Liver stiffness predicts progression to liver-related events in patients with chronic liver disease - A cohort study of 14 414 patients.

BACKGROUND & AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) is a non-invasive diagnostic biomarker of liver fibrosis. It is uncertain if LSM can predict risk for future liver-related outcomes in large, heterogenous populations. METHODS: This Swedish multi-centre cohort study included patients (n = 14 414) from 16 sites who underwent LSM by VCTE between 2008 and 2020. Outcomes were ascertained from national registers. We investigated progression to cirrhosis with portal hypertension or hepatocellular carcinoma (HCC), separately. Cox regression was used to obtain hazard ratios (HRs). Harrel's C-index was used to measure discrimination of VCTE. RESULTS: Included patients had a median age of 46 (interquartile range 34-57), median LSM of 5.9 kPa (4.6-8.0), 59% were male, and the majority had hepatitis C (50.1%). During a median follow-up of 5.9 (4.3-8.0) years, 402 patients (2.7%) developed cirrhosis with portal hypertension. In patients with an LSM ≥25 kPa, 28.7% developed cirrhosis with portal hypertension within 5 years of follow-up, while only .6% of patients with an LSM <10 kPa did. This translated to a HR of 48.3 (95% confidence interval = 37.6-62.0). VCTE had a high discriminative ability, with C-indices above .80 for most liver diseases, including .82 for MASLD. Similar findings were seen for incident HCC. CONCLUSIONS: Increased LSM by VCTE was associated with an increased risk of progression to both cirrhosis with portal hypertension, and to HCC, and had a high discriminative ability across different aetiologies of chronic liver diseases. These results support the use of VCTE to guide follow-up and treatment decisions.

Syndromic testing for respiratory pathogens but not National Early Warning Score can be used to identify viral cause in hospitalised adults with lower respiratory tract infections.

BACKGROUND: Community-acquired lower respiratory tract infection (LRTI) is a common reason for hospitalisation. Antibiotics are frequently used while diagnostic microbiological methods are underutilised in the acute setting. OBJECTIVES: We aimed to investigate the relative proportion of viral and bacterial infections in this patient group and explore methods for proper targeting of antimicrobial therapy. METHODS: We collected nasopharyngeal samples prospectively from adults hospitalised with LRTIs during three consecutive winter seasons (2016-2019). Syndromic nasopharyngeal testing was performed using a multiplex PCR panel including 16 viruses and four bacteria. Medical records were reviewed for clinical data. RESULTS: Out of 220 included patients, a viral pathogen was detected in 74 (34%), a bacterial pathogen in 63 (39%), both viral and bacterial pathogens in 49 (22%), while the aetiology remained unknown in 34 (15%) cases. The proportion of infections with an identified pathogen increased from 38% to 85% when syndromic testing was added to standard-of-care testing. Viral infections were associated with a low CRP level and absence of pulmonary infiltrates. A high National Early Warning Score did not predict bacterial infections. CONCLUSIONS: Syndromic testing by a multiplex PCR panel identified a viral infection or viral/bacterial coinfection in a majority of hospitalised adult patients with community-acquired LRTIs.

Complex norovirus transmission dynamics at hospital wards revealed by deep sequencing.

Detailed knowledge regarding norovirus transmission within hospitals is limited. We investigated a norovirus hospital outbreak affecting 65 patients at five different wards. PCR showed that 61 (94%) of the patients were infected with genotype II.4 strains. Successful Ion Torrent deep sequencing of GII.4 positive samples from 59 patients followed by phylogenetic analysis revealed that all sequences but two clustered into four distinct clades. Two of the clades belonged to GII.4 Sydney 2012, while the other two belonged to GII.4 New Orleans 2009. One of the clades was predominant at two wards, while two clades were predominant at one ward each. The fourth clade was found in sporadic cases at several wards. Thus, at four out of five wards, variants from one clade were predominant. At one ward, a single clade accounted for all cases, while at three wards the predominant clade accounted for 60%-71% of cases. Analysis of quasispecies variation identified positions that could further discriminate between variants from separate wards. The results illustrate a complex transmission of healthcare-associated norovirus infections and show that sequencing can be used to discriminate between related and unrelated cases.

Hospital Admission Rates in Patients with COPD Throughout the COVID-19 Pandemic.

Purpose: Several studies report decreased hospital admissions for acute exacerbations of COPD (AECOPD) during the COVID-19 pandemic. However, there are no studies that compare AECOPD admissions with admissions for respiratory infections, including COVID-19. This study aimed to examine hospital admission rates for AECOPD, pneumonia, influenza, and COVID-19 among COPD patients, before and during the COVID-19 pandemic. Patients and Methods: We obtained anonymized data on hospital admissions of patients with COPD and a primary diagnosis code for AECOPD, pneumonia, influenza, or COVID-19, from the hospital patient admission register at a large Swedish hospital. The study compared the pandemic period (February 2020-March 2022) to a period before the pandemic (June 2017-January 2020). Sequential phases of the pandemic were evaluated separately. Monthly admission rates were compared using Poisson regression, controlling for admission month. Results: Comparing monthly admission rates during the pandemic with the prepandemic period, incidence rate ratios were 0.72 for AECOPD (95% CI 0.67-0.77; p<0.001), 0.56 for pneumonia (95% CI 0.49-0.62; p<0.001), 0.18 for influenza during the winter period (95% CI 0.10-0.30; p<0.001) and 0.79 for total COPD admissions, including COVID-19 (95% CI 0.75-0.84; p<0.001). The study showed significantly lower rate ratios for AECOPD, pneumonia, and total COPD admissions during the first, second, third, and fifth (Omicron) waves. No significant effect on admissions was seen after the withdrawal of restriction measures. Conclusion: There was a significant reduction in the overall rate of hospital admissions among COPD patients for AECOPD, pneumonia, and respiratory viral infections during the pandemic despite the rise in COVID-19 admissions. However, prepandemic admission levels returned in the post-restriction period.

Dismal prognosis for cirrhotic patients with hepatitis C after initial failure of direct acting anti-virals, but salvage therapy may be life-saving.

BACKGROUND: Effective direct-acting antiviral treatment against hepatitis C virus infection is available in many countries worldwide. Despite good treatment results, a proportion of patients does not respond to treatment. The aim of this study was to investigate the long-term prognosis and the outcome of salvage therapy, after an initial treatment failure, in a nation-wide real-life setting. METHOD: Data from all adult patients registered in the national Swedish hepatitis C treatment register who did not achieve sustained virological response after initial antiviral treatment, was retrieved from 2014 through 2018. RESULTS: In total, 288 patients with primary treatment failure were included, of whom 236 underwent a second treatment course as salvage therapy after a median delay of 353 (IQR: 215-650) days. Fifteen patients received a third treatment course as second salvage treatment after a further median delay of 193 (IQR: 160-378) days. One-hundred-eleven out of 124 (90%) non-cirrhotic and 62/79 (78%) cirrhotic patients achieved sustained virological response following the first salvage treatment. Sustained virological response was achieved by 108/112 (96%) patients who received a triple antiviral regimen. In total 69 patients were lost to follow-up or died waiting for salvage treatment. Baseline cirrhosis was associated with poor long-term survival. CONCLUSION: Our study indicates that salvage therapy was effective in most patients with primary treatment failure, in particular when a triple direct acting antiviral regimen was given. To avoid the risk of death or complications, patients with primary treatment failure should be offered salvage therapy with a triple regimen, as soon as possible.

Management of influenza - updated Swedish guidelines for antiviral treatment.

Influenza causes seasonal epidemics of respiratory infection in all parts of the world. Manifestations of influenza range from mild upper to severe lower respiratory tract infection. Medical risk groups are defined by factors predisposing for development of severe disease and are recommended annual vaccination as a protective measure. The previous Swedish treatment guidelines for influenza were issued in 2011, and a review of current evidence was deemed relevant. An important reason to revisit the guidelines is the recent approval of a novel drug for influenza treatment, baloxavir. Updated Swedish evidence-based guidelines created by a group of experts from various research areas, for the management of influenza are presented here. The work has been made in collaboration with the Public Health Agency of Sweden and the Swedish Reference Group for AntiViral therapy (RAV). The updated guidelines include guidelines for diagnostics, treatment and prophylaxis in special groups, including management of pregnant women and children with influenza. A new section about infection control has been added. Pharmacological treatment is covered in detail with regards to indication and dosage. Additionally, drug resistance and environmental aspects are discussed.

Outdoor Absolute Humidity Predicts the Start of Norovirus GII Epidemics.

Seasonal variation of viral gastroenteritis is related to weather conditions, but the relationship with the incidence of viral gastroenteritis (GE) is not fully understood. This study examined the impact of outdoor climate factors on seasonal variation in detection rates of gastroenteritis viruses, with emphasis on norovirus. Weekly detection rates of norovirus genogroup I (GI) and II (GII), rotavirus, adenovirus, astrovirus, and sapovirus were analyzed in relation to average weekly means of meteorological parameters. Associations between rates of PCR detection of the viral GE pathogens and climate factors were investigated with generalized linear models. Low absolute humidity was correlated with increased detection of adenovirus (P = 0.007), astrovirus (P = 0.005), rotavirus (P = 0.004), norovirus GI (P = 0.001), and sapovirus (P = 0.002). In each investigated season, a drop in absolute humidity preceded the increase in norovirus GII detections. We found a correlation between declining absolute humidity and increasing norovirus GII detection rate. Absolute humidity was a better predictor of gastrointestinal virus seasonality compared to relative humidity. IMPORTANCE Viral gastroenteritis causes considerable morbidity, especially in vulnerable groups such as the elderly and chronically ill. Predicting the beginning of seasonal epidemics is important for the health care system to withstand increasing demands. In this paper we studied the association of outdoor climate factors on the detection rates of gastrointestinal viruses and the association between these factors and the onset of annual norovirus epidemics. Declining absolute humidity preceded the increase in diagnosed norovirus GII cases by approximately 1 week. These findings contribute to the understanding of norovirus epidemiology and allow health care services to install timely preventive measures and can help the public avoid transmission.

Teasing apart the joint effect of demography and natural selection in the birth of a contact zone.

Vast population movements induced by recurrent climatic cycles have shaped the genetic structure of plant species. During glacial periods species were confined to low-latitude refugia from which they recolonized higher latitudes as the climate improved. This multipronged recolonization led to many lineages that later met and formed large contact zones. We utilize genomic data from 5000 Picea abies trees to test for the presence of natural selection during recolonization and establishment of a contact zone in Scandinavia. Scandinavian P. abies is today made up of a southern genetic cluster originating from the Baltics, and a northern one originating from Northern Russia. The contact zone delineating them closely matches the limit between two major climatic regions. We show that natural selection contributed to its establishment and maintenance. First, an isolation-with-migration model with genome-wide linked selection fits the data better than a purely neutral one. Second, many loci show signatures of selection or are associated with environmental variables. These loci, regrouped in clusters on chromosomes, are often related to phenology. Altogether, our results illustrate how climatic cycles, recolonization and selection can establish strong local adaptation along contact zones and affect the genetic architecture of adaptive traits.

System dynamic modelling of healthcare associated influenza -a tool for infection control.

BACKGROUND: The transmission dynamics of influenza virus within healthcare settings are not fully understood. Capturing the interplay between host, viral and environmental factors is difficult using conventional research methods. Instead, system dynamic modelling may be used to illustrate the complex scenarios including non-linear relationships and multiple interactions which occur within hospitals during a seasonal influenza epidemic. We developed such a model intended as a support for health-care providers in identifying potentially effective control strategies to prevent influenza transmission. METHODS: By using computer simulation software, we constructed a system dynamic model to illustrate transmission dynamics within a large acute-care hospital. We used local real-world clinical and epidemiological data collected during the season 2016/17, as well as data from the national surveillance programs and relevant publications to form the basic structure of the model. Multiple stepwise simulations were performed to identify the relative effectiveness of various control strategies and to produce estimates of the accumulated number of healthcare-associated influenza cases per season. RESULTS: Scenarios regarding the number of patients exposed for influenza virus by shared room and the extent of antiviral prophylaxis and treatment were investigated in relation to estimations of influenza vaccine coverage, vaccine effectiveness and inflow of patients with influenza. In total, 680 simulations were performed, of which each one resulted in an estimated number per season. The most effective preventive measure identified by our model was administration of antiviral prophylaxis to exposed patients followed by reducing the number of patients receiving care in shared rooms. CONCLUSIONS: This study presents an system dynamic model that can be used to capture the complex dynamics of in-hospital transmission of viral infections and identify potentially effective interventions to prevent healthcare-associated influenza infections. Our simulations identified antiviral prophylaxis as the most effective way to control in-hospital influenza transmission.

Cell-free DNA as a biomarker after lung transplantation: A proof-of-concept study.

BACKGROUND: Lung transplantation (LTx) is a lifesaving procedure burdened with limited long-term survival. The most common cause of death after LTx is chronic lung allograft dysfunction (CLAD). Today, useful biomarkers for the detection of CLAD are lacking. Circulating cell-free DNA (cfDNA) is released during cellular decay and can be detected using polymerase chain reaction (PCR). Thus, donor-derived cfDNA in recipient serum indicates cellular decay in the transplanted organ. In the current study, we explore the possibility of using a novel PCR method to detect cfDNA as a biomarker for clinical events, especially CLAD. METHODS: Four patients were retrospectively tested for levels of both donor and recipient-derived cfDNA using digital droplet PCR after targeted preamplification. The results were correlated to recorded clinical events. RESULTS: All available samples rendered results. Both patients that later developed CLAD showed a persistently elevated ratio between donor-and recipient-derived cfDNA. Also, the mean level of cfDNA was higher in the two patients who later developed CLAD than in patients who did not (p = .0015). CONCLUSIONS: This proof-of-concept study suggests that cfDNA quantified with PCR may be used as a biomarker of significant clinical events such as CLAD.

Mortality of COVID-19 is associated with comorbidity in patients with chronic obstructive pulmonary disease.

BACKGROUND: The aim of this study was to compare the outcome of coronavirus disease 2019 (COVID-19) in hospitalised patients with chronic obstructive pulmonary disease (COPD) with the outcome in matched COVID-19 patients without COPD. METHODS: Sixty-three COPD patients hospitalised for acute COVID-19 from March through August 2020 were retrospectively identified and 63 hospitalised COVID-19 patients without COPD were selected and matched for age, gender and month of hospital admission. RESULTS: COPD patients had a higher rate of comorbidities, especially cardiovascular disease, and a trend towards a higher 30-day mortality than control patients (35% vs. 22%). In the COPD group, high Charlson comorbidity index (p = 0.03) and previous cerebrovascular disease (p = 0.04) were associated with 30-day mortality in univariate analysis. Inhaled corticosteroids maintenance therapy was not associated with lower mortality. CONCLUSION: COPD patients hospitalised for acute COVID-19 disease had significantly more comorbidities and a high risk of severe outcome and death within 30 days. Comorbidity, especially cardiovascular diseases, was associated with mortality among COPD patients.

Severe acute respiratory syndrome coronavirus 2 can be detected in exhaled aerosol sampled during a few minutes of breathing or coughing.

BACKGROUND: The knowledge on the concentration of viral particles in exhaled breath is limited. The aim of this study was to explore if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in aerosol from subjects with the coronavirus disease 2019 (COVID-19) during various types of breathing and coughing and how infection with SARS-CoV-2 may influence the number and size of exhaled aerosol particles. METHODS: We counted and collected endogenous particles in exhaled breath in subjects with COVID-19 disease by two different impaction-based methods, during 20 normal breaths, 10 airway opening breaths, and three coughs, respectively. Breath samples were analyzed with reverse transcription real-time polymerase chain reaction (RT-PCR). RESULTS: Detection of RNA in aerosol was possible in 10 out of 25 subjects. Presence of virus RNA in aerosol was mainly found in cough samples (n = 8), but also in airway opening breaths (n = 3) and in normal breaths (n = 4), with no overlap between the methods. No association between viral load in aerosol and number exhaled particles <5 µm was found. Subjects with COVID-19 exhaled less particles than healthy controls during normal breathing and airway opening breaths (all P < 0.05), but not during cough. CONCLUSION: SARS-CoV-2 RNA can be detected in exhaled aerosol, sampled during a limited number of breathing and coughing procedures. Detection in aerosol seemed independent of viral load in the upper airway swab as well as of the exhaled number of particles. The infectious potential of the amount of virus detected in aerosol needs to be further explored.

Assessment of the FilmArray ME panel in 4199 consecutively tested cerebrospinal fluid samples.

OBJECTIVES: In central nervous system infections, early and correct management is of utmost importance. Rapid syndromic panel testing can potentially provide valuable guidance. The FilmArray meningitis/encephalitis (ME) panel detects 14 pathogens through multiplex PCR. Our study objectives were to assess its performance compared with established diagnostic procedures, especially real-time quantitative PCR for detection of viruses, and to determine the diagnostic and clinical significance of discrepant results. METHODS: All cerebrospinal fluid samples sent for viral diagnostics to our microbiological laboratory over 34 months were analysed with the ME panel and in-house real-time PCR for herpes simplex virus type 1 (HSV-1), HSV-2, varicella zoster virus and enteroviruses. Other pathogens detected by the panel were confirmed by routine diagnostic procedures. Discrepant results were analysed through interpretation of biological and clinical data, and performance data were calculated for individual pathogens. RESULTS: Altogether, 315 pathogens were detected by the ME panel in 4199 cerebrospinal fluid samples (7.5%) and an additional 21 viral targets were identified using real-time PCR. Thirty-four ME panel detections were not confirmed, totalling 55 discrepant results. After discrepancy analysis, 20 false-positive and 21 false-negative ME panel results remained. Performance varied between pathogens. Sensitivity for HSV-1 was calculated at 82.4% (59.0%-93.8%) with three false-negative results. Also noteworthy were 13 false-negative enterovirus and eight false-positive Streptococcus pneumoniae results. CONCLUSIONS: Our analysis shows good performance for the ME panel in diagnosing central nervous system infection. The risk of false-negative HSV-1 results, however, warrants additional testing when encephalitis is suspected. Uncertainties in interpretation of enterovirus and S. pneumoniae results represent other limitations.

Unexpected details regarding nosocomial transmission revealed by whole-genome sequencing of severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

OBJECTIVE: Effective infection prevention and control (IPC) measures are key for protecting patients from nosocomial infections and require knowledge of transmission mechanisms in different settings. We performed a detailed outbreak analysis of the transmission and outcome of coronavirus disease 2019 (COVID-19) in a geriatric ward by combining whole-genome sequencing (WGS) with epidemiological data. DESIGN: Retrospective cohort study. SETTING: Tertiary-care hospital. PARTICIPANTS: Patients and healthcare workers (HCWs) from the ward with a nasopharyngeal sample (NPS) positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA during the outbreak period. METHODS: Patient data regarding clinical characteristics, exposure and outcome were collected retrospectively from medical records. Stored NPSs from 32 patients and 15 HCWs were selected for WGS and phylogenetic analysis. RESULTS: The median patient age was 84 years and 17 (53%) of 32 were male. Also, 14 patients (44%) died within 30 days of sampling. Viral loads were significantly higher among the deceased. WGS was successful in 28 (88%) of 32 patient samples and 14 (93%) of 15 HCW samples. Moreover, 3 separate viral clades were identified: 1 clade and 2 subclades among both patient and HCW samples. Integrated epidemiological and genetic analyses revealed 6 probable transmission events between patients and supported hospital-acquired COVID-19 among 25 of 32 patients. CONCLUSIONS: WGS provided an insight into the outbreak dynamics and true extent of nosocomial COVID-19. The extensive transmission between patients and HCWs indicated that current IPC measures were insufficient. We recommend increased use of WGS in outbreak investigations to identify otherwise unknown transmission links and to evaluate IPC measures.

Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis.

OBJECTIVE: Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. DESIGN: Secondary analysis of randomized controlled trial data. SETTING: Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018. SUBJECTS: A total of 277 ILI patients aged one year or older and symptom duration of ≤72 h. MAIN OUTCOME MEASURES: Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering. RESULTS: At baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0-210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23). CONCLUSION: There was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.Key PointsPredicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians.• There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care.• There was no association between CRP concentration at baseline and benefit from oseltamivir treatment.• We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

COMP: A Potential Early Biomarker of RAS After Lung Transplantation.

BACKGROUND: Chronic rejection, defined as chronic lung allograft dysfunction (CLAD), is the major factor limiting long-term survival after lung transplantation (LTx). A specific subgroup of CLAD is restrictive allograft syndrome (RAS). CLAD's pathogenesis is largely unknown, but previous findings suggest that it is associated with increased fibrosis in the transplanted lung. Cartilage oligomeric matrix protein (COMP) has been associated with multiple fibrotic conditions. The current study aimed to explore the relation between COMP serum levels and development of CLAD, and RAS in particular, in a retrospective cohort of LTx patients. METHODS: This study included retrospective data from patients who underwent LTx during 2009-2011. Blood samples and spirometry data were obtained at follow-up visits 1, 3, 6, 9, and 12 mo after transplantation. Serum samples were analyzed for COMP. CLAD and RAS were defined according to the 2019 International Society for Heart and Lung Transplantation consensus document. RESULTS: Data from 38 patients (19 men and women, respectively) were collected. Twenty-three patients (60.5%) developed CLAD, of whom 6 (26.1 %) fulfilled the criteria for RAS. Patients who developed RAS had higher mean COMP levels between 1 and 3 mo after LTx than those who did not develop RAS (10.9 [3.9-17.5] U/L vs 7.4 [3.9-10.8] U/L, P = 0.008). RAS was also associated with shorter survival. We found no association between COMP levels and CLAD of other types than RAS. CONCLUSIONS: Serum level of COMP early after LTx seems to be associated with RAS development and might serve as a biomarker suitable for clinical use in the LTx setting.

Risk factors for norovirus infection in healthcare workers during nosocomial outbreaks: a cross-sectional study.

BACKGROUND: Norovirus outbreaks cause severe medico-socio-economic problems affecting healthcare workers and patients. The aim of the study was to investigate prevalence of norovirus infection and risk factors for infection in healthcare workers during nosocomial outbreaks. METHODS: A cross-sectional study of norovirus infections in healthcare workers was performed in seven outbreak wards in a large university hospital. Packs (swab for rectal sampling, and questionnaire) were posted to healthcare workers on notification of a ward outbreak. Rectal samples were examined with norovirus-specific real-time PCR. Replies from questionnaires were analysed using logistic regression models with norovirus genogroup (G)II positive findings as dependent variable. The results are expressed as odds ratios (OR) with 95% confidence intervals (CI). Sequencing and phylogenetic analyses (1040 nucleotides) were used to characterize norovirus strains from healthcare workers. Cluster analyses included norovirus GII.4 strains detected in ward patients during the ongoing outbreaks. RESULTS: Of 308 packs issued to healthcare workers, 129 (42%) were returned. norovirus GII was detected in 26 healthcare workers (20.2%). Work in cohort care (OR 4.8, 95% CI 1.4-16.3), work in wards for patients with dementia (OR 13.2, 95% CI 1.01-170.7), and having diarrhoea, loose stools or other gastrointestinal symptoms the last week (OR 7.7, 95% CI 2.5-27.2) were associated with increased norovirus prevalence in healthcare workers. Sequencing revealed norovirus GII.4 in healthcare workers samples, and strains detected in healthcare workers and ward patients during a given ward outbreak showed ≥ 99% similarity. CONCLUSION: Norovirus positive findings in healthcare workers were strongly associated with symptomatic infection, close contact with sick patients, and dementia nursing.

Leveraging breeding programs and genomic data in Norway spruce (Picea abies L. Karst) for GWAS analysis.

BACKGROUND: Genome-wide association studies (GWAS) identify loci underlying the variation of complex traits. One of the main limitations of GWAS is the availability of reliable phenotypic data, particularly for long-lived tree species. Although an extensive amount of phenotypic data already exists in breeding programs, accounting for its high heterogeneity is a great challenge. We combine spatial and factor-analytics analyses to standardize the heterogeneous data from 120 field experiments of 483,424 progenies of Norway spruce to implement the largest reported GWAS for trees using 134 605 SNPs from exome sequencing of 5056 parental trees. RESULTS: We identify 55 novel quantitative trait loci (QTLs) that are associated with phenotypic variation. The largest number of QTLs is associated with the budburst stage, followed by diameter at breast height, wood quality, and frost damage. Two QTLs with the largest effect have a pleiotropic effect for budburst stage, frost damage, and diameter and are associated with MAP3K genes. Genotype data called from exome capture, recently developed SNP array and gene expression data indirectly support this discovery. CONCLUSION: Several important QTLs associated with growth and frost damage have been verified in several southern and northern progeny plantations, indicating that these loci can be used in QTL-assisted genomic selection. Our study also demonstrates that existing heterogeneous phenotypic data from breeding programs, collected over several decades, is an important source for GWAS and that such integration into GWAS should be a major area of inquiry in the future.

Presence of interferon-λ 4, male gender, absent/mild steatosis and low viral load augment antibody levels to hepatitis C virus.

OBJECTIVES: Despite recombinant interferon-λ 4 (IFN-λ4) demonstrating anti-viral activity in vitro and the ancestral functional gene (IFNL4) being conserved in all other primates, there has been speculation that IFN-λ4 may be detrimental in humans. In light of recent rekindled interest in humoral immunity, this study aimed at evaluating the impact of baseline characteristics, including IFNL4, on antibody levels to hepatitis C virus (HCV). MATERIALS AND METHODS: Pretreatment sera from 279 well-characterized North European Caucasians with chronic HCV genotype 2 or 3 infection having undergone liver biopsy were analyzed regarding IFNL4 (rs12979860) and anti-HCV antibody levels using a commercially available assay. RESULTS: Patients producing IFN-λ4 had higher signal to cut-off (S/CO) anti-HCV antibody ratios as compared with those lacking IFN-λ4 (IFNL4rs12979860 CT/TT versus CC, p<.0001, Mann-Whitney U-test). Additionally, in univariate analyses S/CO was significantly higher in men than women (p<.001), as well as in patients with absent/mild interface hepatitis (Ishak grade 0-2 versus 3-4, p = .009), and absent/mild steatosis (grade 0-1 versus 2-3, p = .0005). Also, an inverse correlation with HCV RNA level (rs= -0.14, p = .02) was noted. In multivariate analysis IFN-λ4, gender, steatosis and viral load remained independently associated. CONCLUSIONS: To our knowledge, this is the first report that demonstrates that the ability to produce IFN-λ4, in addition to male gender, absent/mild steatosis, and lower viral load, augments antibody levels against HCV. This indicates that IFN-λ4 may be associated with T helper cell 2 (Th2) immune skewing, which might have clinical implications beyond HCV infection. ClinicalTrials.gov Identifier: NCT00143000.