Does family-based treatment reduce the need for hospitalization in adolescent anorexia nervosa?

OBJECTIVE: We examined the timing and number of days of hospitalization during the course of treatment, hospitalization effects on outcome, and predictors and moderators of the use of hospitalization in adolescents with anorexia nervosa (AN). METHOD: Data used in this study were collected from 158 adolescents (ages 12 to 18 years of age) who met DSM-IVTR criteria for AN (exclusive of the amenorrhea criteria) randomized to receive either Family Based Treatment (FBT) or Systemic Family Therapy (SyFT) in a 7 site study. RESULTS: The trajectory of hospital day use is similar in the first 5 weeks irrespective of treatment allocation. However, days of hospitalization continued to increase throughout SyFT but leveled off in FBT after ∼5 weeks of treatment. Early hospitalization was a negative predictor for improvements in percent weight change for both treatment groups (t(1)=2.6, p = 0.011). Co-morbid psychopathology predicted early hospital use in both treatments. Higher levels of eating related obsessions and depression moderated hospitalization rates suggesting that FBT reduces early hospitalization rates compared to SyFT for these subgroups. DISCUSSION: These data support and extend findings from previous studies by identifying patterns of hospital use, and predictors and moderators of treatment effect for early hospitalization use in adolescent AN. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:891-894).

Service utilization in a sample of preschool children with autism spectrum disorder: A Canadian snapshot.

OBJECTIVE: To describe services received by preschool children diagnosed with autism spectrum disorder (ASD) during the five-year period following their diagnosis. METHOD: An inception cohort of preschoolers diagnosed with ASD from Halifax (Nova Scotia), Montreal (Quebec), Hamilton (Ontario), Edmonton (Alberta) and Vancouver (British Columbia) were invited to participate. Parents/caregivers (n=414) described the services provided to their children at four time points: baseline (T1; within four months of diagnosis; mean age three years); six months later (T2); 12 months later (T3); and at school entry (T4). Data were first coded into 11 service types and subsequently combined into four broader categories (no services, behavioural, developmental and general) for analysis. RESULTS: More than 80% of children at T1, and almost 95% at T4 received some type of service, with a significant number receiving >1 type of service at each assessment point. At T1, the most common service was developmental (eg, speech-language therapy). Subsequently, the most common services were a combination of behavioural and developmental (eg, intensive therapy based on applied behaviour analysis and speech-language therapy). Service provision varied across provinces and over time. DISCUSSION: Although most preschool children with ASD residing in urban centres were able to access specialized services shortly after diagnosis, marked variation in services across provinces remains a concern.

OBJECTIF: Décrire les services qu'ont reçus des enfants d'âge préscolaire ayant un trouble du spectre autistique (TSA) pendant la période de cinq ans suivant leur diagnostic. MÉTHODOLOGIE: Une cohorte initiale d'enfants d'âge préscolaire ayant un TSA diagnostiqué et qui provenaient de Halifax (Nouvelle-Écosse), de Montréal (Québec), de Hamilton (Ontario), d'Edmonton (Alberta) ou de Vancouver (Colombie-Britannique) a été invitée à participer à l'étude. Les parents et les tuteurs (n=414) ont décrit les services fournis à leur enfant à quatre moments : au début (T1; dans les quatre mois suivant le diagnostic, âge moyen de trois ans); six mois plus tard (T2); 12 mois plus tard (T3) et à l'entrée à l'école (T4). Les chercheurs ont d'abord codé les données en 11 types de services, pour ensuite les regrouper en quatre catégories plus vastes (absence de services, comportementaux, développementaux et généraux) en vue de leur analyse. RÉSULTATS: Plus de 80 % des enfants ont reçu certains services à T1, et près de 95 % à T4, et un nombre significatif a reçu plus d'un type de services à chaque évaluation. À T1, le service le plus courant était de type développemental (p. ex., orthophonie). Par la suite, les services les plus courants étaient un mélange de services comportementaux et développementaux (p. ex., thérapie intensive selon l'analyse de comportement appliquée et orthophonie). La prestation des services variait selon les provinces et au fil du temps. EXPOSÉ: Même si la plupart des enfants d'âge préscolaire ayant un TSA qui habitaient dans un centre urbain avaient accès à des services spécialisés peu après le diagnostic, les variations marquées des services entre les provinces demeurent préoccupantes.

Distinct genetic loci control development of benign and malignant skin tumours in mice.

Genetic susceptibility to chemically induced skin cancer in mice is controlled by multiple unlinked genetic loci. Mus spretus mice have dominant resistance genes which confer resistance to interspecific F1 hybrids with susceptible Mus musculus strains. We have mapped three major resistance loci using a combination of Mapmaker/QTL analysis and multiple regression analysis to mouse chromosomes 5 and 7. At least two independent loci on chromosome 7 exert their effects primarily during benign tumour development and have very little influence on tumour progression. On the other hand, probably a single locus on chromosome 5 affects both early and late stages of malignancy. The results indicate that benign and malignant tumours are largely under independent genetic control.

Who is really at risk? Identifying risk factors for subthreshold and full syndrome eating disorders in a high-risk sample.

BACKGROUND: Numerous longitudinal studies have identified risk factors for the onset of most eating disorders (EDs). Identifying women at highest risk within a high-risk sample would allow for focusing of preventive resources and also suggests different etiologies. METHOD: A longitudinal cohort study over 3 years in a high-risk sample of 236 college-age women randomized to the control group of a prevention trial for EDs. Potential risk factors and interactions between risk factors were assessed using the methods developed previously. Main outcome measures were time to onset of a subthreshold or full ED. RESULTS: At the 3-year follow-up, 11.2% of participants had developed a full or partial ED. Seven of 88 potential risk factors could be classified as independent risk factors, seven as proxies, and two as overlapping factors. Critical comments about eating from teacher/coach/siblings and a history of depression were the most potent risk factors. The incidence for participants with either or both of these risk factors was 34.8% (16/46) compared to 4.2% (6/144) for participants without these risk factors, with a sensitivity of 0.75 and a specificity of 0.82. CONCLUSIONS: Targeting preventive interventions at women with high weight and shape concerns, a history of critical comments about eating weight and shape, and a history of depression may reduce the risk for EDs.

A 1-year follow-up of a multi-center treatment trial of adults with anorexia nervosa.

OBJECTIVE: To examine maintenance of recovery following treatment in an adult anorexia nervosa (AN) population. METHOD: One year follow-up of a randomized clinical trial with 122 participants treated with: cognitive behavioral therapy (CBT), drug therapy (fluoxetine), or a combination (CBT+fluoxetine) for 12 months. Participants were assessed at baseline, end of treatment, and follow-up. The primary outcomes were weight and the global scores from the Eating Disorder Examination (EDE) separately and combined. RESULTS: Fifty-two participants completed the follow-up. Mean weight increased from end of treatment to follow-up. Seventy-five percent (75%) of those weight recovered at end of treatment maintained this recovery at follow-up. Recovery of eating disorder psychopathology was stable from end of treatment to follow-up, with 40% of participants with a global EDE score within normal range. Using the most stringent criteria for recovery, only 21% of the completer sample was recovered. DISCUSSION: The findings suggest that while adults with AN improve with treatment and maintain these improvements during follow-up, the majority is not recovered. Additionally, further research is needed to understand barriers to treatment and assessment completion.

The optimum organization for the delivery of colposcopy service in Ontario: a systematic review.

OBJECTIVE: To determine the optimum organization for colposcopy service delivery in Ontario, Canada. METHODS: A multidisciplinary expert panel was convened to develop a systematic review to inform organizational guidelines. MEDLINE, EMBASE, CINAHL, HealthSTAR, and the Cochrane Library databases were searched from 1996 to February 2006 for articles that reported guidance or outcomes relating to improved outcomes in colposcopy training, qualifications, accreditation, maintenance of competency, the delivery of colposcopy, reducing default from colposcopy clinics, and/or strategies to improve patient satisfaction or comfort. In addition, an environmental scan identified unpublished documents related to the delivery of colposcopy services. RESULTS: Sixteen guidance documents related to the delivery of colposcopy services were identified; 5 from the published literature and 11 from the environmental scan. These documents were used by the panel to inform the systematic review and companion guidelines. CONCLUSIONS: Overall, the Ontario Colposcopy Guidelines Development Group believes that the benefits associated with the implementation of colposcopy recommendations in Ontario will result in greater organization of care and improved patient outcomes. In addition, the group anticipates that these recommendations will provide useful guidance to regional planning authorities, hospital administrators, and Cancer Care Ontario, as well as colposcopists and other practitioners, in the planning of integrated regional and provincial cancer screening services.

Validity of autism diagnoses using administrative health data.

It is necessary to monitor autism prevalence in order to plan education support and health services for affected children. This study was conducted to assess the accuracy of administrative health databases for autism diagnoses. Three administrative health databases from the province of Nova Scotia were used to identify diagnoses of autism spectrum disorders (ASD): the Hospital Discharge Abstract Database, the Medical Services Insurance Physician Billings Database and the Mental Health Outpatient Information System database. Seven algorithms were derived from combinations of requirements for single or multiple ASD claims from one or more of the three administrative databases. Diagnoses made by the Autism Team of the IWK Health Centre, using state-of-the-art autism diagnostic schedules, were compared with each algorithm, and the sensitivity, specificity and C-statistic (i.e. a measure of the discrimination ability of the model) were calculated. The algorithm with the best test characteristics was based on one ASD code in any of the three databases (sensitivity=69.3%). Sensitivity based on an ASD code in either the hospital or the physician billing databases was 62.5%. Administrative health databases are potentially a cost efficient source for conducting autism surveillance, especially when compared to methods involving the collection of new data. However, additional data sources are needed to improve the sensitivity and accuracy of identifying autism in Canada.

Residual effect of community antimicrobial exposure on risk of hospital onset healthcare-associated Clostridioides difficile infection: a case-control study using national linked data.

BACKGROUND: Associations between antimicrobial exposure in the community and community-associated Clostridioides difficile infection (CA-CDI) are well documented but associations with healthcare-associated CDI (HA-CDI) are less clear. This study estimates the association between antimicrobial prescribing in the community and HA-CDI. METHODS: A matched case-control study was conducted by linking three national patient level datasets covering CDI cases, community prescriptions and hospitalizations. All validated cases of HA-CDI (August 2010 to July 2013) were extracted and up to three hospital-based controls were matched to each case on the basis of gender, age, hospital and date of admission. Conditional logistic regression was applied to estimate the association between antimicrobial prescribing in the community and HA-CDI. A sensitivity analysis was conducted to consider the impact of unmeasured hospital antimicrobial prescribing. RESULTS: Nine-hundred and thirty unique cases of HA-CDI with onset in hospital and no hospital discharge in the 12 weeks prior to index admission were linked with 1810 matched controls. Individuals with prior prescription of any antimicrobial in the community had an odds ratio (OR) = 1.41 (95% confidence interval (CI) 1.13-1.75) for HA-CDI compared with those without. Individuals exposed to high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR = 1.86 (95% CI: 1.33-2.59). After accounting for the likely impact of unmeasured hospital prescribing, the community exposure, particulary to high-risk antimicrobials, was still associated with elevated HA-CDI risk. CONCLUSIONS: Community antimicrobial exposure is an independent risk factor for HA-CDI and should be considered as part of the risk assessment of patients developing diarrhoea in hospital.

Infants at Risk for Autism Spectrum Disorder: Frequency, Quality, and Variety of Joint Attention Behaviors.

Initiation of joint attention is a critical developmental function related to further social communicative development in infancy. Joint attention appears to be impaired very early in life for children with autism spectrum disorder (ASD), well before a formal diagnosis is established. To observe the early development of joint attention, we prospectively followed infant siblings at high risk for ASD (HR) and low-risk (LR) infants. Initiations of joint attention behaviors were coded with respect to frequency, quality, and variety from videos taken during the administration of the Autism Observation Schedule for Infants. Participants were further stratified based on the presence of ASD (n = 17) or language delay (n = 19) at 3 years of age. Our results revealed that initiations of joint attention are impaired from 12 months of age in both children with ASD and those with language delay, especially for use of gestures (i.e., showing and pointing). At 18 months, fewer initiations of joint attention in all three dimensions distinguished infants with ASD, compared to infants with language delay and HR and LR infants without a diagnosis. Beyond the definition of initiation of joint attention as an early sign for ASD, clinical implications of these results concern the importance of intervening on frequency, quality, and variety of joint attention as early as possible in infants at heightened risk for ASD.

Predictive impact of rare genomic copy number variations in siblings of individuals with autism spectrum disorders.

Identification of genetic biomarkers associated with autism spectrum disorders (ASDs) could improve recurrence prediction for families with a child with ASD. Here, we describe clinical microarray findings for 253 longitudinally phenotyped ASD families from the Baby Siblings Research Consortium (BSRC), encompassing 288 infant siblings. By age 3, 103 siblings (35.8%) were diagnosed with ASD and 54 (18.8%) were developing atypically. Thirteen siblings have copy number variants (CNVs) involving ASD-relevant genes: 6 with ASD, 5 atypically developing, and 2 typically developing. Within these families, an ASD-related CNV in a sibling has a positive predictive value (PPV) for ASD or atypical development of 0.83; the Simons Simplex Collection of ASD families shows similar PPVs. Polygenic risk analyses suggest that common genetic variants may also contribute to ASD. CNV findings would have been pre-symptomatically predictive of ASD or atypical development in 11 (7%) of the 157 BSRC siblings who were eventually diagnosed clinically.

Human papillomavirus--lessons from history and challenges for the future.

Human papillomavirus (HPV) is the most common sexually transmitted infection, and HPV-associated cervical cancer is a significant cause of morbidity and mortality worldwide. Recent advances in molecular biology have facilitated testing for HPV infection. Over the last decade, national and international cervical cancer screening programs have added HPV testing to their guidelines. The use of HPV prophylactic and therapeutic immunization may expand the need for systematic HPV testing to help define eligible subgroups for intervention. Given the worldwide variation in HPV subtype prevalence, basic Pap testing will continue to play an important role in cervical cancer screening, and methods to improve Pap smear sensitivity may help to improve screening in the future. This review focuses on the genetics and cellular biology of HPV infection, the natural history and prevalence of HPV infections, cervical cancer screening around the world and in Canada in particular, and evolving research to improve screening methods.

Clinical assessment of autism in high-risk 18-month-olds.

Earlier intervention improves outcomes for children with autism spectrum disorders (ASDs), but existing identification tools are at the limits of standardization with 18-month-olds. We assessed potential behavioural markers of ASD at 18 months in a high-risk cohort of infant siblings of children with ASD. Prospective data were collected using the Autism Diagnostic Observation Schedule (ADOS) and Autism Observation Scale for Infants (AOSI) on 155 infant siblings and 73 low-risk controls at 18 months. Infants were classified into three groups (ASD sibs, non-ASD sibs, controls) based on blind best-estimate diagnosis at age 3. Fisher's exact tests, followed by discriminant function analyses, revealed that the majority of informative ADOS items came from the social and behavioural domains, and AOSI items measuring behavioural reactivity and motor control contributed additional information. Findings highlight the importance of considering not only social-communication deficits, but also basic dimensions of temperament including state regulation and motor control when assessing toddlers with suspected ASD.

Variability in Verbal and Nonverbal Communication in Infants at Risk for Autism Spectrum Disorder: Predictors and Outcomes.

Early communication impairment is among the most-reported first concerns in parents of young children with autism spectrum disorder (ASD). Using a parent-report questionnaire, we derived trajectory groups for early language and gesture acquisition in siblings at high risk for ASD and in children at low risk, during their first 2 years of life. Developmental skills at 6 months were associated with trajectory group membership representing growth in receptive language and gestures. Behavioral symptoms also predicted gesture development. All communication measures were strongly related to clinical and developmental outcomes. Trajectory groups further indicated slowest language/gesture acquisition in infants with later ASD diagnoses, in particular when associated with language delay. Overall, our results confirm considerable variability in communication development in high-risk infants.

The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted.

BACKGROUND: . Pinpointing the cells from which tumours arise is a major challenge n tumour biology. Previous work has shown that the targeted expression of a mutant ras gene within the interfollicular cell compartment of mouse skin induces the formation of benign papillomas, but these do not spontaneously progress to malignancy. We have investigated the carcinogenic effects of expressing the same oncogene in a different population of epidermal cells. RESULTS: Expression of mutant ras from a truncated keratin 5 gene promoter, which directs expression to the follicular and interfollicular cells of newborn mice and the hair follicle cells of adults, stimulated the development of acanthotic areas in newborn mice. Within one week of birth, the acanthotic skin developed areas of carcinoma in situ and adult mice developed papillomas and keratoacanthomas, the latter having a high frequency of spontaneous malignant transformation to squamous and occasionally spindle carcinomas. The benign tumours that arose had several hallmarks of tumours at a high risk of malignant progression, including suprabasal cell proliferation and heterogeneous expression of keratin 13. In contrast to tumours induced by expressing mutant ras under the control of the keratin 10 or keratin 1 gene promoters, the formation of these lesions was not dependent on wounding or a tumour promoter. CONCLUSIONS: Benign tumours that are at a risk of malignant conversion are primarily derived from cells located within the hair follicle, and the nature of the cell in which tumour initiation occurs is a major determinant of malignant potential.

Development of a continuous cell line, PBLE, from an American eel peripheral blood leukocyte preparation.

A continuous cell line, PBLE, was developed from the adherent cells in a culture of peripheral blood leukocytes from the American eel, Anguilla rostrata. The cells were grown in Leibovitz's L-15 basal medium supplemented with 20% fetal bovine serum (FBS). Under normal culture conditions at 18 degrees C, the morphology of PBLE was fibroblast-like. The cultures have been subcultured over 80 times and have been cryopreserved successfully. These cells have a diploid karyotype of 38 chromosomes, survived temperatures from 5 to 36 degrees C, and proliferated at temperatures from 5 degrees C to at least 30 degrees C. PBLE underwent apoptosis in response to gliotoxin, but did not show a respiratory burst. Results suggest that PBLE may have arisen from a circulating mesenchymal stem cell. PBLE was susceptible to Chum salmon reovirus (CSV) and supported CSV replication. Therefore this cell line should be useful in studying eel specific virus-host interactions.

Two-year outcome of preschool children with autism or Asperger's syndrome.

OBJECTIVE: DSM-IV specifies that Asperger's disorder is a type of pervasive developmental disorder without clinically significant cognitive or language delay. There are no data, however, on the outcome of children with Asperger's disorder or on whether their outcome differs from that of children with autism. The objectives of this study were to compare the outcome of groups of children with these disorders over a period of 2 years on variables independent of the defining criteria and to identify variables that might account for these differences. METHOD: All children 4-6 years of age who came for assessment or were currently in treatment at a pervasive developmental disorder service of one of several centers in a large geographic region were identified. Children who received a diagnosis of autism (N=46) or Asperger's syndrome (N=20) on the basis of a diagnostic interview and had an IQ in the nonretarded range were given a battery of cognitive, language, and behavioral tests. Families were contacted roughly 2 years after the date of their enrollment in the study, and many of the tests were readministered. RESULTS: Children with Asperger's syndrome had better social skills and fewer autistic symptoms 2 years after study enrollment than the children with autism. The differences in outcome could not be explained by initial differences in IQ and language abilities. Children with autism who had developed verbal fluency at follow-up were very similar to the children with Asperger's syndrome at study enrollment. CONCLUSIONS: Although the exact mechanism for the differences in outcome remain to be determined, it appears that Asperger's disorder and autism represent parallel but potentially overlapping developmental trajectories.

The development of writing posture in left-handed children and its relation to sex and reading skills.

Recordings of handwriting posture were taken on left-handed children at grades 1, 3 and 5. The main findings were that most young boys eventually change from a parallel to an inverted posture, while most girls show an early preference for the non-inverted writing posture. The data are discussed in terms of current notions about why the inverted posture develops. Discussion also centers on the finding that for grade 5 boys, the parallel posture is associated with poor reading scores.

Imitation and action in autism: a critical review.

This article considers the evidence for an imitative deficit in autism and for the possible role of deficiencies in the representation of actions. An argument is developed for the claim that the imitation problem is diagnostic of a basic information-processing rather than a social dysfunction. Reviews are offered of the empirical literature on gestural imitation in autism (and other developmental disorders) and the more anecdotal evidence for problems in the domain of action development in autism. An account that may help to integrate these areas is suggested, as are directions for future research.

Pharmacokinetics of high-dose metoclopramide in cancer patients.

The introduction of new cytotoxic drug regimens has been associated with an increase in the incidence and severity of adverse effects. This in turn has highlighted the need for more effective adjuvant therapy. The use of metoclopramide for the prophylaxis of nausea and vomiting, in high intravenous doses (50 to 1000 mg), has become established since 1981. As a lipid-soluble drug, metoclopramide has a large volume of distribution. The reported mean values after high doses range between 2.8 and 4.6 L/kg. The mean values for total body clearance and terminal half-life range from 0.31 to 0.69 L/kg/h and from 4.5 to 8.8 hours, respectively. The values of these pharmacokinetic parameters are essentially similar to those obtained after conventional doses (less than 50mg). Pharmacokinetic parameters appear unaffected by age, although no high-dose study has been conducted in children. Bodyweight is apparently correlated with clearance. An influence of renal function indices on terminal half-life and clearance has been shown, which is rather surprising since renal clearance accounts for only 20% of the total clearance. No thorough investigations exist which examine the influence of hepatic disease, cancer type and cytotoxic drug regimen on the disposition of metoclopramide. A relationship between dose (or concentration) and therapeutic or adverse effects of metoclopramide is outlined. The therapeutic benefit of high doses (up to 14 mg/kg) may be dependent on age, and on the combination of cytotoxic drugs. The advantages of high doses of metoclopramide are most apparent when the drug is used as protection against the adverse effects of high doses of cisplatin (greater than 60 mg/m2). Despite considerable pharmacokinetic variability, intravenous administration of high doses of metoclopramide is relatively safe due to its large therapeutic index.

Effects of phosphodiesterase inhibitors on normal and chemically-skinned isolated airway smooth muscle.

1. The effects of three phosphodiesterase inhibitors (papaverine, isobutyl methyl xanthine (IBMX) and SKF 94120) were examined on tension responses and cyclic nucleotide content (both cyclic AMP and cyclic GMP) of normal and Triton X-100 skinned isolated trachealis of the guinea-pig. 2. The three inhibitors were approximately equipotent in eliciting concentration-dependent relaxation of histamine-induced contractions of the trachealis. 3. Papaverine-induced relaxation was associated with concentration-related increases in the levels of both cyclic nucleotides. 4. IBMX at low concentrations (1 mumol l-1) produced significant relaxation (36%) of histamine-contracted trachealis without changing cyclic nucleotide levels. At a ten fold higher concentration IBMX-induced relaxation (95%) was associated with a selective increase in tissue cyclic GMP levels. Only at the highest concentration tested (100 mumol l-1) did IBMX increase cyclic AMP levels significantly. 5. SKF 94120 (1 mumol l-1) elicited a 23% relaxation of the contracted trachealis without altering the tissue content of either cyclic nucleotide. At the two higher concentrations tested (10 and 100 mumol l-1), SKF 94120-induced relaxation was accompanied by a selective increase in the levels of cyclic AMP. 6. In the skinned trachealis Ca2+ (10 and 20 mumol l-1)-induced contractions were significantly inhibited by the calmodulin antagonist calmidazolium (10 mumol l-1) and by cyclic AMP (10 mumol l-1), the catalytic subunit of cyclic AMP-dependent protein kinase (0.1 mumol l-1) and cyclic GMP (10 mumol l-1). 7. Papaverine (100 mumol l-1) significantly inhibited (31 +/- 6%) the Ca2+-induced contractions of the skinned trachealis. Both IBMX and SKF 94120 were without effect. It is concluded that cyclic nucleotide-dependent mechanisms have an inhibitory action on the biochemical processes that lead to contraction of the guinea-pig trachealis. The results suggest that a functional sarcoplasmic reticular and/or plasma membrane is essential for the expression of IBMXand SKF 94120-induced relaxation. This is not the case for papaverine. The results also highlight the fact that significant relaxant responses of airway smooth muscle can be produced by phosphodiesterase- inhibiting drugs without concomitant elevations in tissue cyclic nucleotide content.