Ingela Johansson

GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

We have previously shown that two injections of 20 μg GAD-alum to recent onset type 1 diabetic children induced GADA levels in parallel to preservation of insulin secretion. Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD(65) enzyme activity. We further studied the specific effect of GAD-alum through analyses of IA-2A, tetanus toxoid and total IgE antibodies. Serum from children receiving GAD-alum or placebo was collected pre-treatment and after 3, 9, 15 and 21 months. At 3 months a reduced percentage of IgG1 and increased IgG3/IgG4 were detected in GAD-alum treated. Further, IA-2A, IgE and tetanus toxoid antibodies, as well as GAD(65) enzyme activity, were unaffected confirming the specific effect of treatment. In the GAD-alum group, higher pre-treatment GADA were associated to more pronounced C-peptide preservation. The induced IgG3/IgG4 and reduced IgG1 suggest a Th2 deviation of the immune response.

Sense of coherence, quality of life, and function among elderly hip fracture patients

The aim was to study whether sense of coherence (SOC) had any predictive power in patients with hip fractures regarding length of stay in hospital, state of confusion and health, functional ability, quality of life, and municipal home-help service. A total of 73 patients admitted from their own homes participated (mean age 80.4 years). The patients were followed during a 4-month period. Acute confusional state was diagnosed using a Swedish version of the NEECHAM Confusion Scale. SOC and self-rated functional health status were assessed during the hospitalization period and one month after discharge; Quality of Life Index (QLI) and instrumental daily activities (SPE) were assessed four months after discharge. Focusing on the differences in outcome between persons with a stronger vs a weaker SOC, there were few significant differences in physical status between the subgroups. However, the persons with a weaker SOC stayed longer in the hospital and reported a significantly lower score on the NEECHAM Confusion Scale, as well as more discomfort and disability symptoms related to communication, mental, and emotional status. Furthermore, these persons had less favorable scores on the overall QLI and subscales respectively, and on all subscales measuring instrumental daily activities. The persons with a weaker SOC were significantly more dependent on assistance before admission to the hospital than those with a stronger SOC. The conclusions drawn from the study indicate that persons with a stronger SOC seem to cope in a better way with their situation after a hip fracture.

Living with life-saving technology - coping strategies in implantable cardioverter defibrillators recipients

AIMS To describe coping strategies and coping effectiveness in recipients with an implantable cardioverter defibrillator and to explore factors influencing coping. BACKGROUND Implantable cardioverter defibrillators are documented as saving lives and are used to treat ventricular tachycardia and ventricular fibrillation. Despite the implantable cardioverter defibrillator not evidently interfering with everyday life, there is conflicting evidence regarding the psychosocial impact of an implantable cardioverter defibrillator implantation such as anxiety, depression, perceived control and quality of life and how these concerns may relate to coping. DESIGN Cross-sectional multicentre design. METHODS Individuals (n = 147, mean age 63 years, 121 men) who had lived with an implantable cardioverter defibrillator between 6-24 months completed the Jalowiec Coping Scale-60, Hospital Anxiety and Depression Scale, Control Attitude Scale and Quality of Life Index-Cardiac version. RESULTS Implantable cardioverter defibrillators recipients seldom used coping strategies, and the coping strategies used were perceived as fairly helpful. Optimism was found to be the most frequently used (1·8 SD 0·68) and most effective (2·1 SD 0·48) coping strategy, and recipients perceived moderate control in life. Anxiety (β = 3·5, p ≤ 0·001) and gender (β = 12·3, p = 0·046) accounted for 26% of the variance in the total use of coping strategies, suggesting that the more symptoms of anxiety and being women the greater use of coping strategies. CONCLUSIONS Most recipients with an implantable cardioverter defibrillator did not appraise daily concerns as stressors in need of coping and seem to have made a successful transition in getting on with their lives 6-24 months after implantation. Relevance to clinical practice.  Nurses working with recipients with an implantable cardioverter defibrillator should have a supportive communication so that positive outcomes such as decreased anxiety and increased perceived control and quality of life can be obtained. Through screening for anxiety at follow-up in the outpatient clinic, these recipients perceiving mental strain in their daily life can be identified.

Organisation of care for Swedish patients with an Implantable Cardioverter Defibrillator, a national survey

AIM To describe the clinical aspects of implantable cardioverter defibrillators care in Sweden with focus on organisation, the role and education of nurses, patient information and education and areas in need of improvement. BACKGROUND Implantable cardioverter defibrillators implantations have developed rapidly in recent years and are now an established arrhythmia treatment. The expanding indication for implantable cardioverter defibrillators implantation demands new competencies and resources in the implantable cardioverter defibrillators team members. METHODS Participants were recruited among physicians and nurses in all of the hospitals implanting implantable cardioverter defibrillators (n = 16). Data were collected by a questionnaire. Additionally, all written educational materials provided to patients pre- and postimplant were collected from all 16 hospitals. Deductive content analysis using Sarvimäki and Stenbock-Hults five holistic dimensions was employed to ascertain how information was provided in brochures and information materials. RESULTS Half of the hospitals (n=8) had nurse-based outpatient clinics and several others planned to introduce them. Three hospitals carried out distance follow-ups by means of tele-monitoring. The nurses had received specific implantable cardioverter defibrillators education from implantable cardioverter defibrillators companies and/or various university courses. The biophysical dimension dominated in the information material, while the emotional, intellectual and socio-cultural dimensions were scarcely described, and the spiritual-existential was not referred to at all. CONCLUSION Holistic care of implantable cardioverter defibrillators patients can be achieved by means of a multidisciplinary implantable cardioverter defibrillators team and more patient-centred educational strategies. In Sweden, the organisation of implantable cardioverter defibrillators care and follow-up is developing towards more nurse-based clinics. RELEVANCE TO CLINICAL PRACTICE Development and implementation of structured care programmes with a more holistic approach can improve future implantable cardioverter defibrillators care. The content of the written educational materials need to be more holistic, rather than mainly focusing on the biophysical and technical aspects of living with an implantable cardioverter defibrillators.

High cortisol in 5-year-old children causes loss of DNA methylation in SINE retrotransposons: a possible role for ZNF263 in stress-related diseases

BackgroundChildhood stress leads to increased risk of many adult diseases, such as major depression and cardiovascular disease. Studies show that adults with experienced childhood stress have specific epigenetic changes, but to understand the pathways that lead to disease, we also need to study the epigenetic link prospectively in children.ResultsHere, we studied a homogenous group of 48 5-year-old children. By combining hair cortisol measurements (a well-documented biomarker for chronic stress), with whole-genome DNA-methylation sequencing, we show that high cortisol associates with a genome-wide decrease in DNA methylation and targets short interspersed nuclear elements (SINEs; a type of retrotransposon) and genes important for calcium transport: phenomena commonly affected in stress-related diseases and in biological aging. More importantly, we identify a zinc-finger transcription factor, ZNF263, whose binding sites where highly overrepresented in regions experiencing methylation loss. This type of zinc-finger protein has previously shown to be involved in the defense against retrotransposons.ConclusionsOur results show that stress in preschool children leads to changes in DNA methylation similar to those seen in biological aging. We suggest that this may affect future disease susceptibility by alterations in the epigenetic mechanisms that keep retrotransposons dormant. Future treatments for stress- and age-related diseases may therefore seek to target zinc-finger proteins that epigenetically control retrotransposon reactivation, such as ZNF263.

Evaluation of a Swedish version of the Watts Sexual Function Questionnaire (WSFQ) in persons with heart disease: A pilot study

Background: As part of preparation for a Swedish multicentre study, exploring sexual and married life in patients with myocardial infarction and their partners, a Swedish validated instrument was required. Aims: The aim of this pilot study was to evaluate the validity and reliability of a Swedish version of the Watts Sexual Function Questionnaire (WSFQ) among persons with a heart disease. Methods: A convenience sample of 79 persons (47 men and 32 women) living with a heart disease was recruited from the members of the National Association of Heart and Lung Patients. They completed a Swedish version of the WSFQ on two occasions. Results: Two separate factor analyses each revealed a two-factor structure on both occasions: “Sexual appetite” and “Sexual expectations” with gender-neutral questions and “Sexual sensitiveness” and “Sexual ability” with gender-specific questions. Cronbachs alpha coefficients ranged from 0.48 to 0.86 and test–retest values for all but one question exceeded 0.70. Conclusions: The Swedish version of the WSFQ showed good validity and stability and acceptable internal homogeneity. Extended evaluations of the questionnaire are recommended.

GAD-specific T cells are induced by GAD-alum treatment in Type-1 diabetes patients

Administration of Glutamic Acid Decarboxylase (GAD)65 formulated in aluminium hydroxide preserved insulin secretion in a phase II trial in recent onset Type 1 Diabetes. A subsequent European phase III trial was closed at 15months after failing to reach primary endpoint, but the majority of the Swedish patients completed the 21months follow-up. We studied the frequencies and phenotype of T cells, suppressive capacity of Tregs, GAD65-induced proliferation, and frequencies of T cells with a GAD65-specific TCR in Swedes participating in the trial. Stimulation with GAD65 induced activated T cells and also cells with a suppressive phenotype. Activated GAD65-specific effector T cells were detected by tetramer staining while the frequency of GAD65-specific Treg was not affected by the treatment. Additional doses of GAD-alum increased frequencies of CD25+CD127+, but had no effect on CD25hiCD127lo. Our findings indicate that GAD-alum treatment primarily induced activated T cells. GAD65-specific cells were mainly of activated phenotype.