Cryptosporidium species and subtypes identified in human domestic cases through the national microbiological surveillance programme in Sweden from 2018 to 2022.

BACKGROUND: The intestinal protozoan parasite Cryptosporidium is an important cause of diarrheal disease worldwide. A national microbiological surveillance programme was implemented in Sweden in 2018 in order to increase knowledge of the molecular epidemiology of human cryptosporidiosis to better understand transmission patterns and potential zoonotic sources. This article summarises the results of the first five years of the surveillance programme. METHODS: Cryptosporidium-positive faecal and DNA samples from domestically acquired infections were collected from clinical microbiological laboratories in Sweden. Species and subtype determination was performed using 60 kDa glycoprotein and/or small subunit ribosomal RNA gene analysis. RESULTS: Between 2018 and 2022, 1654 samples were analysed and 11 different species were identified: C. parvum (n = 1412), C. mortiferum (n = 59), C. hominis (n = 56), C. erinacei (n = 11), C. cuniculus (n = 5), C. meleagridis (n = 3), C. equi (n = 2), C. ubiquitum (n = 2), and one each of C. canis, C. ditrichi and C. felis. Subtyping revealed seven subtype families of C. parvum (new subtype families IIy and IIz) and 69 different subtypes (11 new subtypes). The most common C. parvum subtypes were IIdA22G1c, IIdA24G1, IIdA15G2R1 and IIaA16G1R1b. For C. hominis, four different subtype families and nine different subtypes (two new subtypes) were identified. For additional species, two new subtype families (IIIk and VId) and nine new subtypes were identified. All successfully subtyped C. mortiferum cases were subtype XIVaA20G2T1, confirming previous findings in Sweden. Several outbreaks were identified of which the majority were foodborne and a few were due to direct contact with infected animals. CONCLUSION: Infection with C. parvum is the leading cause of human cryptosporidiosis acquired in Sweden, where more than 90% of domestic cases are caused by this zoonotic species and only a small proportion of cases are due to infection with other species. The rodent-associated C. mortiferum is considered an emerging zoonotic species in Sweden and the number of domestically acquired human cases has surpassed that of infection with C. hominis. A high diversity of species and subtypes, as well as diversity within the same subtype, was detected. Also, cryptosporidiosis appears to affect adults to a great extent in Sweden.

Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study.

BACKGROUND: Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose. OBJECTIVES: The objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH. METHODS: In the Highlow study (NCT01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH. RESULTS: In total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference -11%, 95% CI -20% to -2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference -13%, 95% CI -18% to -8%). CONCLUSION: With spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection.

The use of tourniquet in primary total knee arthroplasty does not increase the risk of venous thromboembolism within 90 days of surgery: a Danish nationwide cohort study of 19,804 patients.

PURPOSE: Existing evidence estimates a twofold risk of venous thromboembolisms (VTEs) if tourniquet is applied during total knee arthroplasties (TKAs). However, this estimate relies on multiple trials with a low number of patients analyzing VTEs as a secondary outcome. We hypothesized that tourniquet-use increases the risk of symptomatic VTE within 90 days of contemporary primary TKA and aimed to use the extensive Danish healthcare registries to quantify this risk. METHODS: Prospectively collected registry data from Danish patients receiving primary TKAs between 2014 and 2018 were included in the study. Patients were divided by tourniquet-use during surgery. By merging information from four nationwide registries, the study included 44 baseline characteristics with the potential to confound the association between tourniquet-use and VTE. Incidence rate and odds ratios were used to compare the risk of VTE within 90 days of surgery. RESULTS: 19,804 patients of whom 10,111 (51%) were operated with tourniquet and 9693 (49%) without were included. The mean age (SD) was 70 (9) in both groups and 62% were females in the tourniquet group compared with 61% in the no tourniquet group. The groups were similarly comparable across all other baseline characteristics except type of post-operative thromboprophylaxis, type of anaesthesia, implant fixation, and year of surgery. The 90-days incidence of VTE was 0.77% (95% CI 0.60-0.94) in the tourniquet group compared with 1.10% (95% CI 0.90-1.31) in the no tourniquet group. Following adjustment for the unbalanced confounders, the odds ratio for VTE was 0.77 (95% CI 0.54-1.10) associated with tourniquet-use. CONCLUSION: In contemporary TKAs the rate of VTE within 90 days is low and not significant altered by tourniquet-use. Thus, tourniquet can safely be applied during primary TKA-surgery without jeopardizing the risk of postoperative VTE. LEVEL OF EVIDENCE: II-prospective cohort study.

Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain. METHODS: In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete. FINDINGS: Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk [RR] 0·69 [95% CI 0·32-1·47]; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 [95% CI 0·65-2·09]). INTERPRETATION: In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism. FUNDING: French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer.

Epidemiological and microbiological investigation of a large increase in vibriosis, northern Europe, 2018.

BackgroundVibriosis cases in Northern European countries and countries bordering the Baltic Sea increased during heatwaves in 2014 and 2018.AimWe describe the epidemiology of vibriosis and the genetic diversity of Vibrio spp. isolates from Norway, Sweden, Denmark, Finland, Poland and Estonia in 2018, a year with an exceptionally warm summer.MethodsIn a retrospective study, we analysed demographics, geographical distribution, seasonality, causative species and severity of non-travel-related vibriosis cases in 2018. Data sources included surveillance systems, national laboratory notification databases and/or nationwide surveys to public health microbiology laboratories. Moreover, we performed whole genome sequencing and multilocus sequence typing of available isolates from 2014 to 2018 to map their genetic diversity.ResultsIn 2018, we identified 445 non-travel-related vibriosis cases in the study countries, considerably more than the median of 126 cases between 2014 and 2017 (range: 87-272). The main reported mode of transmission was exposure to seawater. We observed a species-specific geographical disparity of vibriosis cases across the Nordic-Baltic region. Severe vibriosis was associated with infections caused by Vibrio vulnificus (adjOR: 17.2; 95% CI: 3.3-90.5) or Vibrio parahaemolyticus (adjOR: 2.1; 95% CI: 1.0-4.5), age ≥ 65 years (65-79 years: adjOR: 3.9; 95% CI: 1.7-8.7; ≥ 80 years: adjOR: 15.5; 95% CI: 4.4-54.3) or acquiring infections during summer (adjOR: 5.1; 95% CI: 2.4-10.9). Although phylogenetic analysis revealed diversity between Vibrio spp. isolates, two V. vulnificus clusters were identified.ConclusionShared sentinel surveillance for vibriosis during summer may be valuable to monitor this emerging public health issue.

Cancer risk in persons with new-onset anaemia: a population-based cohort study in Denmark.

BACKGROUND: The time interval from first symptom and sign until a cancer diagnosis significantly affects the prognosis. Therefore, recognising and acting on signs of cancer, such as anaemia, is essential. Evidence is sparse on the overall risk of cancer and the risk of specific cancer types in persons with new-onset anaemia detected in an unselected general practice population. We aimed to assess the risk of cancer in persons with new-onset anaemia detected in general practice, both overall and for selected cancer types. METHODS: This observational population-based cohort study used individually linked electronic data from laboratory information systems and nationwide healthcare registries in Denmark. We included persons aged 40-90 years without a prior history of cancer and with new-onset anaemia (no anaemia during the previous 15 months) detected in general practice in 2014-2018. We measured the incidence proportion and standardised incidence ratios of a new cancer diagnosis (all cancers except for non-melanoma skin cancers) during 12 months follow-up. RESULTS: A total of 48,925 persons (median [interquartile interval] age, 69 [55-78] years; 55.5% men) were included in the study. In total, 7.9% (95% confidence interval (CI): 7.6 to 8.2) of men and 5.2% (CI: 4.9 to 5.5) of women were diagnosed with cancer during 12 months. Across selected anaemia types, the highest cancer incidence proportion was seen in women with 'anaemia of inflammation' (15.3%, CI: 13.1 to 17.5) (ferritin > 100 ng/mL and increased C-reactive protein (CRP)) and in men with 'combined inflammatory iron deficiency anaemia' (19.3%, CI: 14.5 to 24.1) (ferritin < 100 ng/mL and increased CRP). For these two anaemia types, the cancer incidence across cancer types was 10- to 30-fold higher compared to the general population. CONCLUSIONS: Persons with new-onset anaemia detected in general practice have a high cancer risk; and markedly high for 'combined inflammatory iron deficiency anaemia' and 'anaemia of inflammation'. Anaemia is a sign of cancer that calls for increased awareness and action. There is a need for research on how to improve the initial pathway for new-onset anaemia in general practice.

A low level of naturally occurring antibodies associates with functional antibody deficiency.

Functional antibody deficiency is clinically assessed from antibody responses to vaccination. However, diagnostic vaccination is complex and may fail in practice. We hypothesized that the levels of naturally occurring antibodies against galactose-α-1,3-galactose (αGal) may represent alternative markers of functional antibody capacity. We included data from 229 patients with suspected primary immunodeficiency in a retrospective study. Antibody levels against αGal and twelve pneumococcal serotypes were determined with solid-phase immunoassays. Pneumococcal vaccinations and treatment with normal human immunoglobulin were assessed from medical records. Anti-αGal antibody levels correlated positively with anti-pneumococcal antibody levels measured before and after pneumococcal vaccination. Contrary to the anti-pneumococcal antibody levels, the anti-αGal antibody level showed potential for predicting subsequent immunoglobulin treatment - a marker of disease severity. Naturally occurring antibodies may reflect the functional capacity tested by diagnostic vaccination but add more useful clinical data. The clinical utility of this easy test should be evaluated in prospective studies.

Outbreak of Salmonella Newport linked to imported frozen cooked crayfish in dill brine, Sweden, July to November 2019.

In autumn 2019, the Public Health Agency of Sweden identified a cluster of Salmonella Newport cases by whole genome sequencing (WGS). Cases' distribution in place and time indicated a nation-wide ongoing outbreak. An investigation was initiated to identify the source and prevent further cases. We conducted a case-case study based on notified salmonellosis cases and a Salmonella trawling questionnaire, comparing 20 outbreak cases and 139 control cases. Food exposures were compared by adjusted odds ratios (aOR) with 95% confidence interval (CI) using logistic regression. Implicated foods were sampled. Outbreak cases were more likely to have consumed crayfish (aOR = 26; 95% CI: 6.3-105). One specific brand of imported frozen, pre-cooked whole crayfish in dill brine was identified as the source. Salmonella Newport was later detected in different batches from retail and in one sample from border control. Isolates from food samples clustered with the human outbreak strain by WGS. Although the retailer made a complete recall, two more cases were identified long afterwards. This investigation demonstrated the successful use of a case-case study and targeted microbiological testing to identify the source. The immediate action taken by the retailer was important to confirm the source and stop the outbreak.

Atrial fibrillation, liver cirrhosis, thrombosis, and bleeding: A Danish population-based cohort study.

OBJECTIVES: We examined the impact of liver cirrhosis on the risk of thromboembolic events and bleeding complications in patients with atrial fibrillation or flutter (AFF). METHODS: This population-based cohort study used data from Danish health registries. We identified all patients with a first-time diagnosis of AFF during 1995 to 2015, and followed them from their AFF diagnosis until the end of 2016. Patients were categorized according to the presence or absence of liver cirrhosis. We computed incidence rates per 1000 person-years and hazard ratios (HRs) with 95% confidence intervals (CIs) based on Cox regression analyses, adjusting for age, CHA2DS2VASc score, and Charlson Comorbidity Index score. RESULTS: We identified 273 225 patients with AFF. Of these, 1463 (0.54%) had liver cirrhosis. During 0 to 5 years of follow-up, compared to patients without liver cirrhosis, patients with liver cirrhosis had higher incidence rates and hazards of ischemic stroke (29.7 vs 21.6; HR, 1.3; 95% CI, 1.1-1.6), venous thromboembolism (9.2 vs 5.5; HR, 1.5; 95% CI, 1.2-2.3), but not myocardial infarction (10.2 vs 11.2; HR, 0.9; 95% CI, 0.7-1.2). Patients with liver cirrhosis also had higher rates of hemorrhagic stroke (5.8 vs 3.3; HR, 1.7; 95% CI, 1.1-2.6), subdural hemorrhage (5.3 vs 1.6; HR, 3.2; 95% CI, 2.1-4.9), hemorrhage of the lung or urinary tract (24.6 vs 15.2; HR, 1.6; 95% CI, 1.3-2.0), and gastrointestinal hemorrhage (34.5 vs 10.4; HR, 3.3; 95% CI, 2.7-3.9). CONCLUSION: In patients with AFF, liver cirrhosis was associated with an elevated risk of ischemic stroke, venous thromboembolism, and all evaluated bleeding complications.

Diagnostic Vaccination in Clinical Practice.

Testing the antibody response to vaccination (diagnostic vaccination) is crucial in the clinical evaluation of primary immunodeficiency diseases. Guidelines from the American Academy of Allergy, Asthma & Immunology (AAAAI) provide detailed recommendations for diagnostic vaccination with pure pneumococcal polysaccharide vaccines (PPV). However, the degree of compliance with these guidelines and the utility of the guidelines in actual practice are undescribed. To address this, we systematically evaluated diagnostic vaccination in adult patients with suspected primary immunodeficiency diseases in a single tertiary center from 2011 to 2016 (n = 229). We found that full compliance with the AAAAI guidelines was achieved for only 39 patients (17%), suggesting that the guidelines are not easy to follow. Worse, interpretation according to the guidelines was heavily influenced by which serotype-specific antibodies that were used for the evaluation. We found that the arbitrary choices of serotype-specific antibodies could change the fraction of patients deemed to have 'adequate immunity' by a factor of four, exposing an inherent flaw in the guidelines. The flaw relates to dichotomous principles for data interpretation under the AAAAI guidelines. We therefore propose a revised protocol for diagnostic vaccination limited to PPV vaccination, subsequent antibody measurements, and data interpretation using Z-scores. The Z-score compiles multiple individual antibody levels, adjusted for different weighting, into one single continuous variable for each patient. In contrast to interpretation according to the AAAAI guidelines, the Z-scores were robust to variations in the choice of serotype-specific antibodies used for interpretation. Moreover, Z-scores revealed reduced immunity after vaccination in the patients with recurrent pneumonia (a typical symptom of antibody deficiency) compared with control patients. Assessment according to the AAAAI guidelines failed to detect this difference. We conclude that our simplified protocol and interpretation with Z-scores provides more robust clinical results and may enhance the value of diagnostic vaccination.

Diagnostic workup of cancer in patients with new-onset anaemia: a Danish cohort study in general practice.

BACKGROUND: Anaemia is associated with adverse outcomes, including increased morbidity and all-cause mortality. Diagnostic workup of patients with anaemia is essential to detect underlying disease, especially undiagnosed malignancy. OBJECTIVE: To describe the cancer-relevant diagnostic workup in patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and the diagnostic workup. DESIGN: Observational population-based cohort study using electronic laboratory and register data. SETTING: Danish general practice. SUBJECTS: Patients aged 40-90 years with new-onset anaemia (no anaemia in the preceding 15 months) detected in general practice. Patients were identified in Danish laboratory information systems and nationwide registries in 2014-2018. MAIN OUTCOME MEASURES: We measured the proportion of patients receiving predefined diagnostic investigations, that is, cancer patient pathway, colonoscopy, gastroscopy, computerised tomography (CT) scan, faecal test for haemoglobin, and bone marrow examination within three months of the anaemia index date. RESULTS: We included 59,993 patients, and around half of the patients with 'iron deficiency anaemia', 'anaemia of inflammation', or 'combined inflammatory iron deficiency anaemia' had no cancer-relevant diagnostic investigations performed. Patients aged 60-79 years and patients with severe anaemia were more likely to have investigations performed, while patients with comorbidity were less likely to have investigations performed. CONCLUSION: Around half of the patients with anaemia subtypes that may indicate underlying cancer had no cancer-relevant diagnostic investigations performed. This may represent missed diagnostic opportunities. Future interventions are needed to improve the diagnostic workup of cancer in patients with anaemia, for example, laboratory alert systems and clinical decision support.KEY POINTSThe general practitioners are often the first to detect anaemia and its underlying disease (e.g. undiagnosed malignancy).Large-scale studies are needed on the diagnostic workup of patients with anaemia in general practice in relation to an underlying malignancy.This study shows that the majority of patients with anaemia had no cancer-relevant diagnostic investigations performed, which may cause diagnostic delay.Interventions seems needed to improve the diagnostic workup of cancer in these patients to ensure timely diagnosis.

Insufficient classification of anaemia in general practice: a Danish register-based observational study.

BACKGROUND: Anaemia can be a pointer of underlying severe disease, including undiagnosed malignancy. Subsequent blood tests are essential to classify the anaemia into subtypes and to facilitate targeted diagnostic investigation to ensure timely diagnosis of underlying disease. OBJECTIVE: We aimed to describe and classify anaemia based on laboratory tests from patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and unclassified anaemia (not classifiable according to an algorithm). DESIGN: Population-based cross-sectional study. SETTING: Danish general practice. SUBJECTS: A total of 62,731 patients (age: 40-90 years) with new-onset anaemia were identified in Danish laboratory information systems and nationwide registries, and data were obtained for 2014-2018. MAIN OUTCOME MEASURES: We measured the proportion of patients classified into subtypes of anaemia based on blood tests requested by general practitioners within 31 days of the anaemia index date. RESULTS: Of the 62,731 patients with new-onset anaemia, we identified unclassified anaemia in 78.9% (95% confidence interval (CI): 77.3-80.5) of men and 65.1% (CI: 63.4-66.9) of women. The likelihood of unclassified anaemia increased with age, increasing comorbidity and decreasing severity of anaemia. CONCLUSION: The majority of patients with new-onset anaemia could not be classified through a simple algorithm due to missing blood tests, which highlights a potential missed opportunity for diagnosis. Standardised laboratory testing of patients with anaemia is warranted to ensure adequate follow-up and early detection of underlying severe disease.KEY POINTSAnaemia can be a sign of malignancy, and anaemia classification is an important step in the diagnosis of underlying disorders.The majority of patients with anaemia could not be classified according to a simple algorithm due to missing blood tests.Some patient characteristics were associated with a high risk of unclassified anaemia: high age, high comorbidity, and severe anaemia.Standardised laboratory testing in patients with anaemia is needed to inform targeted diagnostic investigation to ensure timely diagnosis.

Cryptosporidium chipmunk genotype I - An emerging cause of human cryptosporidiosis in Sweden.

Most cases of cryptosporidiosis in humans are caused by Cryptosporidium parvum or Cryptosporidium hominis. However, more uncommon species are increasingly being recognised to cause infection in humans. Here we report that Cryptosporidium chipmunk genotype I, which has various rodents as its natural host, is the third most common source of human cryptosporidiosis in Sweden. We also describe the first small outbreak of cryptosporidiosis caused by Cryptosporidium chipmunk genotype I and report the first case of zoonotic transmission of Cryptosporidium chipmunk genotype I from a red squirrel to a human. Cryptosporidium chipmunk genotype I was identified in 20 human cases, including 16 sporadic cases, three outbreak-related cases, and one zoonotic case, as well as in two squirrel samples. Gp60 subtyping which was successful for 19 human cases and two squirrel samples showed that all samples harboured the same subtype, XIVaA20G2T1. The work presented here suggests that red squirrel is a natural host of Cryptosporidium chipmunk genotype I and that infection with Cryptosporidium chipmunk genotype I is an emerging cause of domestic cryptosporidiosis in Sweden and a potential source of outbreaks.

Doppler ultrasound predicts successful discontinuation of biological DMARDs in rheumatoid arthritis patients in clinical remission.

OBJECTIVE: To assess the ability of ultrasound to predict successful tapering and successful discontinuation of biological DMARDs (bDMARDs) at the 2-year follow-up in RA patients in sustained remission. METHODS: Patients in sustained remission (DAS28-CRP ≤ 2.6) and with no radiographic progression the previous year tapered bDMARDs according to a standardized regime. A total of 119 of these patients were included in this ultrasound substudy. At baseline, clinical assessment, MRI, X-ray and ultrasound of 24 joints were performed. Ultrasound-detected synovitis was defined and scored 0-3 using the OMERACT scoring system at the joint level for both grey-scale and Doppler activity. Sum scores for each ultrasound modality were calculated for 24 joints at the patient level. The final state of treatment was assessed after 2 years. The predictive value of ultrasound measures for successful tapering and discontinuation at the 2-year follow-up was assessed via logistic regression analyses. RESULTS: Negative IgM-RF [odds ratio (OR) = 0.29, 95% CI: 0.10-0.85; P = 0.024] and lower Doppler sum score of 24 joints (OR = 0.44, 95% CI: 0.15, 0.87; P = 0.014) were independent predictors for successful discontinuation of bDMARDs at the 2-year follow-up. The predictive value of the Doppler sum score was independent of MRI findings. Previous numbers of bDMARDs were predictive of successful tapering (OR = 0.58, 95% CI: 0.35, 0.91; P = 0.018), whereas ultrasound was not. Clinical parameters were not predictive of successful tapering/discontinuation. CONCLUSION: Doppler sum score was an independent predictor for successful discontinuation of bDMARDs at the 2-year follow-up-the odds for achieving successful discontinuation decreased by 56% per one-unit increase in Doppler sum score. Ultrasound could not predict successful tapering.

Comparison of Patients with Hospital-Recorded Nephrotic Syndrome and Patients with Nephrotic Proteinuria and Hypoalbuminemia: A Nationwide Study in Denmark.

Background: Registry-based studies of nephrotic syndrome (NS) may only include a subset of patients with biochemical features of NS. To address this, we compared patients with laboratory-recorded nephrotic proteinuria and hypoalbuminemia to patients with hospital-recorded NS. Methods: We identified adult patients with first-time hospital-recorded NS (inpatients, outpatients, or emergency-room visitors) in the Danish National Patient Registry and compared them with adults with first-time recorded nephrotic proteinuria and hypoalbuminemia in Danish laboratory databases during 2004-2018, defining the date of admission or laboratory findings as the index date. We characterized these cohorts by demographics, comorbidity, medication use, and laboratory and histopathologic findings. Results: We identified 1139 patients with hospital-recorded NS and 5268 patients with nephrotic proteinuria and hypoalbuminemia; of these, 760 patients were identified in both cohorts. Within 1 year of the first record of nephrotic proteinuria and hypoalbuminemia, 18% had recorded hospital diagnoses indicating the presence of NS, and 87% had diagnoses reflecting any kind of nephropathy. Among patients identified with nephrotic proteinuria and hypoalbuminemia, their most recent eGFR was substantially lower (median of 35 versus 61 ml/min per 1.73 m2), fewer underwent kidney biopsies around the index date (34% versus 61%), and the prevalence of thromboembolic disease (25% versus 17%) and diabetes (39% versus 18%) was higher when compared with patients with hospital-recorded NS. Conclusions: Patients with nephrotic proteinuria and hypoalbuminemia are five-fold more common than patients with hospital-recorded NS, and they have a lower eGFR and more comorbidities. Selective and incomplete recording of NS may be an important issue when designing and interpreting studies of risks and prognosis of NS.

Quantity and Quality of Basophil RNA Depend on the RNA Extraction Technique.

Basophils have been suggested to express low quantities of RNA, challenging the study of gene expression within these cells. However, the purification technique employed might have an impact on the quantity and quality of RNA purified from basophils. This chapter describes a method which gives an optimal RNA output using a TRIzol-based method in contrast to a commercial kit.

Existing Data Sources in Clinical Epidemiology: Laboratory Information System Databases in Denmark.

Routine biomarker results from hospital laboratory information systems, covering hospitals and general practitioners, in Denmark are available to researchers through access to the regional Clinical Laboratory Information System Research Database at Aarhus University and the nationwide Register of Laboratory Results for Research. This review describes these two data sources. The laboratory databases have different geographical and temporal coverage. They both include individual-level biomarker results that are electronically transferred from laboratory information systems. The biomarker results can be linked to all other Danish registries at the individual level, using the unique identifier, the CPR number. The databases include variables such as the CPR number, date and time (hour and minute) of sampling, NPU code, and name of the biomarker, identification code for the laboratory and the requisitioner, the test result with the corresponding unit, and the lower and upper reference limits. Access to the two databases differs since they are hosted by two different institutions. Data cannot be transferred outside Denmark, and direct access is provided only to Danish institutions. It is concluded that access to data on routine biomarkers expands the detailed biological and clinical information available on patients in the Danish healthcare system. The full potential is enabled through linkage to other Danish healthcare registries.

[Venous thromboembolism in patients with COVID-19].

The importance of venous thromboembolism (VTE) as a major complication in patients with severe corona virus disease 2019 (COVID-19) is becoming increasingly evident. In this review, we describe the proposed pathophysiology of the prothrombotic coagulation changes observed in patients with COVID-19. Further, based on a review of the currently available evidence on VTE prevalence in patients with COVID-19, we present and discuss the recommendations from the Danish Society of Thrombosis and Haemostasis on the use of thromboprophylaxis in patients with COVID-19.

Differentiation of Blastocystis and parasitic archamoebids encountered in untreated wastewater samples by amplicon-based next-generation sequencing.

BACKGROUND: Application of next-generation sequencing (NGS) to genomic DNA extracted from sewage offers a unique and cost-effective opportunity to study the genetic diversity of intestinal parasites. In this study, we used amplicon-based NGS to reveal and differentiate several common luminal intestinal parasitic protists, specifically Entamoeba, Endolimax, Iodamoeba, and Blastocystis, in sewage samples from Swedish treatment plants. MATERIALS AND METHODS: Influent sewage samples were subject to gradient centrifugation, DNA extraction and PCR-based amplification using three primer pairs designed for amplification of eukaryotic nuclear 18S ribosomal DNA. PCR products were sequenced using ILLUMINA® technology, and resulting sequences were annotated to species and subtype level using the in-house BION software, sequence clustering, and phylogenetic analysis. RESULTS: A total of 26 samples from eight treatment plants in central/southern Sweden were analysed. Blastocystis sp. and Entamoeba moshkovskii were detected in all samples, and most samples (n = 20) were positive for Entamoeba coli. Moreover, we detected Entamoeba histolytica, Entamoeba dispar, Entamoeba hartmanni, Endolimax nana, and Iodamoeba bütschlii in 1, 11, 4, 10, and 7 samples, respectively. The level of genetic divergence observed within E. nana and E. moshkovskii was 20.2% and 7.7%, respectively, across the ~400-bp region studied, and two clades of E. moshkovskii were found. As expected, Blastocystis sp. subtypes 1-4 were present in almost all samples; however, ST8 was present in 10 samples and was the only subtype not commonly found in humans that was present in multiple samples. CONCLUSIONS: Entamoeba and Blastocystis were identified as universal members of the "sewage microbiome". Blastocystis sp. ST8, which has been rarely reported in humans, was a very common finding, indicating that a hitherto unidentified but common host of ST8 contributed to the sewage influent. The study also provided substantial new insight into the intra-generic diversity of Entamoeba and Endolimax.

Outbreak of unusual H2S-negative monophasic Salmonella Typhimurium strain likely associated with small tomatoes, Sweden, August to October 2019.

Sweden is investigating an outbreak of monophasic Salmonella Typhimurium. Eighty-two nationally-distributed cases have been confirmed, with date of symptom onset between 28 August and 29 October. Cases were 51 years of age on average (range: 0-89) and the majority of cases were female (62%). A case-control study was conducted and suggested small tomatoes as source of the outbreak (adjusted odds ratio (OR): 10.8, 95% confidence interval (CI): 4.15-112.68, p value < 0.001), and a trace-back investigation led to a single, non-Swedish producer in Europe. Both the Salmonella strain and the source of the outbreak are rarely encountered in Europe. Results from investigation at the producer are pending.