Cost-effectiveness of noninvasive fetal RhD blood group genotyping in nonalloimmunized and alloimmunized pregnancies.

BACKGROUND: We sought to determine the cost-effectiveness of noninvasive fetal RhD blood group genotyping in nonalloimmunized and alloimmunized pregnancies in Canada. STUDY DESIGN AND METHODS: We developed two probabilistic state-transition (Markov) microsimulation models to compare fetal genotyping followed by targeted management versus usual care (i.e., universal Rh immunoglobulin [RhIG] prophylaxis in nonalloimmunized RhD-negative pregnancies, or universal intensive monitoring in alloimmunized pregnancies). The reference case considered a healthcare payer perspective and a 10-year time horizon. Sensitivity analysis examined assumptions related to test cost, paternal screening, subsequent pregnancies, other alloantibodies (e.g., K, Rh c/C/E), societal perspective, and lifetime horizon. RESULTS: Fetal genotyping in nonalloimmunized pregnancies (at per-sample test cost of C$247/US$311) was associated with a slightly higher probability of maternal alloimmunization (22 vs. 21 per 10,000) and a reduced number of RhIG injections (1.427 vs. 1.795) than usual care. It was more expensive (C$154/US$194, 95% Credible Interval [CrI]: C$139/US$175-C$169/US$213) and had little impact on QALYs (0.0007, 95%CrI: -0.01-0.01). These results were sensitive to the test cost (threshold achieved at C$88/US$111), and inclusion of paternal screening. Fetal genotyping in alloimmunized pregnancies (at test cost of C$328/US$413) was less expensive (-C$6280/US$7903, 95% CrI: -C$6325/US$7959 to -C$6229/US$7838) and more effective (0.19 QALYs, 95% CrI 0.17-0.20) than usual care. These cost savings remained robust in sensitivity analyses. DISCUSSION: Noninvasive fetal RhD genotyping saves resources and represents good value for the management of alloimmunized pregnancies. If the cost of genotyping is substantially decreased, the targeted intervention can become a viable option for nonalloimmunized pregnancies.

Cesarean Delivery and Vaginal Birth After Cesarean Delivery Rates in a First Nations Community-Based Obstetrical Program in Northwestern Ontario.

OBJECTIVE: To examine rates of cesarean delivery (CD) and vaginal birth after cesarean delivery (VBAC) and the patient profile in a community-based obstetrical practice. METHODS: Retrospective data from 2012 to 2017 for the Sioux Lookout Meno Ya Win Health Centre (SLMHC) were compared to data from the 30 hospitals providing the same level of services (Maternity 1b: maternity care by family physicians/midwives with CD and VBAC capacity) and Ontario. SLMHC VBAC patients were then compared to the general SLMC obstetrical population. Data included maternal age, parity, comorbidities, CD, VBAC, neonatal birth weight, and Apgar scores. RESULTS: The SLMHC obstetrical population differed from comparable obstetrical programs, with significantly higher rates of alcohol, tobacco, and opioid use and a higher prevalence of diabetes. CD rates were significantly lower (25% vs. 28%), and women delivering at SLMHC chose a trial of labour after CD almost twice as often (46% vs. 27%), resulting in a significantly higher VBAC rate (31% vs. 16%). Patients in the VBAC population differed from the general SLMHC obstetrical population, being older (7 years) and of greater parity. The neonates of VBAC patients had equivalent Apgar scores but lower rates of macrosomia and lower birth weights, although the average VBAC birth weight at 3346 g was equivalent to the provincial average. CONCLUSION: The SLMHC obstetrical program has lower CD and higher VBAC rates than expected, despite prevalent risk factors typically associated with CD. Our study demonstrates that VBAC can be safely performed in well-screened and monitored patients in a rural setting with emergency CD capacity.

Perceived need for restrictions on activity for children with epilepsy.

BACKGROUND: Children and youth with epilepsy have long been subjected to excessive restrictions on extracurricular activities due to concerns over risk of injury. Over time physicians and medical regulatory associations have liberalized the advice given for people with epilepsy to promote independence, self-esteem and general health benefits of physical activity. Current evidence suggests that few restrictions are needed for children with epilepsy beyond water-related precautions and avoidance of very high-risk activities. However, more stringent restrictions on daily activities may be imposed by caregivers. This study was aimed at exploring current perceptions of parents regarding restrictions on activity for children with epilepsy and the child's perspective on restrictions related to the diagnosis. METHODS: A self-administered questionnaire was offered to a sample of parent-child dyads of children/youth with epilepsy attending summer camp for children with epilepsy age 8-18years. A 10-item validated HARCES Parent Scale of Childhood Epilepsy was completed by the parent/guardian and a modified-HARCES completed by the child. The primary objective was to assess the degree of restrictions placed on children with epilepsy from the perspective of child and parent assessed independently. Agreement of perceived restrictions between parent-child dyads was also determined. RESULTS: 21 parent/guardian-child pairs were recruited with mean age of children/youth 12.7years (range 9-16years). Total HARCES scores for parents and guardians ranged from 11-26 (x=16.5; SD 4.9) while total scores for children with epilepsy similarly ranged from 10-25 (x=15.2; SD 4.9). There were no differences in total parent scores when analyzed by child's age (<13 or >13years), gender, age of seizure onset, seizure frequency or seizure type. Total HARCES scores showed no agreement between parent and child pairs with correlation of 0.2798 (95% CI -0.173-0.635). CONCLUSIONS: Children and youth with epilepsy often face activity restrictions based on fear of perceived risk of injury. This small sample shows evidence that even more permissive parents and his/her children still feel limited by such restrictions. Parents and children do not perceive these restrictions in the same way despite similar education by physicians highlighting an important secondary role of epilepsy camps in targeting misperceptions and educating families on appropriate precautions.

Food insecurity and migraine in Canada.

AIM: The aim of this study was to examine the prevalence of household food insecurity in individuals reporting migraine within a large population-based sample of Canadians. METHODS: The Canadian Community Health Survey (CCHS) uses a stratified cluster sample design to obtain information on Canadians ≥12 years of age. Data on household food insecurity were assessed for individuals who reported having migraine or not, providing a current point prevalence. This was assessed for stability in two CCHS datasets from four and eight years earlier. Factors associated with food insecurity among those reporting migraine were examined and a logistic regression model of food insecurity was developed. We also examined whether food insecurity was associated with other reported chronic health conditions. RESULTS: Of 48,645 eligible survey respondents, 4614 reported having migraine (weighted point prevalence 10.2%). Food insecurity was reported by 14.8% who reported migraine compared with 6.8% of those not reporting migraine, giving an odds ratio of 2.4 (95% confidence interval 2.0-2.8%). This risk estimate was stable over the previous eight years. The higher risk for food insecurity was not unique to migraine and was seen with some, but not all, chronic health conditions reported in the CCHS. CONCLUSIONS: Food insecurity is more frequent among individuals reporting migraine in Canada.

Does treatment have an impact on incidence and risk factors for autism spectrum disorders in children with infantile spasms?

OBJECTIVE: Infantile spasms (IS) are a severe form of childhood epilepsy associated with autism spectrum disorders (ASD) in up to 35% of cases. The objective of this post hoc analysis of our randomized control trial was to determine whether rapid diagnosis and treatment of IS could limit the incidence of ASD while identifying risk factors related to ASD outcome. METHODS: Patients with IS were randomized in a standardized diagnostic and treatment protocol. Clinical and electroencephalogram (EEG) evaluations were completed at all eight visits over 5 years, while cognitive evaluations were administered at 0, 6, 24 and 60 months, respectively. Autism was initially screened by means of the Checklist for Autism in Toddlers (CHAT) at 24 months, and formally assessed at the 30-and 60-month follow-ups using the Autism Diagnostic Observation Schedule-Generic (ADOS-G). RESULTS: Of the 69 patients included in the study, 25 could not be assessed due to severe delay or death. Eleven of the 42 patients screened with CHAT, were found to be at risk of an ASD outcome. ADOS was performed in 44 and 10 were diagnosed with ASD. The CHAT proved to correlate highly with the ADOS (80% ppv). Only patients with symptomatic IS developed ASD (p = 0.003). Earlier diagnosis or successful treatment did not correlate with a reduced rate of ASD. Other risk factors were identified such as having chronic epileptic discharges in the frontotemporal areas after disappearance of hypsarrhythmia (p = 0.005 and p = 0.007) and being of nonwhite origin (p = 0.009). SIGNIFICANCE: ASD was only observed in children with sympyomatic IS. Other clinical risk factors include chronic frontotemporal epileptic activity and being of non-white origin. Early diagnosis and treatment did not prevent ASD as an outcome of IS. However, patients at risk for ASD could be identified early on and should in the future benefit from early intervention to potentially improve their long-term outcome.

Food insecurity and epilepsy in a nationally representative sample.

BACKGROUND: Food insecurity amongst patients with epilepsy has not been previously studied. The aim of this study was to compare the presence of food insecurity within a nationally representative sample of individuals reporting epilepsy with that within the general population. METHODS: The Canadian Community Health Survey, Cycle 3.1, is a cross-sectional survey that uses a stratified cluster sample design to obtain information on Canadians 12years of age or older. Data on food insecurity were compared for those who reported having epilepsy and the remainder of the population. RESULTS: Of the 102,927 eligible survey respondents, 654 reported having epilepsy. Food insecurity was considerably more likely to be reported amongst those also reporting epilepsy with a rate of 10.8% compared with those not reporting epilepsy with a rate of 5.2% (odds ratio=2.2, (95% CI=1.6, 3.0)). Binary bivariate prediction of food insecurity within the population of respondents reporting epilepsy included the following: education, income, family size, and home ownership. CONCLUSIONS: The experience of food insecurity appears to be more frequent amongst persons living with epilepsy. Whether this is related directly to epilepsy or factors within the epilepsy experience is unclear.

The CNDR: collaborating to translate new therapies for Canadians.

BACKGROUND: Patient registries represent an important method of organizing "real world" patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry. METHODS: We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR). RESULTS: The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 "index disease" patients. Another 618 "non-index" patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. "Index disease" patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS. CONCLUSIONS: The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.

Lanthanum masquerading as foreign body ingestion in a critically ill patient with end-stage renal disease.

PURPOSE: Medication use may affect imaging results. In this case study, we report a case of lanthanum ingestion resulting in imaging consistent with ingested metallic foreign bodies. SUMMARY: Hyperphosphatemia affects most patients with end-stage renal disease (ESRD) and is associated with morbidity and mortality. Lanthanum carbonate reduces daily phosphate absorption and is indicated as a non-calcium-based phosphate binder in patients with ESRD. A 58-year-old man with a medical history of stage 5 chronic kidney disease was admitted to the intensive care unit (ICU) for hyperkalemia and acute respiratory failure after a missed dialysis session. He required vasopressors, intubation, and continuous renal replacement therapy. Admission imaging demonstrated several ingested metallic foreign bodies within the colon. There was consideration of colorectal surgery and gastroenterology consultation. On the initial medication reconciliation, no medications that would have the radiographic appearance of ingested metallic foreign bodies were identified. On further review of prescription data available through the electronic medical record, it was noted that the patient had recently filled a prescription for lanthanum despite its apparent discontinuation on a previous admission. After interviewing the patient's wife, it was confirmed that the patient had continued taking lanthanum and that he was swallowing it whole and not chewing it. No consultations or interventions were performed, and the metallic foreign bodies were no longer present on further imaging after a period of 35 days. CONCLUSION: Escalation of care was avoided in this patient due to the performance of diligent medication reconciliation and recognition of the impact of lanthanum ingestion on imaging.

A randomized controlled trial of flunarizine as add-on therapy and effect on cognitive outcome in children with infantile spasms.

PURPOSE: Cognitive impairment is observed commonly in children with a history of infantile spasms (IS). The goal of this study was to prospectively examine the effect on cognitive outcome of a neuroprotective agent used as adjunctive therapy during treatment of the spasms. METHODS: In a randomized controlled trial, patients received a standardized therapy plus flunarizine or placebo. The standardized treatment consisted of vigabatrin as first-line therapy. Nonresponders were switched to intramuscular synthetic adrenocorticotropic hormone (sACTH depot) after 2 weeks and, if necessary, to topiramate after two additional weeks. The Vineland Adaptive Behavior Scale (VABS) and Bayley Scales of Infant Development (BSID) were used as outcome measures 24 months after the intervention. KEY FINDINGS: Sixty-eight of 101 children diagnosed over 3 years in seven centers in Canada received either adjunctive flunarizine or placebo. Sixty-five of the 68 children (96%) became spasm-free within 8 weeks and no late relapse occurred. Bayley and Vineland results were available at baseline and at 24 months in 45 children. There was no significant difference in the BSID developmental quotient between the flunarizine- and placebo-treated children at baseline (44.3 ± 35.5 vs. 30.9 ± 29.8; p = 0.18) or 24 months later (56.9 ± 33.3 vs. 46 ± 34.2; p = 0.29). However, the 10 flunarizine-treated children with no identified etiology had a better outcome than the eight controls at 24 months on both the Vineland Scale (84.1 ± 11.3 vs. 72.3 ± 9.8; p = 0.03) and the Bayley Scale (87.6 ± 14.7 vs. 69.9 ± 25.3; p = 0.07). SIGNIFICANCE: Our study failed to demonstrate a protective effect of flunarizine on cognitive outcome in a cohort of children with IS. An analysis of subgroups suggested that flunarizine may further improve cognitive outcome in children with no identified etiology.

Reciprocal perspective as a super learner improves drug-target interaction prediction (MUSDTI).

The identification of novel drug-target interactions (DTI) is critical to drug discovery and drug repurposing to address contemporary medical and public health challenges presented by emergent diseases. Historically, computational methods have framed DTI prediction as a binary classification problem (indicating whether or not a drug physically interacts with a given protein target); however, framing the problem instead as a regression-based prediction of the physiochemical binding affinity is more meaningful. With growing databases of experimentally derived drug-target interactions (e.g. Davis, Binding-DB, and Kiba), deep learning-based DTI predictors can be effectively leveraged to achieve state-of-the-art (SOTA) performance. In this work, we formulated a DTI competition as part of the coursework for a senior undergraduate machine learning course and challenged students to generate component DTI models that might surpass SOTA models and effectively combine these component models as part of a meta-model using the Reciprocal Perspective (RP) multi-view learning framework. Following 6 weeks of concerted effort, 28 student-produced component deep-learning DTI models were leveraged in this work to produce a new SOTA RP-DTI model, denoted the Meta Undergraduate Student DTI (MUSDTI) model. Through a series of experiments we demonstrate that (1) RP can considerably improve SOTA DTI prediction, (2) our new double-cold experimental design is more appropriate for emergent DTI challenges, (3) that our novel MUSDTI meta-model outperforms SOTA models, (4) that RP can improve upon individual models as an ensembling method, and finally, (5) RP can be utilized for low computation transfer learning. This work introduces a number of important revelations for the field of DTI prediction and sequence-based, pairwise prediction in general.

A population-based study of dystrophin mutations in Canada.

INTRODUCTION: We carried out a population-based study of dystrophin mutations in patients followed by members of the Canadian Paediatric Neuromuscular Group (CPNG) over a ten-year period. OBJECTIVES: We aimed to describe the changes in diagnostic testing for dystrophinopathy and to determine the frequency of dystrophin mutations from 2000 to 2009. METHODS: De-identified data containing the clinical phenotypes, diagnostic methods, and mutational reports from dystrophinopathy patients followed by CPNG centres from January 2000 to December 2009 were analyzed using descriptive statistics. RESULTS: 773 patients had a confirmed diagnosis of dystrophinopathy based on genetic testing (97%), muscle biopsy (2%), or family history (1%). 573 (74%) had complete deletion/duplication analysis of all 79 exons or whole gene sequencing, resulting in 366 (64%) deletions, 64 (11%) duplications, and 143 (25%) point mutations. The percentage of patients who were diagnosed using currently accepted genetic testing methods varied across Canada, with a mean of 63% (SD 23). 246 (43%) mutations involved exons 45 to 53. The top ten deletions (n=147, 26%) were exons 45-47, 45-48, 45, 45-50, 45-55, 51, 45-49, 45-52, 49-50, and 46-47. 169 (29%) mutations involved exons 2 to 20. The most common duplications (n=29, 5.1%) were exons 2, 2-7, 2-17, 3-7, 8-11, 10, 10-11, and 12. CONCLUSION: This is the most comprehensive report of dystrophin mutations in Canada. Consensus guidelines regarding the diagnostic approach to dystrophinopathy will hopefully reduce the geographical variation in mutation detection rates in the coming decade.

Epilepsy and activity--a population-based study.

PURPOSE: To compare the activity profiles of a nationally representative sample of individuals with epilepsy compared to the general population. METHODS: The Canadian Community Health Survey is a cross-sectional survey that uses a stratified cluster sample design to obtain information on Canadians 12 years of age or older. Data on activity and energy expenditure, among those aged 12-39 years, were compared for those who reported having epilepsy and the remainder of the population. RESULTS: Of the 53,552 respondents, 341 reported having epilepsy. There was no difference in the monthly frequency of leisure physical activity of >15 min duration between those who did and did not have epilepsy. The daily energy expenditure related to leisure physical activity was also similar between the two groups. The choice of leisure activity was similar, but those with epilepsy were more likely to use walking as a leisure physical activity and were less likely to be involved in ice hockey, weight training, and home exercise. DISCUSSION: These results suggest that the negative attitudes toward restricting access to physical activity do not appear to be adversely affecting the leisure activity of Canadian youth and young adults with epilepsy.

Demographics, prevalence and outcomes of diabetes in pregnancy in NW Ontario.

INTRODUCTION: Diabetes in pregnancy confers increased risk. This study examines the prevalence and birth outcomes of diabetes in pregnancy at the Sioux Lookout Meno Ya Win Health Centre (SLMHC) and other small Ontario hospitals. METHODS: This was a retrospective study of maternal profile: age, parity, comorbidities, mode of delivery, neonatal birth weight, APGARS and complications. Data were compared to other Ontario hospitals offering an equivalent level of obstetrical services. RESULTS: Type 2 diabetes mellitus in pregnancy is far more prevalent in mothers who deliver at SLMHC (relative risk [RR]: 20.9, 95% confidence interval [CI]: 16.0-27.2); the rates of gestational diabetes (GDM) are double (RR: 2.0, 95% CI: 1.7-2.3). SLMHC mothers with diabetes were on average 5 years younger and of greater parity with increased substance use. Neonates largely had equivalent outcomes except for increased macrosomia, neonatal hypoglycaemia and hyperbilirubinaemia in GDM pregnancies. CONCLUSION: Patients with diabetes in pregnancy at SLMHC differ substantially from mothers delivering at Ontario hospitals with a comparable level of service. Programming and resources must meet the service needs of these patients.

Résumé Introduction: Le diabète durant la grossesse élève le risque. Cette étude s'est penchée sur la prévalence des issues liées à l'accouchement causées par le diabète durant la grossesse au centre de santé SLMHC (Sioux Lookout Meno Ya Win Health Centre) et dans d'autres petits hôpitaux ontariens. Méthodologie: Il s'agissait d'une étude rétrospective du profil de la mère: âge, parité, comorbidités, méthode d'accouchement, poids du bébé à la naissance, score APGAR et complications. Les données ont été comparées à celles d'autres hôpitaux ontariens qui offrent un niveau équivalent de services obstétriques. Résultats: Le diabète de type 2 durant la grossesse est beaucoup plus répandu chez les femmes qui accouchent au SLMHC (risque relatif [RR]: 20,9; intervalle de confiance [CI] à 95 %: 16,0­27,2); le taux de diabète gestationnel est deux fois plus élevé (RR: 2,0; IC à 95 %: 1,7­2,3). Les femmes diabétiques ayant accouché au SLMHC étaient en moyenne 5 ans plus jeunes, avaient eu plus de naissances et elles consommaient des drogues en plus grand nombre. L'état des nouveau-nés était grandement équivalent, à l'exception d'un plus grand nombre de macrosomies, d'hypoglycémies néonatales et d'hyperbilirubinémies dans les cas de diabète gestationnel. Conclusion: Les patientes diabétiques durant la grossesse vues au SLMHC diffèrent substantiellement des femmes qui accouchent dans les hôpitaux ontariens offrant un niveau comparable de services. La programmation et les ressources doivent répondre aux besoins en matière de services de ces patientes. Mots-clés: Diabete, Premieres Nations, grossesse.

Outcomes of Pregnancies Affected by Gestational Diabetes and Type 2 Diabetes in a Rural First Nations Obstetrical Program in Northwest Ontario.

OBJECTIVES: In this work, we describe diabetes prevalence and birth outcomes in a primarily First Nations obstetrical population in northwest Ontario. METHODS: This retrospective, observational study of maternal and neonatal characteristics and birth outcomes was performed at the Sioux Lookout Meno Ya Win Health Centre between April 1, 2012 and March 31, 2017. RESULTS: The prevalence of pre-existing type 2 diabetes mellitus was 3.7% and gestational diabetes mellitus was 7.9%. Mothers with diabetes, compared to those without diabetes, were, on average, 5 years older and were of greater parity. Average prepregnancy weight was higher, with an increased incidence of hypertension, inductions and caesarean sections. Neonates had increased incidence of macrosomia, hypoglycemia and hyperbilirubinemia. All maternal cohorts had high rates of alcohol, tobacco and illicit opioid use. CONCLUSIONS: We have identified a high prevalence of diabetes in this First Nations obstetrical population, with associated adverse maternal and neonatal outcomes.

Is temperature regulation different in children susceptible to febrile seizures?

OBJECTIVE: To examine the relationship between the presence and magnitude of fever and susceptibility to febrile seizures, defined as a known family history of febrile seizures. METHODS: Reanalysis of a case-control study dataset (Am J Dis Child. 1993; 147: 35-39). The magnitude of presenting fever was examined between the incident febrile seizure group (N = 75) and febrile control group (N = 150) for a family history of febrile seizures. The presence of fever was examined between the febrile control group (N = 150) and the afebrile control group (N = 150) for a family history of febrile seizures. RESULTS: Children with incident febrile seizures had a higher temperature in the emergency department than febrile controls (39.3 degrees C vs 39.0 degrees C, p = .004). Febrile control children with a known family history of febrile seizures had higher temperatures than those without a known family history (39.5 degrees C vs 38.9 degrees C, p = .04). A model of fever magnitude within the febrile group (seizures and controls) suggested that most of this relationship was on the basis of family history of febrile seizures rather than seizure or control status, with a possibility of interaction. Within the control children (febrile and afebrile), a known family history of febrile seizures was associated with fever (OR 3.4, 95% CI: 1.1,10.7). CONCLUSIONS: Children susceptible to febrile seizures through a known family history of febrile seizures appear more likely to present to emergency departments with fever, and when compared to their febrile counterparts, a fever of higher magnitude. This data supports Rantala's assertion "It may be that regulation of temperature is different in children susceptible to febrile seizures".

Open-book pelvic fracture in late pregnancy.

Pelvic fractures in pregnancy are a relatively rare event. Special consideration needs to be considered when evaluating these patients. We present a case of a 15-year-old pregnant teenager who was an unrestrained passenger in a motor vehicle collision who sustained an open-book pelvic fracture. Care of the patient requires a coordination of care between the patient and the fetus.

Canadian adolescents with migraine: impaired health-related quality of life.

The objective of this study was to determine the impact of migraine headaches on health-related quality of life among Canadian adolescents. The Canadian Community Health Survey (CCHS) collects information related to health status, health care utilization, and health determinants for the Canadian population. Analysis was limited to those adolescents 12-19 years of age residing in Manitoba. Respondents reported whether they had migraine and mood/anxiety disorders. Health-related quality of life was measured using the Short Form-36 survey, which covers 8 health concepts related to functional status, well-being, and overall health. Multivariate linear regression analysis was used to model each Short Form-36 scale against age (12-14 years vs 15-19 years), gender, migraine, and the presence of a mood or anxiety disorder. The CCHS was completed by 994 respondents; 9.3% (95% confidence interval, 7.3%-11.5%) reported a diagnosis of migraine. Reported migraine predicted both statistically (P < .0001) and clinically significantly lower health-related quality of life in all Short Form-36 domains except vitality and general health perceptions. Adolescents reporting a mood disorder (2.1%) scored significantly lower in 6 of 8 health-related quality of life domains, most pronounced for emotional role, general mental health, and social functioning. Canadian adolescents with migraine report clinically and statistically significant impairment in health-related quality of life compared to their peers, independent of psychiatric comorbidities.

Ophthalmoscopy: a 7-step program.

BACKGROUND: Fundoscopy is viewed as a difficult or impossible task by many students and physicians. We have used a novel seven-step approach to teach trainees to use the ophthalmoscope. The technique is based on the premise that success is most easily achieved if the necessary motor skills are mastered first. A step by step approach will enable others to teach their trainees to attain the ability to routinely view the fundi of their pediatric patients. METHODS: Step 1 involves examination of the trainee's fundi to ensure there is no impediment to their success. In Step 2 the student examines the teacher. This identifies major errors. The next step teaches the trainee how to hold the ophthalmoscope. Step 4 gets the learner to read a journal article through the ophthalmoscope. In Step 5 they examine the teacher's eyes again and with a little help they are always successful. In the last two steps an older patient is first examined and finally the student examines a young child. CONCLUSION: This method differs from most other approaches by leaving the cognitive component of ophthalmoscopy until the student is comfortable with handling the instrument. It has been uniformly successful among our students and residents.

Status epilepticus in children.

Status epilepticus is defined as a continuous seizure lasting for at least 30 minutes or recurrent seizures persisting for over 30 minutes, without recovery of consciousness. The estimated incidence in childhood is approximately 20 per 100,000 children per year. The incidence is higher in those under one year of age, with an incidence of approximately 50 per 100,000 per year. Among 1-4 year olds, approximately 30 per 100,000 per year will have an episode of status and in those aged 5-9 years, the incidence is approximately 10 per 100,000 per year. Those aged 10-15 years have the lowest incidence (approximately 2 per 100,000 per year). The mortality associated with status epilepticus in children is estimated at 2.5-5%, and is primarily related to the underlying cause of the episode of status. Neurological morbidity is seen in less than 15% of affected children. In most cases, the episode of status is either a single isolated event or is the first manifestation of epilepsy. Only 12% of cases occur in children with a prior diagnosis of epilepsy. It is essential to have an organized approach for dealing with status epilepticus. There is little data to support the contention that one protocol is better than another. It is recommended that each center should decide on a protocol that is rational and is standard practice for their patients. Most centers initiate therapy with either buccal or intravenous lorazepam. Alternate initial therapies include diazepam or midazolam. Early treatment is generally recommended although, in humans, there is minimal evidence that the length of seizure directly affects outcome. There is however, abundant evidence in animals, which indicates that longer seizures are harmful and result in poorer outcome. Early intervention does, however, increase the likelihood of attaining seizure control in humans. The optimal management of the child in a prolonged seizure therefore demands an understanding of the potential causes, appropriate investigations, and therapy.

Linkage and mutational analysis of CLCN2 in childhood absence epilepsy.

In order to assess the chloride channel gene CLCN2 as a candidate susceptibility gene for childhood absence epilepsy, parametric and non-parametric linkage analysis was performed in 65 nuclear pedigrees. This provided suggestive evidence for linkage with heterogeneity: NPL score=2.3, p<0.009; HLOD=1.5, alpha=0.44. Mutational analysis of the entire genomic sequence of CLCN2 was performed in 24 unrelated patients from pedigrees consistent with linkage, identifying 45 sequence variants including the known non-synonymous polymorphism rs2228292 (G2154C, Glu718Asp) and a novel variant IVS4+12G>A. Intra-familial association analysis using the pedigrees and a further 308 parent-child trios showed suggestive evidence for transmission disequilibrium of the G2154C minor allele: AVE-PDT chi(1)2 = 5.17, p<0.03. Case-control analysis provided evidence for a protective effect of the IVS4+12G>A minor allele: chi(1)2 = 7.27, p<0.008. The 65 nuclear pedigrees were screened for three previously identified mutations shown to segregate with a variety of idiopathic generalised epilepsy phenotypes (597insG, IVS2-14del11 and G2144A) but none were found. We conclude that CLCN2 may be a susceptibility locus in a subset of cases of childhood absence epilepsy.