Search

In response to strong selection, new mutations can arise quickly and sweep through populations, particularly, if survival and reproduction depend on certain allele copies for adaptation to rapidly changing environments, like resistance against deadly diseases or strong toxins. Since the 1950s, resistance to anticoagulant rodenticides in several rodents has emerged through single nucleotide mutations in the vitamin-K-epoxid-reductase-complex-subunit-1 (VKORC1) gene, often located in its exon 3. Detection of high prevalence and concentrations of anticoagulant rodenticides in non-target vertebrates, including carnivorous Mustelidae, let us assume that secondary exposure by feeding on poisoned prey may also cause selection along the food chain and we hypothesized that VKORC1-based resistance might also have evolved in rodents’ predators. Using newly-developed mustelid-specific primers for direct sequencing of genomic DNA, we studied VKORC1-DNA-polymorphisms in 115 mustelids of five species (Martes martes, M. foina, Mustela nivalis, M. erminea, M. putorius), obtained from northern Denmark, yielding six sites with nonsynonymous and several synonymous amino acid polymorphisms in exon 3. Comparison of these VKORC1-genotypes with hepatic rodenticide residues (obtained by HPLC combined with fluorescence or mass spectrometry) in 83 individuals (except M. martes), using generalized linear models, suggested that anticoagulant levels depended on species and specific polymorphisms. Although most VKORC-1 polymorphisms may present standing genetic variation, some are situated in resistance-mediating membrane parts of the VKORC1-encoded protein, and might be a result of selection due to exposure to anticoagulant poisons. Our new molecular markers might allow detecting indirect effects of anticoagulant rodenticides on rodent predator populations in the future. [ABSTRACT FROM AUTHOR]

Background: Although increasingly used, the benefit of surgical treatment of displaced 2-part proximal humerus fractures has not been proven. This trial evaluates the clinical effectiveness of surgery with locking plate compared with non-operative treatment for these fractures.Methods and Findings: The NITEP group conducted a superiority, assessor-blinded, multicenter randomized trial in 6 hospitals in Finland, Estonia, Sweden, and Denmark. Eighty-eight patients aged 60 years or older with displaced (more than 1 cm or 45 degrees) 2-part surgical or anatomical neck proximal humerus fracture were randomly assigned in a 1:1 ratio to undergo either operative treatment with a locking plate or non-operative treatment. The mean age of patients was 72 years in the non-operative group and 73 years in the operative group, with a female sex distribution of 95% and 87%, respectively. Patients were recruited between February 2011 and April 2016. The primary outcome measure was Disabilities of Arm, Shoulder, and Hand (DASH) score at 2-year follow-up. Secondary outcomes included Constant-Murley score, the visual analogue scale for pain, the quality of life questionnaire 15D, EuroQol Group's 5-dimension self-reported questionnaire EQ-5D, the Oxford Shoulder Score, and complications. The mean DASH score (0 best, 100 worst) at 2 years was 18.5 points for the operative treatment group and 17.4 points for the non-operative group (mean difference 1.1 [95% CI -7.8 to 9.4], p = 0.81). At 2 years, there were no statistically or clinically significant between-group differences in any of the outcome measures. All 3 complications resulting in secondary surgery occurred in the operative group. The lack of blinding in patient-reported outcome assessment is a limitation of the study. Our assessor physiotherapists were, however, blinded.Conclusions: This trial found no significant difference in clinical outcomes at 2 years between surgery and non-operative treatment in patients 60 years of age or older with displaced 2-part fractures of the proximal humerus. These results suggest that the current practice of performing surgery on the majority of displaced proximal 2-part fractures of the humerus in older adults may not be beneficial.Trial Registration: ClinicalTrials.gov NCT01246167. [ABSTRACT FROM AUTHOR]

Background: Intermittent auscultation (IA) is the technique of listening to and counting the fetal heart rate (FHR) for short periods during active labour and continuous cardiotocography (CTC) implies FHR monitoring for longer periods. Although the evidence suggests that IA is the best way to monitor healthy women at low risk of complications, there is no scientific evidence for the ideal device, timing, frequency and duration for IA. We aimed to give an overview of the field, identify and describe methods and practices for performing IA, map the evidence and accuracy for different methods of IA, and identify research gaps. Methods: We conducted a systematic scoping review following the Joanna Briggs methodology. Medline, EMBASE, Cinahl, Maternity & Infant Care, Cochrane Library, SveMed+, Web of Science, Scopus, Lilacs and African Journals Online were searched for publications up to January 2019. We did hand searches in relevant articles and databases. Studies from all countries, international guidelines and national guidelines from Denmark, United Kingdom, United States, New Zealand, Australia, The Netherlands, Sweden, Denmark, and Norway were included. We did quality assessment of the guidelines according to the AGREEMENT tool. We performed a meta-analysis assessing the effects of IA with a Doppler device vs. Pinard device using methods described in The Cochrane Handbook, and we performed an overall assessment of the summary of evidence using the GRADE approach. Results: The searches generated 6408 hits of which 26 studies and 11 guidelines were included in the review. The studies described slightly different techniques for performing IA, and some did not provide detailed descriptions. Few of the studies provided details of normal and abnormal IA findings. All 11 guidelines recommended IA for low risk women, although they had slightly different recommendations on the frequency, timing, and duration for IA, and the FHR characteristics that should be observed. Four of the included studies, comprising 8436 women and their babies, were randomised controlled trials that evaluated the effect of IA with a Doppler device vs. a Pinard device. Abnormal FHRs were detected more often using the Doppler device than in those using the Pinard device (risk ratio 1.77; 95% confidence interval 1.29–2.43). There were no significant differences in any of the other maternal or neonatal outcomes. Four studies assessed the accuracy of IA findings. Normal FHR was easiest to identify correctly, whereas identifying periodic FHR patterns such as decelerations and saltatory patterns were more difficult. Conclusion: Although IA is the recommended method, no trials have been published that evaluate protocols on how to perform it. Nor has any study assessed interrater agreements regarding interpretations of IA findings, and few have assessed to what degree clinicians can describe FHR patterns detected by IA. We found no evidence to recommend Doppler device instead of the Pinard for IA, or vice versa. [ABSTRACT FROM AUTHOR]

Background: Despite improvements in treatment for rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (axSpA), several key unmet needs remain, such as fatigue. The objective of this study was to describe the severity of fatigue, disease characteristics and socioeconomic factors in people with RA, PsA and axSpA. Methods: The study was designed as a cross-sectional survey collecting patient characteristics such as disease characteristics, socioeconomic factors and fatigue in people with RA, PsA and axSpA in Denmark. Respondents were consecutively recruited for the study over a six-month period in 2018 via routine visits to outpatient rheumatology clinics. Study nurses collected information on diagnosis, current disease-related treatment and disease activity from medical journals. People were invited to complete a questionnaire related to socioeconomic factors and containing the FACIT-Fatigue subscale. Descriptive statistics were analyzed using SAS. Results: We invited 633 people to participate, and 488 (77%) completed the questionnaire. Women constituted 62% of respondents, and the mean age was 53.5 years. Respondents had on average been diagnosed between 11 and 15 years ago. Overall, 79% had no changes to their disease-related treatment during the past year, and the average disease activity as indicated by DAS28 for RA and PsA was 2.48 and 2.36, respectively, and BASDAI for axSpA was 28.40. Fatigue was present in all three diagnoses (mean: 34.31). The mean fatigue score varied from respondents answering that they suffered from no or little fatigue (mean: 45.48) to extreme fatigue (mean: 10.11). Analyses demonstrated that the respondents were not considerably different from nonrespondents, and the study population is considered representative compared with Danish RA and axSpA patients in the Danish National Rheumatology Registry, the DANBIO database. Conclusion: We found that the majority of the study population were fatigued (61%). They had low disease activity and few disease-related treatment changes. [ABSTRACT FROM AUTHOR]

Objective: To examine the test performance of careHPV, Hybrid Capture2 (HC2) and visual inspection with acetic acid (VIA) for detection of cytologically diagnosed high-grade cervical lesions or cancer (HSIL+). Design: Cross-sectional study. Setting: Ocean Road Cancer Institute (ORCI) and Kilimanjaro Christian Medical Center (KCMC), Tanzania. Population: Women attending routine cervical cancer screening. Method: We enrolled 4080 women (25–60 years) in the study. The women were interviewed on lifestyle habits, and tested for HIV. A cervical specimen for careHPV testing (performed at ORCI and KCMC), and a liquid-based cytology sample for HPV DNA detection using HC2 (performed at Tuebingen University Hospital, Germany) and for cytology assessment (performed at Vejle Hospital, Denmark) were obtained at a gynecological examination. Subsequently, VIA was performed. With cytology as gold standard, the sensitivity and specificity of careHPV, HC2, and VIA for detection of HSIL+ were calculated. Results: Altogether, 23.6% had a positive careHPV test, 19.1% had positive HC2 test, and 6.3% had a positive VIA test. The sensitivity/specificity was 88.9%/78.9% for careHPV and 91.1%/83.7%, for HC2. VIA showed a low sensitivity of 31.1% but a high specificity (94.6%) for detection of HSIL+. The sensitivity of careHPV, HC2 and VIA was higher among younger women, and among HIV positive women. VIA triage of careHPV positive women improved specificity, but sensitivity dropped to 27%. Conclusion: Our results confirm the low sensitivity of VIA for detection of HSIL+ and further document that careHPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. A suitable triage test has to be identified. [ABSTRACT FROM AUTHOR]

Monitoring and managing customers’ satisfaction are key features to benefit from today’s competitive environment. In higher education context, only a few studies are available on satisfaction and loyalty of the main customers who are the students, which signifies the need to investigate the field more thoroughly. The aim of this research is to measure the strength of determinants of students’ satisfaction and the importance of antecedents in students’ satisfaction and loyalty in Denmark. Our research model is the modification of European Performance Satisfaction Index (EPSI), which takes the university’s image direct effects on students’ expectations into account from students’ perspective. The structural equation model of student satisfaction and loyalty has been evaluated using partial least square path modelling. Our findings confirm that the EPSI framework is applicable on student satisfaction and loyalty among Danish universities. We show that all the relationships among variables of the research model are significant except the relationship between quality of software and students’ loyalty. Results further verify the significance of antecedents in students’ satisfaction and loyalty at Danish universities; the university image and student satisfaction are the antecedents of student loyalty with a significant direct effect, while perceived value, quality of hardware, quality of software, expectations, and university image are antecedents of student satisfaction. Eventually, our findings may be of an inspiration to maintain and improve students’ experiences during their study at the university. Dedicating resources to identified important factors from students’ perception enable universities to attract more students, make them highly satisfied and loyal. [ABSTRACT FROM AUTHOR]

Background: Congenital toxoplasmosis (CT) causes a substantial disease burden worldwide. The aim of this study was to estimate the disease burden of CT in Denmark, a developed country with free public healthcare and nationwide data available. Methods: Using data primarily from two public health surveillance programmes conducted between 1992 and 2007, we estimated the incidence, occurrence of sequelae, mortality and the burden of disease in terms of disability-adjusted life years (DALYs) of CT in Denmark in 2014. Findings: We estimated that 14 children were born with CT in 2014, of which six will have developed sequelae by the age of 12. CT resulted in a total disease burden of 123 DALYs (95% uncertainty interval [UI], 100–148), of which 78 (95% UI, 64–94) were due to foetal loss and 2 (95% UI, 1–3) were due to neonatal death; the remaining burden was due to moderate to severe life-long sequelae. A comparison of the estimated incidence of CT with the number of reported CT cases in 2008–2014 indicated that for each reported CT case, at least five other CT cases could be expected to have occurred and gone unreported. Interpretation: Early onset, severity, and life-long duration of sequelae have a major effect on the disease burden of CT. Our data suggest that CT is under-diagnosed or under-reported in Denmark. The estimated disease burden and public health impact in Denmark is lower than in other European countries, highlighting the need for country-specific studies. [ABSTRACT FROM AUTHOR]

Objective: To audit the clinical management preceding peripartum hysterectomy and evaluate if peripartum hysterectomies are potentially avoidable and by which means. Material and Methods: We developed a structured audit form based on explicit criteria for the minimal mandatory management of the specific types of pregnancy and delivery complications leading to peripartum hysterectomy. We evaluated medical records of the 50 Danish women with peripartum hysterectomy identified in the Nordic Obstetric Surveillance Study 2009–2012 and made short narratives of all cases. Results: The most frequent indication for hysterectomy was hemorrhage. The two main initial causes were abnormally invasive placenta (26%) and lacerations (26%). Primary atony was third and occurred in 20%. Before hysterectomy another 26% had secondary atony following complications such as lacerations, retained placental tissue or coagulation defects. Of the 50 cases, 24% were assessed to be avoidable and 30% potentially avoidable. Hysterectomy following primary and secondary atony was assessed to be avoidable in 4/10 and 4/13 cases, respectively. Early sufficient suturing of lacerations and uterine ruptures, as well as a more widespread use of intrauterine balloons alone or in combination with uterine compression sutures (the sandwich model), could presumably have prevented about one fourth of the peripartum hysterectomies. Conclusion: More than 50% of peripartum hysterectomies seem to be avoidable by simple measures. In order to minimize the number of unnecessary peripartum hysterectomies, obstetricians and anesthesiologists should investigate individual cases by structured clinical audit, and disseminate and discuss the results for educational purposes. An international collaboration is warranted to strengthen our recommendations and reveal if they are generally applicable. [ABSTRACT FROM AUTHOR]

Background: Dialysis-requiring acute kidney injury (AKI) is associated with substantial mortality and risk of end-stage renal disease (ESRD). Despite considerable growth in incidence of severe AKI, information pertaining to trends in outcomes remains limited. We evaluated time trends in one year risks of ESRD and death in patients with dialysis-requiring AKI over an eight year period in Denmark. Methods: In a retrospective nationwide study based on national registers, all adults requiring acute renal replacement therapy between 2005 and 2012 were identified. Patients with preceding ESRD were excluded. Through individual-level cross-referencing of administrative registries, information pertaining to comorbidity, preceding surgical interventions, and concurrent other organ failure and sepsis was ascertained. Comparisons of period-specific one year odds ratios for ESRD and death were calculated in a multiple logistic regression model. Results: A total of 13,819 patients with dialysis-requiring AKI were included in the study. Within one year, 1,017 (7.4%) patients were registered with ESRD, and 7,908 (57.2%) patients died. The one-year rate of ESRD decreased from 9.0% between 2005 and 2006 to 6.1% between 2011 and 2012. Simultaneously, the one-year mortality rate decreased from 58.2% between 2005 and 2006 to 57.5% between 2011 and 2012. Consequently, the adjusted odds ratios for the period 2011–2012 (with the period 2005–2006 as reference) were 0.75 (0.60–0.95, p = 0.015) and 0.87 (95% CI 0.78–0.97, p = 0.010) for ESRD and death, respectively. Conclusions: In a nationwide retrospective study on time trends in one year outcomes following dialysis-requiring AKI, risk of all-cause mortality and ESRD decreased over a period of 8 years. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a well-known occupational hazard. Based on more than two decades (1992–2012) of centralized nationwide genotyping of all Mycobacterium tuberculosis culture-positive TB patients in Denmark, we compared M. tuberculosis genotypes from all cases notified as presumed occupational (N = 130) with M. tuberculosis genotypes from all TB cases present in the country (N = 7,127). From 1992 through 2006, the IS6110 Restriction Fragment Length Polymorphism (RFLP) method was used for genotyping, whereas from 2005 to present, the 24-locus-based Mycobacterial Interspersed Repetitive Unit-Variable Number of Tandem Repeat (MIRU-VNTR) was used. An occupational TB case was classified as clustered if the genotype was 100% identical to at least one other genotype. Subsequently, based on genotype, time period, smear positivity, geography, susceptibility pattern, and any reported epidemiological links between the occupational cases and any potential source cases, the occupational case was categorized as confirmed, likely, possible or unlikely occupationally infected. Among the 130 notified presumed occupational cases, 12 (9.2%) could be classified as confirmed and 46 (35.4%) as unlikely, accounting for nearly half of all cases (44.6%). The remaining 72 cases (55.4%) were categorized as possible. Within this group, 15 cases (11.5%) were assessed to be likely occupational. Our study shows that genotyping can serve as an important tool for disentangle occupational TB in high-income low incidence settings, but still needs to be combined with good epidemiological linkage information. [ABSTRACT FROM AUTHOR]

Introduction: Dialysis-requiring acute kidney injury is a severe illness associated with poor prognosis. However, information pertaining to incidence rates and prevalence of risk factors remains limited in spite of increasing focus. We evaluate time trends of incidence rates and changing patterns in prevalence of comorbidities, concurrent medication, and other risk factors in nationwide retrospective cohort study. Materials and Methods: All patients with dialysis-requiring acute kidney injury were identified between January 1st 2000 and December 31st 2012. By cross-referencing data from national administrative registries, the association of changing patterns in dialysis treatment, comorbidity, concurrent medication and demographics with incidence of dialysis-requiring acute kidney injury was evaluated. Results: A total of 18,561 adult patients with dialysis-requiring AKI were identified between 2000 and 2012. Crude incidence rate of dialysis-requiring AKI increased from 143 per million (95% confidence interval, 137–144) in 2000 to 366 per million (357–375) in 2006, and remained stable hereafter. Notably, incidence of continuous veno-venous hemodialysis (CRRT) and use of acute renal replacement therapy in elderly >75 years increased substantially from 23 per million (20–26) and 328 per million (300–355) in 2000, to 213 per million (206–220) and 1124 per million (1076–1172) in 2012, respectively. Simultaneously, patient characteristics and demographics shifted towards increased age and comorbidity. Conclusions: Although growth in crude incidence rate of dialysis-requiring AKI stabilized in 2006, continuous growth in use of CRRT, and acute renal replacement therapy of elderly patients >75 years, was observed. Our results indicate an underlying shift in clinical paradigm, as opposed to unadulterated growth in incidence of dialysis-requiring AKI. [ABSTRACT FROM AUTHOR]

In December 2012, an outbreak of acute gastrointestinal illness occurred in a geographical distinct area in Denmark covering 368 households. A combined microbiological, epidemiological and environmental investigation was initiated to understand the outbreak magnitude, pathogen(s) and vehicle in order to control the outbreak. Norovirus GII.4 New Orleans 2009 variant was detected in 15 of 17 individual stool samples from 14 households. Norovirus genomic material from water samples was detected and quantified and sequencing of longer parts of the viral capsid region (>1000 nt) were applied to patient and water samples. All five purposely selected water samples tested positive for norovirus GII in levels up to 1.8×104 genomic units per 200 ml. Identical norovirus sequences were found in all 5 sequenced stool samples and 1 sequenced water sample, a second sequenced water sample showed 1 nt (<0.1%) difference. In a cohort study, including 256 participants, cases were defined as residents of the area experiencing diarrhoea or vomiting onset on 12–14 December 2012. We found an attack rate of 51%. Being a case was associated with drinking tap-water on 12–13 December (relative risk = 6.0, 95%CI: 1.6–22) and a dose-response relation for the mean glasses of tap-water consumed was observed. Environmental investigations suggested contamination from a sewage pipe to the drinking water due to fall in pressure during water supply system renovations. The combined microbiological, epidemiological and environmental investigations strongly indicates the outbreak was caused by norovirus contamination of the water supply system. [ABSTRACT FROM AUTHOR]

Denmark has an extraordinarily large and well-preserved collection of archaeological skin garments found in peat bogs, dated to approximately 920 BC – AD 775. These objects provide not only the possibility to study prehistoric skin costume and technologies, but also to investigate the animal species used for the production of skin garments. Until recently, species identification of archaeological skin was primarily performed by light and scanning electron microscopy or the analysis of ancient DNA. However, the efficacy of these methods can be limited due to the harsh, mostly acidic environment of peat bogs leading to morphological and molecular degradation within the samples. We compared species assignment results of twelve archaeological skin samples from Danish bogs using Mass Spectrometry (MS)-based peptide sequencing, against results obtained using light and scanning electron microscopy. While it was difficult to obtain reliable results using microscopy, MS enabled the identification of several species-diagnostic peptides, mostly from collagen and keratins, allowing confident species discrimination even among taxonomically close organisms, such as sheep and goat. Unlike previous MS-based methods, mostly relying on peptide fingerprinting, the shotgun sequencing approach we describe aims to identify the complete extracted ancient proteome, without preselected specific targets. As an example, we report the identification, in one of the samples, of two peptides uniquely assigned to bovine foetal haemoglobin, indicating the production of skin from a calf slaughtered within the first months of its life. We conclude that MS-based peptide sequencing is a reliable method for species identification of samples from bogs. The mass spectrometry proteomics data were deposited in the ProteomeXchange Consortium with the dataset identifier PXD001029. [ABSTRACT FROM AUTHOR]

The objectives of this study were to assess whether current surveillance capacity is sufficient to fulfill EU and Danish regulations to control a hypothetical foot-and-mouth disease (FMD) epidemic in Denmark, and whether enlarging the protection and/or surveillance zones could minimize economic losses. The stochastic spatial simulation model DTU-DADS was further developed to simulate clinical surveillance of herds within the protection and surveillance zones and used to model spread of FMD between herds. A queuing system was included in the model, and based on daily surveillance capacity, which was 450 herds per day, it was decided whether herds appointed for surveillance would be surveyed on the current day or added to the queue. The model was run with a basic scenario representing the EU and Danish regulations, which includes a 3 km protection and 10 km surveillance zone around detected herds. In alternative scenarios, the protection zone was enlarged to 5 km, the surveillance zone was enlarged to 15 or 20 km, or a combined enlargement of the protection and surveillance zones was modelled. Sensitivity analysis included changing surveillance capacity to 200, 350 or 600 herds per day, frequency of repeated visits for herds in overlapping surveillance zones from every 14 days to every 7, 21 and 30 days, and the size of the zones combined with a surveillance capacity increased to 600 herds per day. The results showed that the default surveillance capacity is sufficient to survey herds on time. Extra resources for surveillance did not improve the situation, but fewer resources could result in larger epidemics and costs. Enlarging the protection zone was a better strategy than the basic scenario. Despite that enlarging the surveillance zone might result in shorter epidemic duration, and lower number of affected herds, it resulted frequently in larger economic losses. [ABSTRACT FROM AUTHOR]

Background: The QuantiFERON-TB-Gold Test (QFT) is more specific than the Mantoux skin-test to discriminate between Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterial (NTM) infections. Here we study the performance of the QFT in patients with NTM disease. Methods: From 2005 to 2011, nationwide patient data on positive NTM cultures (n = 925) were combined with nationwide data on QFT results (n = 16,133), both retrieved from the International Reference Laboratory of Mycobacteriology, Denmark. A total of 112 patients with NTM infections had a QFT performed, 53 patients had definite NTM disease, 10 had possible disease and 49 had NTM colonization. Results: QFT was positive in 8% (4/53) of patients with definite disease, 40% (4/10) with possible disease and 31% (15/49) with colonization. Positivity rate was lowest among patients with definite disease infected with NTM without the RD1 region 4% (2/50). None of the 15 children with MAC lymphadenitis had a positive QFT. Conclusion: This study is one of the largest assessing IGRAs in patients with NTM disease in a TB low-incidence setting. Our study showed that the QFT holds potential to discriminate between NTM and MTB infections. We found no positive IGRA test results among children with NTM not sharing the RD1-region of MTB resulting in a 100% specificity and we suggest that a QFT in a child presenting with cervical lymphadenitis may be helpful in distinguishing NTM from TB lymphadenitis. [ABSTRACT FROM AUTHOR]