Ethical Advocacy Across the Autism Spectrum: Beyond Partial Representation.

Recent debates within the autism advocacy community have raised difficult questions about who can credibly act as a representative of a particular population and what responsibilities that role entails. We attempt to answer these questions by defending a set of evaluative criteria that can be used to assess the legitimacy of advocacy organizations and other nonelectoral representatives. With these criteria in hand, we identify a form of misrepresentation common but not unique to autism advocacy, which we refer to as partial representation. Partial representation occurs when an actor claims to represent a particular group of people but appropriately engages with only a subset of that group. After highlighting symbolic and substantive harms associated with partial representation, we propose several strategies for overcoming it.

Incidence of and risk factors for major haemorrhage in patients treated with ibrutinib: An integrated analysis.

Ibrutinib, a Bruton tyrosine kinase inhibitor, is approved for treatment of various B-cell malignancies. In ibrutinib clinical studies, low-grade haemorrhage was common, whereas major haemorrhage (MH) was infrequent. We analysed the incidence of and risk factors for MH from 15 ibrutinib clinical studies (N = 1768), including 4 randomised controlled trials (RCTs). Rates of any-grade bleeding were similar for single-agent ibrutinib and ibrutinib combinations (39% and 40%). Low-grade bleeding was more common in ibrutinib-treated than comparator-treated patients (35% and 15%), and early low-grade bleeding was not associated with MH. The proportion of MH in RCTs was higher with ibrutinib than comparators (4.4% vs. 2.8%), but after adjusting for longer exposure with ibrutinib (median 13 months vs. 6 months), the incidence of MH was similar (3.2 vs. 3.1 per 1000 person-months). MH led to treatment discontinuation in 1% of all ibrutinib-treated patients. Use of anticoagulants and/or antiplatelets (AC/AP) during the study was common (~50% of patients) and had an increased exposure-adjusted relative risk for MH in both the total ibrutinib-treated population (1.9; 95% confidence interval, 1.2-3.0) and RCT comparator-treated patients (2.4; 95% confidence interval, 1.0-5.6), indicating that ibrutinib may not alter the effect of AC/AP on the risk of MH in B-cell malignancies.

"This lifetime commitment": Public conceptions of disability and noninvasive prenatal genetic screening.

Recently, new noninvasive prenatal genetic screening technologies for Down syndrome and other genetic conditions have become commercially available. Unique characteristics of these screening tests have reignited long-standing concerns about prenatal testing for intellectual and developmental disabilities. We conducted a web-based survey of a sample of the US public to examine how attitudes towards disability inform views of prenatal testing in the context of these rapidly advancing prenatal genetic screening technologies. Regardless of opinion toward disability, the majority of respondents supported both the availability of screening and the decision to continue a pregnancy positive for aneuploidy. Individuals rationalized their support with various conceptions of disability; complications of the expressivist argument and other concerns from the disability literature were manifested in many responses analyzed.

No effect of single-dose intranasal insulin treatment on verbal memory and sustained attention in patients with schizophrenia.

BACKGROUND: Impairments in verbal memory and attention are among the most severe and disabling cognitive deficits in patients with schizophrenia. Whereas efficacy for cognition has not yet been established for any pharmacologic strategy in schizophrenia, an accumulating body of evidence suggests a possible beneficial role of insulin. METHODS: We conducted a double-blind, placebo-controlled trial to examine the effect of single-dose intranasal insulin treatment on cognition in nondiabetic patients with schizophrenia. After fasting for 12 hours, subjects received either 40 IU regular human insulin or placebo administered by intranasal pump. The Hopkins Verbal Learning Test and the Continuous Performance Test-Identical Pairs were administered before and 30 minutes after intranasal treatment. RESULTS: Thirty patients were enrolled and completed the study. The 2 treatment groups (insulin vs placebo, n = 15 in each group) did not differ on any demographic or general clinical variable (P > 0.40). There was no significant difference between the 2 treatment groups in change on Hopkins Verbal Learning Test immediate recall total score and delayed recall score, or on CPT d', hits rate, reaction time of hits, or false-alarm rate (P > 0.1). CONCLUSIONS: Results of the present study suggest that single-dose intranasal insulin treatment does not have a large-enough effect on verbal memory or sustained attention to be detected by a sample of this size in patients with schizophrenia but was safe and well tolerated. Longitudinal studies to explore cognitive benefits of repeated dosing of intranasal insulin treatment are needed.

Triglyceride/high-density lipoprotein cholesterol ratio: a surrogate to predict insulin resistance and low-density lipoprotein cholesterol particle size in nondiabetic patients with schizophrenia.

OBJECTIVE: Insulin resistance, changes in lipid parameters, and cardiometabolic adverse events have been reported in some patients during clinical trials of antipsychotic agents. The present study examined whether the triglyceride/high-density lipoprotein (HDL) ratio can be used as a better surrogate than other conventional lipid measures (low-density lipoprotein [LDL], HDL, triglyceride) in predicting insulin resistance and LDL particle size in nondiabetic patients with schizophrenia. METHOD: Outpatients 18 to 75 years old diagnosed with schizophrenia or schizoaffective disorder (DSM-IV criteria) and receiving olanzapine, risperidone, or typical antipsychotics participated in a multicenter, cross-sectional study. Fasting blood samples were obtained to determine the levels of glucose, insulin, lipids, and lipid particle size. The study was conducted from July 2001 to March 2002. RESULTS: In the sample of 206 patients, significant correlations were found between various lipid measures (LDL, HDL, triglyceride, and triglyceride/HDL ratio) and the homeostasis model of assessment of insulin resistance (P < .05). However, stepwise multiple regression analysis suggested that the triglyceride/HDL ratio is a stronger predictor of insulin resistance and of LDL particle size than other conventional lipoprotein measures after other potential confounding variables, including age, gender, race, family history of diabetes, body mass index, and antipsychotic agent, were taken into consideration (P < .001). Further, logistic regression analysis indicated that the triglyceride/HDL ratio and male gender predict the existence of a small LDL particle size pattern (pattern B LDL phenotype), with a sensitivity of 75.9% and a specificity of 85.4%. CONCLUSIONS: The triglyceride/HDL ratio, a simple, readily available and inexpensive measure, can be a useful surrogate to identify those with insulin resistance as well as those with more atherogenic small LDL particles in nondiabetic patients with schizophrenia.

Phenotypic characteristics in metabolically obese but normal weight non-diabetic patients with schizophrenia.

BACKGROUND: A unique group of individuals termed metabolically obese but normal weight (MONW) has been identified in the general population. The present study examined phenotypic characteristics of MONW individuals in a sample of normal weight, non-diabetic patients with schizophrenia. METHODS: Outpatients 19 to 75 years old diagnosed with schizophrenia or schizoaffective disorder participated in a multi-center, cross-sectional study. Those with normal weight (body-mass-index (BMI)<25 kg/m(2)) were included in the present analysis. Patients were further defined as MONW or metabolically nonobese based on a cut-off value of the homeostasis model assessment of insulin resistance (HOMA-IR = 1.86). Fasting blood samples were collected to determine levels of various metabolic parameters. In addition, lipoprotein subclass concentrations and sizes were analyzed using nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Seventeen MONW individuals and 17 metabolically nonobese individuals matched by BMI and gender were identified from a study sample of 206 patients with schizophrenia. There were no significant differences between the two groups on anthropometric measures (waist circumference and waist/hip ratio, ps>0.3). However, the MONW group had significantly higher levels of intermediate VLDL particle and Apolipoprotein B, and significantly lower levels of large HDL particle compared with the metabolically nonobese group (p = 0.012, p = 0.036 and p = 0.041 respectively). CONCLUSION: The MONW individuals in non-diabetic schizophrenia patients seem to have an unfavorable metabolic profile and significant atherogenecity. Clinicians should be vigilant about the risk of cardiometabolic comorbidity even when the patient' body weight is normal.

Higher white blood cell counts are associated with an increased risk for metabolic syndrome and more severe psychopathology in non-diabetic patients with schizophrenia.

BACKGROUND: Unequivocal evidence has emerged linking inflammation to the risk of metabolic problems. Previous research also has suggested a relationship between inflammation and schizophrenia. The present study examined whether white blood cell count (WBC), a marker of systemic inflammation, is associated with metabolic syndrome and psychiatric symptoms in non-diabetic patients with schizophrenia. METHODS: Outpatients 19 to 75 years old diagnosed with schizophrenia or schizoaffective disorder participated in a multi-center, cross-sectional study. Vital signs and anthropometric measures were obtained. Fasting blood samples were collected to determine levels of glucose, lipids and WBC. Psychiatric symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). RESULTS: In the sample of 199 patients, multiple logistic regression showed that WBC (log transformed) strongly predicted the condition of metabolic syndrome after potential confounding variables including age, gender, race, age of illness onset, family history of diabetes, smoking status and antipsychotic agent used were taken into consideration (odds ratio 47.2, 95% CI 3.4-658.7, p=0.004). On the other hand, significant correlations were found between WBC (log transformed) and BPRS-total score (r=0.18, p=0.014), negative symptom score (r=0.15, p=0.039) as well as anxious depression factor score (r=0.21, p=0.004) after potential confounding variables were taken into consideration. CONCLUSION: This study suggested that WBC, a simple, readily available and inexpensive measure, may potentially be a useful marker to predict an increased risk for metabolic syndrome and more severe psychiatric symptoms in non-diabetic patients with schizophrenia.

Elevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia.

The present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRP

Diminished insulin resistance with weight loss in severely overweight youth.

BACKGROUND: The influence of weight loss on insulin resistance was determined in severely overweight (BMI Z-score: 7.3 +/- 0.9 z-units) hyperinsulinemic (mean fasting serum insulin concentration: 33.0 +/- 6.7 muIU/mL) youth. METHODS: Eight overweight youth and obese parents were studied at baseline and then at 6 and 12 months after behavioral weight loss therapy. Non-treated lean youth (n = 8) served as controls for normal interval growth. The groups were matched for sex, race, age (10.2 versus 10.1 years), and pubertal maturation, and evaluated for weight, height, blood pressure, and the homeostasis model of insulin resistance (HOMA-IR). RESULTS: Overweight youth had reductions (p

Does low bone mineral density start in post-teenage years in women with type 1 diabetes?

OBJECTIVE: Type 1 diabetes has been associated with decreased bone mineral density (BMD). However, the natural history and etiopathogenesis of osteoporosis in type 1 diabetes are not clear. The aims of this study were to assess BMD in a cohort of young women with type 1 diabetes compared with nondiabetic control subjects and to evaluate the possible association of BMD with diabetes duration, HbA(1c), and biomarkers of bone metabolism. RESEARCH DESIGN AND METHODS: BMD was measured by dual-energy X-ray absortiometry scan in 39 teenage (age 13-19 years) and 33 post-teenage females (age 20-37 years) with type 1 diabetes and 91 female age-matched control subjects. Serum osteocalcin, IGF-I, IGF binding protein-3 (IGFBP-3), HbA(1c), and urine N-telopeptides were measured. RESULTS: After adjustment for age and BMI, BMD values were significantly lower at the femoral neck and lateral spine in women with type 1 diabetes older than age 20 years compared with control subjects but not in the case subjects younger than age 20 years, nor at the anterio-posterior spine, wrist, or whole body. No association was found between BMD and diabetes duration or glycemic control. IGF-I, IGFBP-3, osteocalcin, and N-telopeptides were similar in diabetic subjects and control subjects. CONCLUSIONS: This study indicates that women with type 1 diabetes exhibit BMD differences early in life with significant differences already present in the post-teenage years. Lower hip BMD in these young women may explain, in part, the higher incidence of hip fracture experienced in postmenopausal women with type 1 diabetes.