Validation of the arthritis self-efficacy short-form scale in German fibromyalgia patients.

Self-efficacy is assumed to account for significant variance in the treatment outcome of chronic pain patients. The aim of this study was to provide a German version of an approved measure of disease-related self-efficacy in fibromyalgia (FM) patients which assesses treatment outcomes and specific differences compared to other pain patients. The 8-item short-form of the arthritis self-efficacy scale was translated into German (ASES-D) and administered to 148 FM patients and 53 patients with rheumatoid arthritis (RA). In addition, similar cognitive constructs (locus of control, optimism/pessimism, and general self-efficacy) and disease-related variables (pain, functioning, depression, and coping) were assessed. The instrument was further applied to 43 FM patients who underwent interdisciplinary group therapy. Validation methods consisted of correlation, principal component analysis and difference testing between the disease groups. The instrument met good psychometric properties. Evidence for construct validity was provided. Self-efficacy was sensitive to changes and could be used in predicting the treatment outcome in FM patients. The German short-form ASES-D is a further step toward an internationally comparable assessment of disease-related self-efficacy in FM.     

Experimental investigation of intravascular OCT for imaging of intracranial aneurysms

Purpose

Rupture risk assessment of an intracranial aneurysm (IA) is an important factor for indication of therapy. Until today, there is no suitable objective prediction method. Conventional imaging modalities cannot assess the IA’s vessel wall. We investigated the ability of intravascular optical coherence tomography (OCT) as a new tool for the characterization and evaluation of IAs.

Materials and methods

An experimental setup for acquisition of geometrical aneurysm parameters was developed. Object of basic investigation was a silicone phantom with six IAs from patient data. For structural information, three circle of Willis were dissected and imaged postmortem. All image data were postprocessed by medical imaging software.

Results

Geometrical image data of a phantom with six different IAs were acquired. The geometrical image data showed a signal loss, e.g., in aneurysms with a high bottleneck ratio. Imaging data of vessel specimens were evaluated with respect to structural information that is valuable for the characterization of IAs. Those included thin structures (intimal flaps), changes of the vessel wall morphology (intimal thickening, layers), adjacent vessels, small vessel outlets, arterial branches and histological information.

Conclusion

Intravascular OCT provides new possibilities for diagnosis and rupture assessment of IAs. However, currently used imaging system parameters have to be adapted and new catheter techniques have to be developed for a complete assessment of the morphology of IAs.

     

Small- and Large-Fiber Neuropathy After 40 Years of Type 1 Diabetes: Associations with glycemic control and advanced protein glycation: the Oslo Study

OBJECTIVE

To study large- and small-nerve fiber function in type 1 diabetes of long duration and associations with HbA_1c and the advanced glycation end products (AGEs) N-ε-(carboxymethyl)lysine (CML) and methylglyoxal-derived hydroimidazolone.

RESEARCH DESIGN AND METHODS

In a long-term follow-up study, 27 persons with type 1 diabetes of 40 ± 3 years duration underwent large-nerve fiber examinations, with nerve conduction studies at baseline and years 8, 17, and 27. Small-fiber functions were assessed by quantitative sensory thresholds (QST) and intraepidermal nerve fiber density (IENFD) at year 27. HbA_1c was measured prospectively through 27 years. Serum CML was measured at year 17 by immunoassay. Serum hydroimidazolone was measured at year 27 with liquid chromatography–mass spectrometry.

RESULTS

Sixteen patients (59%) had large-fiber neuropathy. Twenty-two (81%) had small-fiber dysfunction by QST. Heat pain thresholds in the foot were associated with hydroimidazolone and HbA_1c. IENFD was abnormal in 19 (70%) and significantly lower in diabetic patients than in age-matched control subjects (4.3 ± 2.3 vs. 11.2 ± 3.5 mm, P < 0.001). IENFD correlated negatively with HbA_1c over 27 years (r = −0.4, P = 0.04) and CML (r = −0.5, P = 0.01). After adjustment for age, height, and BMI in a multiple linear regression model, CML was still independently associated with IENFD.

CONCLUSIONS

Small-fiber sensory neuropathy is a major manifestation in type 1 diabetes of 40 years duration and more prevalent than large-fiber neuropathy. HbA_1c and the AGEs CML and hydroimidazolone are important risk factors in the development of large- and small-fiber dysfunction in long-term type 1 diabetes.Peripheral neuropathy is one of many complications of type 1 diabetes, resulting in significant morbidity and mortality. Small-diameter nerve fibers represent 70–90% of all peripheral nerve fibers and are believed to be the earliest fibers to be damaged in diabetes (1). Small-fiber injury has also been associated with neuropathic pain (2,3), which is one of the most disabling symptoms in patients with diabetic neuropathy.The severity of diabetic polyneuropathy increases with the duration of diabetes and degree of hyperglycemic exposure (4). In the Oslo Study, intensified insulin treatment with insulin pumps during 2 years improved large-fiber neuropathy at an early stage (5). After 8 years, near normoglycemia delayed progression of neuropathy (6), and after 18 years of fair glycemic control the peripheral nerve function was preserved for those with a mean HbA_1c <8.4% (68 mmol/mol) (7). In the Diabetes Control and Complications Trial (DCCT) and Epidemiology of Diabetes Interventions and Complications Study (EDIC) study, the benefits of previous intensive insulin treatment persisted for 13–14 years after DCCT closeout and provided further evidence of a durable effect of prior intensive treatment and that good glycemic control is important to prevent development of neuropathy (8). The EURODIAB study reported higher cumulative incidence of neuropathy related to higher HbA_1c value (9). Controversies exist regarding whether there is a definitive threshold of glycemic exposure for any diabetes complication to develop. Orchard et al. (10) did show that the average number of total glycemic exposure did not vary for the different microvascular complications to develop. They suggested an integrated measure of glycemic control called “A1c months” (both duration and degree) and that a value <1,000 A1c months was a minimal treatment goal (10).How hyperglycemia may cause damage to the nervous system is not fully understood. One consequence of hyperglycemia is the generation of advanced glycation end products (AGEs) that can form nonenzymatically between glucose, lipids, and amino groups. It is believed that AGEs are involved in the pathophysiology of neuropathy. AGEs tend to affect cellular function by altering protein function (11). One of the AGEs, N-ε-(carboxymethyl)lysine (CML), has been found in excessive amounts in the human diabetic peripheral nerve (12). High levels of methylglyoxal in serum have been found to be associated with painful peripheral neuropathy (13).In recent years, differentiation of affected nerves is possible by virtue of specific function tests to distinguish which fibers are damaged in diabetic polyneuropathy: large myelinated (Aα, Aβ), small thinly myelinated (Aδ), or small nonmyelinated (C) fibers. The DCCT/EDIC, EURODIAB, and other cohort studies have not focused especially on small-fiber damage. Therefore, little data are available on the prevalence and mechanisms of small-fiber dysfunction in long-term type 1 diabetes.Our aims were to evaluate large- and small-nerve fiber function in long-term type 1 diabetes and to search for longitudinal associations with HbA_1c and the AGEs CML and methylglyoxal-derived hydroimidazolone.     

Psychometric Properties,Norms, and Factor Structure of the Diabetes Eating Problem Survey–Revised in a Large Sample of Children and Adolescents With Type 1 Diabetes

OBJECTIVE

The purpose of this study was to examine the psychometric properties of the Diabetes Eating Problem Survey–Revised (DEPS-R) in a large sample of young patients with type 1 diabetes, to establish norms, and to validate it against the Eating Attitudes Test–12 (EAT-12).

RESEARCH DESIGN AND METHODS

A total of 770 children and adolescents aged 11–19 years with type 1 diabetes completed the DEPS-R and the EAT-12. In addition, age- and sex-standardized BMI and HbA_1c data were obtained from the Norwegian Childhood Diabetes Registry. In addition to tests of validity, principal axis factoring was conducted to investigate the factor structure of the 16-item DEPS-R.

RESULTS

The DEPS-R demonstrated satisfactory Cronbach α (0.89) and was significantly correlated with the EAT-12 (0.65; P < 0.01), indicating convergent validity. The mean (SD) DEPS-R scores were 11.0 (10.7) for the total sample and 7.7 (7.4) and 14.2 (2.4) for males and females, respectively.

CONCLUSIONS

This study replicates and extends previous research demonstrating the psychometric properties of the abbreviated 16-item DEPS-R. Findings support the utility of this important screening tool to identify disturbed eating in young patients with type 1 diabetes.Numerous studies indicate that type 1 diabetes is a risk factor for the development of disturbed eating behavior (DEB) (1,2), a term that will be used here to refer to the entire range of clinical and subclinical eating pathologies. DEB is common and persistent among young women with type 1 diabetes, with prevalences being more than double those in nondiabetic populations (3,4). Studies indicate that males with type 1 diabetes may also have an increased risk of developing DEB (5). When DEB and type 1 diabetes occur together, morbidity and mortality are dramatically increased. The study by Nielsen et al. (6) of comorbid type 1 diabetes and anorexia nervosa showed crude mortalities at 10-year follow-up of 2.5% for type 1 diabetes and 6.5% for anorexia nervosa; however, the mortality rose to 34.8% when these conditions occurred together.The presence of DEB can severely impair metabolic control and advance the onset of long-term complications (7). Insulin restriction is an efficient weight loss strategy uniquely available to patients with type 1 diabetes, and this behavior is reported in as many as 37% of adolescents and young adult females with type 1 diabetes (4,8,9). Insulin restriction is associated with physical complications, and in previous research self-reported insulin restriction at baseline led to a threefold increased risk of mortality during 11 years of follow-up (9).Given the deleterious effects of comorbidity, routine screening is important to identify DEB in individuals with type 1 diabetes to facilitate early intervention and prevent the development of serious physical complications. In a clinical setting, with limited time and resources, it is important to have access to a valid and sensitive screening instrument that requires few resources and is easy to administer and interpret. There are several screening instruments for the detection of eating pathology, such as the Eating Disorder Examination Questionnaire (10), the SCOFF questionnaire (the acronym was created from the questions) (11), the Eating Attitudes Test (EAT) (12), and the Diabetes Eating Problem Survey–Revised (DEPS-R) (13). In contrast to traditional eating disorders screening measures, such as the Eating Disorder Examination Questionnaire and the EAT, the DEPS-R is designed to assess disturbed eating specific to type 1 diabetes, including insulin restriction to lose weight. Insulin restriction is not likely to be detected by use of generic screening measures of eating pathology, and this represents a serious limitation of those instruments. The Diabetes Eating Problem Survey (DEPS) was first developed in 2001 and consisted of 28 items but was recently revised and shortened to the DEPS-R by Markowitz et al. (13). The original validation study of the DEPS-R included 112 youths (aged 13–19 years) with type 1 diabetes, and results showed that the DEPS-R correlated positively with age, age- and sex-standardized BMI (zBMI), and HbA_1c, and that females scored significantly higher than did males. Despite promising initial psychometric properties of the DEPS-R, the instrument has not been validated against an established measure of eating pathology and remains limited by a small sample. We aimed to investigate the internal consistency and construct validity of the DEPS-R, to identify the factor structure, and to establish normative data in a large sample of young patients with type 1 diabetes.     

Migraine,headache and development of metabolic syndrome: An 11-year follow-up in the Nord-Trøndelag Health Study (HUNT)

Migraine with aura is associated with an increased incidence of stroke and cardiovascular disease, but the biological mechanisms are poorly understood. This study examined the incidence of metabolic syndrome and its relationship to migraine with and without aura and to nonmigraine headache. In the population-based the Nord-Trøndelag Health Study (HUNT), 19,895 individuals were followed for the development of metabolic syndrome, with a median follow-up time of 11.3 years. Headache diagnoses were based on a validated headache questionnaire, and metabolic syndrome was based on a modified version of the National Cholesterol Education Program’s Adult Treatment Panel (ATP) III criteria, using objective anthropometric measurements and blood biochemistry. Using the Poisson regression model, migraine with aura was associated with an increased risk for developing metabolic syndrome. The effect was modified by smoking, with an adjusted incident risk ratio (IRR) among smokers of 2.10 (95% CI 1.53-2.89) and among nonsmokers of 1.39 (95% CI 1.03-1.86), when compared to headache-free controls. A moderate risk increase was seen for migraine without aura (IRR 1.26, 95% CI 1.12-1.42) and nonmigraine headache (IRR 1.22, 95% CI 1.13-1.32), not modified by smoking. The results suggest that traditional risk factors may be one of the mechanisms through which migraine with aura is linked to an increased risk for cardiovascular disease. A heightened vigilance concerning cardiovascular risk factors in this patient group may be warranted.     

CD47 fusion protein targets CD172a+ cells in Crohn’s disease and dampens the production of IL-1β and TNF

In mice, the transfer of CD172a⁺ (SIRP-α) dendritic cells (DCs) elicits T cell–driven colitis, whereas treatment with CD47-Fc protein, a CD172a-binding agent, confers protection. The aim of this study was to elucidate the nature and functional properties of human CD172a⁺ DCs in chronic intestinal inflammation. Here, we show that CD172a⁺CD11c⁺ cells accumulate in the mesenteric lymph nodes (mLNs) and inflamed intestinal mucosa in patients with Crohn’s disease (CD). These cells are distinct from resident DCs and may coexpress markers typically associated with monocyte-derived inflammatory DCs such as CD14 and/or DC-SIGN, E-Cadherin, and/or CX₃CR1. Spontaneous IL-1β and TNF production by HLA-DR⁺ cells in CD tissues is restricted to those expressing CD172a. An avidity-improved CD47 fusion protein (CD47-Var1) suppresses the release of a wide array of inflammatory cytokines by CD172a⁺ cells, which may include HLA-DR⁻CD172a⁺ neutrophils, in inflamed colonic explant cultures and impairs the ability of HLA-DR⁺CD172a⁺ cells to activate memory Th17 but not Th1 responses in mLNs. In conclusion, targeting CD172a⁺ cells may represent novel therapeutic perspectives for patients with CD.The gastrointestinal tract is lined with a single layer of epithelial cells that separates the gut lumen from the connective tissue and the immune system (Kaser et al., 2010; MacDonald et al., 2011). Because it is constantly exposed to dietary and environmental antigens and to an estimated community of 10¹⁴ commensal bacteria, the immune system is confronted with the difficult task of enforcing tolerance to innocuous environmental antigens while also protecting against invading pathogens. An aberrant immune response to the intestinal microbiota contributes to the pathogenesis of Crohn’s disease (CD), a chronic inflammatory bowel disease (IBD) that affects genetically predisposed individuals (Chassaing and Darfeuille-Michaud, 2011; Maloy and Powrie, 2011).Mononuclear phagocytes, which include a large population of macrophages (MΦ) and rare subsets of DCs, are critical for the establishment and maintenance of gut homeostasis (Coombes and Powrie, 2008; Varol et al., 2010). However, myeloid cell heterogeneity in phenotype, origin, and function has led to confusion over the classification between MΦ and DCs, especially in mucosal tissues (Gautier et al., 2012; Miller et al., 2012). In murine tissues, CD11c is not an adequate marker to identify DCs because it is also expressed in varying levels on F4/80⁺ MΦ (Medina-Contreras et al., 2011; Rivollier et al., 2012). This is in contrast to resident MΦ in human lamina propria (LP), which do not express CD11c (Smith et al., 2011). In mice, macrophage–dendritic cell progenitors (MDPs) give rise to dedicated common DC precursors (precDCs) and monocytes via developmental pathways that are governed by Flt3L and M-CSF, respectively (Liu et al., 2009). Both the CD103⁺CD11b⁺ and CD103⁺CD11b⁻ DC subsets originate from precDCs. Tissue-resident CD103⁻CX₃CR1⁺ mononuclear phagocytes, which are the dominant population in the murine gut LP, derive from Ly6C^high circulating monocytes. Murine intestinal homeostasis has been demonstrated to critically depend on a delicate equilibrium between tolerogenic migratory CD103⁺CX₃CR1⁻ DCs and pathogenic CD103⁻CX₃CR1⁺ mononuclear phagocytes (Jaensson et al., 2008; Bogunovic et al., 2009; Varol et al., 2009). In fact, mice genetically depleted of CD103⁺ DCs and CX₃CR1⁺ MΦ do not develop spontaneous inflammation (Birnberg et al., 2008). Animals that have a predominance of CX₃CR1⁺ cells in the LP develop exacerbated colitis (Varol et al., 2009). However, both CX₃CR1⁺F4/80⁺CD103⁻ LP MΦ and CD103⁺ DCs can induce gut tolerance through the generation and/or maintenance of the suppressive activity of Foxp3⁺ regulatory T cells, and CX₃CR1 deficiency leads to exacerbated DSS-induced colitis (Denning et al., 2007; Sun et al., 2007; Medina-Contreras et al., 2011).Recent studies have independently demonstrated that CD103⁻E-Cadherin⁺ and CD103⁻SIRP-α⁺ (CD172a) cells induce experimental colitis in mice (Fortin et al., 2009; Siddiqui et al., 2010). These pathogenic cells accumulate in the inflamed colons and/or LNs. The CD103⁻E-Cadherin⁺ cells originate from Ly6C^high circulating monocytes that migrate in a CCR7-independent manner to the mesenteric LNs (mLNs), whereas the CD103⁻CD172a⁺ DCs accumulate in the inflamed colons and mLNs via a CD47-dependent process. These cell populations promote T cell driven anti-CD40–mediated colitis and drive Th17-associated TNBS colitis in mice; the latter can be ameliorated by the administration of a CD47-Fc fusion protein that putatively targets the CD172a⁺ cells. Whether human equivalents of the colitogenic CD103⁻CD172a⁺ cells exist and whether they can be targeted by CD47-Fc in the mLNs (inductive site) and/or intestinal tissues (effector site) of CD patients remains unknown.Previous studies have reported the presence of CD14⁺ MΦ in situ in the colons of CD patients (Grimm et al., 1995a). Imaging analyses of intestinal mucosal tissues of CD patients have also revealed the existence of several distinct DC populations including DC-SIGN (CD209)⁺CD11c⁺ DCs, CD83⁺ DCs, CD103⁺ DCs, plasmacytoid DCs (pDCs) and Slan⁺ monocytes/DCs (de Baey et al., 2003; Jaensson et al., 2008; te Velde et al., 2003; Verstege et al., 2008). In addition, a CD33⁺CD14⁺ intermediate MΦ/DC subset has been detected at similar frequencies throughout the nonlesional and lesional gut mucosa in CD patients (Kamada et al., 2008).In this study, we provide compelling evidence for the accumulation of proinflammatory cytokine-producing HLA-DR⁺CD172a⁺ cells that coexpress or not E-Cadherin and CX₃CR1 in the mLNs and inflamed mucosa of CD patients. These cells are a major source of IL-1β, IL-6, and TNF and can be targeted by an avidity-improved CD47 fusion protein (CD47-Var1) in inflamed CD tissues.     

Chemokines in the brain: neuroimmunology and beyond.

Chemokines in the brain have been recognised as essential elements in neurodegenerative diseases and related neuroinflammation. Recent studies suggest that in addition to the orchestration of chemotaxis of immune cells, chemokines are also involved in neurodevelopment and neurophysiological signalling.     

What Explains Willingness to Pay for Smoking-Cessation Treatments —Addiction Level, Quit-Rate Effectiveness or the Opening Bid?

Background: Several countries have now passed laws that place limitations on where smokers may smoke. A range of smoking-cessation treatments have become available, many of which have documented increased quit rates. Population surveys show that most smokers wish to quit, and most nonsmokers would prefer to reduce the prevalence of smoking in society. The strengths of these preferences, however, as measured by their willingness to pay (WTP), have not yet been investigated. Objective: This study aims to identify variables that explain variations in people’s answers to WTP questions on smoking-cessation treatments. Methods: A representative sample of the Norwegian population was asked their WTP in terms of an earmarked contribution to a public smokingcessation programme. A sub-group of daily smokers was, in addition, asked about their WTP for a hypothetical treatment that would remove their urge to smoke. The impact of variation in the question format (different opening bids) on stated WTP was compared with that of factors suggested by economic theory, such as quit-rate effectiveness, degree of addiction as measured by the 12-item Cigarette Dependence Scale (CDS-12), and degree of peer group influence as measured by the proportion of one’s friends who smoke. Results: In both programmes, the most important determinant for explaining variations in WTP was the size of the opening bid. Differences in quit-rate effectiveness did not matter for people’s WTP for the smoking-cessation programme. Addiction, and having a small proportion of friends who smoke, were positively associated with smokers’ WTP to quit smoking. Conclusion: Variations in WTP were influenced more by how the question was framed in terms of differences in opening bids, than by variables reflecting the quality (effectiveness) and need (addiction level) for the good in question. While the WTP method is theoretically attractive, the findings that outcomes in terms of different quit rates did not affect WTP, and that WTP answers can be manipulated by the chosen opening bid, should raise further doubts on the ability of this method to provide valid and reliable answers that reflect true preferences for health and healthcare.