Recovery of hypoglycemia awareness in long-standing type 1 diabetes: a multicenter 2 × 2 factorial randomized controlled trial comparing insulin pump with multiple daily injections and continuous with conventional glucose self-monitoring (HypoCOMPaSS)

To determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG).

Characterizing problematic hypoglycaemia: iterative design and preliminary psychometric validation of the Hypoglycaemia Awareness Questionnaire (HypoA-Q)

AIMS: To design and conduct preliminary validation of a measure of hypoglycaemia awareness and problematic hypoglycaemia, the Hypoglycaemia Awareness Questionnaire.

METHODS: Exploratory and cognitive debriefing interviews were conducted with 17 adults (nine of whom were women) with Type 1 diabetes (mean ± sd age 48±10 years). Questionnaire items were modified in consultation with diabetologists/psychologists. Psychometric validation was undertaken using data from 120 adults (53 women) with Type 1 diabetes (mean ± sd age 44±16 years; 50% with clinically diagnosed impaired awareness of hypoglycaemia), who completed the following questionnaires: the Hypoglycaemia Awareness Questionnaire, the Gold score, the Clarke questionnaire and the Problem Areas in Diabetes questionnaire.

RESULTS: Iterative design resulted in 33 items eliciting answers on awareness of hypoglycaemia when awake/asleep and hypoglycaemia frequency, severity and impact (healthcare utilization). Psychometric analysis identified three subscales reflecting 'impaired awareness', 'symptom level' and 'symptom frequency'. Convergent validity was indicated by strong correlations between the impaired awareness subscale and existing measures of awareness: (Gold: rs =0.75, P<0.01; Clarke: rs =0.76, P<0.01). Divergent validity was indicated by weaker correlations with diabetes-related distress (Problem Areas in Diabetes: rs =0.25, P<0.01) and HbA1c (rs =-0.05, non-significant). The impaired awareness subscale and other items discriminated between those with impaired and intact awareness (Gold score). The impaired awareness subscale and other items contributed significantly to models explaining the occurrence of severe hypoglycaemia and hypoglycaemia when asleep.

CONCLUSIONS: This preliminary validation shows the Hypoglycaemia Awareness Questionnaire has robust face and content validity; satisfactory structure; internal reliability; convergent, divergent and known groups validity. The impaired awareness subscale and other items contribute significantly to models explaining recall of severe and nocturnal hypoglycaemia. Prospective validation, including determination of a threshold to identify impaired awareness, is now warranted.

Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial.

OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial. RESEARCH DESIGN AND METHODS: Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies. RESULTS: After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780] vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [-771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation. CONCLUSIONS: Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.

Young Australian adults' beliefs about alcohol's role in sexual aggression and victimisation

Beliefs and misconceptions about sex, gender, and rape have been explored extensively to explain people’s attributions concerning alcohol-involved sexual violence. However, less is known about the specific beliefs that people hold about how alcohol facilitates sexual aggression and victimisation. The present study aimed to identify these alcohol-related beliefs among young Australian adults. Six men and nine women (N = 15; 18-24 years) in focus groups (n = 13) and interviews (n = 2) were asked to discuss the role of alcohol in a hypothetical alcohol-involved rape. Using a consensual qualitative research methodology, the effects of alcohol that were seen to introduce, progress, and intensify risks for rape were: increased confidence; character transformation: impaired cognition; behavioural disinhibition; altered sexual negotiation; enhanced self-centredness; impaired awareness of wrongdoing; increased/decreased sexual assertiveness; and compromised self-protection. Some of the beliefs identified in this study are not currently captured in alcohol expectancy measures which assess people’s beliefs about alcohol’s effects on cognition, emotion, and behaviour. This study’s findings offer a conceptual basis for the development of a new alcohol expectancy measure that can be used in future rape-perception research.

Comparison of optimised MDI versus pumps with or without sensors in severe hypoglycaemia (the Hypo COMPaSS trial)

Background
Severe hypoglycaemia (SH) is one of the most feared complications of type 1 diabetes (T1DM) with a reported prevalence of nearly 40%. In randomized trials of Multiple Daily Injections (MDI) and Continuous Subcutaneous Insulin Infusion (CSII) therapy there is a possible benefit of CSII in reducing SH. However few trials have used basal insulin analogues as the basal insulin in the MDI group and individuals with established SH have often been excluded from prospective studies. In published studies investigating the effect of Real Time Continuous Glucose Monitoring (RT-CGM) benefit in terms of reduced SH has not yet been demonstrated. The primary objective of this study is to elucidate whether in people with T1DM complicated by impaired awareness of hypoglycaemia (IAH), rigorous prevention of biochemical hypoglycaemia using optimized existing self-management technology and educational support will restore awareness and reduce risk of recurrent SH.

Methods/design
This is a multicentre prospective RCT comparing hypoglycaemia avoidance with optimized MDI and CSII with or without RT-CGM in a 2×2 factorial design in people with type 1 diabetes who have IAH. The primary outcome measure for this study is the difference in IAH (Gold score) at 24 weeks. Secondary outcomes include biomedical measures such as HbA1c, SH incidence, blinded CGM analysis, self monitored blood glucose (SMBG) and response to hypoglycaemia in gold standard clamp studies. Psychosocial measures including well-being and quality of life will also be assessed using several validated and novel measures. Analysis will be on an intention-to-treat basis.

Discussion
Most existing RCTs using this study’s interventions have been powered for change in HbA1c rather than IAH or SH. This trial will demonstrate whether IAH can be reversed and SH prevented in people with T1DM in even those at highest risk by using optimized conventional management and existing technology.

Severe hypoglycaemia in type 1 diabetes mellitus: underlying drivers and potential strategies for successful prevention

Hypoglycaemia remains an over-riding factor limiting optimal glycaemic control in type 1 diabetes. Severe hypoglycaemia is prevalent in almost half of those with long-duration diabetes and is one of the most feared diabetes-related complications. In this review, we present an overview of the increasing body of literature seeking to elucidate the underlying pathophysiology of severe hypoglycaemia and the limited evidence behind the strategies employed to prevent episodes. Drivers of severe hypoglycaemia including impaired counter-regulation, hypoglycaemia-associated autonomic failure, psychosocial and behavioural factors and neuroimaging correlates are discussed. Treatment strategies encompassing structured education, insulin analogue regimens, continuous subcutaneous insulin infusion pumps, continuous glucose sensing and beta-cell replacement therapies have been employed, yet there is little randomized controlled trial evidence demonstrating effectiveness of new technologies in reducing severe hypoglycaemia. Optimally designed interventional trials evaluating these existing technologies and using modern methods of teaching patients flexible insulin use within structured education programmes with the specific goal of preventing severe hypoglycaemia are required. Individuals at high risk need to be monitored with meticulous collection of data on awareness, as well as frequency and severity of all hypoglycaemic episodes.

Investigation of factors related to employment outcome following traumatic brain injury: a critical review and conceptual model

Purpose : The purpose of this article is to critically review the literature to examine factors that are most consistently related to employment outcome following traumatic brain injury (TBI), with a particular focus on metacognitive skills. It also aims to develop a conceptual model of factors related to employment outcome. Method : The first stage of the review considered 85 studies published between 1980 and December 2003 which investigated factors associated with employment outcome following TBI. English-language studies were identified through searches of Medline and PsycINFO, as well as manual searches of journals and reference lists. The studies were evaluated and rated by two independent raters (Kappa = 0.835) according to the quality of their methodology based upon nine criteria. Fifty studies met the criteria for inclusion in the second stage of the review, which examined the relationship between a broad range of variables and employment outcome. Results : The factors most consistently associated with employment outcome included pre-injury occupational status, functional status at discharge, global cognitive functioning, perceptual ability, executive functioning, involvement in vocational rehabilitation services and emotional status. Conclusions : A conceptual model is presented which emphasises the importance of metacognitive, emotional and social environment factors for improving employment outcome.

Assessing phonemic awareness skills in hearing impaired students

This paper discusses phonemic awareness and its role in providing appropriate literacy instruction to both hearing and hearing impaired children. The ability of hearing-impaired students to gain phonological awareness skills is examined and instructional models for teaching phonological and phonemic awareness skills are presented. Also included is a checklist to be used to assess phonological and phonemic awareness skills in hearing-impaired students.