Early weight gain trajectories in first episode anorexia: predictors of outcome for emerging adults in outpatient treatment.

BACKGROUND: Early response to treatment has been shown to be a predictor of later clinical outcomes in eating disorders (EDs). Specifically, early weight gain trajectories in anorexia nervosa (AN) have been shown to predict higher rates of later remission in inpatient treatment. However, no study has, as of yet, examined this phenomenon within outpatient treatment of first episode cases of AN or in emerging adults. METHODS: One hundred seven patients with AN, all between the ages of 16 and 25 and with an illness duration of < 3 years, received treatment via the first episode rapid early intervention in eating disorders (FREED) service pathway. Weight was recorded routinely across early treatment sessions and recovery outcomes (BMI > 18.5 kg/m2 and eating psychopathology) were assessed up to 1 year later. Early weight gain across the first 12 treatment sessions was investigated using latent growth mixture modelling to determine distinct classes of change. Follow-up clinical outcomes and remission rates were compared between classes, and individual and clinical characteristics at baseline (treatment start) were tested as potential predictors. RESULTS: Four classes of early treatment trajectory were identified. Three of these classes (n = 95), though differing in their early change trajectories, showed substantial improvement in clinical outcomes at final follow-up. One smaller class (n = 12), characterised by a 'higher' start BMI (> 17) and no early weight gain, showed negligible improvement 1 year later. Of the three treatment responding groups, levels of purging, depression, and patient reported carer expressed emotion (in the form of high expectations and low tolerance of the patient) determined class membership, although these findings were not significant after correcting for multiple testing. A higher BMI at treatment start was not sufficient to predict optimal clinical outcomes. CONCLUSION: First episode cases of AN treated via FREED fit into four distinct early response trajectory classes. These may represent subtypes of first episode AN patients. Three of these four trajectories included patients with substantial improvements 1 year later. For those in the non-response trajectory class, treatment adjustments or augmentations could be considered earlier, i.e., at treatment session 12.

A key feature of anorexia nervosa (AN) is an unhealthily low body weight. Previous studies show that more weight gained early in inpatient treatment leads to better outcomes. This study tried to see if this was also true for outpatients receiving treatment for the first time. All participants were emerging adults between the ages of 16 and 25 who had been ill for less than 3 years. Weight was recorded across the first 12 weekly treatment sessions. Statistics showed that the patients fit roughly into four different groups in early treatment, each with different starting weights and rates of weight gain in the first 12 treatment sessions. The group a patient belonged to could sometimes be predicted by vomiting behaviours, level of depression, and patients' perception of parental tolerance and expectations at the start of treatment. Out of the four groups, three did relatively well 1 year later, but one small group of patients did not. This small group had a higher starting weight than many of the other groups but did not gain any weight across the first 12 sessions. These patients could benefit from a change or increase in the amount or intensity of treatment after the first 12 treatment sessions.

Close proximity to alcohol outlets is associated with increased crime and hazardous drinking: Pooled nationally representative data from New Zealand.

This nationwide study investigated the relationship between proximity to alcohol outlets (off-licence, on-licence, and other-licence) and two adverse outcomes; hazardous drinking and crime (common assault, non-aggravated sexual assault, aggravated sexual assault, and tobacco and liquor offences). After adjustment for important individual- and area-level factors, close proximity to alcohol outlets was associated with increased risk of hazardous drinking, with strong associations for on-licence outlets. Proximity alcohol outlets was also strongly associated with all crime outcomes, often with a dose-response relationship. Nationally representative New Zealand data showed that close proximity to alcohol outlets was associated with increased crime and hazardous drinking.

Adult Asthma Diagnosis: Physician Reported Challenges in Alberta-Based Primary Care Practices.

INTRODUCTION: An estimated 8.1% of Canadians adults have asthma. While there are challenges associated with the use of objective measurement of lung function in the diagnosis of asthma, we are uncertain of the barriers that impact the use of objective measures, and have limited understanding of the challenges experienced by primary care providers in diagnosis of asthma. The objectives of this quality improvement initiative were to identify primary care providers' methods of diagnosing asthma and to identify challenges with diagnosis. METHODS: An online survey was disseminated using a snowball methodology. SETTING: Primary care practices in Alberta, Canada. PARTICIPANTS: A total of 84 primary care providers completed the survey. MAIN OUTCOME MEASURES: Participants were asked their ideal and sufficient methods for diagnosing asthma and to identify challenges in their practice related to asthma diagnosis. RESULTS: They identified full pulmonary function testing (54%), pre- and postbronchodilator spirometry (54%), complete history and physical (42%), peak flow measurement overtime (26%), pulmonary consult (26%), and trial of asthma medication(s) (23%), as ideal methods of diagnosing asthma. The most significant barriers to diagnosis included episodic care-care provided typically during times of worsening symptoms without ongoing preventative/maintenance care (55%), patient follow-up (44%), conflict between clinical impression and pulmonary function results (43%), patient already on asthma medications (43%), and interpreting spirometry/pulmonary function results (39%). CONCLUSION: The results of this survey indicate that the majority of primary care providers would choose full pulmonary function testing or pre- and postbronchodilator spirometry as the ideal methods of diagnosing asthma. However, barriers related to the nature of asthma care, patient factors, and challenges with diagnostic testing create challenges. This study also highlights that primary care providers have adapted to challenges in leveraging objective measurement and may rely upon other methods for diagnosis such as trials of medications.

HLA-E: exploiting pathogen-host interactions for vaccine development.

Viruses, when used as vectors for vaccine antigen delivery, can induce strong cellular and humoral responses against target epitopes. Recent work by Hansen et al. describes the use of a cytomegalovirus-vectored vaccine, which is able to generate a stable effector-memory T cell population at the sites of vaccination in rhesus macaques. This vaccine, targeted towards multiple epitopes in simian immunodeficiency virus (SIV), did not induce classical CD8+ T cells. However, non-canonical CD8+ T cell induction occurred via major histocompatibility complex (MHC) class II and MHC-E. The MHC-E-restricted T cells could recognize broad epitopes across the SIV peptides, and conferred protection against viral challenge to 55% of vaccinated macaques. The human homologue, human leucocyte antigen (HLA)-E, is now being targeted as a new avenue for vaccine development. In humans, HLA-E is an unusually oligomorphic class Ib MHC molecule, in comparison to highly polymorphic MHC class Ia. Whereas MHC class Ia presents peptides derived from pathogens to T cells, HLA-E classically binds defined leader peptides from class Ia MHC peptides and down-regulates NK cell cytolytic activity when presented on the cell surface. HLA-E can also restrict non-canonical CD8+ T cells during natural infection with various pathogens, although the extent to which they are involved in pathogen control is mostly unknown. In this review, an overview is provided of HLA-E and its ability to interact with NK cells and non-canonical T cells. Also discussed are the unforeseen beneficial effects of vaccination, including trained immunity of NK cells from bacille Calmette-Guérin (BCG) vaccination, and the broad restriction of non-canonical CD8+ T cells by cytomegalovirus (CMV)-vectored vaccines in pre-clinical trials.

Factors associated with poor asthma control in children aged five to 13 years.

BACKGROUND: Most children with asthma should be able to achieve acceptable control. However, are there differences between those with acceptable and poor control, and if so, how can health care approaches be modified accordingly? OBJECTIVE: To examine the characteristics of elementary school children aged five to 13 years with acceptable and poor levels of asthma control. METHODS: The present cross-sectional study of children with asthma used five indicators of control, as outlined by the Canadian Asthma Consensus Report, to categorize acceptable and poor asthma control. RESULTS: Of 153 children, 115 (75%) were rated as having poorly controlled asthma. Of those with poor control, 65 (64%) children were currently using inhaled corticosteroids, and 65% of those reported using inhaled corticosteroids daily versus as needed. Fifty-one per cent of the children with poorly controlled asthma had exposure to tobacco smoke, whereas 79% of the children with asthma under acceptable control were from households with no smokers (P=0.002). The poor control group also had significantly worse parental perceptions of the psychosocial impact of asthma on their child. No significant difference was found in the percentage of those who had written action plans in the poor control group (28%) compared with the acceptable control group (26%), and similar percentages in each group stated that they used the plans. CONCLUSIONS: Despite the high use of inhaled corticosteroids, the majority of children had poorly controlled asthma. The poor control group had more exposure to tobacco smoke and a worse psychosocial impact due to asthma. Few children had past asthma education and action plans, suggesting that there is a need to improve access to and tools for education.

Separating item-related electrophysiological indices of retrieval effort and retrieval orientation.

The relationship between two classes of retrieval process-retrieval orientation and retrieval effort-was investigated using electrophysiological (ERP) and behavioural measures. ERPs were recorded during retrieval phases of exclusion tasks in which participants focused on retrieval of either phonological or semantic associates that were generated in a prior study phase. Participants were separated into two groups on the basis of the relative accuracy of their memory judgments in the retrieval tasks (high vs. low relative difficulty) as a means of assessing retrieval effort. The critical contrasts were between the ERPs evoked by unstudied test items separated according to group and emphasis of the retrieval task (semantic vs. phonological). Reliable differences according to task were evident in the high relative difficulty group only. This finding is consistent with the view that, for this task pair at least, ERPs are sensitive to the processes set in train in pursuit of task relevant information (retrieval orientations) only when relative difficulty is high.

The influence of response-time demands on electrophysiological correlates of successful episodic retrieval.

Event-related potentials (ERPs) were acquired in two memory retrieval tasks. In Experiment 1 a 2.5 s response-time limit was imposed at test, while in Experiment 2 there was no explicit upper limit. There were no other structural differences between the two experiments. The response-time manipulation did not influence the accuracy of memory judgements, but resulted in qualitative changes in the ERP old/new effects that were elicited in the two tasks. In Experiment 2, the ERP old/new effects from 700 ms post-stimulus onwards comprised a relatively greater positivity for correct judgements to old items in comparison to correct judgements to new items. In keeping with findings in previous studies, this relative positivity was largest at anterior sites over the right hemisphere. In Experiment 1, by contrast, the ERP old/new effects during the same time window were most prominent at right hemisphere central electrode locations, and comprised a relatively greater positivity for correct judgements to new rather than to old test items. In combination, the findings in the two experiments are consistent with the view that the imposition of different response-time demands results in the engagement of neurally and functionally distinct processes during episodic retrieval. The time course of these distinct ERP old/new effects suggests that different post-retrieval monitoring operations were engaged according to the time available to make memory judgements.

Detoxification of the plant toxin fluoroacetate by a genetically modified rumen bacterium.

We isolated the fluoroacetate dehalogenase gene (H1), from Moraxella species strain B, and placed it under the transcriptional control of a 154 bp fragment of the erm gene promoter. The promoter/gene construct was attached to the Butyrivibrio fibrisolvens shuttle vector pBHerm, and the resulting dehalogenase expression plasmid (pBHf) was transferred to B. fibrisolvens OB156 by electroporation. The erm gene promoter directed expression of dehalogenase activity in both E. coli and B. fibrisolvens OB156. Cell-free lysates of the genetically modified OB156 defluorinated 10.6 nmol fluoroacetate/min/mg protein. Growing cultures of OB156 were able to detoxify fluoroacetate in the culture medium, at the rate of 9.9 nmol/min/mg. Plasmid pBHf was retained by 100% of OB156 cells after 500 generations of non-selective culture. The restriction pattern of pBHf remained unchanged after extensive non-selective growth and host bacteria continued to produce active dehalogenase. The construction of rumen bacteria that are able to detoxify an important natural poison supports the feasibility of using genetically modified rumen bacteria to aid animal production.

Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: linkage and loss of heterozygosity.

Nevoid basal cell carcinoma syndrome (NBCCS; basal cell nevus syndrome or Gorlin syndrome) is a cancer-predisposition syndrome characterized by multiple basal cell carcinomas (BCCs) and diverse developmental defects. The gene for NBCCS has been mapped to 9q23.1-q31 in North American and European families. In addition, loss of heterozygosity (LOH) for genetic markers in this region has been detected in sporadic BCCs, indicating that the NBCCS gene is probably a tumor-suppressor gene. In this study we have determined that the NBCCS gene is also linked to this region in Australasian pedigrees and that there is no significant evidence of heterogeneity. We have defined the localization of the gene by multipoint and haplotype analysis of 15 families, using four microsatellite markers. LOH at these loci was detected in 50% of sporadic BCCs, a rate that is significantly higher than that in other skin lesions used as controls.

Reasons for attending GP or health authority clinics.

A survey of 564 users of health authority and general practitioner-run child health clinics since the introduction of the 1991 GP contract revealed a level of 91 per cent satisfaction with the service regardless of the venue, write Hilary Sharpe and Del Loewenthal. However, the demand for health visiting expertise to cover both GP and health authority child surveillance services and the requests of many users for more health visitor input highlight the need for an adequately resourced health visiting service.