Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays.

BACKGROUND: Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity. METHODS: IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor's office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1-10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented. FINDINGS: The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC. INTERPRETATION: ADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes. FUNDING: Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and the Novo Nordisk Foundation.

Prevalence of Thyroid Peroxidase and Thyroglobulin Autoantibodies in the Swedish Population.

Autoimmune thyroid disease (AITD) may be detected prior to clinical symptoms through the presence of autoantibodies against thyroid peroxidase (TPOab), thyroglobulin (TGab), or both.The present study aimed to develop a novel radiobinding assay (RBA) for TPOab and to determine the prevalence of TPOab and TGab in the Swedish population.Patient samples from 27 newly diagnosed Graves' disease patients in longitudinal follow-up and 124 AITD autoantibody-positive children in prospective follow-up for increased risk of type 1 diabetes were included to validate the novel RBA for TPO. The results of RBA were compared with those obtained by commercial radioimmunoassay (RIA) and electrochemiluminescence (ECL). Furthermore, 476 serum samples from adult blood donors and 297 from 13-year-old school children were analyzed for the presence of TPOab and TGab.Receiver operating characteristics analysis for the novel TPOab resulted in an area under curve (AUC) value of 0.82 (p<0.0001), a sensitivity of 77.8%, and a specificity of 91.9% in adult blood donors, and an AUC value of 0.70 (p<0.0001), a sensitivity of 53.2% and a specificity of 95.3% in the 13-year-old school children, respectively. TPOab levels in RBA correlated with both ECL (r=0.8950, p<0.0001) and RIA (r=0.9295, p<0.0001). The prevalence of TPOab and TGab was 6.3% and 7.6% in adult blood donors and 2.9 and 3.7% in 13-year-old school children.In conclusion, a novel RBA for the determination of TPOab was developed and validated with current methodologies. This study also reports an increasing prevalence of thyroid autoantibodies from adolescence to adulthood.

Digital Health Testbeds in Sweden: An exploratory study.

OBJECTIVE: This study explored the Swedish digital health testbeds through the lens of complexity science. METHODS: The purposive sampling was used to identify 38 digital health testbed organizations to conduct interviews in written or audio-conferencing. The interview responses were aggregated and analyzed using thematic analysis. The themes were mainly generated through complexity theory and the principles of complex adaptive systems. RESULTS: Fifteen testbed organizations responded, comprising 13 written responses and two audio-conferencing. Five main theoretical themes were generated: agents and diversity, connections and communication, adaptation and learning, perturbations, and path dependence. Agents and diversity depicted different types of testbeds, stakeholders and innovation, and the primary function and purpose of the testbeds. Various factors enhancing connections and communications among multiple stakeholders were identified, such as the quality of e-health solutions and the 2030 Agenda for Sustainable Development. Some adaptation and learning factors, such as internal reorganization, sharing and creating learning opportunities, and additional funding, guaranteed the sustainability of testbeds. Perturbations were characterized by two factors: non-linear interactions - lack of commitment and transparency in stakeholders' engagement, and uncertainty about testbed definitions and concepts. Path dependence highlighted the importance of history, such as previous positive and negative experiences. CONCLUSION: This study provided insights into testbeds' organization, their functions, how various aspects were challenged, and how they adapted to overcome and improve the system issues. Identifying the stakeholders and relevant factors, commissioning an evaluation, backing up with a contingency plan, securing adequate funding, and disseminating the findings can improve the testbeds' design and implementation.

Neutralizing Ljungan virus antibodies in children with newly diagnosed type 1 diabetes.

Ljungan virus (LV), a Parechovirus of the Picornavirus family, first isolated from a bank vole at the Ljungan river in Sweden, has been implicated in the risk for autoimmune type 1 diabetes. An assay for neutralizing Ljungan virus antibodies (NLVA) was developed using the original 87-012 LV isolate. The goal was to determine NLVA titres in incident 0-18 years old newly diagnosed type 1 diabetes patients (n=67) and school children controls (n=292) from Jämtland county in Sweden. NLVA were found in 41 of 67 (61 %) patients compared to 127 of 292 (44 %) controls (P=0.009). In the type 1 diabetes patients, NLVA titres were associated with autoantibodies to glutamic acid decarboxylase (GADA) (P=0.023), but not to autoantibodies against insulin (IAA) or islet antigen-2 (IA-2A). The NLVA assay should prove useful for further investigations to determine levels of LV antibodies in patients and future studies to determine a possible role of LV in autoimmune type 1 diabetes.

Islet autoantibodies present in association with Ljungan virus infection in bank voles (Myodes glareolus) in northern Sweden.

Bank voles are known reservoirs for Puumala hantavirus and probably also for Ljungan virus (LV), a suggested candidate parechovirus in type 1 diabetes etiology and pathogenesis. The aim of this study was to determine whether wild bank voles had been exposed to LV and if exposure associated to autoantibodies against insulin (IAA), glutamic acid decarboxylase 65 (GADA), or islet autoantigen-2 (IA-2A). Serum samples from bank voles (Myodes glareolus) captured in early summer or early winter of 1997 and 1998, respectively, were analyzed in radio binding assays for antibodies against Ljungan virus (LVA) and Puumala virus (PUUVA) as well as for IAA, GADA, and IA-2A. LVA was found in 25% (189/752), IAA in 2.5% (18/723), GADA in 2.6% (15/615), and IA-2A in 2.5% (11/461) of available bank vole samples. LVA correlated with both IAA (P = 0.007) and GADA (P < 0.001), but not with IA-2A (P = 0.999). There were no correlations with PUUVA, detected in 17% of the bank voles. Compared to LVA negative bank voles, LVA positive animals had higher levels of both IAA (P = 0.002) and GADA (P < 0.001), but not of IA-2A (P = 0.205). Levels of LVA as well as IAA and GADA were higher in samples from bank voles captured in early summer. In conclusion, LVA was detected in bank voles and correlated with both IAA and GADA but not with IA-2A. These observations suggest that exposure to LV may be associated with islet autoimmunity. It remains to be determined if islet autoantibody positive bank voles may develop diabetes in the wild. J. Med. Virol. 89:24-31, 2017. © 2016 Wiley Periodicals, Inc.

Patients' views on electronic patient information leaflets.

BACKGROUND: Information in society and in health care is currently undergoing a transition from paper to digital formats, and the main source of information will probably be electronic in the future. OBJECTIVE: To explore patients' use and perceptions of the patient information leaflet included in the medication package, and their attitude towards a transition to an electronic version. METHODS: The data was collected during October to November 2014 among individuals in South-Eastern Sweden, using a questionnaire (n=406, response rate 78%) and interviews (n=15). RESULTS: The questionnaire showed that the majority of the respondents (52%) occasionally read the patient information leaflet, 37% always read it, and 11% never read it. Almost half of the patients (41%) were positive towards reading the patient information leaflet electronically while 32% were hesitant and 26% neutral. A majority of the patients would request to get the patient information leaflet printed at the pharmacy if it was not included in the package. There were differences in attitude related to age and gender. The interviews showed that patients had mixed views on a transition to an electronic patient information leaflet. The patients perceived several positive aspects with an electronic patient information leaflet but were concerned about elderly patients. CONCLUSION: Although many were positive towards reading the patient information leaflet electronically, the majority prefer the patient information leaflet in paper form. Providing appropriate and useful eHealth services for patients to access the patient information leaflet electronically, along with education, could prepare patients for a transition to electronic patient information leaflet.

Patients' views on electronic patient information leaflets

Background: Information in society and in health care is currently undergoing a transition from paper to digital formats, and the main source of information will probably be electronic in the future. Objective: To explore patients’ use and perceptions of the patient information leaflet included in the medication package, and their attitude towards a transition to an electronic version. Methods: The data was collected during October to November 2014 among individuals in South-Eastern Sweden, using a questionnaire (n=406, response rate 78%) and interviews (n=15). Results: The questionnaire showed that the majority of the respondents (52%) occasionally read the patient information leaflet, 37% always read it, and 11% never read it. Almost half of the patients (41%) were positive towards reading the patient information leaflet electronically while 32% were hesitant and 26% neutral. A majority of the patients would request to get the patient information leaflet printed at the pharmacy if it was not included in the package. There were differences in attitude related to age and gender. The interviews showed that patients had mixed views on a transition to an electronic patient information leaflet. The patients perceived several positive aspects with an electronic patient information leaflet but were concerned about elderly patients. Conclusion: Although many were positive towards reading the patient information leaflet electronically, the majority prefer the patient information leaflet in paper form. Providing appropriate and useful eHealth services for patients to access the patient information leaflet electronically, along with education, could prepare patients for a transition to electronic patient information leaflet (AU)

No disponible

Implementation of a cross-border health service: physician and pharmacists' opinions from the epSOS project.

OBJECTIVES: To explore the opinions of health professionals with experience of the European Patient Smart Open Services (epSOS) system regarding the epSOS services perceived utility, potential impact and main barriers and facilitators to its use. METHODS: Qualitative study design involving focus groups with health care professionals with experience of epSOS system. A semi-structured topic guide was developed to guide the discussion. RESULTS: epSOS services were seen as interesting intuitive services and easy to operate. The greatest impact was in terms of positive impact on communication, clinical safety and patient management. Data reliability, difficulties in accessing the service and aspects related to information technology architecture were considered the most relevant barriers. CONCLUSION: This study has provided insights into the strengths and limitations of two new eHealth services for use across countries within the European Union, and has provided indications of how those services could be improved.

A/H1N1 antibodies and TRIB2 autoantibodies in narcolepsy patients diagnosed in conjunction with the Pandemrix vaccination campaign in Sweden 2009-2010.

Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the <13 years old (n = 12) compared to patients who were older than 30 years (n = 12, p = 0.014). Being HLA-DQB1*06:02 positive was associated with higher A/H1N1 antibody levels in both patients and controls (p = 0.026). Serum autoantibody levels to TRIB2 were low overall and high binders did not differ between patients and controls. We observed an association between levels of A/H1N1 antibodies and TRIB2 autoantibody levels particularly among the youngest narcolepsy patients (r = 0.819, p < 0.001). In conclusion, following the 2009 influenza pandemic vaccination, A/H1N1 antibody levels were associated with young age-at-onset narcolepsy patients positive for HLA-DQB1*06:02. The possibility that TRIB2 is an autoantigen in narcolepsy remains to be clarified. We could verify autoantibody responses against TRIB2 which needs to be determined in larger patient cohorts and control populations.

Relationship between Ljungan virus antibodies, HLA-DQ8, and insulin autoantibodies in newly diagnosed type 1 diabetes children.

Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n=676) and controls (n=309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA). LVAb at 75(th) percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4(th) quartile LVAb were found in 25% (170/676) of which 64% were <10 (n=108, p<0.0001), and 27% were<5 (n=45; p<0.0001) years old. The 4(th) quartile LVAb in children <10 years of age correlated to HLA DQ2/8, 8/8, and 8/X (p<0.0001). Furthermore, in the group with 4(th) quartile LVAb, 55% were IAA positive (p=0.01) and correlation was found between 4(th) quartile LVAb and IAA in children <10 years of age (p=0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4(th) quartile LVAb correlated with IAA; and 3) there was a correlation between 4(th) quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D.