Behaviour change in diabetes: behavioural science advancements to support the use of theory.

Behaviour is central to the management of diabetes, both for people living with diabetes and for healthcare professionals delivering evidence-based care. This review outlines the evolution of behavioural science and the application of theoretical models in diabetes care over the past 25 years. There has been a particular advancement in the development of tools and techniques to support researchers, healthcare professionals and policymakers in taking a theory-based approach, and to enhance the development, reporting and replication of successful interventions. Systematic guidance, theoretical frameworks and lists of behavioural techniques provide the tools to specify target behaviours, identify why ideal behaviours are not implemented, systematically develop theory-based interventions, describe intervention content using shared terminology, and evaluate their effects. Several examples from a range of diabetes-related behaviours (clinic attendance, self-monitoring of blood glucose, retinal screening, setting collaborative goals in diabetes) and populations (people with type 1 and type 2 diabetes, healthcare professionals) illustrate the potential for these approaches to be widely translated into diabetes care. The behavioural science approaches outlined in this review give healthcare professionals, researchers and policymakers the tools to deliver care and design interventions with an evidence-based understanding of behaviour. The challenge for the next 25 years is to refine the tools to increase their use and advocate for the role of theoretical models and behavioural science in the commissioning, funding and delivery of diabetes care.

The preferences of young adults with Type 1 diabetes at clinics using a discrete choice experiment approach: the D1 Now Study.

AIM: Attending routine outpatient clinic appointments is a central self-management behaviour of individuals living with Type 1 diabetes. A large number of young adults with Type 1 diabetes disengage from diabetes services, which may contribute to poor psychosocial and diabetes outcomes. The aim of this study is to elicit preferences from young adults with Type 1 diabetes regarding clinic-related services to inform service delivery. METHODS: A discrete choice experiment was developed to understand the preferences of young adults with Type 1 diabetes for clinic-related services. RESULTS: Young adults recruited from young adult Type 1 diabetes clinics in 2016 completed the experiment (n = 105). Young adults with Type 1 diabetes showed a preference for shorter waiting times, seeing a nurse and a consultant, relative to a nurse alone, and a flexible booking system compared with fixed appointment times. Results suggest no preference for a nurse and a doctor, relative to a nurse alone, or other optional services (e.g. seeing dietitians or psychologists), type of HbA1c test and digital blood glucose diaries over paper-based diaries. CONCLUSION: This study highlights aspects of routine clinic appointments that are valued by young adults living with Type 1 diabetes, namely shorter waiting times at clinic, the option to see both a nurse and consultant at each visit and a flexible clinic appointment booking system. These findings suggest young adults with Type 1 diabetes value convenience and should help services to restructure their clinics to be more responsive to the needs of young adults.

Strength in Numbers: an international consensus conference to develop a novel approach to care delivery for young adults with type 1 diabetes, the D1 Now Study.

PLAIN ENGLISH SUMMARY: Many young adults with type 1 diabetes struggle with the day-to-day management of their condition. They often find it difficult to find the time to attend their clinic appointments and to meet with their diabetes healthcare team. Young adults living with type 1 diabetes are not routinely involved in research that may help improve health services other than being invited to take part in studies as research participants. A 3-day international conference was held in Galway in June 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". It aimed to bring together people from a broad variety of backgrounds with an interest in young adults with type 1 diabetes. Young people with type 1 diabetes came together with healthcare professionals, researchers, software developers and policy makers to come up with and agree on a new approach for engaging young adults with type 1 diabetes with their health services and to improve how they manage their diabetes.The people involved in the conference aimed to reach agreement (consensus) on a fixed set of outcome measures called a core outcome set (COS) that the group would recommend future studies involving young adults with type 1 diabetes to use, to suggest a new approach (intervention) for providing health services to young adults with type 1 diabetes, and to come up with health technology ideas that could help deliver the new intervention. Over the 3 days, this diverse international group of people that included young adults living with type 1 diabetes, agreed on a COS, 3 key parts of a new intervention and 1 possible health technology idea that could help with how the overall intervention could be delivered.Involving young adults living with type 1 diabetes in a 3-day conference along with other key groups is an effective method for coming up with a new approach to improve health services for young adults with type 1 diabetes and better support their self-management. ABSTRACT: Background A 3-day international consensus meeting was hosted by the D1 Now study team in Galway on June 22-24, 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". The aim of the meeting was to bring together young adults with type 1 diabetes, healthcare providers, policy makers and researchers to reach a consensus on strategies to improve engagement, self-management and ultimately outcomes for young adults living with type 1 diabetes. Methods This diverse stakeholder group participated in the meeting to reach consensus on (i) a core outcome set (COS) to be used in future intervention studies involving young adults with type 1 diabetes, (ii) new strategies for delivering health services to young adults and (iii) potential digital health solutions that could be incorporated into a future intervention. Results A COS of 8 outcomes and 3 key intervention components that aim to improve engagement between young adults with type 1 diabetes and service providers were identified. A digital health solution that could potentially compliment the intervention components was proposed. Conclusion The outputs from the 3-day consensus conference, that held patient and public involvement at its core, will help the research team further develop and test the D1 Now intervention for young adults with type 1 diabetes in a pilot and feasibility study and ultimately in a definitive trial. The conference represents a good example of knowledge exchange among different stakeholders for health research and service improvement.

A systematic review of interventions to improve outcomes for young adults with Type 1 diabetes.

BACKGROUND: Many young adults with Type 1 diabetes experience poor outcomes. The aim of this systematic review was to synthesize the evidence regarding the effectiveness of interventions aimed at improving clinical, behavioural or psychosocial outcomes for young adults with Type 1 diabetes. METHODS: Electronic databases were searched. Any intervention studies related to education, support, behaviour change or health service organizational change for young adults aged between 15-30 years with Type 1 diabetes were included. A narrative synthesis of all studies was undertaken due to the large degree of heterogeneity between studies. RESULTS: Eighteen studies (of a possible 1700) were selected and categorized: Health Services Delivery (n = 4), Group Education and Peer Support (n = 6), Digital Platforms (n = 4) and Diabetes Devices (n = 4). Study designs included one randomized controlled trial, three retrospective studies, seven feasibility/acceptability studies and eight studies with a pre/post design. Continuity, support, education and tailoring of interventions to young adults were the most common themes across studies. HbA1c was the most frequently measured outcome, but only 5 of 12 studies that measured it showed a significant improvement. CONCLUSION: Based on the heterogeneity among the studies, the effectiveness of interventions on clinical, behavioural and psychosocial outcomes among young adults is inconclusive. This review has highlighted a lack of high-quality, well-designed interventions, aimed at improving health outcomes for young adults with Type 1 diabetes.

Young adult type 1 diabetes care in the West of Ireland: an audit of hospital practice.

BACKGROUND: It is well recognised that management of young adults with type 1 diabetes (T1DM) poses difficult challenges for physicians and health care organisations as a whole. In Ireland and in particular the west of Ireland there has been little audit or research on young adults with T1DM and the services available to them. DESIGN: In 2011 a retrospective review of this patient population in our territory referral centre was carried out. RESULTS: The average glycaemic control in this population was poor at 81mmols/mol and diabetes related complications were present in 32%. Engagement by this population with services was poor with an average of 3 missed clinic appointments over a 24 month period. CONCLUSION: These results have prompted a re think of how health care professionals can deliver a service that better suits the needs of this challenging patient group.

Unilateral nevoid telangiectasia: occurrence in two patients with hepatitis C.

Unilateral nevoid telangiectasia, a rarely reported disorder, has been said to be related to increased estrogen receptors in involved skin. The lesions may be congenital or acquired. When acquired it arises almost exclusively during periods of relatively increased estrogen levels such as during pregnancy or puberty, or in association with alcoholic cirrhosis. We describe unilateral nevoid telangiectasia in two young men without any evidence of cirrhosis, but with serologic evidence of hepatitis C infection. Tissue specimens from these men were analyzed for estrogen and progesterone receptors, but there was no difference in involved versus uninvolved skin.

Effect of locus of control and consideration of future consequences on time tradeoff utilities for current health.

Comments from subjects undergoing utility assessment suggest that personality traits may affect responses. We sought to describe the association between time-tradeoffs utility for current health and measures of two personality traits: (1) perceived control over one's life and (2) concern over immediate vs. future outcomes. One hundred subjects were recruited from the cafeteria of a large tertiary care hospital. Time-tradeoff utilities were assessed for current health relative to perfect health and death. Subjects also completed two previously validated scales, the Locus of Control (LOC), and Consideration of Future Consequences (CFC) instruments. The interview failure rate was less than 3%. The correlation between LOC score and utility for current health was modest (Spearman's rho = 0.196, p = 0.071), but increased substantially when subjects unwilling to trade were excluded (Spearman's rho = 0.33, p = 0.0043). The CFC scale was weakly correlated with utility for current health (Spearman's rho = 0.12, p = 0.2676). The Consideration of Future Consequences scale explains little of the variation in time-tradeoff utilities. In contrast, Locus of Control appears to partially explain the variation in time-tradeoff utilities for current health, even after controlling for health status.

The importance of patient preference in the decision to screen for prostate cancer. Prostate Patient Outcomes Research Team.

OBJECTIVE: Routine screening for prostate cancer is controversial because of frequent false-positive results, the potential for slow, non-life-threatening growth of untreated cancer, the uncertainty regarding whether treatment can extend life, and the potential for treatment complications. This study examines how information about prostate-specific antigen (PSA) testing and the uncertain benefits of treating prostate cancer affects patients' desire for PSA testing. DESIGN: An educational videotape designed to inform men about the uncertainty surrounding PSA screening and the treatment of early-stage prostate cancer was presented to two groups of male patients 50 years of age or older. SETTING: Dartmouth-Hitchcock Medical Center. PATIENTS/PARTICIPANTS: For study 1, men seeking a free prostate cancer screening were preassigned to view the educational videotape (N = 184) or another videotape (N = 185). For study 2, men scheduled to visit a general internal medicine clinic viewed either the educational videotape (N = 103) or no videotape (N = 93). MEASUREMENTS AND MAIN RESULTS: The men's information and preferences about prostate cancer screening and treatment and actual choice of PSA test at the next test opportunity were measured. Men who viewed the educational videotape were: better informed about PSA tests, prostate cancer, and its treatment; preferred no active treatment if cancer were found; and preferred not to be screened (all significant at p < or = .002 in both studies). Men viewing the educational video were less likely to have a PSA test (p = .041, study 2). This tendency was not significant at the free-PSA clinic (p = .079). CONCLUSIONS: Preference regarding cancer screening and treatment is greatly affected by information about medical uncertainties. Because informed patient choices vary. PSA screening decisions should incorporate individual preferences.

Non-isotopic method for quantitation of platelets and erythrocytes in experimental thrombi.

Experimental animal models of thrombosis have been established in several species to examine factors responsible for thrombotic disorders in man. One technical facet of all thrombosis models is the need to quantitate cell deposition on thrombogenic surfaces, and this is routinely accomplished with radioisotopic labeling of specific components. Data reported here demonstrate that formalin-fixed thrombi can be hydrolyzed with chymotrypsin allowing recovery and quantitation of platelets and erythrocytes incorporated within the clot. Recovery of platelets from in vitro generated, model thrombi averaged 99 +/- 10% (mean +/- 1 SD; n = 7; range 88-116%) of calculated content; recovery of erythrocytes was 94.1 +/- 1.1% (n = 6) as measured by recovery of cellular hemoglobin after chymotrypsin hydrolysis of clots. Chymotrypsin was also shown to release platelets and erythrocytes from string-bound thrombi generated in vivo with an arterio-venous shunt model in beagle dogs. Platelet recovery from these string clots after chymotrypsin hydrolysis was independently verified with a quantitative Western blot assay of platelet antigens. These data demonstrate that experimental thrombi can be hydrolyzed with chymotrypsin, thereby not only eliminating the need for radioisotopes, but also permitting flow cytometric analysis of cells comprising the thrombus.

Quantitation of platelet life span in splenectomized dogs.

Platelet life spans in dogs were measured pre- and post- splenectomy utilizing in vitro whole blood biotinylation. Four splenectomized dogs were found to have significantly lengthened platelet life spans, 193 +/- 7 hours (mean +/- 1 SD;n=4) postsurgery vs. control life spans of 131 +/- 15 hours (n=6; p< 0.01) when analyzed with the multiple-hit model. Additionally, platelets from normal dogs transfused into splenectomized dogs were found to have convex survival curves with extended life spans approximating that of the splenectomized dog. These data indicate that the spleen is a significant determinant of platelet life span in dogs, with survivals increasing approximately 47% upon splenectomy.

Automated utility assessment of global health.

The objective of this study was to characterize the performance of an automated utility assessment instrument for measuring preferences for overall health. The study population consisted of 83 subjects recruited from the cafeteria of a large tertiary care hospital. We assessed utilities for current health relative to perfect health and death using the rating scale, time tradeoff and standard gamble metrics. To validate the instrument, we compared utilities with the General Health subscale of the SF-36 Health Survey instrument, satisfaction with current health, and degree of bother due to current health. We evaluated interview failure rate based on irrational orderings of two practice assessments (monocular and binocular blindness) or inability to complete the interview. As expected, utility for overall health was statistically significantly associated with the General Health subscale score and measures of satisfaction with current health and degree of bother. There is substantial variation in utilities among patients with similarly severe overall health, and substantial overlap in utilities among subjects with different levels of overall health. The failure rate in the study was acceptable (9.6%). Automated assessment of utility for overall health provides a feasible means for estimating individual preferences.

Demonstration that thiazole-orange-positive platelets in the dog are less than 24 hours old.

Approximately 6% of dog platelets are positive for staining with thiazole orange, a dye frequently used to stain ribonucleic acid. In this report, thiazole-orange positivity is shown to mark platelets that are less than 24 hours old. Dog platelets were derivatized in vivo with N-hydroxysuccinimido biotin such that greater than 95% of all platelets were biotinylated. Newly synthesized, nonbiotinylated platelets were then monitored by flow cytometry for their ability to bind thiazole orange. After biotinylation, the percentage of biotin-negative, thiazole-orange-positive platelets increased gradually from 0.72% at 30 minutes to 5.44% at 24 hours. These data indicate that thiazole-orange staining does label newly synthesized platelets.

Fluorescein derivatization of fibrinogen for flow cytometric analysis of fibrinogen binding to platelets.

Dog and human fibrinogen were derivatized with N-hydroxysuccinimido-fluorescein and utilized for flow cytometric estimation of fibrinogen binding to activated platelets. Fluorescein-fibrinogen binding fulfilled the criteria for specific binding to platelets; the binding was saturable, dependent on agonist activation, and inhibited by unlabeled fibrinogen. In addition, EDTA and barbourin, a KGD-containing peptide, were found to inhibit the binding of fluorescein-fibrinogen. Fluorescein-fibrinogen bound to dog platelets with an apparent affinity of 0.31 microM after stimulation with either adenosine-5'-diphosphate (ADP) or plateletactivating factor. The labeled fibrinogen was also used to study the fibrinogen binding capacity of aged, biotinylated platelets. Aged platelets were indistinguishable from young platelets with regard to fibrinogen binding in response to ADP. These studies document that direct derivatization of fibrinogen with fluorescein generates a useful probe for analyzing fibrinogen binding to platelets with flow cytometry.

Dog platelets accumulate intracellular fibrinogen as they age.

The alpha granules of circulating platelets are dynamic structures that acquire endogenous and exogenous components by synthesis and uptake, respectively. The uptake of exogenous components is a result of either receptor-mediated endocytosis or fluid-phase pinocytosis. Despite many detailed studies on the function and content of alpha-granules, little is known of the impact of platelet age on these organelles. In this report, we describe the use of platelet biotinylation to identify and isolate aged platelets for the analysis of alpha-granule contents. When aged platelets were permeabilized and examined by flow cytometry utilizing fluorescently labeled antibodies, two exogenously acquired proteins, fibrinogen and immunoglobulin G, were found to increase significantly with platelet age. The levels of intracellular fibrinogen were found to be elevated relative to control, 114 +/- 2% and 119 +/- 5% on days 4 and 5 postbiotinylation, respectively; the life span of dog platelets is 6.0 days. Intracellular immunoglobulin G content increased similarly. Levels of two endogenously synthesized proteins, thrombospondin and P-selectin, were not elevated in aged platelets. Confirmation of the flow cytometric data was obtained by isolating aged, biotinylated platelets by fluorescence-activated cell sorting and quantitating the fibrinogen levels with an ELISA assay. For platelets averaging 4.6 days of age, the fibrinogen level was elevated to 128 +/- 23% of the level for the entire platelet population. These data demonstrate that age-dependent changes in exogenously acquired alpha-granule proteins do occur and that the uptake mechanism for these proteins is active throughout the platelet life span.

Nonsense mutations of the ornithine decarboxylase structural gene of Neurospora crassa.

Ornithine decarboxylase (ODC) (EC 4.1.1.17) is an early enzyme of polyamine synthesis, and its activity rises quickly at the onset of growth and differentiation in most eucaryotes. Some have speculated that the enzyme protein may have a role in the synthesis of rRNA in addition to its role in catalyzing the decarboxylation of ornithine (G. D. Kuehn and V. J. Atmar, Fed. Proc. 41:3078-3083, 1982; D. H. Russell, Proc. Natl. Acad. Sci. USA 80:1318-1321, 1983). To test this possibility, we sought mutational evidence for the indispensability of the ODC protein for normal growth of Neurospora crassa. We found three new, ODC-deficient mutants that lacked ODC protein. Among these and by reversion analysis of an earlier set of mutants, we found that two ODC-deficient mutants carried nonsense mutations in the ODC structural gene, spe-1. Allele LV10 imparted a complete deficiency for enzyme activity (less than 0.006% of normal) and had no detectable ODC antigen. Allele PE4 imparted a weak activity to cells (0.1% of derepressed spe+ cultures) and encoded a lower-molecular-weight ODC subunit (Mr = 43,000) in comparison to that of the wild-type strain (Mr = 53,000). Strains carrying either mutation, like other spe-1 mutants, grew at a normal rate in exponential culture if the medium was supplemented with spermidine, the main end product of the polyamine pathway in N. crassa. Unless an antigenically silent, N-terminal fragment with an indispensable role persists in the LV10-bearing mutant, we conclude that the ODC protein has no role in the vegetative growth of this organism other than the synthesis of polyamines. The data extend earlier evidence that spe-1 is the structural gene for ODC in N. crassa. The activity found in mutants bearing allele PE4 suggests that the amino acids nearest the carboxy terminus do not contribute to the active site of the enzyme.

Effect of labetalol and YM-09538 on neuronal uptake of (3H)norepinephrine in the rat vas deferens.

Labetalol and YM-09538 are combined alpha and beta receptor antagonists with demonstrated antihypertensive activity. Both compounds inhibited the uptake of (3H)norepinephrine into nerves in the rat vas deferens. However, labetalol was approximately 5 fold more potent than YM-09538 as an inhibitor of neuronal uptake. Inhibition of neuronal uptake occurred at concentrations 43 and 3800 times higher than necessary for inhibition of alpha receptors by labetalol and YM-09538, respectively. Thus YM-09538 shows a greater separation between neuronal uptake blocking properties and alpha receptor blocking properties than labetalol. This separation of activities may contribute to greater antihypertensive efficacy of YM-09538 relative to labetalol.