was found in 31.9% of children with hematochezia versus 6.6% without bloody diarrhea (difference 25.4%, 95% CI 17.2, 34.7). In children with hematochezia, the most commonly detected bacteria were Salmonella spp. (N = 15), Shiga toxin-producing E. coli (N = 9), Campylobacter spp. (N = 7), and Shigella spp. (N = 5). Viruses were detected in 32.8% of children with bloody diarrhea, most commonly adenovirus (N = 15), norovirus (N = 14), sapovirus (N = 8) and rotavirus (N = 7). Conclusion: Children with hematochezia differed clinically from those without hematochezia and required more healthcare resources. While bacterial etiologies are common, several viruses were also detected.
Although no pharmacological treatment has proved to be highly effective for reducing cocaine dependence, several medications have been tested over the last decade and have shown promising efficacy. Modafinil (Provigil), known as a treatment for day time sleepiness, and Topiramate (Topamax), an anti-epileptic medication also prescribed for migraine, have been shown to be effective in controlled clinical trials. We have recently started a major study utilizing Positron Emission Tomography (PET) brain imaging to monitor the progress of pharmacotherapy with modafinil or topiramate in cocaine-dependent and methadone-maintained cocaine-dependent patients. Patients will be assessed before treatment, and again after 4 weeks of pharmacotherapy. The aims of the project are to study effects of the two medications on cocaine dependence and craving, and on dopamine binding in the brain. At each assessment session, patients will undergo PET with [11C] raclopride to image the dopamine receptor DRD2. To trigger craving, patients will then be exposed to a videotape showing cocaine use; a questionnaire will be used to record their subjective responses, and a second PET scan will be performed with [18F] fluorodeoxyglucose (FDG) to image cerebral glucose metabolism during craving. This protocol was designed to enable us to study changes resulting from pharmacotherapy on dopamine binding in the brain, and on craving as reflected both in subjective measures and regional cerebral glucose metabolism. In addition, we will investigate the association between subjective measures of craving for cocaine and the level of dopamine DRD2 receptor occupancy in the brain before and after treatment. Notwithstanding the complexity of the clinical and therapeutic reality characterizing cocaine dependence, we hope to present preliminary evidence for the relative efficacy of these two promising medications in treatment for cocaine. dependence. This evidence could also elucidate the brain mechanisms underlying cocaine craving and dependence in cocaine-dependent patients.
Maternal inflammation in early pregnancy has been identified epidemiologically as a prenatal pathogenic factor for the offspring's later mental illness. Early newborn manifestations of the effects of maternal inflammation on human fetal brain development are largely unknown.
Maternal infection, depression, obesity, and other factors associated with inflammation were assessed at 16 weeks gestation, along with maternal C-reactive protein (CRP), cytokines, and serum choline. Cerebral inhibition was assessed by inhibitory P50 sensory gating at 1 month of age, and infant behavior was assessed by maternal ratings at 3 months of age.
Maternal CRP diminished the development of cerebral inhibition in newborn males but paradoxically increased inhibition in females. Similar sex-dependent effects were seen in mothers' assessment of their infant's self-regulatory behaviors at 3 months of age. Higher maternal choline levels partly mitigated the effect of CRP in male offspring.
The male fetal-placental unit appears to be more sensitive to maternal inflammation than females. Effects are particularly marked on cerebral inhibition. Deficits in cerebral inhibition 1 month after birth, similar to those observed in several mental illnesses, including schizophrenia, indicate fetal developmental pathways that may lead to later mental illness. Deficits in early infant behavior follow. Early intervention before birth, including prenatal vitamins, folate, and choline supplements, may help prevent fetal development of pathophysiological deficits that can have life-long consequences for mental health.
This study investigated whether higher maternal choline levels mitigate effects of marijuana on fetal brain development. Choline transported into the amniotic fluid from the mother activates α7-nicotinic acetylcholine receptors on fetal cerebro-cortical inhibitory neurons, whose development is impeded by cannabis blockade of their cannabinoid-1(CB1) receptors.
Marijuana use was assessed during pregnancy from women who later brought their newborns for study. Mothers were informed about choline and other nutrients, but not specifically for marijuana use. Maternal serum choline was measured at 16 weeks gestation.
Marijuana use for the first 10 weeks gestation or more by 15% of mothers decreased newborns' inhibition of evoked potentials to repeated sounds (d’ = 0.55, p < 0.05). This effect was ameliorated if women had higher gestational choline (rs = −0.50, p = 0.011). At 3 months of age, children whose mothers continued marijuana use through their 10th gestational week or more had poorer self-regulation (d’ = −0.79, p < 0.05). This effect was also ameliorated if mothers had higher gestational choline (rs = 0.54, p = 0.013). Maternal choline levels correlated with the children's improved duration of attention, cuddliness, and bonding with parents.
Prenatal marijuana use adversely affects fetal brain development and subsequent behavioral self-regulation, a precursor to later, more serious problems in childhood. Stopping marijuana use before 10 weeks gestational age prevented these effects. Many mothers refuse to cease use because of familiarity with marijuana and belief in its safety. Higher maternal choline mitigates some of marijuana's adverse effects on the fetus.
Background: There is an unmet need for blood-based biomarkers that can reliably detect MS disease activity. Serum Biomarkers of interest includ Neurofilament-light-chain (NfL), Glial-fibrillary-strocyte-protein(GFAP) and Tau. Bone Marrow Transplantation (BMT) is reserved for aggressive forms of MS and has been shown to halt detectable CNS inflammatory activity for prolonged periods. Significant pre-treatment tissue damage at followed by inflammatory disease abeyance should be reflected longitudinal sera collected from these patients. Methods: Sera were collected from 23 MS patients pre-treatment, and following BMT at 3, 6, 9 and 12-months in addition from 33 non-inflammatory neurological controls. Biomarker quantification was performed with SiMoA. Results: Pre-AHSCT levels of serum NfL and GFAP but not Tau were elevated compared to controls (p=0.0001), and NfL correlated with lesion-based disease activity (6-month-relapse, MRI-T2 and Gadolinium-enhancement). 3-months post-treatment, while NfL levels remained elevated, Tau/GFAP paradoxically increased (p=0.0023/0.0017). These increases at 3m correlated with MRI ‘pseudoatrophy’ at 6-months. NfL/Tau levels dropped to that of controls by 6-months (p=0.0036/0.0159). GFAP levels dropped progressively after 6-months although even at 12-months remained higher than controls (p=0.004). Conclusions: NfL was the closest correlate of MS disease activity and treatment response. Chemotherapy-related toxicity may account for transient increases in NfL, Tau and MRI brain atrophy post-BMT.
Introduction: Although acute gastroenteritis is an extremely common childhood illness, there is a paucity of literature characterizing the associated pain and its management. Our primary objective was to quantify the pain experienced by children with acute gastroenteritis in the 24-hours prior to emergency department (ED) presentation. Secondary objectives included describing maximum pain, analgesic use, discharge recommendations, and factors that influenced analgesic use in the ED. Methods: Study participants were recruited into this prospective cohort study by the Alberta Provincial Pediatric EnTeric Infection TEam between January 2014 and September 2017. This study was conducted at two Canadian pediatric EDs; the Alberta Children's Hospital (Calgary) and the Stollery Children's Hospital (Edmonton). Eligibility criteria included < 18 years of age, acute gastroenteritis (□ 3 episodes of diarrhea or vomiting in the previous 24 hours), and symptom duration □ 7 days. The primary study outcome, caregiver-reported maximum pain in the 24-hours prior to presentation, was assessed using the 11-point Verbal Numerical Rating Scale. Results: We recruited 2136 patients, median age 20.8 months (IQR 10.4, 47.4); 45.8% (979/2136) female. In the 24-hours prior to enrolment, 28.6% (610/2136) of caregivers reported that their child experienced moderate (4-6) and 46.2% (986/2136) severe (7-10) pain in the preceding 24-hours. During the emergency visit, 31.1% (664/2136) described pain as moderate and 26.7% (571/2136) as severe. In the ED, analgesia was provided to 21.2% (452/2131) of children. The most commonly administered analgesics in the ED were ibuprofen (68.1%, 308/452) and acetaminophen (43.4%, 196/452); at home, acetaminophen was most commonly administered (77.7%, 700/901), followed by ibuprofen (37.5%, 338/901). Factors associated with analgesia use in the ED were greater pain scores during the visit, having a primary-care physician, shorter illness duration, fewer diarrheal episodes, presence of fever and hospitalization. Conclusion: Although children presenting to the ED with acute gastroenteritis experience moderate to severe pain, both prior to and during their emergency visit, analgesic use is limited. Future research should focus on appropriate pain management through the development of effective and safe pain treatment plans.
To describe trends of childhood stunting among under-5s in Uganda and to assess the impact of maternal education, wealth and residence on stunting.
Serial and pooled cross-sectional analyses of data from Uganda Demographic and Health Surveys (UDHS) of 1995, 2001, 2006 and 2011. Prevalence of stunting and mean height-for-age Z-score were computed by maternal education, wealth index, region and other sociodemographic characteristics. Multivariable logistic and linear regression models were fitted to survey-specific and pooled data to estimate independent associations between covariates and stunting or Z-score. Sampling weights were applied in all analyses.
Children aged <5 years.
Weighted sample size was 14 747 children. Stunting prevalence decreased from 44·8% in 1995 to 33·2% in 2011. UDHS reported stunting as 38% in 1995, underestimating the decline because of transitioning from National Center for Health Statistics/Centers for Disease Control and Prevention standards to WHO standards. Nevertheless, one in three Ugandan children was still stunted by 2011. South Western, Mid Western, Kampala and East Central regions had highest odds of stunting. Being born in a poor or middle-income household, of a teen mother, without secondary education were associated with stunting. Other persistent stunting predictors included small birth size, male gender and age 2–3 years.
Sustained decrease in stunting suggests that child nutrition interventions have been successful; however, current prevalence does not meet Millennium Development Goals. Stunting remains a public health concern and must be addressed. Customizing established measures such as female education and wealth creation while targeting the most vulnerable groups may further reduce childhood stunting.
In order to characterize the nature and extent of neuropsychological dysfunction in primary lateral sclerosis (PLS), we studied prospectively cognitive, emotional, and behavioral functioning in PLS, and compared performances to functioning in amyotrophic lateral sclerosis (ALS).
Eighteen patients with PLS and 13 patients with ALS completed a neuropsychological test battery assessing both cognitive skills and emotional/behavioral functioning.
Both PLS and ALS groups scored broadly within normal limits (mean T-scores greater than 40) on all cognitive measures and no significant between-group differences were found with the exception of one variable. However, when examined on a case by case basis, the data revealed considerable heterogeneity amongst patients in both groups. Overall, 39% of PLS patients and 31% of ALS patients were considered cognitively impaired. A higher than expected frequency of abnormal scores was noted for several tests of executive function in both groups, and a majority of PLS patients also exhibited abnormal behavioural symptoms. There was no relationship in PLS or ALS groups between cognitive functioning and disease duration, current site of disease, site of onset, functional status, and respiratory variables. Comparison between the PLS and ALS groups indicated virtually no differences in cognitive test scores and overall emotional/behavioural symptoms.
We observed deficits in cognition and behaviour in a significant proportion of PLS patients which were comparable to those observed in ALS cases. Although deficits were not in the range of frontotemporal dementia, both ALS and PLS cases demonstrated deficits most prominently on tests of executive functioning.
Introduction: Gastroenteritis accounts for 1.7 million emergency department visits by children annually in the United States. We conducted a double-blind trial to determine whether twice daily probiotic administration for 5 days, improves outcomes. Methods: 886 children aged 348 months with gastroenteritis were enrolled in six Canadian pediatric emergency departments. Participants were randomly assigned to twice daily Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0052, 4.0 x 109 CFU, in a 95:5 ratio or placebo. Primary outcome was development of moderate-severe disease within 14 days of randomization defined by a Modified Vesikari Scale score 9. Secondary outcomes included duration of diarrhea and vomiting, subsequent physician visits and adverse events. Results: Moderate-severe disease occurred in 108 (26.1%) participants administered probiotics and 102 (24.7%) participants allocated to placebo (OR 1.06; 95%CI: 0.77, 1.46; P=0.72). After adjustment for site, age, and frequency of vomiting and diarrhea, treatment assignment did not predict moderate-severe disease (OR, 1.11, 95%CI, 0.80 to 1.56; P=0.53). In the probiotic versus placebo groups, there were no differences in the median duration of diarrhea [52.5 (18.3, 95.8) vs. 55.5 (20.2, 102.3) hours; P=0.31], vomiting [17.7 (0, 58.6) vs. 18.7 (0, 51.6) hours; P=0.18], physician visits (30.2% vs. 26.6%; OR 1.19; 95% CI0.87. 1.62; P=0.27), or adverse events (32.9% vs. 36.8%; OR 0.83; 95%CI 0.62. 1.11; P=0.21). Conclusion: In children presenting to an emergency department with gastroenteritis, twice daily administration of 4.0 x 109 CFU of a Lactobacillus rhamnosus/helveticus probiotic does not prevent development of moderate-severe disease or improvements in other outcomes measured.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
Introduction: Multiples barriers to appropriate analgesia are reported in the paediatric emergency department (PED), including limited accessibility to effective strategies. Our objective: was to evaluate the improvement in the accessibility of pain and anxiety management strategies in Canadian PEDs, after the creation of a national pediatric pain Quality Improvement Collaborative (QIC), through Pediatric Emergency Research Canada (PERC). Methods: In 2013, the TRAPPED 1 survey was administered to Canadian PEDs, in order to evaluate what resources were in place for pain and anxiety management. A pain QIC was then created to stimulate the implementation of new strategies, through information sharing between PEDs. In 2015, the TRAPPED 2 cross sectional survey was administered. Its focus was to evaluate the improvement in the accessibility of specific strategies reported by each centre, after participating in this QIC, and working to implement change within their own PEDs. Results: All 15/15 Canadian PEDs responded to the TRAPPED 1 survey in 2013 and 11 agreed to participate in the national pain QIC. In-person, phone meetings, follow up surveys and email communications were employed for information sharing. Strategies identified by the QIC to be newly introduced in individual centres were educational initiatives, distraction options, nurse-initiated protocols and intranasal (IN) medications. All 15 PEDs completed the TRAPPED 2 survey. Compared to 2013, an increased number of PEDs used face-based pain scales (14/15 vs 6/15) and behavioural scales (5/15 vs 1/15) for pain assessment in 2015. Use of reminder posters on pain management at triage increased from 4/15 to 6/15 PEDs. Availability of tablets for distraction increased from 4/15 to 10/15 PEDs. Nurse-initiated protocols for topical anesthetic and oral sucrose (for needle procedures) increased from 10/15 to 12/15 sites and from 12/15 to 14/15 sites respectively. Availability of IN medications increased; fentanyl from 9/15 to 14/15 sites and midazolam from 8/15 to 10/15 sites. Ten of the 11 PEDs involved in the QIC strategy reported the implementation of at least one of their own identified strategies. Conclusion: This study suggests that the use of a QIC may improve the introduction of new strategies to reduce pain and anxiety in EDs. QICs may also be helpful to other centres when introducing new strategies.
99mTc-HM-PAO single photon emission computed tomography (SPECT) was used to image 30 patients referred for the assessment of dementia. SPECT images revealed various patterns of regional cerebral perfusion (rCBF) in the subgroups of patients with the clinical diagnoses of Alzheimer's disease (AD, n = 14), Pick's disease (n = 1), and multi-infarct dementia (n = 7). In three patients, SPECT clarified the clinical differential diagnostic possibilities. Using a relative rCBF quantification technique, the relationship between specific cognitive impairments and rCBF in the AD patients was determined. There was a significant correlation between language impairment and left hemisphere hypoperfusion, whereas, apraxia correlated with hypoperfusion in the left parietal region. Thus, HMPAO SPECT is useful as an aid in the differential diagnosis of dementia and the technique of relative rCBF quantification with SPECT may contribute to the understanding of the clinico-anatomical relations of cognitive deficits in dementia.