Objective To evaluate the impact of nocturia on patients quality of life and healthcare resource utilisation (HRU) compared with overactive bladder (OAB) and benign prostatic hyperplasia (BPH). Methods Data were drawn from a multinational (France, Germany, Spain, UK and US) survey of physician and patient-reported outcomes. The patient groups of interests were those diagnosed with only nocturia, with only OAB, and with only BPH. Health-related quality of life (HRQoL) and productivity measures were derived from the EuroQoL-5D, OAB-q and the Work Productivity and Activity Impairment Questionnaire (WPAI). Measures of HRU included lower urinary tract symptoms (LUTS)-relevant surgeries, hospitalisations, current use of pads and related physician visits. Bivariate and multivariate regression analyses were used to evaluate associations between HRQoL/HRU/Productivity and nocturia status. Multivariate analysis was used to address any potential confounding factors among the groups, ie age, gender, body mass index (BMI), ethnicity and comorbidities. Results A total of 3552 patients were identified including 358 nocturia patients, 1415 OAB patients and 1779 BPH patients. The mean age of the nocturia patients was 61.2 years with a mean BMI of 27.3. About 60.6% were women, 87.2% were Caucasian, and their most common comorbidities included depression, hypertension and diabetes. In terms of impact, nocturia patients were significantly worse off than OAB patients in their HRQoL. There was no significant difference regarding HRU and productivity measurement. Nocturia patients also presented with significantly worse HRQoL and lower productivity compared with BPH patients. Nocturia patients also had more physician visits. Conclusions Nocturia should be emphasised as a standalone LUTS disease with substantial patient impact. Compared with OAB and/or BPH, nocturia patients presented with a significant reduction on patients quality of life, reduced work productivity and increased utilisation of healthcare resources.

The objective of this study was to investigate the possible effects of environmental cadmium (Cd) exposure on the levels of serumsex hormones in a Chinese population group. A total of 263 male volunteers were included. Blood samples were collected for thedetermination of serum testosterone (T), measured by radioimmunoassay, and follicle stimulating hormone (FSH) and luteinizinghormone (LH), both measured by enzyme immunoassays. Urinary and blood Cd were analyzed by atomic absorption spectroscopy(AAS). We found a dose–response relationship between urinary Cd excretion and the prevalence of abnormally high serum T levels,but, through multiple regression analysis, we could not trace exposure to Cd as a significant determinant of serum T levels. Exposureto Cd also failed to influence the levels of FSH and LH in serum. In contrast, we found that age, body mass index (BMI), andsmoking habits are significant determinants of FSH and LH and of T and LH, respectively. We conclude that oral Cd exposure isnot a critical determinant of hormone homeostasis in males, but lifestyle and some biological factors, such as age and BMI, areimportant. The relationship found between urinary Cd and high T levels may be of importance for male reproductive morbidity andshould be investigated further.

To explore possible effects of environmental cadmium exposure on prostate in humans, and the possible relationship of serum sex hormones to occurrence of clinic signs of tissue changes in the prostate, a case-control study was undertaken in the southeast part of China in 1998. A total of 297 male volunteers from a control area and two cadmium-polluted areas were included as subjects in this study. All the subjects were required to answer a questionnaire and to undergo a complete physical examination including digital-rectal examination (DRE). Blood and urine samples were collected. Serum total prostate specific antigen (PSA), total serum testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay and enzymeimmunoassay method, respectively. The data of urinary cadmium (U-Cd) and blood cadmium (B-Cd) were obtained by atomic absorption spectrometry (AAS) as an indicator of cadmium body burden. Statistical analysis was applied to investigate a possible relation between cadmium exposure and prostate pathological changes. The results show that there is a clear dose-response relationship between cadmium exposure and the prevalence of cases with abnormal PSA. The blood cadmium content in cases with positive DRE was significantly higher than that of subjects with negative DRE (P<0.05). Significant differences in the level of FSH between cases with positive DRE and the normal subjects were also noted (P<0.05). These results indicate that chronic environmental cadmium exposure is associated with injuries to human prostate. A possible relationship to changes in circulating sex hormones needs further investigation.

Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD.

Background: South Africa (SA) has the highest global projected increase in diabetes risk. Factors typically associated with insulin resistance and type 2 diabetes risk in Caucasians are not significant correlates in black African populations. Therefore, we aimed to identify circulating metabolite patterns that predict type 2 diabetes development in this high-risk, yet understudied SA population.

Methods: We conducted a prospective cohort study in black SA women with normal glucose tolerance (NGT). Participants were followed for 13 years and developed (i) type 2 diabetes (n = 20, NGT-T2D), (ii) impaired glucose tolerance (IGT) (n = 27, NGT-IGT), or (iii) remained NGT (n = 28, NGT-NGT). Mass-spectrometry based metabolomics and multivariate analyses were used to elucidate metabolite patterns at baseline and at follow-up that were associated with type 2 diabetes development.

Results: Metabolites of phospholipid, bile acid and branched-chain amino acid (BCAA) metabolism, differed significantly between the NGT-T2D and NGT-NGT groups. At baseline: the NGT-T2D group had i) a higher lysophosphatidylcholine:lysophosphatidylethanolamine ratio containing linoleic acid (LPC(C18:2):LPE(C18:2)), ii) lower proliferation-related bile acids (ursodeoxycholic- and chenodeoxycholic acid), iii) higher levels of leucine and its catabolic intermediates (ketoleucine and C5-carnitine), compared to the NGT-NGT group. At follow-up: the NGT-T2D group had i) lower LPC(C18:2) levels, ii) higher apoptosis-related bile acids (deoxycholic- and glycodeoxycholic acid), and iii) higher levels of all BCAAs and their catabolic intermediates.

Conclusions: Changes in lysophospholipid metabolism and the bile acid pool occur during the development of type 2 diabetes in black South African women. Further, impaired leucine catabolism precedes valine and isoleucine catabolism in the development of type 2 diabetes. These metabolite patterns can be useful to identify and monitor type 2 diabetes risk >10 years prior to disease onset and provide insight into the pathophysiology of type 2 diabetes in this high risk, but under-studied population.

Objective: Emerging evidence supports a bidirectional phenotypic association between stress-related disorders and autoimmune disease. However, the biological underpinnings remain unclear. Here, the authors examined whether and how shared genetics contribute to the observed phenotypic associations.

Methods: Based on data from 4,123,631 individuals identified from Swedish nationwide registers, familial coaggregation of stress-related disorders (any disorder or posttraumatic stress disorder [PTSD]) and autoimmune disease were initially estimated in seven cohorts with different degrees of kinship. Polygenic risk score (PRS) analyses were then performed with individual-level genotyping data from 376,871 participants in the UK Biobank study. Finally, genetic correlation analyses and enrichment analyses were performed with genome-wide association study (GWAS) summary statistics.

Results: Familial coaggregation analyses revealed decreasing odds of concurrence of stress-related disorders and autoimmune disease with descending kinship or genetic relatedness between pairs of relatives; adjusted odds ratios were 1.51(95% CI=1.09-2.07), 1.28 (95% CI=0.97-1.68), 1.16 (95% CI=1.14-1.18), and 1.01 (95% CI=0.98-1.03) for monozygotic twins, dizygotic twins, full siblings, and half cousins, respectively. Statistically significant positive asso-ciations were observed between PRSs of stress-related disorders and autoimmune disease, as well as between PRSs of autoimmune disease and stress-related disorders. GWAS summary statistics revealed a genetic correlation of 0.26 (95% CI=0.14-0. 38) between these two pheno-types and identified 10 common genes and five shared functional modules, including one module related to G-protein-coupled receptor pathways. Similar analyses performed for PTSD and specific autoimmune diseases (e.g., autoimmune thyroid disease) largely recapitulated the results of the main analyses.

Conclusions: This study demonstrated familial coaggregation, genetic correlation, and common biological pathways between stress-related disorders and autoimmune disease.

Sarcopenia and cognitive impairment are associated with an increased risk of negative outcomes, but their prognostic interplay has not been investigated so far. We aimed to investigate the prognostic interaction of sarcopenia and cognitive impairment concerning 12-month mortality among older patients discharged from acute care wards in Italy. Our series consisted of 624 patients (age = 80.1 +/- 7.0 years, 56.1% women) enrolled in a prospective observational study. Sarcopenia was defined following the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. Cognitive impairment was defined as age- and education-adjusted Mini-Mental State Examination (MMSE) score < 24 or recorded diagnosis of dementia. The study outcome was all-cause mortality during 12-month follow-up. The combination of sarcopenia and cognitive ability was tested against participants with intact cognitive ability and without sarcopenia. Overall, 159 patients (25.5%) were identified as having sarcopenia, and 323 (51.8%) were cognitively impaired. During the follow-up, 79 patients (12.7%) died. After adjusting for potential confounders, the combination of sarcopenia and cognitive impairment has been found associated with increased mortality (HR = 2.12, 95% CI = 1.05-4.13). Such association was also confirmed after excluding patients with dementia (HR = 2.13, 95% CI = 1.06-4.17), underweight (HR = 2.18, 95% CI = 1.03-3.91), high comorbidity burden (HR = 2.63, 95% CI = 1.09-6.32), and severe disability (HR = 2.88, 95% CI = 1.10-5.73). The co-occurrence of sarcopenia and cognitive impairment may predict 1-year mortality in older patients discharged from acute care hospitals.

Objective: The community of residence (ie, urban vs rural) is one of the known factors of influence on substance use and misuse (SUM). The aim of this study was to explore the community-specific prevalence of SUM and the associations that exist between scholastic, familial, sports and sociodemographic factors with SUM in adolescents from Bosnia and Herzegovina. Methods: In this cross-sectional study, which was completed between November and December 2014, the participants were 957 adolescents (aged 17 to 18 years) from Bosnia and Herzegovina (485; 50.6% females). The independent variables were sociodemographic, academic, sport and familial factors. The dependent variables consisted of questions on cigarette smoking and alcohol consumption. We have calculated differences between groups of participants (gender, community), while the logistic regressions were applied to define associations between the independent and dependent variables. Results: In the urban community, cigarette smoking is more prevalent in girls (OR= 2.05; 95% CI 1.27 to 3.35), while harmful drinking is more prevalent in boys (OR= 2.07; 95% CI 1.59 to 2.73). When data are weighted by gender and community, harmful drinking is more prevalent in urban boys (OR= 1.97; 95% CI 1.31 to 2.95), cigarette smoking is more frequent in rural boys (OR= 1.61; 95% CI 1.04 to 2.39), and urban girls misuse substances to a greater extent than rural girls (OR= 1.70; 95% CI 1.16 to 2.51, OR= 2.85; 95% CI 1.88 to 4.31, OR= 2.78; 95% CI 1.67 to 4.61 for cigarette smoking, harmful drinking and simultaneous smoking-drinking, respectively). Academic failure is strongly associated with a higher likelihood of SUM. The associations between parental factors and SUM are more evident in urban youth. Sports factors are specifically correlated with SUM for urban girls. Conclusions: Living in an urban environment should be considered as a higher risk factor for SUM in girls. Parental variables are more strongly associated with SUM among urban youth, most probably because of the higher parental involvement in children' personal lives in urban communities (ie, college plans, for example). Specific indicators should be monitored in the prevention of SUM.

Objective The community of residence (ie, urban vs rural) is one of the known factors of influence on substance use and misuse (SUM). The aim of this study was to explore the community-specific prevalence of SUM and the associations that exist between scholastic, familial, sports and sociodemographic factors with SUM in adolescents from Bosnia and Herzegovina.

Methods In this cross-sectional study, which was completed between November and December 2014, the participants were 957 adolescents (aged 17 to 18 years) from Bosnia and Herzegovina (485; 50.6% females). The independent variables were sociodemographic, academic, sport and familial factors. The dependent variables consisted of questions on cigarette smoking and alcohol consumption. We have calculated differences between groups of participants (gender, community), while the logistic regressions were applied to define associations between the independent and dependent variables.

Results In the urban community, cigarette smoking is more prevalent in girls (OR=2.05; 95% CI 1.27 to 3.35), while harmful drinking is more prevalent in boys (OR=2.07; 95% CI 1.59 to 2.73). When data are weighted by gender and community, harmful drinking is more prevalent in urban boys (OR=1.97; 95% CI 1.31 to 2.95), cigarette smoking is more frequent in rural boys (OR=1.61; 95% CI 1.04 to 2.39), and urban girls misuse substances to a greater extent than rural girls (OR=1.70; 95% CI 1.16 to 2.51,OR=2.85; 95% CI 1.88 to 4.31,OR=2.78; 95% CI 1.67 to 4.61 for cigarette smoking, harmful drinking and simultaneous smoking-drinking, respectively). Academic failure is strongly associated with a higher likelihood of SUM. The associations between parental factors and SUM are more evident in urban youth. Sports factors are specifically correlated with SUM for urban girls.

Conclusions Living in an urban environment should be considered as a higher risk factor for SUM in girls. Parental variables are more strongly associated with SUM among urban youth, most probably because of the higher parental involvement in children’ personal lives in urban communities (ie, college plans, for example). Specific indicators should be monitored in the prevention of SUM.

The COVID-19 pandemic and the social distancing implemented shortly after influence physical activity levels (PALs). The purpose of this investigation was to evaluate the changes in PAL and factors associated with PALs among Croatian adolescents while considering the impact of community (urban vs. rural living environment). The sample included 823 adolescents (mean age: 16.5 ± 2.1 years) who were tested on baseline (from October 2019 to March 2020; before COVID-19 pandemic in Croatia) and follow-up (in April 2020; during the COVID-19 pandemic and imposed rules of social distancing). Baseline testing included anthropometrics, physical fitness status, and evaluation of PALs, while follow-up included only PALs (evaluated by a standardized questionnaire through an internet application). The results showed a significant influence of the living environment on the decrease of PAL, with a larger decrease in urban adolescents. Logistic regression showed a higher likelihood for normal PALs at baseline in adolescents who had better fitness status, with no strong confounding effect of the urban/rural environment. The fitness status of urban adolescents predicted their PALs at follow-up. The differences between urban and rural adolescents with regard to the established changes in PALs and relationships between the predictors and PALs are explained by the characteristics of the living communities (lack of organized sports in rural areas), and the level of social distancing in the studied period and region/country.

Syftet med studien var att undersöka bakgrunden till föräldrars beslut att söka akut sjukvård med barn som har en luftvägsinfektion samt beskriva deras upplevelser och förväntningar innan den första bedömningen av triage sjuksköterskan vid besök på barnakutmottagning.

Bakgrund: Sjuksköterskan i vårdvetenskapen syftar till att upprätthålla patientens värdighet. En god människosyn innebär att se patienten som en helhet och inte sjukdom. Tvångsåtgärder används oavsett om patienten är delaktig eller ej. Inom den psykiatriska heldygnsvården finns lagar i Sverige som styrker och ger sjuksköterskan en maktposition att förhålla sig till. Syftet: Att belysa sjuksköterskans etiska förhållningssätt i samband med tvångsvård inom psykiatrisk vård. Metoden: Kvalitativ litteraturstudie med induktiv ansats. Resultatet: Flera studier visade på etiska svårigheter inom tvångsvård och hur sjuksköterskan bemöter patienten samt synen på patienten och dess bakgrund. Studier visar att ett nära arbete med patient utan att bli emotionellt berörd eller distanserad påverkar patientens vård. Slutsatsen: Den goda vårdande relation mellan sjuksköterskan och patienten är viktig. Ses patienten som människa skapas en relation och ett samarbete som bidrar till att värdighet bevaras. Innebörden blev att sjuksköterskan kan undvika utnyttja sin maktposition och använda tvångsåtgärder som kan kränka patienten, ett tydligt mönster som är förenligt med konsekvensetiken.

OBJECTIVES: Effective anticoagulant therapy is a contraindication to thrombolysis, which is an effective treatment of ischemic stroke if given within 4.5 hours of symptom onset. INR above 1.7 is generally considered a contraindication for thrombolysis. Rapid measurement of INR in warfarin-treated patients is therefore of major importance in order to be able to decide on thrombolysis or not. We asked whether INR measured on a point-of-care instrument would be as good as a central laboratory instrument.

MATERIAL AND METHODS: A total of 529 consecutive patients who arrived at the emergency department at a large urban teaching hospital with stroke symptoms were enrolled in the study. INR was measured with a CoaguChek and a Sysmex instrument. Basic clinical information such as age, sex, and diagnosis (if available) was recorded. INR from the instruments was compared using linear regression and Bland-Altman plot.

RESULTS:  = 0.97). In the current setting, CoaguChek was in median 63 minutes faster than Sysmex.

CONCLUSION: Our results indicate that point-of-care testing is a safe mean to rapidly acquire a patient's INR value in acute clinical situations.

BackgroundPatients with liver cirrhosis are recommended ultrasonography screening for early detection of hepatocellular carcinoma to increase the chances of curative treatment. However, ultrasonography alone lacks in sensitivity. Adding plasma biomarkers may increase the detection rate. We performed a broad exploratory analysis to find new plasma proteins with potential applicability for HCC screening in patients with cirrhosis.MethodsIn a protein discovery cohort of 172 patients with cirrhosis or HCC, we screened for 481 proteins with suspension bead array or proximity extension assay. From these, 24 proteins were selected for further analysis in a protein verification cohort (n = 160), using ELISA, Luminex or an electrochemiluminescence platform. A cut-off model and a stepwise logistic regression model were used to find combinations of proteins with the best discriminatory performance between HCC and cirrhosis.ResultsStepwise logistic regression revealed alpha-fetoprotein (AFP), decarboxy-prothrombin (DCP), thioredoxin reductase 1 (TXNRD1), and fibroblast growth factor 21 (FGF21) as the proteins with the best discriminatory performance between HCC and cirrhosis. Adding TXNRD1 to DCP and AFP increased the AUC from 0.844 to 0.878, and combining AFP, DCP and TXNRD1 with age and sex resulted in an AUC of 0.920. FGF21, however, did not further increase the performance when including age and sex.ConclusionIn the present study, TXNRD1 improves the sensitivity and specificity of AFP and DCP as HCC screening tools in patients with cirrhosis. We suggest that TXNRD1 should be validated in prospective settings as a new complementary HCC biomarker together with AFP and DCP.

Background: Patients with liver cirrhosis are recommended ultrasonography screening for early detection of hepatocellular carcinoma to increase the chances of curative treatment. However, ultrasonography alone lacks in sensitivity. Adding plasma biomarkers may increase the detection rate. We performed a broad exploratory analysis to find new plasma proteins with potential applicability for HCC screening in patients with cirrhosis. Methods: In a protein discovery cohort of 172 patients with cirrhosis or HCC, we screened for 481 proteins with suspension bead array or proximity extension assay. From these, 24 proteins were selected for further analysis in a protein verification cohort (n = 160), using ELISA, Luminex or an electrochemiluminescence platform. A cut-off model and a stepwise logistic regression model were used to find combinations of proteins with the best discriminatory performance between HCC and cirrhosis. Results: Stepwise logistic regression revealed alpha-fetoprotein (AFP), decarboxy-prothrombin (DCP), thioredoxin reductase 1 (TXNRD1), and fibroblast growth factor 21 (FGF21) as the proteins with the best discriminatory performance between HCC and cirrhosis. Adding TXNRD1 to DCP and AFP increased the AUC from 0.844 to 0.878, and combining AFP, DCP and TXNRD1 with age and sex resulted in an AUC of 0.920. FGF21, however, did not further increase the performance when including age and sex. Conclusion: In the present study, TXNRD1 improves the sensitivity and specificity of AFP and DCP as HCC screening tools in patients with cirrhosis. We suggest that TXNRD1 should be validated in prospective settings as a new complementary HCC biomarker together with AFP and DCP.

Bakgrund: Schizofreni är en psykisk sjukdom där personen har förändrade verklighetsuppfattningar såsom vanföreställningar, tankestörningar, förvirring och hallucinationer. Schizofreni kan ge svårigheter i exempelvis relationer och arbete. Genom att fokusera på att förstå händelser i personens dagliga liv får sjuksköterskan kunskap om problem och varför dessa uppstått. Sådan kunskap kan hjälpa sjuksköterskan att utforma omvårdnadsåtgärder som matchar personens behov. Syfte: Syftet med litteraturstudien var att belysa dagligt liv för personer med schizofreni och därmed öka sjuksköterskans kunskap om personens omvårdnadsbehov.

Metod: En allmän litteraturstudie baserad på fem kvalitativa artiklar och 15 kvantitativa artiklar. Resultat: De faktorer som påverkade dagligt liv för personer med schizofreni var relationer, sysselsättning och hälsotillstånd.

Slutsats: Litteraturstudien visar att personer med schizofreni har problem i sitt dagliga liv som kan åtgärdas med hjälp av meningsfulla aktiviteter, möjlighet till arbete, förbättrade sociala färdigheter och ökad motivation. Sjuksköterskan kan motivera och stödja personen att skaffa ett arbete eller annan meningsfull aktivitet för att stärka personens självförtroende och självständighet. Vidare forskning behövs om hur sjuksköterskan kan motivera en person med schizofreni till att börja arbeta och utföra dagliga aktiviteter i hemmet.

Background: Retinopathy of prematurity (ROP), a potentially blinding disease, affects preterm infants. High levels of oxygen saturation are a well-known risk factor for ROP.

Objectives: To assess the frequency of ROP type 1 needing treatment after improved oxygen monitoring (2011) in a Mexican preterm population selected for WINROP analyses and to retrospectively revalidate WINROP, an online surveillance system identifying infants at risk of developing ROP type 1.

Methods: Preterm infants born with birth weight (BW) <1,750 g and/or at gestational age (GA) ≤34 weeks, screened for ROP in 2012-2014 at the Hospital Civil de Guadalajara, Mexico were included (n = 151). Eighty-five infants with GA <32 weeks qualified for WINROP analyses. GA, BW, maximal ROP stage, ROP treatment and weekly weights were recorded. The results in the present study were compared to those of a previous WINROP study in the same hospital (2005-2010; n = 352).

Results: In the present WINROP cohort, 11.8% of the infants born at GA <32 weeks received treatment compared to 51.0% of the infants in the previous WINROP cohort. One infant (3%) born at GA ≥32 weeks received treatment during the present study period compared to 35.6% during the previous period. WINROP displayed 80.0% sensitivity in infants born at GA <32 weeks in the present study compared to 84.7% in the previous study.

Conclusions: Uncontrolled oxygen supplementation is the major risk factor for severe ROP in infants born at GA ≥32 weeks. After improved oxygen monitoring, the frequency of ROP treatment was dramatically reduced at the Hospital Civil de Guadalajara, Mexico.

Utbrändhet orsakar mänskligt lidande, kostar mycket tid, pengar och arbetskraft. Syftet med denna kvantitativlitteraturstudie var att identifiera arbetsfaktorer som bidrar till att sjuksköterskan blir utbränd. Vetenskapliga artiklar granskades och 10 stycken redovisas i resultatet. Resultatet visar fyra tema som är faktorer av betydelse för utbrändhet hos sjuksköterskor; brister i den psykosociala arbetsmiljön, obalans mellan krav och resurser, organisation och ledarskap samt kunskap och utbildning. De sjuksköterskor som arbetar i en organisation utan ett stöttande ledarskap, är inte tillfredställda med sitt arbete. Sjuksköterskor som inte har balans mellan psykiska krav och påverkningsmöjligheter, blir utbrända. De sjuksköterskor som får utbildning i ökad kunskap inom sitt arbetsområde är de sjuksköterskor som blir minst utbrä

The description of the reorientational dynamics of flexible molecules is a challenging task, in particular when the rates of internal and global motions are comparable. The commonly used simple mode-decoupling models are based on the assumption of statistical independence between these motions. This assumption is not valid when the time scale separation between their rates is small, a situation that was found to arise in oligosaccharides in the context of certain internal motions. To make possible the interpretation of NMR spin relaxation data from such molecules, we developed a comprehensive approach generally applicable to flexible rotators with one internal degree of freedom. This approach integrates a stochastic description of coupled global tumbling and internal torsional motion, quantum chemical calculations of the local potential and the local geometry at the site of the restricted torsion, and hydrodynamics-based calculations of the diffusive properties. The method is applied to the disaccharide -D-Glcp-(16)--D-[6-¹³C]-Manp-OMe dissolved in a DMSO-d₆/D₂O cryosolvent. The experimental NMR relaxation parameters, associated with the ¹³CH₂ probe residing at the glycosidic linkage, include ¹³C T₁ and T₂ and ¹³C-{¹H} nuclear Overhauser enhancement (NOE) as well as longitudinal and transverse dipole-dipole cross-correlated relaxation rates, acquired in the temperature range of 253–293 K. These data are predicted successfully by the new theory with only the H–C–H angle allowed to vary. Previous attempts to fit these data using mode-decoupling models failed.

Simple Summary Despite the increasing use of checkpoint inhibitors for early and metastatic breast cancer, Programmed Death Ligand 1 (PD-L1) remains the only validated albeit imperfect predictive biomarker. Significant discordance in PD-L1 protein expression depending on the antibody used has been demonstrated, while the weak correlation and discordant prognostic information between protein and gene expression underscore its biologic heterogeneity. In this study, we use material from two patient cohorts of early breast cancer and multiple methodologies (immunohistochemistry, RNA fluorescent in situ hybridization, immunofluorescence, bulk gene expression, and multiplex fluorescent immunohistochemistry) to demonstrate the significant discordance in PD-L1 expression among various methods and between different areas of the same tumor, which hints toward the presence of spatial, intratumoral and biological heterogeneity. We aimed to assess if the discrepant prognostic information between Programmed Death Ligand 1 (PD-L1) protein versus mRNA expression in early breast cancer (BC) could be attributed to heterogeneity in its expression. PD-L1 protein and mRNA expression in BC tissue microarrays from two clinical patient cohorts were evaluated (105 patients; cohort 1: untreated; cohort 2: neoadjuvant chemotherapy-treated). Immunohistochemistry (IHC) with SP142, SP263 was performed. PD-L1 mRNA was evaluated using bulk gene expression and RNA-FISH RNAscope, the latter scored in a semi-quantitative manner and combined with immunofluorescence (IF) staining for the simultaneous detection of PD-L1 protein expression. PD-L1 expression was assessed in cores as a whole and in two regions of interest (ROI) from the same core. The cell origin of PD-L1 expression was evaluated using multiplex fluorescent IHC. IHC PD-L1 expression between SP142 and SP263 was concordant in 86.7% of cores (p < 0.001). PD-L1 IF/IHC was weakly correlated with spatial mRNA expression (concordance 54.6-71.2%). PD-L1 was mostly expressed by lymphocytes intra-tumorally, while its stromal expression was mostly observed in macrophages. Our results demonstrate only moderate concordance between the various methods of assessing PD-L1 expression at the protein and mRNA levels, which may be attributed to both analytical performance and spatial heterogeneity.

Background: We have previously shown the prognostic value of PD-L1 protein and gene expression in early breast cancer (BC), however, the prognostic role of PD-1 expression remains unclear.

Methods: The prognostic value of PD-1 in early BC was investigated using three different approaches: i) evaluation of PD-1 at the protein (IHC, immunohistochemistry in tissue microarrays) and mRNA levels in a retrospective patient cohort of 586 patients treated for early BC in Stockholm, Sweden between 1997-2005, ii) systematic review and trial-level meta-analysis of studies published in Medline, Embase, Cochrane Library and Web of Science Core Collection libraries on the prognostic value of PD-1 IHC expression, and iii) pooled analysis of transcriptomic data from 39 publicly available datasets for the prognostic capacity of PD-1 gene expression. Univariate and multivariable Cox regression models were used.

Results: In the retrospective study cohort, PD-1 protein was significantly associated with biologically high-risk characteristics. PD-1 protein, but not gene expression, was correlated with improved overall survival (OS) (adjusted HR = 0.73, 95% CI 0.55 – 0.96, p = 0.023 and adjusted HR = 0.88, 95% CI 0.68 – 1.13, p = 0.307, respectively). In the trial-level meta-analysis, 4736 entries were initially identified and 15 studies, including our original cohort, fulfilled the predefined eligibility criteria. PD-1 IHC expression was not prognostic in unselected patients. However, a significant correlation to improved disease-free survival was seen within the triple-negative subtype (pooled multivariate HR = 0.57, 95% CI 0.29 – 0.90, p = 0.02). In the pooled gene expression analysis, PD-1 gene expression was associated with improved OS in the entire population (adjusted HR = 0.89, 95% CI 0.80 – 0.99, p = 0.025) and in basal-like (adjusted HR = 0.77, 95% CI 0.63 – 0.95, p = 0.014) tumors.

Conclusions: PD-1 expression at the RNA and protein levels represent promising prognostic factors, especially in the triple-negative and basal-like subtypes. Standardization and further validation are needed prior to clinical implementation.

Emerging data indicate that genomic alterations can shape immune cell composition in early breast cancer. However, there is a need for complementary imaging and sequencing methods for the quantitative assessment of combined somatic copy number alteration (SCNA) and immune profiling in pathological samples. Here, we tested the feasibility of three approaches-CUTseq, for high-throughput low-input SCNA profiling, multiplexed fluorescent immunohistochemistry (mfIHC) and digital-image analysis (DIA) for quantitative immuno-profiling- in archival formalin-fixed paraffin-embedded (FFPE) tissue samples from patients enrolled in the randomized SBG-2004-1 phase II trial. CUTseq was able to reproducibly identify amplification and deletion events with a resolution of 100 kb using only 6 ng of DNA extracted from FFPE tissue and pooling together 77 samples into the same sequencing library. In the same samples, mfIHC revealed that CD4 + T-cells and CD68 + macrophages were the most abundant immune cells and they mostly expressed PD-L1 and PD-1. Combined analysis showed that the SCNA burden was inversely associated with lymphocytic infiltration. Our results set the basis for further applications of CUTseq, mfIHC and DIA to larger cohorts of early breast cancer patients.

Background: Increased baseline tumor-infiltrating lymphocytes (TILs) are associated with improved pathological complete response rates and better prognosis in HER2+ and triple negative breast cancer (TNBC) patients receiving neoadjuvant therapy (NAT). However, the role of TILs dynamics/change (DTILs) at the neoadjuvant setting remains unclear, thus a meta-analysis of the published studies was carried out.

Methods: Medline, Embase, Cochrane Library and Web of Science Core Collection were searched for studies reporting on TILs expression in paired invasive breast cancer patient tissue samples before and after NAT. Data were extracted by two investigators (Y.Z., E.T.) and discordances were resolved by a third (I.Z.). Outcomes included pooled TILs rates pre- & post-treatment (also per subtype), pooled rates of DTILs and direction of change after NAT as well as correlation of DTILs with survival outcomes. Heterogeneity was assessed using the I2 statistic.

Results: Of 1569 identified entries, 22 studies fulfilled the criteria and provided adequate data for the outcomes of interest. Overall, a significantly decreased level of TILs was observed after NAT in paired samples (pooled OR = 1.60, 95% CI: 1.12-2.30, p = 0.01; TILs as categorical variable). Regarding pooled rates of DTILs, a change was observed after NAT, irrespective of BC subtype. Among the different subtypes, the effect of NAT on TILs was most prominent in HER2+ disease with a direction towards decreased TILs to be more common (pooled DTILs rates: 14.4% increased vs 46.2%, decreased). In TNBC, bi-directional TIL kinetics were noted (pooled DTILs rates: 41.6% increased vs 37.1% decreased). An increase in DTILs in TNBC was associated with better disease-free/relapse-free survival in univariate analysis (HR = 0.59, 95% CI: 0.37–0.95, p = 0.03). Substantial between-study heterogeneity was observed in most analyses.

Conclusions: The first to our knowledge meta-analysis on TILs dynamics during NAT in BC informs about differences in matched pre- and post-treatment patient samples and the prognostic implications of DTILs in TNBC. The potential clinical utility of the longitudinal assessment of immune response during neoadjuvant therapy warrants further investigation in prospective trials.

Malaria, caused by the Plasmodium parasite and transmitted by mosquitoes, kills almost half a million people each year. Drug resistance in both the parasite and its vector make preventative measures increasingly important, and a fully protective vaccine is absolutely necessary to eradicate the disease. However, genetic diversity of the parasite makes vaccine development difficult. One of the best vaccine candidates is MSP2, a surface protein present during the blood stage of P. falciparum infection. Antibodies, which are important for natural immunity, have been shown to bind MSP2 and prevent parasite infection of blood cells. The purpose of this study was to analyze MSP2 sequence diversity in a cohort of patients infected while traveling or living in sub-Saharan Africa, and to investigate patient antibody responses to MSP2 variants infecting other individuals. Parasite isolates from our cohort were made up of 47% 3D7 alleles and 53% FC27 alleles. Protein sequences showed similar levels of conservation within allelic families, and blocks of conserved amino acids between different variants suggest there may be epitopes that can induce antibody production targeting multiple variants. Antibody reactivity tests suggest the variable region of MSP2 is important for antibody binding to variants of the same allelic type, while the conserved region is important for reactivity to different allelic types. This thesis gives evidence to the importance of including epitopes from conserved and variable regions of both MSP2 allelic families in order to induce strain-transcending immunity against P. falciparum malaria. 

Bakgrund: Stroke är en globalt betydande orsak till både dödlighet och funktionshinder och rankas som den tredje vanligaste dödsorsaken.

Syfte: Syftet med denna systematiska litteraturöversikt var att beskriva vuxna personers upplevelser av dagligt liv efter stroke.

Metod: Fjorton vetenskapliga originalartiklar med kvalitativt innehåll inkluderades från databaserna Cinahl och PubMed. Dessa artiklar genomgick en granskning enligt Fribergs granskningsmall. Analyser utfördes med hjälp av Graneheim och Lundmans metod för innehållsanalys.

Resultat: Resultaten av studien reflekterade de upplevelser som vuxna personer hade i sitt dagliga liv efter att ha drabbats av en stroke. Dessa upplevelser delades in i tre huvudkategorier: kroppsliga förändringar, emotionell sårbarhet och sorg, samt dagliga utmaningar. Deltagarna i studierna delade generöst med sig av sina erfarenheter och utmaningar som var kopplade till dessa funktionsnedsättningar och beskrev hur dessa faktorer påverkade deras vardagsliv och övergripande livskvalitet.

Diskussion: Personer som har drabbats av stroke upplevde olika former av förändringar i sin vardag. Dessa förändringar orsakade fysiska, sociala och psykiska förändringar som väckte känslor av rädsla, oro, isolering, hopplöshet och maktlöshet. Personer som har drabbats av stroke upplever själsligt och andligt lidande som påverkar deras självbild, självkänsla och livskvalitet. Sjuksköterskor spelar en viktig roll i att stödja strokedrabbade patienter genom att hjälpa dem att behålla hoppet och stärka sin självbild samt förebygga lidande och depression genom att ta hänsyn till deras fysiska, psykiska och sociala behov.

Slutsats: Litteraturöversikten konstaterar att stroke påverkar fysisk, psykisk, kognitiv och emotionell hälsa, med möjliga utmaningar i vardagen. Framtida forskning behövs för att fördjupa förståelsen och förbättra vårdstödet för strokepatienter.

Bakgrund: Patienter med substansmissbruk upplever negativa attityder när de söker vård. Substansmissbruk förekommer i stor utsträckning men det finns fortfarande fördomar och negativa föreställningar om dessa patienter. Sjuksköterskans roll är viktig i mötet med patienter som har substansmissbruk, och med rätt kompetens kan dessa patienter få ett professionellt bemötande när de söker vård. Personcentrerad vård användes som referensram i litteraturöversikten. Syfte: Syftet var att beskriva sjuksköterskors upplevelse av att vårda patienter med substansmissbruk inom somatisk vård. Metod: Kvalitativ metod med induktiv ansats användes. Litteratursökningen genomfördes i CINAHL och PsycInfo. Utifrån Fribergs fem steg analyserades 12 artiklar. Resultat: Sjuksköterskorna upplevde att utbildning kring substansmissbruk var bristfällig vilket gjorde det svårt att vårda patienterna. De upplevde att behoven var komplexa och att kompetensen inte räckte till. Oförutsägbarheten bidrog till negativa känslor och fördomar som påverkade sjuksköterskornas medkänsla gentemot patienterna. Slutsats: Mötet mellan sjuksköterskor och patienter med substansmissbruk präglas av utmaningar på grund av rädsla, osäkerhet och brist på kunskap. Sjuksköterskor behöver fortlöpande utbildning för att kunna ge kvalitativ vård och för att känna trygghet i professionen vid vårdandet av patienter med substansmissbruk.

abstract

Background: Dementia affected patients have increasing problems with memory , impaired language ability, which affects communication and behaviour is considerable. These difficulties may provide an outlet for aggression, agitation and anxiety, and are common in dementia, which is exhausting for patients and their relatives and carers. Behavioural changes are common condition in patients with dementia and affects quality of life and cause unnecessary suffering . Pharmacological treatment that is inserted to relieve these symptoms have many side effects. Printed out more knowledge about non- pharmacological nursing interventions that can facilitate care for patients , relatives and carers are great.

Aim: To describe non- pharmacological nursing interventions in dementia care .

Method: A general literature review of thirteen scientific papers compiled and described in a result.

Results: Compilation resulted in two themes,  Music in dementia care and Stimulation in dementia care and four subthemes, Singing in the care, Listening to music, Activities and Consolation and fillip that showed a dominant positive effect on dementia affected patients and carers and there by create opportunities for caring in dementia care .

Conclusion: The different nursing interventions may be useful in dementia care when they show a dominant positive effect on various behavioural changes, it seems memory stimulant and promotes communication between patients and carers which favours caring .

Keywords: Agitated behaviour, dementia, non- pharmacological, literature review, nursing.

SAMMANFATTNING

Syfte: Uppsatsens syfte var att undersöka om det fanns några samband mellan ålder, iso-BMI, upplevt problem av övervikten och motivation till förändring hos barnen som behandlas på överviktsenheten för barn och ungdom. Metod: Designen var en tvärsnittstudie med kvantitativ ansats och materialet är delar av de anamnesformulär som barnen fyllt i inför nybesöket på överviktsenheten samt iso-BMI från sjukhusjournaler. Statistiska analyser gjordes i SPSS. I studien ingick 118 barn; 54 flickor och 64 pojkar.                                                                   Resultat: Studien visade att 94,4 % av flickorna och 76,6% av pojkarna upplevde att deras övervikt var ett problem. Det fanns inget samband mellan iso-BMI och hur stort problem övervikten upplevdes som, men ett negativt samband mellan ålder och problemets upplevda storlek sågs i båda grupperna. Pojkar som upplevde övervikten som ett mindre problem hade högre tankar om sin förmåga att agera mot övervikten jämfört med de som upplevde övervikten som ett större problem. Resultaten visade även att de barn som trodde mycket på sin förmåga att agera mot övervikten också var mer redo att agera. Slutsats: Merparten av barnen som har kontakt med överviktsenheten upplever att deras övervikt är ett problem och det finns en koppling mellan barnets ålder och hur stort problemet upplevs. Övervikt och fetma hos barn och ungdom är ett stort samhällsproblem och fortsatta studier och utveckling av behandlingsmetoder är av stor vikt.

Ny teknik och utglesning av stæder har inneburit att mænniskor inte rør på sig tillræckligt. Den stillasittande livsstilen medfør høga samhælleliga kostnader, samt en rad hælsoproblem såsom hjært- och kærlsjukdomar, diabetes, høgt blodtryck, cancer, stress, samt øvervikt och fetma. En av de høgt prioriterade folkhælsouppgifterna i samhællet ær att bryta ner den stillasittande livsstilen hos befolkningen, och att se till att fysisk aktivitet blir en del av vardagen. Syftet med denna litteraturstudie var att undersøka den byggda miljøns påverkan på fysisk aktivitet i dagligt liv. Studien ær baserad på nio internationellt publicerade vetenskapliga artiklar, som annalyserats med en kvalitativt manifest innehållsanalys. Analysen resulterade i tre kategorier: egenskaper inom den byggda miljøn, behovet av externa faktorer och individuella førutsættningar. Konklusion av denna litteraturstudie: korta avstånd mellan bostad och service/affærer eller arbetsplats, god tillgång till gång- och cykelbanor, att området kænns tryggt och sækert samt estetiskt tilltalande; allt detta fræmjar fysisk aktivitet i vardagen. Men individens vilja, motivation, kunskap och information samspelar med den byggda miljøn i syfte att motverka det dagliga stillasittandet. Dessutom har den politiska viljan en stor betydelse i fræmjandet av fysisk aktivitet.

Bakgrund: Diabetes mellitus typ 2 är en kronisk metabolisk sjukdom som fortsätter att öka drastiskt i flera länder. Den fortsatta utvecklingen av sjukdomen orsakas av ärftlighet och ohälsosamma levnadsvanor i form av stilla- sittande livsstil, rökning och ohälsosamma kostintag. Förändrade levnadsvanor är centralt för sjukdomen och minskar risken för dödsfall och sena komplikationer i både nerver och blodkärl. Sjuksköterskor arbetar utifrån ett personcentrerat förhållningssätt i form av stöd och information med målet att underlätta patientens egenvårdskapacitet.

Syfte: Syftet med denna studie var att beskriva patienters upplevelse av att leva med diabetes typ 2.

Metod: En litteraturöversikt tillämpades som metod i enlighet med Friberg (2017). Litteratursökningen har utförts i databaserna CINAHL Complete och PubMed och är baserad på 8 vetenskapliga artiklar av kvalitativ metod. Innehållet i artiklarna analyserades och sammanställdes som teman i resultatdelen.

Resultat: I resultatet framkom fyra teman: sociala och existentiella utmaningar, utmaningar i samband med kostförändringar, vårdrelationens betydelse och närståendes betydelse.

Slutsats: I resultatet framkommer det att livet med diabetes typ 2 väcker flera negativa känslor. Att leva med diabetes typ 2 innebär ett anpassat och strukturerad liv vilket kan upplevas som en kamp i livet. Stödjande insatser från sjukvården och närstående är en central aspekt vid egenvårdshanteringen. Närståendes traditioner och kulturer var även någonting som försvårade patientens egenvårdskapacitet.

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Background The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly. Methods We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro–brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index). Results During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit. Conclusions Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors.

Defects in insulin secretion and insulin action are the major abnormalities in the development of Type 2 diabetes. Hyperinsulinemia is a risk marker for Type 2 diabetes and according to some, but not in all studies also for coronary heart disease (CHD). Conventional insulin assays measure immunoreactive insulin including proinsulin-like molecules.

Proinsulin and insulin measured by specific methods, insulin sensitivity measured by the euglycemic insulin clamp and early insulin response after a glucose challenge give more detailed information and may be better estimates of true risk for Type 2 diabetes and CHD.

This study examined relationships between proinsulin, insulin, insulin secretion and insulin sensitivity for the development of Type 2 diabetes and CHD. The investigation of the prognostic significance of proinsulin and insulin for the development of Type 2 diabetes and CHD was performed in prospective studies of 50-year and 70-year-old men in a population-based cohort. The results indicated, that increased proinsulin concentrations, was a marker of increased risk for Type 2 diabetes independent of measurements of insulin secretion and insulin sensitivity whereas insulin was not. Proinsulin was shown to be a predictor for CHD mortality and morbidity, respectively, independent of conventional risk factors, whereas insulin was not. Insulin sensitivity measured by the gold standard euglycemic insulin clamp at age 70 was a predictor of CHD morbidity, independently of established risk factors.

In summary, these data provide evidence that an increased concentration of proinsulin and not an elevated plasma insulin level per se, that constitutes the association with Type 2 diabetes and CHD and that insulin resistance per se, is associated with CHD risk.

Background: During the COVID-19 vaccination campaign in Sweden, pulmonary embolism (PE) was a frequently reported suspected serious adverse drug reaction. The aim was to estimate risk of PE following vaccination for COVID-19 in the Swedish population aged 18 to 84 years.

Methods: Population-based cohort study using the CoVacSafe-SE established platform including national registers. PE-case definition: Individuals discharged from inpatient-care or visiting specialized outpatient-care with a main diagnosis of PE occurring between 27-Dec-2020 and 31-Dec-2022 without simultaneous diagnosis of COVID-19 infection. Time-to-event analysis was performed using multi-variable Cox' proportional hazard's models. Hazard Ratios (HR) adjusted for age, sex and co-morbidities were modelled. The vaccines were BNT162b2/Comirnaty (R), mRNA1273/Spikevax (R) and ChAdOx1 nCoV-19/Vaxzevria (R) without regard to variants. Doses number one to five were studied.

Results: Eighty percent of the study-population (approximate to 6.1 million people) received at least two doses of COVID-19 vaccine. A total of 12,456 cases of PE were identified. Twenty-eight days after vaccinations we observed 99 cases after 701,455 1st doses of ChAdOx1 nCoV-19, HRadj, 1.29 (95%-CI, 1.05-1.59). Corresponding for BNT162b2 was 361 cases after 4,708,284 1st doses of BNT162b2 HR adj of 1.19 (95%-CI, 1.06-1.34) driven by age group 65-84; HR adj, 1.24 (95%-CI, 1.07-1.44). No increased risks were observed for mRNA1273.

Conclusion: In this nation-wide study, no strong associations were found between COVID-19 vaccinations and pulmonary embolism. Small increases in relative risk for the earliest doses of vaccines may be associated with prioritizing the frailest groups of people in the vaccination campaign, thus selection bias or unmeasured residual confounding is possible.

BACKGROUND: Impaired acute insulin response (AIR) and insulin resistance (IR) are characteristics of Type 2 diabetes (T2DM). The aim was to develop risk models for T2DM and impaired fasting glucose (IFG), reflecting estimates both of AIR and IR, and of their interaction, as predictors over 20 years of follow-up. METHODS: We developed predictive models using hierarchic multiple regression analyses in a population-based cohort of 1227 men with normal fasting blood glucose at baseline (1970-73) and were reinvestigated after 10 and after 20 years. Using IVGTT-variables correlated either to AIR or to IR, separate models were developed. Combined models were also estimated from which prediction scores, representing individual risk, were calculated. RESULTS: In combined models, interaction between prediction scores reflecting AIR and IR predicted T2DM and IFG. Lowest tertile of AIR and the highest tertile of IR showed a relative risk (RR) of 15.3 (95%-CI=5.58-41.84) for T2DM compared to the contrast group (high AIR and low IR). Corresponding RR for IFG was 13.23 (95%-CI=6.53-26.78). C-statistic increased from 0.76 to 0.79 (p=0.018) for T2DM and from 0.77 to 0.80 for IFG (p=0.062) taking interaction into account. Main effects of lowest tertile of AIR and highest tertile of IR versus best were: RR for T2DM, 8.80 (95%-CI=4.25-18.21) and 6.31 (95%-CI=3.26-12.21); for IFG, 9.07, (95%-CI=5.38-15.29) and 4.49 (95%-CI=2.98-6-76). CONCLUSION: The interaction between low AIR and high IR revealed a high relative risk for T2DM or IFG reflecting the interplay between these factors over long time on worsening glucose tolerance and development of manifest disease.

BACKGROUND: The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly. METHODS: We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro-brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index). RESULTS: During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit. CONCLUSIONS: Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors.

BACKGROUND: Some, but not all, studies have reported a relationship between plasma insulin and coronary heart disease (CHD). Conventional nonspecific insulin assays are also measuring various fractions of proinsulin-like molecules due to cross-reactivity. The long-term relationship between proinsulin-like molecules and CHD is largely unknown. For this reason, the longitudinal relationships between intact proinsulin, split proinsulin, specific insulin, immunoreactive insulin, and CHD, were studied in a population-based cohort of 50-year-old men (n=874), with a follow-up of 27 years.

METHODS AND RESULTS: Fasting proinsulin-like molecule and specific-insulin concentrations were measured in plasma (stored frozen since baseline 1970 to 1973) by specific 2-site immunometric assays. Immunoreactive insulin concentrations were determined at baseline. The associations between proinsulin-like molecules, specific insulin, immunoreactive insulin, and CHD mortality (International Classification of Diseases [9th revision] codes 410 to 414) were analyzed using Cox's proportional hazards regression and presented as hazard ratios (HRs) with their 95% confidence intervals (CIs) for a 1-SD increase in a predictor variable. In the univariate analysis, intact proinsulin (HR, 1.69; 95% CI, 1.41 to 2.01) was the strongest predictor of death from CHD. In the multivariate analysis, smoking (HR, 1.57; 95% CI, 1.03 to 2.38), intact proinsulin (HR, 1.47; 95% CI, 1.18 to 1.82), systolic blood pressure (HR, 1.38; 95% CI, 1.14 to 1.66), and LDL/HDL cholesterol ratio (HR, 1.31; 95% CI, 1.12 to 1.53) were independent predictors of CHD mortality (adjusted for body mass index, triglycerides, and fasting glucose), whereas specific insulin and immunoreactive insulin were not (HR, 1.12; 95% CI, 0.90 to 1.40). The increased risk was restricted to the upper third of the proinsulin distribution.

CONCLUSION: Increased proinsulin concentrations predict death and morbidity caused by CHD over a period of 27 years, independent of other major cardiovascular risk factors.

Aim: The predictive effect of various insulin resistance indexes for risk of cardiovascular diseases (CVD) or type 2 diabetes (T2DM) is still unclear. Methods: One thousand and forty-nine 71-years-old male subjects from the Swedish ULSAM study, mean follow-up 9 years. All subjects performed the euglycemic insulin clamp for M/I [glucose disposal/mean insulin], and 75-g oral glucose tolerance test for Ceder-IR: 1/glucose uptake rate/[mean glucose x log mean insulin]; Matsuda-IR: 1/10,000/square root [glucose0 x insulin0 x glucose120 x insulin120]; Belfiore-IR: 1/([glucose0 + glucose120]/normal mean glucose x [insulin0 + insulin120]/normal mean insulin)+1); and HOMA-IR: [glucose0 x insulin0]/22.5. Results: Bland-Altman plots showed best agreement between M/I versus Belfiore-IR and Ceder-IR with mean difference near zero, -0.21 to -0.46, while -0.68 to -0.77 for the other indexes. ISI-Ceder was the strongest predictor for incident nonfatal/fatal ischemic heart disease (CHD) or CVD at Cox regression in all subjects, and for incident T2DM at logistic regression in 1024 subjects with no baseline T2DM, with significantly higher hazard ratios or odds ratios than with all other indexes, also with best model fit, after adjusting for clinical characteristics and the traditional cardiovascular risk factors, including metabolic syndrome for CVD risk. Conclusion: Ceder-IR performed strongest as independent predictor for incidences of CHD/CVD and T2DM.

AIM:

We assessed the association between risk factors and cardiovascular disease (CVD) in an observational study of type 2 diabetes patients from the Swedish National Diabetes Register.

METHODS:

A derivation sample of 24,288 patients, aged 30-74 years, 15.3% with previous CVD, baseline 2002, 2488 CVD events when followed for 5 years until 2007. A separate validation data set of 4906 patients, baseline 2003, 522 CVD events when followed for 4 years.

RESULTS:

Adjusted hazard ratios at Cox regression for fatal/nonfatal CVD were: onset-age 1.59, diabetes duration 1.55, total-cholesterol-to-HDL-cholesterol ratio 1.20, HbA1c 1.12, systolic BP 1.09, BMI 1.07 (1 SD increase in natural log continuous variables); males 1.41, smoker 1.35, microalbuminuria 1.27, macroalbuminuria 1.53, atrial fibrillation 1.50, previous CVD 1.98 (all p<0.001 except BMI p=0.0018). All 12 variables were used to elaborate an equation for 5-year CVD risk in the derivation dataset: mean 5-year risk 11.9±8.4%. Calibration in the validation dataset was adequate: ratio predicted 4-year risk/observed rate 0.97. Discrimination was sufficient: C statistic 0.72, sensitivity 51% and specificity 78% for top quartile.

CONCLUSION:

This CVD risk model from a large observational study of patients in routine care showed adequate calibration and discrimination, and can be useful for clinical practice.

Aims/hypothesis Atrial fibrillation (AF) is more frequent in patients with diabetes than in the general population. However, characteristics contributing to AF risk in diabetes remain speculative. Methods Observational study of 83,162 patients with type 2 diabetes, aged 30-79 years, with no baseline AF, 17% had history of cardiovascular disease (CVD) and 3.3% history of congestive heart failure (CHF), followed up for development of AF during mean 6.8 years from 2005-2007 to 2012. A subgroup of 67,780 patients without history of CVD or CHF was also analysed. Results Using Cox regression, cardiovascular risk factors associated with risk for AF were updated mean BMI (HR 1.31 per 5 kg/m(2)) or obesity (HR 1.51), updated mean systolic BP (SBP; HR 1.13 per 10 mmHg) or hypertension (HR 1.71), and cumulative microalbuminuria (HR 1.21), p < 0.001 for all analyses. Male sex, increasing age and height were also significant predictors. HRs were 1.76 for a history of CHF and 2.56 for in-study CHF, while 1.32 for history of CVD and 1.38 for in-study CHD (p < 0.001). Among patients without history of CVD or CHF, significant predictors were similarly BMI, SBP, and cumulative microalbuminuria and CHF. The risk of AF differed in the subgroups achieving or not achieving a target BP < 140/85 mmHg. The HRs for AF were (per 10 mmHg increase) 0.88 and 1.24, respectively. Conclusions/interpretation The modifiable risk factors high BP, high BMI and albuminuria were strongly associated with AF in type 2 diabetes. CVD, advancing age and height were also associated with AF in type 2 diabetes.