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INTRODUCTION: A coeliac disease (CD) diagnosis is likely in children with levels of tissue transglutaminase autoantibodies (anti-TG2) >10 times the upper reference value, whereas children with lower anti-TG2 levels need an intestinal biopsy to confirm or rule out CD. A blood sample is easier to obtain than an intestinal biopsy sample, and stabilised blood is suitable for routine diagnostics because transcript levels are preserved at sampling. Therefore, we investigated gene expression in stabilised whole blood to explore the possibility of gene expression-based diagnostics for the diagnosis and follow-up of CD. DESIGN: We performed RNA sequencing of stabilised whole blood from active CD cases (n=10), non-CD cases (n=10), and treated CD cases on a gluten-free diet (n=10) to identify diagnostic CD biomarkers and pathways involved in CD pathogenesis. RESULTS: No single gene was differentially expressed between the sample groups. However, by using gene set enrichment analysis (GSEA), significantly differentially expressed pathways were identified in active CD, and these pathways involved the inflammatory response, negative regulation of viral replication, translation, as well as cell proliferation, differentiation, migration, and survival. The results indicate that there are differences in pathway regulation in CD, which could be used for diagnostic purposes. Comparison between GSEA results based on stabilised blood with GSEA results based on small intestinal biopsies revealed that type I interferon response, defence response to virus, and negative regulation of viral replication were identified as pathways common to both tissues. CONCLUSIONS: Stabilised whole blood is not a suitable sample for clinical diagnostics of CD based on single genes. However, diagnostics based on a pathway-focused gene expression panel may be feasible, but requires further investigation., Funding agencies: Futurum-the Academy for Health and Care, Region Jonkoping County; Medical Research Council of Southeast Sweden

There are only few studies with specific focus on predictors of survival in nursing home residents (NHRs). The aim was to study whether 1-year changes in complete blood count (including hemoglobin, red blood cells, erythrocyte volume fraction, mean corpuscular volume, mean corpuscular hemoglobin concentration, white blood cells count and platelet count), C-reactive protein and interleukin-1 beta (IL-1 beta), IL-1Ra, IL-6, IL-8 and IL-10, are associated with 8-year survival in elderly NHRs, aged amp;gt;= 80 years. Complete blood count, C-reactive protein and interleukins were measured at baseline, after 6 and 12 months from 167 NHRs aged 80-101 years, mean age 88 +/- 4.5 years, 75% of whom were women. Dates of death were collected from the National Death Register 8 years after baseline. Levels of hemoglobin, red blood cells and mean corpuscular hemoglobin concentration were lower after 1-year, but higher for mean corpuscular volume and IL-1 beta, compared to baseline or 6 month follow-up. In the Cox regression model with a time-dependent covariate, raised levels of C-reactive protein and IL-8 were associated with reduced survival time. Elevated levels of C-reactive protein and IL-8 during 1-year follow-up were related to reduce lengths of survival in elderly NHRs., Funding Agencies|Research Council of Southeast Sweden; Futurum County Council of Jonkoping, Sweden

Background Clinical understanding of gastrointestinal symptoms is commonly based on patient reports of symptom experience. For diagnosis and treatment choices to be appropriate, symptom reports need to be accurate. We examined the agreement between questionnaire recall and prospective diary enumeration of symptoms relevant to the irritable bowel syndrome. Patients and methods Data are reported from a randomly selected general population sample (n=238) and also a primary healthcare centre (PHC) sample (n=503, 10 PHCs). All the patients completed the questionnaires, which included Rome III-qualifying irritable bowel syndrome items and a stool and symptom diary over either 7 or 14 days. Agreement between retrospective questionnaire reports and prospective diaries was evaluated. Results Concordance between questionnaires and diaries was highest for the simple construct of the occurrence of abdominal pain, although after adjusting for possible chance, agreement was only moderate in the general population sample. More complex constructs, such as pain relieved by defecation, yielded poorer concordance. In general, concordance was stronger among PHC respondents than in the general population sample. Conclusion Concordance between questionnaires and diaries was generally poor and related to the complexity of the symptom construct and the type of respondent. The information used to classify individuals based on patient self-report may be unreliable, and therefore, more effort is needed to develop data collection instruments., Funding Agencies|FORSS (research fund in South of Sweden); Stockholm County Council, Sweden: Ersta Hospital, Stockholm, Sweden; AstraZeneca RD, Sweden; Mag-Tarmforbundet, Sweden

Background: Reference intervals are widely used as decision tools, providing the physician with information about whether the analyte values indicate ongoing disease process. Reference intervals are generally based on individuals without diagnosed diseases or use of medication, which often excludes elderly. The aim of the study was to assess levels of albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine and gamma-glutamyl transferase (gamma-GT) in frail, moderately healthy and healthy elderly indivuduals. Methods: Blood samples were collected from individuals amp;gt; 80 years old, nursing home residents, in the Elderly in Linkoping Screening Assessment and Nordic Reference Interval Project, a total of 569 individuals. They were divided into three cohorts: frail, moderately healthy and healthy, depending on cognitive and physical function. Albumin, ALT, AST, creatinine and gamma-GT were analyzed using routine methods. Results: Linear regression predicted factors for 34% of the variance in albumin were activities of daily living (ADL), gender, stroke and cancer. ADLs, gender and weight explained 15% of changes in ALT. For AST levels, ADLs, cancer and analgesics explained 5% of changes. Kidney disease, gender, Mini Mental State Examination (MMSE) and chronic obstructive pulmonary disease explained 25% of the variation in creatinine levels and MMSE explained three per cent of gamma-GT variation. Conclusions: Because a group of people are at the same age, they should not be assessed the same way. To interpret results of laboratory tests in elderly is a complex task, where reference intervals are one part, but far from the only one, to take into consideration., Funding Agencies|Landstinget i Ostergotland Sverige [LIO-359661]

Establishing a celiac disease (CD) diagnosis can be difficult, such as when CD-specific antibody levels are just above cutoff or when small intestinal biopsies show low-grade injuries. To investigate the biological pathways involved in CD and select potential biomarkers to aid in CD diagnosis, RNA sequencing of duodenal biopsies from subjects with either confirmed Active CD (n=20) or without any signs of CD (n=20) was performed. Gene enrichment and pathway analysis highlighted contexts, such as immune response, microbial infection, phagocytosis, intestinal barrier function, metabolism, and transportation. Twenty-nine potential CD biomarkers were selected based on differential expression and biological context. The biomarkers were validated by real-time polymerase chain reaction of eight RNA sequencing study subjects, and further investigated using an independent study group (n=43) consisting of subjects not affected by CD, with a clear diagnosis of CD on either a gluten-containing or a gluten-free diet, or with low-grade intestinal injury. Selected biomarkers were able to classify subjects with clear CD/non-CD status, and a subset of the biomarkers (CXCL10, GBP5, IFI27, IFNG, and UBD) showed differential expression in biopsies from subjects with no or low-grade intestinal injury that received a CD diagnosis based on biopsies taken at a later time point. A large number of pathways are involved in CD pathogenesis, and gene expression is affected in CD mucosa already in low-grade intestinal injuries. RNA sequencing of low-grade intestinal injuries might discover pathways and biomarkers involved in early stages of CD pathogenesis., Funding Agencies|Futurum-the Academy for Health and Care, Region Jonkoping County; Medical Research Council of Southeast Sweden; National Genomics Infrastructure - Swedish Research Council

Background: Variation in baseline ear temperature, taken in the unadjusted mode, has yet to be established in different age groups. Because normal body temperatures show large variations, the same may be expected for increased temperatures in fever. The aims were to study variations in normothermic body temperatures measured with an ear thermometer and to determine differences between actual and perceived body temperature during a febrile episode (referred to as difftemp) in apparently healthy children and adults. Methods: Ear temperature was measured once in 2,006 individuals (61.7% females): 683 children aged 2 and 4 years, 492 adolescents aged 10-18 years, 685 adults aged 19-65 years and 146 elderly aged 66-89 years. Difftemp was estimated as the difference between the individuals ear body temperature, measured in the present study, and the respondents reported temperature when feverish. Results: Mean ear temperature was 36.4 +/- 0.6 degrees C overall and in the child and adult groups. In adolescents, it was 36.5 +/- 0.5 degrees C, and in elderly, 36.1 +/- 0.5 degrees C. Temperature in men was 36.3 +/- 0.6 degrees C, and in women, 36.5 +/- 0.5 degrees C. Difftemp was 1.1 +/- 0.7 degrees C in adolescents, 1.5 +/- 0.7 degrees C in children and adults, and 1.6 +/- 0.7 degrees C in those amp;gt; 65 years. Conclusions: Ear body temperature is lower than traditionally reported and differs with age and sex. An individual difftemp of 1.0-1.5 degrees C along with malaise might indicate fever., Funding Agencies|Covidien/Medtronic (Boston, MA)

OBJECTIVE: Stress is an important component in the pathophysiology of irritable bowel syndrome (IBS). Long term Hypothalamus Pituitary Adrenal (HPA)-axis activity can be studied by measuring hair cortisol concentrations (HCC). Some previous studies have indicated a dysregulated HPA-axis in IBS patients, but cortisol levels in hair have not yet been studied. We investigated whether HCC and self-reported stress differentiate IBS patients from controls. METHODS: In a cross-sectional study within 10 Swedish Primary Health Care Centers we compared patients in working age with active IBS to patients without GI complaints. The participants donated hair samples and completed questionnaires including a scale of self-reported perceived stress (PSS). 169 Rome III-fulfilling IBS patients and 316 non-IBS patients were available for final analyses. RESULTS: IBS patients had significantly lower HCC, median=16.3pg/mg, IQR=26.9pg/mg, compared to non-IBS patients, median=22.8pg/mg, IQR=29.1pg/mg. There was also a difference in the distribution of HCC quintiles between the two groups, with 30.2% IBS patients and 14.2% of non-IBS patients in the lowest quintile of HCC. PSS was higher among IBS patients with a mean (SD) total score of 25.3 (8.0) compared to controls 21.4, (7.5). Quintiles of HCC and PSS stayed significantly but very weakly related to IBS (B=-0.332, Std error=0.146, p<0.005) in multivariable analyses. CONCLUSION: This study suggests a possible suppression of the HPA-axis activity in a considerable portion of IBS patients., Funding agencies: research council of Southeast Sweden (FORSS)

Aim: The aim was to compare 5-year survival in two included cohorts (from year 2000 and year 2007) of 249 nursing home residents (NHR) in this retrospective, comparative study. Methods: The cohorts were compared regarding chronic diseases, medication, physical/cognitive/nutritional status, body mass index, body temperature and 5-year mortality. Factors correlated with 5-year survival were determined using Cox regression analysis. Results: In average, cohort 2007 survived 31 +/- 16 months and cohort 2000, 38 +/- 13 months, p amp;lt; 0.001. Dementia, ageing and circulatory failure were more common as cause of death 2007, while stroke, chronic obstructive pulmonary disease (COPD) and pneumonia were less common, compared with 2000. NHR belonging to cohort 2007 were significantly older when admitted to nursing homes (NH), more dependent in activities of daily living (ADL), had dementia, stroke, autoimmune disease and treatment with antidepressants, while malnutrition and treatment with paracetamol were more common 2000. In 2000, medication with antidepressants, the presence of stroke and diabetes, irrespective of gender, and in women cardiovascular disease, two to threefold significantly increased survival, while autoimmune disease, influenza vaccination and dependency in ADL decreased survival. In 2007, maintaining BMI, irrespective of gender, and autoimmune disease and COPD in women significantly increased survival, while malnutrition, influenza vaccination, dependency in ADL and medication with sedatives/tranquillisers or paracetamol severely reduced survival. Conclusions: The present results indicate a trend that individuals are older and frailer when admitted to NH and that survival time after admission has been shortened. Hence, the need of daily support and care has increased, irrespective of housing. Also, predictors of survival, possible to influence, have changed., Funding Agencies|Research Council of Southeast Sweden; Futurum County Council of Jonkoping

The purpose of this project is to describe the use of the Swedish National Diabetes Register (NDR) in clinical practice in a Swedish county and to specifically monitor the diabetes care routines at two separate primary health-care centres (PHCC) with a special focus on older patients. Background: According to Swedish law, all health-care units have to maintain a system for quality evaluation and improvement. As the NDR holds the most important quality indicators, implementation of the NDR in primary care was carried out by an implementation project in 2002-2005. Methods: Initially, a digital questionnaire about NDR routines was sent to all PHCC. Statistics about hemoglobin adult 1c (HbA1c) and blood pressure (BP) was presented for the diabetes teams at two centres who were also interviewed. The responses became the basis for a focus group interview with both teams together, with data subject to content analysis. Findings: The study showed that reporting to the NDR has become a compulsory routine in primary care. The diabetes nurse specialist was responsible for the practical management of the register and used the NDR for continuous monitoring of the patients. Most centres used the NDRs statistics for evaluation and analyses annually. The diabetes nurse adapted the visits to the patients wishes and general condition. Only in terms of target values for HbA1c and BP did they accept slightly higher values for the older patients. Since the NDR was implemented, the registration rate has remained at 75% and has not increased. The reason given was that patients with diabetes living in nursing homes are checked up by the municipal nurse who does not use the NDR. However, the risk of omitting older patients in the NDR could be considerably decreased if data could be transferred from the electronic patient record.

Background. NSAIDs are a known source of increased faecal calprotectin (FC) levels. Currently, there is a lack of knowledge about how long it takes for an increased FC level to return to normal after NSAID intake. Objective. The aim was to investigate how oral diclofenac intake affects FC levels and assess how long it takes for an increased FC level to return to normal after oral diclofenac intake. Material and methods. Thirty healthy volunteers received diclofenac 50 mg three times daily for 14 days. Participants provided a stool sample on Days 0, 2, 4, 7, 14 during intake and Days 17, 21, 28 after discontinuation. FC levels were then followed at 7-day intervals until normalization. Results. During diclofenac intake, eight participants (27%) had FC levels exceeding the upper limit of normal (median, 76 mu g/g; range, 60-958 mu g/g), corresponding to 8.3% of measurements. FC was not constantly increased and became normal in most participants during diclofenac intake. FC levels were on average significantly higher during intake (M = 9.5, interquartile range (IQR) = 13.4) than on baseline (M = 7.5, IQR = 0.0), p = 0.003. After discontinuation, two participants had increased FC on Days 17 and 21, respectively. No significant differences in FC levels were found between baseline and measurements after discontinuation. Two weeks after discontinuation, all participants had normal FC levels. Conclusions. Short-term oral diclofenac intake is associated with increased FC levels. However, the likelihood of an increased test result is low. Our results suggest that 2 weeks of diclofenac withdrawal is sufficient to get an uninfluenced FC test result., Funding Agencies|County Council of Ostergotland, Sweden

Background: Signs and symptoms of infection in frail elderly are atypical, causing delay in diagnosis and treatment. To improve communication between healthcare staff of signs and symptoms of infection we developed an instrument, using qualitative data from observations by nursing assistants when they suspected infection. The aim of this study was to assess the validity of nursing assistants observations by developing and testing the instrument for early detection of infection in elderly nursing home residents. Methods: The early detection of infection (EDIS) instrument was based on data from focus interviews with nursing assistants. Over one year the nursing assistants used EDIS to document episodes of suspected early signs and symptoms of infection in 204 nursing home residents. Two physicians classified documented episodes as "no infection", "possible infection", and "infection". The content validity of the 13 items of the EDIS was established to explore the relationships between the items. The construct validity was used to explore the relationship between the items and the presence or absence of infection. The predictive value of the developed model was evaluated by the percentage of correct classifications of the observed cases. Generalized linear model (ordinal multinomial distribution and logit link) was used. Results: Of the 388 events of suspected infection, 20 % were assessed as no infection, 31 % as possible infection and 49 % as infection. Content validity analysis showed that 12/13 of the items correlated significantly with at least one other statement. The range in number of significant inter-correlations was from 0 ("pain") to 8 ("general signs and symptoms of illness"). The construct validity showed that the items "temperature", "respiratory symptoms" and "general signs and symptoms of illness" were significantly related to "infection", and these were also selected in the model-building. These items predicted correct alternative responses in 61 % of, Funding Agencies|Medical Research Council of Southeast Sweden; Futurum/The Academy for Health and Care, Jonkoping County, Sweden

Signs and symptoms of infection in Nursing Home Residents (NHR) are often atypical with a lack of specific ones, causing a delay in diagnosis and treatment. The complexity of detecting infections in NHR can be explained by difficulties in understanding and interpreting non-specific signs and symptoms and co-existing chronic diseases that blur the clinical picture. The case of Mr. Nilsson illustrates the process from the first signs and symptoms of infection to diagnosis in an elderly person with severe cognitive decline and physical impairment. What we can learn from this case is to reflect on changed behavior from habitual status and/or non-specific symptoms as possible suspected infection, and to consider a rise from individual baseline temperature, so called DiffTemp™, instead of traditional decided cut-off values for fever.

Background Irritable Bowel Syndrome (IBS) is a chronic, relapsing gastrointestinal disorder,that affects approximately 10% of the general population and the majority are diagnosed in primary care. IBS has been reported to be associated with altered psychological and cognitive functioning such as mood disturbances, somatization, catastrophizing or altered visceral interoception by negative emotions and stress. The aim was to investigate the psychosocial constructs of self-esteem and sense of coherence among IBS patients compared to non-IBS patients in primary care. Methods A case–control study in primary care setting among IBS patients meeting the ROME III criteria (n = 140) compared to controls i.e. non-IBS patients (n = 213) without any present or previous gastrointestinal complaints. The data were collected through self-reportedquestionnaires of psychosocial factors. Results IBS-patients reported significantly more negative self-esteem (p < 0.001), lower scores for positive self-esteem (p < 0.001), and lower sense of coherence (p < 0.001) than the controls. The IBS-cases were also less likely to report ‘good’ health status (p < 0.001) and less likely to report a positive belief in the future (p < 0.001). After controlling for relevant confounding factors in multiple regressions, the elevation in negative self-esteem among IBS patients remained statistically significant (p =0.02), as did the lower scores for sense of coherence among IBS cases (p = 0.04). Conclusions The more frequently reported negative self-esteem and inferior coping strategies among IBS patients found in this study suggest the possibility that psychological therapies might be helpful for these patients. However these data do not indicate the causal direction of the observed associations. More research is therefore warranted to determine whether these psychosocial constructs are more frequent in IBS patients., Funding Agencies|FORSS (Research fund in South of Sweden)

When we say that someone has a fever, what do we really mean? Most people only take their temperature when they have a fever, and with good reason: fever is part of a larger response in the body. Assessment of Fever, a problem-based learning (PBL) textbook, uses inter-professional discussions of scenarios from clinical practice to examine the question of body temperature. The authors start by examining the historical perspective and go on to consider technical measurement accuracy and thermoregulation from a physiological and immunological perspective. They address evaluations of body temperature and inflammatory activity in various conditions. They end by discussing how evidence-based knowledge can inform clinical practice, looking at different scenarios in the shape of case histories and realistic situations from clinical practice. These clinical scenarios are pertinent both in an inter-professional perspective in clinical practice and in the advanced education of health-care professionals, research scientists, and technicians. Each chapter concludes with a number of reflections and additional questions that the reader will be able to answer using the material presented in the book.

Background: Blood-based diagnostics has the potential to simplify the process of diagnosing celiac disease (CD). Although high levels of autoantibodies against tissue transglutaminase (anti-TG2) are strongly indicative of active CD, several other scenarios involve a need for additional blood-based CD markers. Methods: We investigated the levels of messenger RNA (mRNA) in whole blood (n = 49) and protein in plasma (n = 22) from cases with active CD (n = 20), with confirmed CD and normalized histology (n = 15), and without a CD diagnosis (n = 14). Group differences were analyzed using Kruskal-Wallis one-way analysis of variance by ranks. We also investigated correlations between levels of potential markers, histopathology according to the modified Marsh scale, and CD risk gradient based on HLA type, using Spearman rank correlation. The relation between HLA-DQ2 gene dose effect and the expression levels of selected blood-based markers was investigated using the Mann-Whitney U test. Finally, the diagnostic performance of anti-TG2, potential blood-based CD markers, and logistic regression models of combined markers was evaluated using receiver operating characteristic (ROC) curve analysis. Results: CXCL11 protein levels and TNFRSF9 and TNFSF13B mRNA levels were identified as potential CD markers. These are all affected by or involved in the regulation of the NF-kappa B complex. CXCL11 protein levels and IL21 and IL15 mRNA levels were correlated with histopathology according to the modified Marsh scale, as were the established CD markers. HLA genotype risk and HLA-DQ2 gene dose effect did not show any significant relations with either the potential CD markers or the established CD markers. ROC curve analysis revealed a slight, non-significant increase in the area under the curve for the combined use of anti-TG2 and different constellations of potential blood-based CD markers compared to anti-TG2 alone. Conclusions: The CD markers identified in this study further emphasize, Funding Agencies|Futurum - the Academy for Healthcare; Jonkoping County Council; Medical Research Council of Southeast Sweden

Assessment of body temperature is important for decisions in nursing care, medical diagnosis, treatment and the need of laboratory tests. The definition of normal body temperature as 37°C was established in the middle of the 19th century. Since then the technical design and the accuracy of thermometers has been much improved. Knowledge of physical influence on the individual body temperature, such as thermoregulation and hormones, are still not taken into consideration in body temperature assessment. It is time for a change; the unadjusted mode should be used, without adjusting to another site and the same site of measurement should be used as far as possible. Peripheral sites, such as the axillary and the forehead site, are not recommended as an assessment of core body temperature in adults. Frail elderly individuals might have a low normal body temperature and therefore be at risk of being assessed as non-febrile. As the ear site is close to the hypothalamus and quickly responds to changes in the set point temperature, it is a preferable and recommendable site for measurement of body temperature.

Introduction In Sweden, quality indicators in health care have been the basis for developing National Quality Registers. The Swedish National Diabetes Register (NDR) – one of the largest diabetes registers globally – was introduced in primary health care (PHC) in the county of Östergötland by an implementation project, 2002–2005. Aim The aim of the present paper was to investigate, by using the results of the NDR, whether the registration led to sustained outcomes of medical results of diabetes care in PHC in the county during the period 2005–2009. Method HbA1c, blood pressure (BP), albuminuria and low-density lipoprotein-cholesterol were registered online in the NDR. In 2005 and 2006, goal achievement for HbA1c was measured and compared between PHC centres (PHCC) within the county. In 2007, achievements to national goals were compared between the PHCCs within the county and with those Swedish counties that had attained a sufficiently high registration rate. In 2008 and 2009, the average county results were compared with the corresponding national average measurements for all 21 Swedish counties combined. Result In 2005, a clear improvement trend for HbA1c and BP was shown within the county. In 2007–2009, goal achievements in the county studied were slightly better than the other counties measured and the country as a whole in almost every comparison. Discussion The present study has shown association between medical results and registration in the NDR. As the project was primarily a quality improvement work, the results have continuously influenced the development of diabetes care. Both the health professions and the county council now have – in the NDR – an effective and rapid method for evaluation and follow-up of diabetes care. The systematic documentation, followed by comparisons and analyses, create ideas for care improvements.