Modeling geographic vaccination strategies for COVID-19 in Norway.

Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.

Short-term safety of COVID-19 mRNA vaccines with respect to all-cause mortality in the older population in Norway.

BACKGROUND: There have been concerns about COVID-19 vaccination safety among frail older individuals. We investigated the relationship between COVID-19 mRNA vaccination and mortality among individuals aged ≥ 70 years and whether mortality varies across four groups of health services used. METHODS: In this nationwide cohort study, we included 688,152 individuals aged ≥ 70 years at the start of the Norwegian vaccination campaign (December 27, 2020). We collected individual-level data from theNorwegian Emergency Preparedness Register for COVID-19. Vaccinated and unvaccinated individuals were matched (1:1 ratio) on the date of vaccination based on sociodemographic and clinical characteristics. The main outcome was all-cause mortality during 21 days after first dose of COVID-19 mRNA vaccination. Kaplan-Meier survival functions were estimated for the vaccinated and unvaccinated groups. We used Cox proportional-hazards regression to estimate hazard ratios (HRs) of death between vaccinated and unvaccinated individuals, with associated 95% confidence intervals (CIs), overall and by use of health services (none, home-based, short- and long-term nursing homes) and age group. RESULTS: Between December 27, 2020, and March 31, 2021, 420,771 older individuals (61.1%) were vaccinated against COVID-19. The Kaplan-Meier estimates based on the matched study sample showed a small absolute risk difference in all-cause mortality between vaccinated and unvaccinated individuals, with a lower mortality in the vaccinated group (overall HR 0.28 [95% CI: 0.24-0.31]). Similar results were obtained in analyses stratified by use of health services and age group. CONCLUSION: We found no evidence of increased short-term mortality among vaccinated individuals in the older population after matching on sociodemographic and clinical characteristics affecting vaccination and mortality.

A national study of the causes, consequences and amelioration of adverse events in the use of MRI, CT, and conventional radiography in Norway.

BACKGROUND: Rapid technological developments, increased complexity, and increased demand have made patient safety a challenge in radiology. PURPOSE: To uncover the causes and consequences behind patient injury compensation claims in the use of MRI, CT, and conventional X-ray examinations, and to determine the system factors that need to be focused on in order to prevent these events. MATERIAL AND METHODS: This descriptive cross-sectional study uses data acquired from The Norwegian System of Patient Injury Compensation. A total of 240 cases from 2012-2016 were included. RESULTS: According to our study, the main factors contributing to patient injury compensation claims in radiology were false-negative findings (48.7%), misinterpretation (13.1%), and "satisfaction of search" (12%). Another source of error was routines (8.7%), mainly where the patient should have been (further) examined using another modality. Other causes were related to communication (7.6%), procedures (2.9%), technical factors (2.5%), organizational and management factors (1.5%), competence (0.7%), location of the lesion (0.7%), patient factors (0.7%), false-positive findings (0.4%), and work environment (0.4%). These events led to delayed diagnosis and/or treatment in the range of 0-3650 days. CONCLUSION: Errors of perception (false negative and "satisfaction of search") and cognitive errors (misinterpretation) were the main reasons behind patient injury compensation claims in radiology. We suggest that a combination of double-reading, specialization, increased collaboration between professionals, as well as a reduction of unnecessary examinations should be considered to reduce adverse events in radiology.

Nurses' reports of staffing adequacy and surgical site infections: A cross-sectional multi-centre study.

BACKGROUND: It is indicated that healthcare personnel's perceptions of the work environment may reflect the clinical outcomes for the patients they care for. However, the body of evidence is inconsistent when it comes to the association between work environment and surgical site infection. OBJECTIVES: The aim of this study is to examine the associations between nurse-reported characteristics of the work environment and incidence of surgical site infections after total hip arthroplasty. DESIGN AND SETTINGS: This is a cross-sectional multicentre study conducted in 16 Norwegian hospitals. PARTICIPANTS: Clinical outcomes for 2885 patients >18years that underwent total hip arthroplasty are combined with work environment descriptions from 320 nurses. MATERIALS AND METHODS: We combine data about surgical site infections from The Norwegian Surveillance System for Antibiotic Consumption and Healthcare-Associated Infections and hospital characteristics such as overall survival probability (from administrative patient data) and nurses' reports of characteristics of the work environment (from a multicentre survey among nurses in Norwegian hospitals). Stepwise mixed-effects logistic regression model was performed to examine the associations between characteristics of the work environment and surgical site infections. RESULTS: The incidence of surgical site infection among 2885 patients undergoing total hip arthroplasty in 16 Norwegian hospitals was 2.6%. Older age, elective procedures and high scores for staffing adequacy were associated with risk for surgical site infection. The association between high scores for adequate staffing and low risk for surgical site infections was present for patients that were admitted for an elective procedure, but not for patients admitted for a non-elective procedure. CONCLUSION: Our results show that the risk of surgical site infections after elective total hip arthroplasty was lower in hospitals where nurses assessed staffing as adequate. Our findings add to the existing literature that examines the linkage between work environment and clinical outcomes.

Outer membrane phospholipase A's roles in Helicobacter pylori acid adaptation.

BACKGROUND: The pH of the human gastric mucosa varies around 2.5 so that only bacteria with strong acidic stress tolerance can colonize it. The ulcer causing Helicobacter pylori thrives in the gastric mucosa. We analyse the roles of the key outer membrane protein OMPLA in its roles in acid tolerance. RESULTS: The homology model of Helicobacter pylori outer membrane phospholipase A (OMPLA) reveals a twelve stranded ß-barrel with a pore that allows molecules to pass with a diameter up to 4 Å. Structure based multiple sequence alignments revealed the functional roles of many amino acids, and led to the suggestion that OMPLA has multiple functions. Besides its role as phospholipase it lets urea enter and ammonium exit the periplasm. Combined with an extensive literature study, our work leads to a comprehensive model for H. pylori's acid tolerance. This model is based on the conversion of urea into ammonium, and it includes multiple roles for OMPLA and involves two hitherto little studied membrane channels in the OMPLA operon. CONCLUSION: The three-dimensional model of OMPLA predicts a transmembrane pore that can aid H. pylori's acid tolerance through urea influx and ammonium efflux. After urea passes through OMPLA into the periplasm, it passes through the pH-gated inner membrane channel UreI into the cytoplasm where urease hydrolyses it into NH3 and CO2. Most of the NH3 becomes NH4+ that is likely to need an inner membrane channel to reach the periplasm. Two genes that are co-regulated with OMPLA in gastric Helicobacter operons could aid this transport. The NH4+ that might leave the cell through the OMPLA pore has been implicated in H. pylor's pathogenesis.

In Silico Structure and Sequence Analysis of Bacterial Porins and Specific Diffusion Channels for Hydrophilic Molecules: Conservation, Multimericity and Multifunctionality.

Diffusion channels are involved in the selective uptake of nutrients and form the largest outer membrane protein (OMP) family in Gram-negative bacteria. Differences in pore size and amino acid composition contribute to the specificity. Structure-based multiple sequence alignments shed light on the structure-function relations for all eight subclasses. Entropy-variability analysis results are correlated to known structural and functional aspects, such as structural integrity, multimericity, specificity and biological niche adaptation. The high mutation rate in their surface-exposed loops is likely an important mechanism for host immune system evasion. Multiple sequence alignments for each subclass revealed conserved residue positions that are involved in substrate recognition and specificity. An analysis of monomeric protein channels revealed particular sequence patterns of amino acids that were observed in other classes at multimeric interfaces. This adds to the emerging evidence that all members of the family exist in a multimeric state. Our findings are important for understanding the role of members of this family in a wide range of bacterial processes, including bacterial food uptake, survival and adaptation mechanisms.

GFRA3 promoter methylation may be associated with decreased postoperative survival in gastric cancer.

BACKGROUND: A large number of epigenetic alterations has been found to be implicated in the etiology of gastric cancer. We have studied the DNA methylation status of 27 500 gene promoter regions in 24 gastric adenocarcinomas from a Norwegian cohort, and aimed at identifying the hypermethylated regions. We have compared our findings to the gene expression in the same tissue, and linked our results to prognosis and survival. METHODS: Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 24 patients following surgical resection of the tumor. Genome-wide DNA methylation profiling of the tumor and matched non-cancerous mucosa was performed. The results were compared to whole transcriptome cDNA microarray analysis of the same material. RESULTS: Most of the gene promoter regions in both types of tissue showed a low degree of methylation, however there was a small, but significant hypermethylation of the tumors. Hierarchical clustering showed separate grouping of the tumor and normal tissue. Hypermethylation of the promoter region of the GFRA3 gene showed a strong correlation to post-operative survival and several of the clinicopathological parameters, however no difference was found between the two main histological types of gastric cancer. There was only a modest correlation between the DNA methylation status and gene expression. CONCLUSIONS: The different DNA methylation clusters of the tumors and normal tissue indicate that aberrant DNA methylation is a distinct feature of gastric cancer, although there is little difference in the overall, and low, methylation levels between the two tissue types. The GFRA3 promoter region showed marked hypermethylation in almost all tumors, and its correlation with survival and other clinicopathological parameters may have important prognostic significance.

A systematic review of hospital accreditation: the challenges of measuring complex intervention effects.

BACKGROUND: The increased international focus on improving patient outcomes, safety and quality of care has led stakeholders, policy makers and healthcare provider organizations to adopt standardized processes for evaluating healthcare organizations. Accreditation and certification have been proposed as interventions to support patient safety and high quality healthcare. Guidelines recommend accreditation but are cautious about the evidence, judged as inconclusive. The push for accreditation continues despite sparse evidence to support its efficiency or effectiveness. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library using Medical Subject Headings (MeSH) indexes and keyword searches in any language. Studies were assessed using the Cochrane Risk of Bias Tool and AMSTAR framework. 915 abstracts were screened and 20 papers were reviewed in full in January 2013. Inclusion criteria included studies addressing the effect of hospital accreditation and certification using systematic reviews, randomized controlled trials, observational studies with a control group, or interrupted time series. Outcomes included both clinical outcomes and process measures. An updated literature search in July 2014 identified no new studies. RESULTS: The literature review uncovered three systematic reviews and one randomized controlled trial. The lone study assessed the effects of accreditation on hospital outcomes and reported inconsistent results. Excluded studies were reviewed and their findings summarized. CONCLUSION: Accreditation continues to grow internationally but due to scant evidence, no conclusions could be reached to support its effectiveness. Our review did not find evidence to support accreditation and certification of hospitals being linked to measurable changes in quality of care as measured by quality metrics and standards. Most studies did not report intervention context, implementation, or cost. This might reflect the challenges in assessing complex, heterogeneous interventions such as accreditation and certification. It is also may be magnified by the impact of how accreditation is managed and executed, and the varied financial and organizational healthcare constraints. The strategies hospitals should impelment to improve patient safety and organizational outcomes related to accreditation and certification components remains unclear.

Monitoring adverse events in Norwegian hospitals from 2010 to 2013.

OBJECTIVES: To describe how adverse event (AE) rates were monitored and estimated nationally across all Norwegian hospitals from 2010 to 2013, and how they developed during the monitoring period. Monitoring was based on medical record review with Global Trigger Tool (GTT). SETTING: All publicly and privately owned hospitals were mandated to review randomly selected medical records to monitor AE rates. The initiative was part of the Norwegian patient safety campaign, launched by the Norwegian Ministry of Health and Care Services. It started in January 2011 and lasted until December 2013. 2010 was the baseline for the review. One of the main aims of the campaign was to reduce patient harm. METHOD: To standardise the medical record reviews in all hospitals, GTT was chosen as a standard method. GTT teams from all hospitals reviewed 40,851 medical records randomly selected from 2,249,957 discharges from 2010 to 2013. Data were plotted in time series for local measurement and national AE rates were estimated, plotted and monitored. RESULTS: AE rates were estimated and published nationally from 2010 to 2013. Estimated AE rates in severity categories E-I decreased significantly from 16.1% in 2011 to 13.0% in 2013 (-3.1% (95% CI -5.2% to -1.1%)). CONCLUSIONS: Monitoring estimated AE rates emerges as a potential element in national systems for patient safety. Estimated AE rates in the category of least severity decreased significantly during the first 2 years of the monitoring.

Surgical Site Infections in Orthopaedic Surgery Demonstrate Clones Similar to Those in Orthopaedic Staphylococcus aureus Nasal Carriers.

BACKGROUND: Staphylococcus aureus is the main microbial pathogen in orthopaedic infections, and it adds considerable extra costs to the national health-care system each year. Nasal carriers of Staphylococcus aureus have an increased risk of invasive disease, including surgical site infection. The purpose of the present study was to investigate whether the Staphylococcus aureus carrier clones found in patients undergoing elective orthopaedic surgery were the same as the clones found in isolates from orthopaedic patients with Staphylococcus aureus surgical site infections. METHODS: Patients admitted for elective orthopaedic surgery underwent nasal cultures for Staphylococcus aureus. Further, orthopaedic patients with a deep surgical site infection caused by Staphylococcus aureus were characterized using the same genotyping methods: multilocus sequence typing and staphylococcal protein A typing. RESULTS: Multilocus sequence typing revealed a large number of genotypes in the two populations. However, 85% of nasal carriers and 90% of surgical site infection isolates could be classified into the same four multilocus sequence typing clonal complexes. The risk of Staphylococcus aureus surgical site infection in nasal carriers compared with non-carriers was 5.8 times higher (95% confidence interval, 1.5 to 23.1 times). Of the nasal carriers, 6.3% (95% confidence interval, 1.7% to 10.9% [seven of 111 patients]) developed a deep Staphylococcus aureus surgical site infection, and all but one patient had identical genotypes in the nasal and surgical site infection isolates. CONCLUSIONS: Staphylococcus aureus isolates from nasal carriers and patients with surgical site infection clustered into the same few multilocus sequence typing clonal complexes. This finding confirms the existence of some commonly occurring Staphylococcus aureus clones in different population groups within a geographically restricted area. The almost complete individual concordance between Staphylococcus aureus genotypes in carriers who developed a deep surgical site infection strongly supports transmission from the nose, skin surfaces, and other endogenous body regions as a possible route. CLINICAL RELEVANCE: Surgical site infections might be more frequently caused by endogenous transmission than was previously assumed. Perioperative preventive efforts must focus more on this route to further decrease the risk of postoperative orthopaedic infections.

An observational study: associations between nurse-reported hospital characteristics and estimated 30-day survival probabilities.

BACKGROUND: There is a growing body of evidence for associations between the work environment and patient outcomes. A good work environment may maximise healthcare workers' efforts to avoid failures and to facilitate quality care that is focused on patient safety. Several studies use nurse-reported quality measures, but it is uncertain whether these outcomes are correlated with clinical outcomes. The aim of this study was to determine the correlations between hospital-aggregated, nurse-assessed quality and safety, and estimated probabilities for 30-day survival in and out of hospital. METHODS: In a multicentre study involving almost all Norwegian hospitals with more than 85 beds (sample size=30, information about nurses' perceptions of organisational characteristics were collected. Subscales from this survey were used to describe properties of the organisations: quality system, patient safety management, nurse-physician relationship, staffing adequacy, quality of nursing and patient safety. The average scores for these organisational characteristics were aggregated to hospital level, and merged with estimated probabilities for 30-day survival in and out of hospital (survival probabilities) from a national database. In this observational, ecological study, the relationships between the organisational characteristics (independent variables) and clinical outcomes (survival probabilities) were examined. RESULTS: Survival probabilities were correlated with nurse-assessed quality of nursing. Furthermore, the subjective perception of staffing adequacy was correlated with overall survival. CONCLUSIONS: This study showed that perceived staffing adequacy and nurses' assessments of quality of nursing were correlated with survival probabilities. It is suggested that the way nurses characterise the microsystems they belong to, also reflects the general performance of hospitals.

Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival.

BACKGROUND: The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. METHODS: Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. RESULTS: 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. CONCLUSIONS: CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post-operative prognosis, and may have important prognostic value. IL-8 and CLDN1 may represent central links between the gene response seen in acute H. pylori infection of gastric epithelial cells, and ultimately gastric cancer.

A cross-sectional study to identify organisational processes associated with nurse-reported quality and patient safety.

OBJECTIVES: The purpose of this study was to identify organisational processes and structures that are associated with nurse-reported patient safety and quality of nursing. DESIGN: This is an observational cross-sectional study using survey methods. SETTING: Respondents from 31 Norwegian hospitals with more than 85 beds were included in the survey. PARTICIPANTS: All registered nurses working in direct patient care in a position of 20% or more were invited to answer the survey. In this study, 3618 nurses from surgical and medical wards responded (response rate 58.9). Nurses' practice environment was defined as organisational processes and measured by the Nursing Work Index Revised and items from Hospital Survey on Patient Safety Culture. OUTCOME MEASURES: Nurses' assessments of patient safety, quality of nursing, confidence in how their patients manage after discharge and frequency of adverse events were used as outcome measures. RESULTS: Quality system, nurse-physician relation, patient safety management and staff adequacy were process measures associated with nurse-reported work-related and patient-related outcomes, but we found no associations with nurse participation, education and career and ward leadership. Most organisational structures were non-significant in the multilevel model except for nurses' affiliations to medical department and hospital type. CONCLUSIONS: Organisational structures may have minor impact on how nurses perceive work-related and patient-related outcomes, but the findings in this study indicate that there is a considerable potential to address organisational design in improvement of patient safety and quality of care.

In silico evolutionary analysis of Helicobacter pylori outer membrane phospholipase A (OMPLA).

BACKGROUND: In the past decade, researchers have proposed that the pldA gene for outer membrane phospholipase A (OMPLA) is important for bacterial colonization of the human gastric ventricle. Several conserved Helicobacter pylori genes have distinct genotypes in different parts of the world, biogeographic patterns that can be analyzed through phylogenetic trees. The current study will shed light on the importance of the pldA gene in H. pylori. In silico sequence analysis will be used to investigate whether the bacteria are in the process of preserving, optimizing, or rejecting the pldA gene. The pldA gene will be phylogenetically compared to other housekeeping (HK) genes, and a possible origin via horizontal gene transfer (HGT) will be evaluated through both intra- and inter-species evolutionary analyses. RESULTS: In this study, pldA gene sequences were phylogenetically analyzed and compared with a large reference set of concatenated HK gene sequences. A total of 246 pldA nucleotide sequences were used; 207 were from Norwegian isolates, 20 were from Korean isolates, and 19 were from the NCBI database. Best-fit evolutionary models were determined with MEGA5 ModelTest for the pldA (K80 + I + G) and HK (GTR + I + G) sequences, and maximum likelihood trees were constructed. Both HK and pldA genes showed biogeographic clustering. Horizontal gene transfer was inferred based on significantly different GC contents, the codon adaptation index, and a phylogenetic conflict between a tree of OMPLA protein sequences representing 171 species and a tree of the AtpA HK protein for 169 species. Although a vast majority of the residues in OMPLA were predicted to be under purifying selection, sites undergoing positive selection were also found. CONCLUSIONS: Our findings indicate that the pldA gene could have been more recently acquired than seven of the HK genes found in H. pylori. However, the common biogeographic patterns of both the HK and pldA sequences indicated that the transfer occurred long ago. Our results indicate that the bacterium is preserving the function of OMPLA, although some sites are still being evolutionarily optimized.

mRNA expression of adipocytokines and glucocorticoid-related genes are associated with downregulation of E-cadherin mRNA in colorectal adenocarcinomas.

BACKGROUND: There is a consistently reported relationship between the incidence of colon cancer and obesity. It is thought that adipose tissue, particularly visceral fat, which secretes systemic factors that alter immunological, metabolic and endocrine milieu and promotes insulin resistance by producing adipocytokines, is important in cancer progression. Systemic high concentrations of adipocytokines, such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and glucocorticoid metabolism-related genes have been associated with gastrointestinal cancer. However, limited information exists about the expression of these cytokines within tumour tissue. MATERIAL AND METHODS: mRNA expression of TNF-α, IL-6,IL-8, IL-10, IL-1RN, glucocorticoid receptor alpha (GR-α), 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), plasminogen activator inhibitor-1 (PAI-1), Slug, vimentin, Snail and E-cadherin was analysed in paired samples of tumour tissue and normal mucosa in 60 surgical patients for Dukes B and C colorectal adenocarcinomas using quantitative reverse transcription PCR and microarray technology. The mRNA expression level of analysed genes was compared between tumour tissue and normal mucosa from the same patients, and a correlation to mRNA expression of E-cadherin in the same tissue samples was also performed. RESULTS: A highly significant difference in mRNA expression level of several of the analysed genes was observed between tumour tissue and the normal intestinal mucosa. Inverse correlation between mRNA expression of 11ßHSD1, IL-6, GR-α and PAI-1 on one hand and mRNA expression of E-cadherin on the other hand was observed. CONCLUSION: Results show that the adipocytokines and glucocorticoid metabolism-related genes are overexpressed in colorectal adenocarcinomas, and expression of these genes is associated with the downregulation of E-cadherin mRNA, connecting these genes to carcinogenesis and progression of colorectal cancer.

Interleukin-8 is the single most up-regulated gene in whole genome profiling of H. pylori exposed gastric epithelial cells.

BACKGROUND: The association between Helicobacter pylori infection and upper gastrointestinal disease is well established. However, only a small fraction of H. pylori carriers develop disease, and there are great geographical differences in disease penetrance. The explanation to this enigma lies in the interaction between the bacterium and the host. H. pylori Outer Membrane Phospholipase A (OMPLA) has been suggested to play a role in the virulence of this bacterium. The aim of this study was to profile the most significant cellular pathways and biological processes affected in gastric epithelial cells during 24 h of H. pylori exposure, and to study the inflammatory response to OMPLA⁺ and OMPLA⁻ H. pylori variants. RESULTS: Interleukin-8 was the most significantly up-regulated gene and appears to play a paramount role in the epithelial cell response to H. pylori infection and in the pathological processes leading to gastric disease. MAPK and NF-kappaB cellular pathways were powerfully activated, but did not seem to explain the impressive IL-8 response. There was marked up-regulation of TP53BP2, whose corresponding protein ASPP2 may interact with H. pylori CagA and cause marked p53 suppression of apoptosis. Other regulators of apoptosis also showed abberant regulation. We also identified up-regulation of several oncogenes and down-regulation of tumor suppressor genes as early as during the first 24 h of infection. H. pylori OMPLA phase variation did not seem to influence the inflammatory epithelial cell gene response in this experiment. CONCLUSION: In whole genome analysis of the epithelial response to H. pylori exposure, IL-8 demonstrated the most marked up-regulation, and was involved in many of the most important cellular response processes to the infection. There was dysregulation of apoptosis, tumor suppressor genes and oncogenes as early as in the first 24 h of H. pylori infection, which may represent early signs of gastric tumorigenesis. OMPLA⁺/⁻ did not affect the acute inflammatory response to H. pylori.

Nasal carriage of Staphylococcus aureus: frequency and molecular diversity in a randomly sampled Norwegian community population.

A randomly selected, healthy Norwegian community population was studied for nasal carriage of Staphylococcus aureus (S. aureus) to describe frequency and molecular diversity in a non-hospital cohort (n = 95). Multilocus sequence typing revealed 31 sequence types (STs) belonging to 15 clonal complexes (CCs). The majority of isolates (71%) were classified as CC 15, 30 or 45. This clustering was confirmed by spa typing. There was no statistically significant difference in the distribution of CCs between this community population and a previously studied group of orthopaedic health care workers from a hospital in the same community. The study may indicate that microbial and host factors may be stronger determinants for S. aureus colonization than exposures associated with the hospital environment.

The Generic Short Patient Experiences Questionnaire (GS-PEQ): identification of core items from a survey in Norway.

BACKGROUND: Questionnaires are commonly used to collect patient, or user, experiences with health care encounters; however, their adaptation to specific target groups limits comparison between groups. We present the construction of a generic questionnaire (maximum of ten questions) for user evaluation across a range of health care services. METHODS: Based on previous testing of six group-specific questionnaires, we first constructed a generic questionnaire with 23 items related to user experiences. All questions included a "not applicable" response option, as well as a follow-up question about the item's importance. Nine user groups from one health trust were surveyed. Seven groups received questionnaires by mail and two by personal distribution. Selection of core questions was based on three criteria: applicability (proportion "not applicable"), importance (mean scores on follow-up questions), and comprehensiveness (content coverage, maximum two items per dimension). RESULTS: 1324 questionnaires were returned providing subsample sizes ranging from 52 to 323. Ten questions were excluded because the proportion of "not applicable" responses exceeded 20% in at least one user group. The number of remaining items was reduced to ten by applying the two other criteria. The final short questionnaire included items on outcome (2), clinician services (2), user involvement (2), incorrect treatment (1), information (1), organisation (1), and accessibility (1). CONCLUSION: The Generic Short Patient Experiences Questionnaire (GS-PEQ) is a short, generic set of questions on user experiences with specialist health care that covers important topics for a range of groups. It can be used alone or with other instruments in quality assessment or in research. The psychometric properties and the relevance of the GS-PEQ in other health care settings and countries need further evaluation.

Genome profiles in maternal blood during early onset preeclampsia and towards term.

AIMS: inflammatory processes are present during preeclampsia and in normal pregnancy. Maternal inflammatory reactions may change towards term. Our objective was to evaluate genome signaling in blood during preeclampsia and towards term using microarrays. METHODS: RNA microarrays (Illumina) were conducted on blood from preeclamptic pregnancies delivered preterm, normal pregnancies at term and normal pregnancies at gestational week 31. Two statistical methods (Q-value cut-off 1%) identified data structures in the three groups and retrieved activated genes along a time axis and a diseased-healthy axis. Signaling genes were localized within known pathways and gene sets, and genes associated with inflammation were identified. RESULTS: early onset preeclampsia and term pregnancies both showed distinct expression patterns when compared to normal pregnancy at gestational week 31. In preeclampsia, 19 genes were differentially expressed, including a down-regulation of CC-chemokine receptor 3 (CCR3). Among the 183 differentially expressed genes towards term, tumor necrosis factor superfamily member 15 (TNFSF15) was up-regulated and interferon-γ receptor 2 (IFNGR2) and CXC-chemokine receptor type 4 (CXCR4) were down-regulated. Seven of the genes were similarly changed during preeclampsia and towards term. CONCLUSIONS: a possible type 1 immune response was identified both during preeclampsia and towards term. In pre-eclampsia a premature activation of leucocytes might be present.