Izaak Walton Killam Health Centre

The SAGE Working Group on Vaccine Hesitancy concluded that vaccine hesitancy refers to delay in acceptance or refusal of vaccination despite availability of vaccination services. Vaccine hesitancy is complex and context specific, varying across time, place and vaccines. It is influenced by factors such as complacency, convenience and confidence. The Working Group retained the term 'vaccine' rather than 'vaccination' hesitancy, although the latter more correctly implies the broader range of immunization concerns, as vaccine hesitancy is the more commonly used term. While high levels of hesitancy lead to low vaccine demand, low levels of hesitancy do not necessarily mean high vaccine demand. The Vaccine Hesitancy Determinants Matrix displays the factors influencing the behavioral decision to accept, delay or reject some or all vaccines under three categories: contextual, individual and group, and vaccine/vaccination-specific influences.

During the last 2 decades, major advances have been made in understanding the development of executive functions (EFs) in early childhood. This article reviews the EF literature during the preschool period using an integrative framework. The framework adopted considers EF to be a unitary construct with partially dissociable components (A. Miyake et al., 2000). The authors focus on 3 EF components: working memory, response inhibition, and shifting. For the present purposes, the central executive is conceived of as a central attention system that is involved in all EF component operations. Research to date suggests that elementary forms of the core EF components are present early during the preschool period. Changes in EF during the latter half of the preschool period appear to be due to the development of attention and integration of component EFs. Finally, the review outlines a number of areas that warrant further investigation if researchers are to move forward in understanding early EF development.

Pseudomonas aeruginosa is an opportunistic pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals. Eradication of P. aeruginosa has become increasingly difficult due to its remarkable capacity to resist antibiotics. Strains of Pseudomonas aeruginosa are known to utilize their high levels of intrinsic and acquired resistance mechanisms to counter most antibiotics. In addition, adaptive antibiotic resistance of P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections. The discovery and development of alternative therapeutic strategies that present novel avenues against P. aeruginosa infections are increasingly demanded and gaining more and more attention. Although mostly at the preclinical stages, many recent studies have reported several innovative therapeutic technologies that have demonstrated pronounced effectiveness in fighting against drug-resistant P. aeruginosa strains. This review highlights the mechanisms of antibiotic resistance in P. aeruginosa and discusses the current state of some novel therapeutic approaches for treatment of P. aeruginosa infections that can be further explored in clinical practice.

The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagen-encoding genes, or in genes encoding collagen-modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes. © 2017 Wiley Periodicals, Inc.

Chronic and recurrent pain not associated with a disease is very common in childhood and adolescence, but studies of pain prevalence have yielded inconsistent findings. This systematic review examined studies of chronic and recurrent pain prevalence to provide updated aggregated prevalence rates. The review also examined correlates of chronic and recurrent pain such as age, sex, and psychosocial functioning. Studies of pain prevalence rates in children and adolescents published in English or French between 1991 and 2009 were identified using EMBASE, Medline, CINAHL, and PsycINFO databases. Of 185 published papers yielded by the search, 58 met inclusion criteria and were reviewed, and 41 were included in the review. Two independent reviewers screened papers for inclusion, extracted data, and assessed the quality of studies. Prevalence rates ranged substantially, and were as follows: headache: 8-83%; abdominal pain: 4-53%; back pain: 14-24%; musculoskeletal pain: 4-40%; multiple pains: 4-49%; other pains: 5-88%. Pain prevalence rates were generally higher in girls and increased with age for most pain types. Lower socioeconomic status was associated with higher pain prevalence especially for headache. Most studies did not meet quality criteria.

Transition metal complexes are of increasing interest as photosensitizers in photodynamic therapy (PDT) and, more recently, for photochemotherapy (PCT). In recent years, Ru(II) polypyridyl complexes have emerged as promising systems for both PDT and PCT. Their rich photochemical and photophysical properties derive from a variety of excited-state electronic configurations accessible with visible and near-infrared light, and these properties can be exploited for both energy- and electron-transfer processes that can yield highly potent oxygen-dependent and/or oxygen-independent photobiological activity. Selected examples highlight the use of rational design in coordination chemistry to control the lowest-energy triplet excited-state configurations for eliciting a particular type of photoreactivity for PDT and/or PCT effects. These principles are also discussed in the context of the development of TLD1433, the first Ru(II)-based photosensitizer for PDT to enter a human clinical trial. The design of TLD1433 arose from a tumor-centered approach, as part of a complete PDT package that includes the light component and the protocol for treating non-muscle invasive bladder cancer. Briefly, this review summarizes the challenges to bringing PDT into mainstream cancer therapy. It considers the chemical and photophysical solutions that transition metal complexes offer, and it puts into context the multidisciplinary effort needed to bring a new drug to clinical trial.

Beyond structural and chemical barriers to pathogens, the immune system has two fundamental lines of defense: innate immunity and adaptive immunity. Innate immunity is the first immunological mechanism for fighting against an intruding pathogen. It is a rapid immune response, initiated within minutes or hours after aggression, that has no immunologic memory. Adaptive immunity, on the other hand, is antigen-dependent and antigen-specific; it has the capacity for memory, which enables the host to mount a more rapid and efficient immune response upon subsequent exposure to the antigen. There is a great deal of synergy between the adaptive immune system and its innate counterpart, and defects in either system can provoke illness or disease, such as inappropriate inflammation, autoimmune diseases, immunodeficiency disorders and hypersensitivity reactions. This article provides a practical overview of innate and adaptive immunity, and describes how these host defense mechanisms are involved in both heath and illness.

In March 2012, the SAGE Working Group on Vaccine Hesitancy was convened to define the term "vaccine hesitancy", as well as to map the determinants of vaccine hesitancy and develop tools to measure and address the nature and scale of hesitancy in settings where it is becoming more evident. The definition of vaccine hesitancy and a matrix of determinants guided the development of a survey tool to assess the nature and scale of hesitancy issues. Additionally, vaccine hesitancy questions were piloted in the annual WHO-UNICEF joint reporting form, completed by National Immunization Managers globally. The objective of characterizing the nature and scale of vaccine hesitancy issues is to better inform the development of appropriate strategies and policies to address the concerns expressed, and to sustain confidence in vaccination. The Working Group developed a matrix of the determinants of vaccine hesitancy informed by a systematic review of peer reviewed and grey literature, and by the expertise of the working group. The matrix mapped the key factors influencing the decision to accept, delay or reject some or all vaccines under three categories: contextual, individual and group, and vaccine-specific. These categories framed the menu of survey questions presented in this paper to help diagnose and address vaccine hesitancy.

IMPORTANCE: Approximately one-third of children experiencing acute concussion experience ongoing somatic, cognitive, and psychological or behavioral symptoms, referred to as persistent postconcussion symptoms (PPCS). However, validated and pragmatic tools enabling clinicians to identify patients at risk for PPCS do not exist. OBJECTIVE: To derive and validate a clinical risk score for PPCS among children presenting to the emergency department. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study (Predicting and Preventing Postconcussive Problems in Pediatrics [5P]) enrolled young patients (aged 5-<18 years) who presented within 48 hours of an acute head injury at 1 of 9 pediatric emergency departments within the Pediatric Emergency Research Canada (PERC) network from August 2013 through September 2014 (derivation cohort) and from October 2014 through June 2015 (validation cohort). Participants completed follow-up 28 days after the injury. EXPOSURES: All eligible patients had concussions consistent with the Zurich consensus diagnostic criteria. MAIN OUTCOMES AND MEASURES: The primary outcome was PPCS risk score at 28 days, which was defined as 3 or more new or worsening symptoms using the patient-reported Postconcussion Symptom Inventory compared with recalled state of being prior to the injury. RESULTS: In total, 3063 patients (median age, 12.0 years [interquartile range, 9.2-14.6 years]; 1205 [39.3%] girls) were enrolled (n = 2006 in the derivation cohort; n = 1057 in the validation cohort) and 2584 of whom (n = 1701 [85%] in the derivation cohort; n = 883 [84%] in the validation cohort) completed follow-up at 28 days after the injury. Persistent postconcussion symptoms were present in 801 patients (31.0%) (n = 510 [30.0%] in the derivation cohort and n = 291 [33.0%] in the validation cohort). The 12-point PPCS risk score model for the derivation cohort included the variables of female sex, age of 13 years or older, physician-diagnosed migraine history, prior concussion with symptoms lasting longer than 1 week, headache, sensitivity to noise, fatigue, answering questions slowly, and 4 or more errors on the Balance Error Scoring System tandem stance. The area under the curve was 0.71 (95% CI, 0.69-0.74) for the derivation cohort and 0.68 (95% CI, 0.65-0.72) for the validation cohort. CONCLUSIONS AND RELEVANCE: A clinical risk score developed among children presenting to the emergency department with concussion and head injury within the previous 48 hours had modest discrimination to stratify PPCS risk at 28 days. Before this score is adopted in clinical practice, further research is needed for external validation, assessment of accuracy in an office setting, and determination of clinical utility.

BACKGROUND: In 1998, folic acid fortification of a large variety of cereal products became mandatory in Canada, a country where the prevalence of neural-tube defects was historically higher in the eastern provinces than in the western provinces. We assessed changes in the prevalence of neural-tube defects in Canada before and after food fortification with folic acid was implemented. METHODS: The study population included live births, stillbirths, and terminations of pregnancies because of fetal anomalies among women residing in seven Canadian provinces from 1993 to 2002. On the basis of published results of testing of red-cell folate levels, the study period was divided into prefortification, partial-fortification, and full-fortification periods. We evaluated the relationship between baseline rates of neural-tube defects in each province and the magnitude of the decrease after fortification was implemented. RESULTS: A total of 2446 subjects with neural-tube defects were recorded among 1.9 million births. The prevalence of neural-tube defects decreased from 1.58 per 1000 births before fortification to 0.86 per 1000 births during the full-fortification period, a 46% reduction (95% confidence interval, 40 to 51). The magnitude of the decrease was proportional to the prefortification baseline rate in each province, and geographical differences almost disappeared after fortification began. The observed reduction in rate was greater for spina bifida (a decrease of 53%) than for anencephaly and encephalocele (decreases of 38% and 31%, respectively). CONCLUSIONS: Food fortification with folic acid was associated with a significant reduction in the rate of neural-tube defects in Canada. The decrease was greatest in areas in which the baseline rate was high.

This is the second update of a Cochrane Review (Issue 4, 2006). Pain and distress from needle-related procedures are common during childhood and can be reduced through use of psychological interventions (cognitive or behavioral strategies, or both). Our first review update (Issue 10, 2013) showed efficacy of distraction and hypnosis for needle-related pain and distress in children and adolescents.To assess the efficacy of psychological interventions for needle-related procedural pain and distress in children and adolescents.We searched six electronic databases for relevant trials: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; PsycINFO; Embase; Web of Science (ISI Web of Knowledge); and Cumulative Index to Nursing and Allied Health Literature (CINAHL). We sent requests for additional studies to pediatric pain and child health electronic listservs. We also searched registries for relevant completed trials: clinicaltrials.gov; and World Health Organization International Clinical Trials Registry Platform (www.who.int.trialsearch). We conducted searches up to September 2017 to identify records published since the last review update in 2013.We included peer-reviewed published randomized controlled trials (RCTs) with at least five participants per study arm, comparing a psychological intervention with a control or comparison group. Trials involved children aged two to 19 years undergoing any needle-related medical procedure.Two review authors extracted data and assessed risks of bias using the Cochrane 'Risk of bias' tool. We examined pain and distress assessed by child self-report, observer global report, and behavioral measurement (primary outcomes). We also examined any reported physiological outcomes and adverse events (secondary outcomes). We used meta-analysis to assess the efficacy of identified psychological interventions relative to a comparator (i.e. no treatment, other active treatment, treatment as usual, or waitlist) for each outcome separately. We used Review Manager 5 software to compute standardized mean differences (SMDs) with 95% confidence intervals (CIs), and GRADE to assess the quality of the evidence.We included 59 trials (20 new for this update) with 5550 participants. Needle procedures primarily included venipuncture, intravenous insertion, and vaccine injections. Studies included children aged two to 19 years, with few trials focused on adolescents. The most common psychological interventions were distraction (n = 32), combined cognitive behavioral therapy (CBT; n = 18), and hypnosis (n = 8). Preparation/information (n = 4), breathing (n = 4), suggestion (n = 3), and memory alteration (n = 1) were also included. Control groups were often 'standard care', which varied across studies. Across all studies, 'Risk of bias' scores indicated several domains at high or unclear risk, most notably allocation concealment, blinding of participants and outcome assessment, and selective reporting. We downgraded the quality of evidence largely due to serious study limitations, inconsistency, and imprecision.Very low- to low-quality evidence supported the efficacy of distraction for self-reported pain (n = 30, 2802 participants; SMD -0.56, 95% CI -0.78 to -0.33) and distress (n = 4, 426 participants; SMD -0.82, 95% CI -1.45 to -0.18), observer-reported pain (n = 11, 1512 participants; SMD -0.62, 95% CI -1.00 to -0.23) and distress (n = 5, 1067 participants; SMD -0.72, 95% CI -1.41 to -0.03), and behavioral distress (n = 7, 500 participants; SMD -0.44, 95% CI -0.84 to -0.04). Distraction was not efficacious for behavioral pain (n = 4, 309 participants; SMD -0.33, 95% CI -0.69 to 0.03). Very low-quality evidence indicated hypnosis was efficacious for reducing self-reported pain (n = 5, 176 participants; SMD -1.40, 95% CI -2.32 to -0.48) and distress (n = 5, 176 participants; SMD -2.53, 95% CI -3.93 to -1.12), and behavioral distress (n = 6, 193 participants; SMD -1.15, 95% CI -1.76 to -0.53), but not behavioral pain (n = 2, 69 participants; SMD -0.38, 95% CI -1.57 to 0.81). No studies assessed hypnosis for observer-reported pain and only one study assessed observer-reported distress. Very low- to low-quality evidence supported the efficacy of combined CBT for observer-reported pain (n = 4, 385 participants; SMD -0.52, 95% CI -0.73 to -0.30) and behavioral distress (n = 11, 1105 participants; SMD -0.40, 95% CI -0.67 to -0.14), but not self-reported pain (n = 14, 1359 participants; SMD -0.27, 95% CI -0.58 to 0.03), self-reported distress (n = 6, 234 participants; SMD -0.26, 95% CI -0.56 to 0.04), observer-reported distress (n = 6, 765 participants; SMD 0.08, 95% CI -0.34 to 0.50), or behavioral pain (n = 2, 95 participants; SMD -0.65, 95% CI -2.36 to 1.06). Very low-quality evidence showed efficacy of breathing interventions for self-reported pain (n = 4, 298 participants; SMD -1.04, 95% CI -1.86 to -0.22), but there were too few studies for meta-analysis of other outcomes. Very low-quality evidence revealed no effect for preparation/information (n = 4, 313 participants) or suggestion (n = 3, 218 participants) for any pain or distress outcome. Given only a single trial, we could draw no conclusions about memory alteration. Adverse events of respiratory difficulties were only reported in one breathing intervention.We identified evidence supporting the efficacy of distraction, hypnosis, combined CBT, and breathing interventions for reducing children's needle-related pain or distress, or both. Support for the efficacy of combined CBT and breathing interventions is new from our last review update due to the availability of new evidence. The quality of trials and overall evidence remains low to very low, underscoring the need for improved methodological rigor and trial reporting. Despite low-quality evidence, the potential benefits of reduced pain or distress or both support the evidence in favor of using these interventions in clinical practice.

BACKGROUND: The differential effectiveness of parent training has led researchers to examine a variety of child, parent, and familial variables that may predict treatment response. Studies have identified a diverse set of child, parent psychological/behavioral and demographic variables that are associated with treatment outcome and dropout. METHOD: The parent training literature was examined to isolate child, parent, and family variables that predict response to parent training for child externalizing behavior problems. A literature review was conducted spanning articles published from 1980 to 2004 of indicated prevention (children with symptoms) and treatment (children with diagnosis) studies. Meta-analyses were conducted to determine standardized effect sizes associated with the identified predictors. RESULTS: Many of the predictors of treatment response examined in this meta-analysis resulted in moderate standardized effect sizes when study results were subjected to meta-analytic procedures (i.e., low education/occupation, more severe child behavior problems pretreatment, maternal psychopathology). Only low family income resulted in a large standardized effect size. Predictors of drop-out resulted in standardized effect sizes in the small or insubstantial range. CONCLUSIONS: Response to parent training is often influenced by variables not directly involving the child, with socioeconomic status and maternal mental health being particularly salient factors.

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM." CONCLUSION: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

When faced with vaccine hesitancy, public health authorities are looking for effective strategies to address this issue. In this paper, the findings of 15 published literature reviews or meta-analysis that have examined the effectiveness of different interventions to reduce vaccine hesitancy and/or to enhance vaccine acceptance are presented and discussed. From the literature, there is no strong evidence to recommend any specific intervention to address vaccine hesitancy/refusal. The reviewed studies included interventions with diverse content and approaches that were implemented in different settings and targeted various populations. Few interventions were directly targeted to vaccine hesitant individuals. Given the paucity of information on effective strategies to address vaccine hesitancy, when interventions are implemented, planning a rigorous evaluation of their impact on vaccine hesitancy/vaccine acceptance will be essential.

BACKGROUND: Some copy-number variants are associated with genomic disorders with extreme phenotypic heterogeneity. The cause of this variation is unknown, which presents challenges in genetic diagnosis, counseling, and management. METHODS: We analyzed the genomes of 2312 children known to carry a copy-number variant associated with intellectual disability and congenital abnormalities, using array comparative genomic hybridization. RESULTS: Among the affected children, 10.1% carried a second large copy-number variant in addition to the primary genetic lesion. We identified seven genomic disorders, each defined by a specific copy-number variant, in which the affected children were more likely to carry multiple copy-number variants than were controls. We found that syndromic disorders could be distinguished from those with extreme phenotypic heterogeneity on the basis of the total number of copy-number variants and whether the variants are inherited or de novo. Children who carried two large copy-number variants of unknown clinical significance were eight times as likely to have developmental delay as were controls (odds ratio, 8.16; 95% confidence interval, 5.33 to 13.07; P=2.11×10(-38)). Among affected children, inherited copy-number variants tended to co-occur with a second-site large copy-number variant (Spearman correlation coefficient, 0.66; P<0.001). Boys were more likely than girls to have disorders of phenotypic heterogeneity (P<0.001), and mothers were more likely than fathers to transmit second-site copy-number variants to their offspring (P=0.02). CONCLUSIONS: Multiple, large copy-number variants, including those of unknown pathogenic significance, compound to result in a severe clinical presentation, and secondary copy-number variants are preferentially transmitted from maternal carriers. (Funded by the Simons Foundation Autism Research Initiative and the National Institutes of Health.).

Beyond structural and chemical barriers to pathogens, the immune system has two fundamental lines of defense: innate immunity and adaptive immunity. Innate immunity is the first immunological mechanism for fighting against an intruding pathogen. It is a rapid immune response, initiated within minutes or hours after aggression, that has no immunologic memory. Adaptive immunity, on the other hand, is antigen-dependent and antigen-specific; it has the capacity for memory, which enables the host to mount a more rapid and efficient immune response upon subsequent exposure to the antigen. There is a great deal of synergy between the adaptive immune system and its innate counterpart, and defects in either system can provoke illness or disease, such as inappropriate inflammation, autoimmune diseases, immunodeficiency disorders and hypersensitivity reactions. This article provides a practical overview of innate and adaptive immunity, and describes how these host defense mechanisms are involved in both heath and illness.

BACKGROUND: Global vaccine development efforts have been accelerated in response to the devastating coronavirus disease 2019 (COVID-19) pandemic. We evaluated the impact of a 2-dose COVID-19 vaccination campaign on reducing incidence, hospitalizations, and deaths in the United States. METHODS: We developed an agent-based model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and parameterized it with US demographics and age-specific COVID-19 outcomes. Healthcare workers and high-risk individuals were prioritized for vaccination, whereas children under 18 years of age were not vaccinated. We considered a vaccine efficacy of 95% against disease following 2 doses administered 21 days apart achieving 40% vaccine coverage of the overall population within 284 days. We varied vaccine efficacy against infection and specified 10% preexisting population immunity for the base-case scenario. The model was calibrated to an effective reproduction number of 1.2, accounting for current nonpharmaceutical interventions in the United States. RESULTS: Vaccination reduced the overall attack rate to 4.6% (95% credible interval [CrI]: 4.3%-5.0%) from 9.0% (95% CrI: 8.4%-9.4%) without vaccination, over 300 days. The highest relative reduction (54%-62%) was observed among individuals aged 65 and older. Vaccination markedly reduced adverse outcomes, with non-intensive care unit (ICU) hospitalizations, ICU hospitalizations, and deaths decreasing by 63.5% (95% CrI: 60.3%-66.7%), 65.6% (95% CrI: 62.2%-68.6%), and 69.3% (95% CrI: 65.5%-73.1%), respectively, across the same period. CONCLUSIONS: Our results indicate that vaccination can have a substantial impact on mitigating COVID-19 outbreaks, even with limited protection against infection. However, continued compliance with nonpharmaceutical interventions is essential to achieve this impact.

OBJECTIVE: To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders (PDD). METHODS: In this 8-week, randomized, double-blind, placebo-controlled trial, risperidone/placebo solution (0.01-0.06 mg/kg/day) was administered to 79 children who were aged 5 to 12 years and had PDD. Behavioral symptoms were assessed using the Aberrant Behavior Checklist (ABC), Nisonger Child Behavior Rating Form, and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events, and laboratory tests. RESULTS: Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive, and overly sensitive subscales of the Nisonger Child Behavior Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% versus 7.7% of subjects (risperidone vs placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs 1.0 kg), pulse rate, and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups. CONCLUSIONS: Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children.

Neuropathic pain (NeP), generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics) and anticonvulsants (gabapentin and pregabalin). Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.

BACKGROUND: The present study examined the disengage and shift operations of visual attention in young children with autism. METHODS: For this purpose, we used a simple visual orienting task that is thought to engage attention automatically. Once attention was first engaged on a central fixation stimulus, a second stimulus was presented on either side, either simultaneously or successively. Latency to begin an eye movement to the peripheral stimulus served as the main dependent measure. The two stimulus conditions (simultaneous and successive) provided independent measures of disengaging and shifting attention, respectively. Performance of children with autism was compared to that of children with Down syndrome and a normal group. RESULTS: The main finding was that relative to both comparison groups, children with autism had marked difficulty in disengaging attention. Indeed, on 20% of trials they remained fixated on the first of two competing stimuli for the entire 8-second trial duration. Evidence is also provided for a more subtle problem in executing rapid shifts of attention. CONCLUSIONS: Our findings on disengagement in autism parallel those reported in normal 2-month-olds, in whom attention has been described as 'obligatory'. Discussion focuses on the potential role of general versus domain-specific processes in producing some of the core features of autism.