Development of 'gastrostomy tube - is it for me?', a web-based patient decision aid for people living with motor neurone disease considering having a gastrostomy tube placed.

Objective: To develop and pilot a web-based patient decision aid (PDA) to support people living with motor neurone disease (plwMND) considering having a gastrostomy tube placed. Methods: In Phase 1, content and design were informed by semi-structured interviews, literature reviews and a prioritization survey. In Phase 2, the prototype PDA was tested with users and developed iteratively with feedback from surveys and 'think-aloud' interviews. Phase 1 and 2 participants were plwMND, carers and healthcare professionals (HCPs). In Phase 3, the PDA was evaluated by plwMND using validated questionnaires and HCPs provided feedback in focus groups. Results: Sixteen plwMND, 16 carers and 25 HCPs took part in Phases 1 and 2. Interviews and the literature review informed a prioritization survey with 82 content items. Seventy-seven per cent (63/82) of the content of the PDA was retained. A prototype PDA, which conforms to international standards, was produced and improved during Phase 2. In Phase 3, 17 plwMND completed questionnaires after using the PDA. Most plwMND (94%) found the PDA completely acceptable and would recommend it to others in their position, 88% had no decisional conflict, 82% were well prepared and 100% were satisfied with their decision-making. Seventeen HCPs provided positive feedback and suggestions for use in clinical practice. Conclusion: Gastrostomy Tube: Is it for me? was co-produced with stakeholders and found to be acceptable, practical and useful. Freely available from the MND Association website, the PDA is a valuable tool to support the shared decision-making process for gastrostomy tube placement.

Supportive care needs of patients following treatment for colorectal cancer: risk factors for unmet needs and the association between unmet needs and health-related quality of life-results from the ColoREctal Wellbeing (CREW) study.

PURPOSE: To investigate unmet needs of patients with colorectal cancer (CRC) at the end of treatment and whether unmet needs improve over time. Identify predictors of need following treatment and whether unmet need is associated with worse health-related quality of life (HRQoL). METHODS: As part of the UK ColoREctal Wellbeing (CREW) cohort study, patients treated for CRC completed the Supportive Care Needs Survey Short Form-34 (SCNS SF-34) 15 and 24 months following surgery, along with questionnaires measuring HRQoL, wellbeing, life events, social support, and confidence to manage their cancer before surgery, 3, 9, 15, and 24 months post-surgery. RESULTS: The SCNS SF-34 was completed by 526 patients at 15 months and 510 patients at 24 months. About one-quarter of patients had at least one moderate or severe unmet need at both time points. Psychological and physical unmet needs were the most common and did not improve over time. Over 60% of patients who reported 5 or more moderate or severe unmet needs at 15 months experienced the same level of unmet need at 24 months. HRQoL at the beginning of treatment predicted unmet needs at the end of treatment. Unmet needs, specifically physical, psychological, and health system and information needs, were associated with poorer health and HRQoL at the end of treatment. CONCLUSIONS: Unmet needs persist over time and are associated with HRQoL. Evaluation of HRQoL at the start of treatment would help inform the identification of vulnerable patients. Assessment and care planning in response to unmet needs should be integrated into person-centred care. IMPLICATIONS FOR CANCER SURVIVORS: Early identification of CRC patients at risk of unmet needs will help infrom personalised survivorship care plans. The implementation of personalised and tailored services are likely to confer HRQoL gains.

A systematic review to establish health-related quality-of-life domains for intervention targets in cancer cachexia.

OBJECTIVES: To develop a model of the impact of cancer cachexia on patients by identifying the relevant health-related quality-of-life (HRQOL) issues, and to use the model to identify opportunities for intervention. METHODS: Standard systematic review methods were followed to identify papers which included direct quotes from cancer patients with cachexia or problems with eating or weight loss. Following thematic synthesis methodology, the quotes were coded, and themes and metathemes were extracted. The metathemes were used to develop a model of the patient's experience of cachexia. RESULTS: 18 relevant papers were identified which, in total, contained interviews with more than 250 patients. 226 patient quotes were extracted from the papers and 171 codes. 26 themes and 8 metathemes were formulated. The model developed from the metathemes demonstrated a direct link between eating and food problems and negative emotions and also a link mediated by the associated physical decline. These links provide opportunities for interventions. CONCLUSIONS: There are a vast number of HRQOL issues associated with cancer cachexia as identified from patients' own words. The model generated from these issues indicates that relationships, coping and knowledge of the condition are important components of new psychosocial interventions.

International validation of the EORTC QLQ-ELD14 questionnaire for assessment of health-related quality of life elderly patients with cancer.

BACKGROUND: Older people represent the majority of cancer patients but their specific needs are often ignored in the development of health-related quality of life (HRQOL) instruments. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-ELD15 was developed to supplement the EORTC's core questionnaire, the QLQ-C30, for measuring HRQOL in patients aged >70 years in oncology studies. METHODS: Patients (n=518) from 10 countries completed the QLQ-C30, QLQ-ELD15 and a debriefing interview. Eighty two clinically stable patients repeated the questionnaires 1 week later (test-retest analysis) and 107 others, with an expected change in clinical status, repeated the questionnaires 3 months later (response to change analysis, RCA). RESULTS: Information from the debriefing interview, factor analysis and item response theory analysis resulted in the removal of one item (QLQ-ELD15QLQ-ELD14) and revision of the proposed scale structure to five scales (mobility, worries about others, future worries, maintaining purpose and illness burden) and two single items (joint stiffness and family support). Convergent validity was good. In known-group comparisons, the QLQ-ELD14 differentiated between patients with different disease stage, treatment intention, number of comorbidities, performance status and geriatric screening scores. Test-retest and RCA analyses were equivocal. CONCLUSION: The QLQ-ELD14 is a validated HRQOL questionnaire for cancer patients aged 70 years. Changes in elderly patients' self-reported HRQOL may be related to both cancer evolution and non-clinical events.

Quality of life in pulmonary surgery: choosing, using, and developing assessment tools.

There is mounting recognition that, to aid surgical decision making, treatment efficacy needs to be measured in a variety of ways, with health-related quality of life now widely regarded as an important outcome in pulmonary surgical populations. The aim of this review is to provide a comprehensive overview of the key issues to consider if an investigator wishes to incorporate health-related quality of life assessment into trials and studies of pulmonary surgery, drawing on recent studies of lung cancer surgery as an example.

Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome.

Genetic studies of autism spectrum conditions (ASC) have mostly focused on the "low functioning" severe clinical subgroup, treating it as a rare disorder. However, ASC is now thought to be relatively common ( approximately 1%), and representing one end of a quasi-normal distribution of autistic traits in the general population. Here we report a study of common genetic variation in candidate genes associated with autistic traits and Asperger syndrome (AS). We tested single nucleotide polymorphisms in 68 candidate genes in three functional groups (sex steroid synthesis/transport, neural connectivity, and social-emotional responsivity) in two experiments. These were (a) an association study of relevant behavioral traits (the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ)) in a population sample (n=349); and (b) a case-control association study on a sample of people with AS, a "high-functioning" subgroup of ASC (n=174). 27 genes showed a nominally significant association with autistic traits and/or ASC diagnosis. Of these, 19 genes showed nominally significant association with AQ/EQ. In the sex steroid group, this included ESR2 and CYP11B1. In the neural connectivity group, this included HOXA1, NTRK1, and NLGN4X. In the socio-responsivity behavior group, this included MAOB, AVPR1B, and WFS1. Fourteen genes showed nominally significant association with AS. In the sex steroid group, this included CYP17A1 and CYP19A1. In the socio-emotional behavior group, this included OXT. Six genes were nominally associated in both experiments, providing a partial replication. Eleven genes survived family wise error rate (FWER) correction using permutations across both experiments, which is greater than would be expected by chance. CYP11B1 and NTRK1 emerged as significantly associated genes in both experiments, after FWER correction (P<0.05). This is the first candidate-gene association study of AS and of autistic traits. The most promising candidate genes require independent replication and fine mapping.

Predicting Autism Spectrum Quotient (AQ) from the Systemizing Quotient-Revised (SQ-R) and Empathy Quotient (EQ).

BACKGROUND: Empathizing is a specific component of social cognition. Empathizing is also specifically impaired in autism spectrum condition (ASC). These are two dimensions, measurable using the Empathy Quotient (EQ) and the Autism Spectrum Quotient (AQ). ASC also involves strong systemizing, a dimension measured using the Systemizing Quotient (SQ). The present study examined the relationship between the EQ, AQ and SQ. The EQ and SQ have been used previously to test for sex differences in 5 'brain types' (Types S, E, B and extremes of Type S or E). Finally, people with ASC have been conceptualized as an extreme of the male brain. METHOD: We revised the SQ to avoid a traditionalist bias, thus producing the SQ-Revised (SQ-R). AQ and EQ were not modified. All 3 were administered online. SAMPLE: Students (723 males, 1038 females) were compared to a group of adults with ASC group (69 males, 56 females). AIMS: (1) To report scores from the SQ-R. (2) To test for SQ-R differences among students in the sciences vs. humanities. (3) To test if AQ can be predicted from EQ and SQ-R scores. (4) To test for sex differences on each of these in a typical sample, and for the absence of a sex difference in a sample with ASC if both males and females with ASC are hyper-masculinized. (5) To report percentages of males, females and people with an ASC who show each brain type. RESULTS: AQ score was successfully predicted from EQ and SQ-R scores. In the typical group, males scored significantly higher than females on the AQ and SQ-R, and lower on the EQ. The ASC group scored higher than sex-matched controls on the SQ-R, and showed no sex differences on any of the 3 measures. More than twice as many typical males as females were Type S, and more than twice as many typical females as males were Type E. The majority of adults with ASC were Extreme Type S, compared to 5% of typical males and 0.9% of typical females. The EQ had a weak negative correlation with the SQ-R. DISCUSSION: Empathizing is largely but not completely independent of systemizing. The weak but significant negative correlation may indicate a trade-off between them. ASC involves impaired empathizing alongside intact or superior systemizing. Future work should investigate the biological basis of these dimensions, and the small trade-off between them.

Screening adults for Asperger Syndrome using the AQ: a preliminary study of its diagnostic validity in clinical practice.

The Autism Spectrum Quotient (AQ) has been developed to measure the degree to which an adult with normal intelligence has autistic traits. In this paper it is evaluated for its potential as a screening questionnaire in clinical practice on one hundred consecutive referrals to a diagnostic clinic for adults suspected of having Asperger Syndrome or high functioning autism (AS/HFA). The results indicate that it has good discriminative validity and good screening properties at a threshold score of 26. The implications of these results are discussed.

The link between autism and skills such as engineering, maths, physics and computing: a reply to Jarrold and Routh.

In the first edition of this journal, we published a paper reporting that fathers and grandfathers of children with autism were over-represented in the field of engineering. This result was interpreted as providing supporting evidence for the folk-psychology/folk-physics theory of autism. After carrying out further analyses on the same data, Jarrold and Routh found that fathers of children with autism were also over-represented in accountancy and science. They suggested that these results could either provide additional support for the folk-psychology/folk-physics theory or be accounted for by an over-representation of professionals amongst the fathers of children with autism. Here we present evidence that engineers are still over-represented among fathers of children with autism, even taking into account the professional bias.

Commentary: The Modified Checklist for Autism in Toddlers.

The question of when it is best to screen for autism may only be answered by a series of empirical studies. These will be difficult to plan, fund, and conduct, and will by necessity take many years because of the need to systematically follow up the whole cohort screened. In our study, we identified 19 of the 50 children with autism by their profile at the 18-month screen (though note that some fell out of risk status at the repeat screen 1 month later--thus sacrificing sensitivity for improved positive predictive power). Through the subsequent surveillance methods we employed, we identified the remaining cases as follows: 5 at 42 months, 4 between 42 months and 7 years, and 25 at 7 years. We do not mean to end on a pessimistic note. Our experiences have been positive both in regard to the instrument we developed and the effects that using it have had on the health practitioners involved in the research study. In discussion, practitioners have commented on the usefulness of knowing what prelanguage and prosocial skills can reliably be looked at during the 18-month check. Training using the CHAT and eliciting its behaviors improved the skills and confidence of primary health practitioners. It is our view that this has had the effect of reducing the age at which autism is recognized and cases are referred on for a developmental assessment. The work reported by Robins er al. makes an important contribution to this ongoing research and clinical process as we attempt to accurately identify children with autism at a young age.

The autism-spectrum quotient (AQ): evidence from Asperger syndrome/high-functioning autism, males and females, scientists and mathematicians.

Currently there are no brief, self-administered instruments for measuring the degree to which an adult with normal intelligence has the traits associated with the autistic spectrum. In this paper, we report on a new instrument to assess this: the Autism-Spectrum Quotient (AQ). Individuals score in the range 0-50. Four groups of subjects were assessed: Group 1: 58 adults with Asperger syndrome (AS) or high-functioning autism (HFA); Group 2: 174 randomly selected controls. Group 3: 840 students in Cambridge University; and Group 4: 16 winners of the UK Mathematics Olympiad. The adults with AS/HFA had a mean AQ score of 35.8 (SD = 6.5), significantly higher than Group 2 controls (M = 16.4, SD = 6.3). 80% of the adults with AS/HFA scored 32+, versus 2% of controls. Among the controls, men scored slightly but significantly higher than women. No women scored extremely highly (AQ score 34+) whereas 4% of men did so. Twice as many men (40%) as women (21%) scored at intermediate levels (AQ score 20+). Among the AS/HFA group, male and female scores did not differ significantly. The students in Cambridge University did not differ from the randomly selected control group, but scientists (including mathematicians) scored significantly higher than both humanities and social sciences students, confirming an earlier study that autistic conditions are associated with scientific skills. Within the sciences, mathematicians scored highest. This was replicated in Group 4, the Mathematics Olympiad winners scoring significantly higher than the male Cambridge humanities students. 6% of the student sample scored 32+ on the AQ. On interview, 11 out of 11 of these met three or more DSM-IV criteria for AS/HFA, and all were studying sciences/mathematics, and 7 of the 11 met threshold on these criteria. Test-retest and interrater reliability of the AQ was good. The AQ is thus a valuable instrument for rapidly quantifying where any given individual is situated on the continuum from autism to normality. Its potential for screening for autism spectrum conditions in adults of normal intelligence remains to be fully explored.

The 2nd to 4th digit ratio and autism.

It has been suggested that autism may arise as the result of exposure to high concentrations of prenatal testosterone. There is evidence that the ratio of the lengths of the 2nd and 4th digit (2D:4D) may be negatively correlated with prenatal testosterone. We measured 2D:4D in 95 families recruited via the National Autistic Society, UK. The sample comprised a total 72 children with autism (62 males, 10 females; age range 2 to 14 years), including 23 children (20 males, three females) with Asperger syndrome (AS), 34 siblings, 88 fathers, 88 mothers and sex- and age-matched control participants. We found that the 2D:4D ratios of children with autism, their siblings, fathers and mothers were lower than population normative values. Children with AS, who share the social and communicative symptoms of autism but have normal or even high IQ, had higher 2D:4D ratios than children with autism but lower ratios than population normative values. There were positive associations between 2D:4D ratios of children with autism and the ratios of their relatives. Children with autism had lower than expected 2D:4D ratios and children with AS higher ratios than expected in relation to their fathers' 2D:4D ratio. It was concluded that 2D:4D ratio may be a possible marker for autism which could implicate prenatal testosterone in its aetiology.

The "Reading the Mind in the Eyes" Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism.

In 1997 in this Journal we published the "Reading the Mind in the Eyes" Test, as a measure of adult "mentalising". Whilst that test succeeded in discriminating a group of adults with Asperger syndrome (AS) or high-functioning autism (HFA) from controls, it suffered from several psychometric problems. In this paper these limitations are rectified by revising the test. The Revised Eyes Test was administered to a group of adults with AS or HFA (N = 15) and again discriminated these from a large number of normal controls (N = 239) drawn from different samples. In both the clinical and control groups the Eyes Test was inversely correlated with the Autism Spectrum Quotient (the AQ), a measure of autistic traits in adults of normal intelligence. The Revised Eyes Test has improved power to detect subtle individual differences in social sensitivity.

A screening instrument for autism at 18 months of age: a 6-year follow-up study.

OBJECTIVES: A population of 16,235 children aged 18 months was screened using the Checklist for Autism in Toddlers (CHAT) to identify childhood autism (CA). Two further screening procedures were conducted at age 3 and 5 years. The population was followed up at age 7 years in order to establish the sensitivity, specificity, and positive predictive value of the instrument. METHOD: A brief checklist assessing joint attention and pretend play behaviors was administered by primary health care practitioners when the children were 18 months old. Follow-up methods included screening through parents and health practitioners and checking medical and educational records. RESULTS: Nineteen cases of CA were successfully identified by the CHAT at 18 months. At follow-up a total of 50 cases of CA were identified via all surveillance methods. Thus, the CHAT has a sensitivity of 38% and a specificity of 98% for identifying CA. The positive predictive value of the instrument was maximized by concentration on the highest-risk group. Repeated screening 1 month later increased the positive predictive value to 75% for identification of CA but reduced the sensitivity to 20%, although the specificity was close to 100%. The screen also identified cases of pervasive developmental disorder as well as children with language and other developmental disorders. CONCLUSIONS: The CHAT can be used to identify cases of autism and related pervasive developmental disorders at 18 months of age. It is emphasized that the CHAT is not a diagnostic instrument but can identify potential cases of autism spectrum disorders for a full diagnostic assessment.

The amygdala theory of autism.

Brothers (Brothers L. Concepts in Neuroscience 1990;1:27-51) proposed a network of neural regions that comprise the "social brain", which includes the amygdala. Since the childhood psychiatric condition of autism involves deficits in "social intelligence", it is plausible that autism may be caused by an amygdala abnormality. In this paper we review the evidence for a social function of the amygdala. This includes reference to the Kluver-Bucy syndrome (which Hetzler and Griffin suggested may serve as an animal model of autism). We then review evidence for an amygdala deficit in people with autism, who are well known to have deficits in social behaviour. This includes a detailed summary of our recent functional magnetic resonance imaging (fMRI) study involving judging from the expressions of another person's eyes what that other person might be thinking or feeling. In this study, patients with autism or AS did not activate the amygdala when making mentalistic inferences from the eyes, whilst people without autism did show amygdala activity. The amygdala is therefore proposed to be one of several neural regions that are abnormal in autism. We conclude that the amygdala theory of autism contains promise and suggest some new lines of research.

Autism spectrum disorders at 20 and 42 months of age: stability of clinical and ADI-R diagnosis.

The association between, and stability of, clinical diagnosis and diagnosis derived from the Autism Diagnostic Interview-Revised (ADI-R; Lord, Rutter, & Le Couteur, 1994) was examined in a sample of prospectively identified children with childhood autism and other pervasive developmental disorders assessed at the age of 20 months and 42 months. Clinical diagnosis of autism was stable, with all children diagnosed with childhood autism at age 20 months receiving a diagnosis of childhood autism or a related pervasive developmental disorder (PDD) at age 42 months. Clinical diagnosis of childhood autism was also reasonably sensitive, with all children who went on to receive a clinical diagnosis of childhood autism at 42 months being identified as having autism or PDD at 20 months. However, clinical diagnosis for PDD and Asperger's syndrome lacked sensitivity at 20 months, with several children who subsequently received these diagnoses at 42 months receiving diagnoses of language disorder or general developmental delay, as well as in two cases being considered clinically normal, at the earlier timepoint. The ADI-R was found to have good specificity but poor sensitivity at detecting childhood autism at 20 months; however, the stability of diagnosis from 20 to 42 months was good. In addition, the ADI-R at age 20 months was not sensitive to the detection of related PDDs or Asperger's syndrome. The continuity and discontinuity between behavioural abnormalities identified at both timepoints in the three domains of impairment in autism was examined, both in children who met final clinical criteria for an autistic spectrum disorder, and for children with language disorder who did not, as well as for a small sample of typically developing children.

Cerebral correlates of preserved cognitive skills in autism: a functional MRI study of embedded figures task performance.

When considering the cognitive abilities of people with autism, the majority of studies have explored domains in which there are deficits. However, on tests of local processing and visual search, exemplified by the Embedded Figures Task (EFT), people with autism have been reported to demonstrate superiority over normal controls. This study employed functional MRI of subjects during the performance of the EFT to test the hypothesis that normal subjects and a group with autism would activate different brain regions and that differences in the patterns of these regional activations would support distinct models of cerebral processing underlying EFT performance in the two groups. It was found that several cerebral regions were similarly activated in the two groups. However, normal controls, as well as demonstrating generally more extensive task-related activations, additionally activated prefrontal cortical areas that were not recruited in the group with autism. Conversely, subjects with autism demonstrated greater activation of ventral occipitotemporal regions. These differences in functional anatomy suggest that the cognitive strategies adopted by the two groups are different: the normal strategy invokes a greater contribution from working memory systems while the autistic group strategy depends to an abnormally large extent on visual systems for object feature analysis. This interpretation is discussed in relation to a model of autism which proposes a predisposition towards local rather than global modes of information processing.

Social intelligence in the normal and autistic brain: an fMRI study.

There is increasing support for the existence of 'social intelligence' [Humphrey (1984) Consciousness Regained], independent of general intelligence. Brothers et al. 1990) J. Cog. Neurosci., 4, 107-118] proposed a network of neural regions that comprise the 'social brain': the orbito-frontal cortex (OFC), superior temporal gyrus (STG) and amygdala. We tested Brothers' theory by examining both normal subjects as well as patients with high-functioning autism or Asperger syndrome (AS), who are well known to have deficits in social intelligence, and perhaps deficits in amygdala function [Bauman & Kemper (1988) J. Neuropath. Exp. Neurol., 47, 369]. We used a test of judging from the expressions of another person's eyes what that other person might be thinking or feeling. Using functional magnetic resonance imaging (fMRI) we confirmed Brothers' prediction that the STG and amygdala show increased activation when using social intelligence. Some areas of the prefrontal cortex also showed activation. In contrast, patients with autism or AS activated the fronto-temporal regions but not the amygdala when making mentalistic inferences from the eyes. These results provide support for the social brain theory of normal function, and the amygdala theory of autism.