Characteristics and long-term prognosis of Danish residents with a positive intrathecal antibody index test for herpes simplex virus or varicella-zoster virus compared with individuals with a positive cerebrospinal fluid PCR: a nationwide cohort study.

OBJECTIVES: We compared characteristics and outcomes of individuals who in the cerebrospinal fluid (CSF) were positive for herpes simplex virus (HSV) or varicella-zoster virus (VZV)-intrathecal antibody index test ([AI]-positive) vs. individuals who were PCR-positive for HSV type 1 (HSV1), type 2 (HSV2), and for VZV. METHODS: Nationwide cohort study of all Danish residents with positive CSF-AI or -PCR for HSV or VZV (1995-2021). We calculated short- and long-term risks as age-, sex-, and comorbidity-adjusted odds ratios (aOR), adjusted hazard ratios (aHR), and absolute risk differences with 95% CIs. RESULTS: Compared with individuals with positive PCR for HSV1 (n = 321), HSV2 (n = 497), and VZV (n = 1054), individuals with a positive AI for HSV (n = 177) and VZV (n = 219) had CSF pleocytosis less frequently (leucocyte count >10/µL: HSV-AI: 39%, VZV-AI: 52%, HSV1-PCR: 81%, HSV2-PCR: 92%, VZV-PCR: 83%), and were less frequently diagnosed with central nervous system infection ([aOR {95%CI}]: HSV-AI vs. HSV1-PCR: [0.1 {0.1, 0.2}], HSV-AI vs. HSV2-PCR: [0.1 {0.0, 0.1}], VZV-AI vs. VZV-PCR: [0.2 {0.2, 0.3}]). Individuals with a positive HSV-AI or VZV-AI had increased risk of demyelinating disease ([aOR {95%CI}; aHR {95%CI}]: HSV-AI vs. HSV1-PCR: [4.6 {0.9, 24.5}; aHR not applicable], HSV-AI vs. HSV2-PCR: [10.4 {2.3, 45.9}; 12.4 {2.3, 66.0}], VZV-AI vs. VZV-PCR: [aOR not applicable; 10.3 {1.8, 58.8}]). Disability pension was less frequent among HSV-AI than HSV1-PCR cohort members (5-year risk difference: -23.6%, 95%CI: -35.2, -11.8), and more frequent among VZV-AI than VZV-PCR cohort members (5-year risk difference: 16.8%, 95%CI: 5.0, 28.7). DISCUSSION: AI-positive individuals differ from PCR-positive individuals in several aspects. AI appears unspecific for current central nervous system infections.

Temporal changes in incidence of hospital-diagnosed acute pyelonephritis: A 19-year population-based Danish cohort study.

Objectives: To examine temporal changes in the incidence of hospital-diagnosed acute pyelonephritis (APN) and characterize associated demographics. Methods: Cohort study including Danish patients with hospital-diagnosed APN during 2000-2018, identified by International Classification of Diseases, 10th Revision codes. Annual sex- and age-standardized incidence rates per 10,000 person years with 95% confidence intervals (CIs) were stratified by sex, age group, diagnosis code, and region of residence. Incidence rates for selected urinary tract infections and sepsis diagnoses were also computed. Results: We included 66,937 hospital-diagnosed APN episodes in 57,162 patients. From 2000 to 2018, the incidence increased from 6.8 (95% CI: 6.8-6.8) to 15.4 (95% CI: 15.4-15.4) in women and from 2.7 (95% CI: 2.7-2.7) to 4.5 (95% CI: 4.5-4.5) in men. Among infants, the rate rose from 7.4 (95% CI: 7.4-7.4) to 64.8 (95% CI: 64.7-64.9) in girls and from 17.1 (95% CI: 17.1-17.2) to 52.5 (95% CI: 52.4-52.6) in boys. Concomitant declines were observed in incidences of hospital-diagnosed unspecified urinary tract infections and sepsis. Conclusion: The APN incidence roughly doubled during 2000-2018. The increase was largely driven by a prominently increasing incidence among young children which was not explained by the enlarging prevalence of congenital anomalies of the kidney and urinary tract.

Whole genomes from bacteria collected at diagnostic units around the world 2020.

The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species prediction and identification of acquired resistance genes.

Evaluating the diagnostic accuracy and clinical utility of 16S and 18S rRNA gene targeted next-generation sequencing based on five years of clinical experience.

BACKGROUND: The use of 16S/18S rRNA targeted next-generation sequencing (tNGS) has improved microbial diagnostics, however, the use of tNGS in a routine clinical setting requires further elucidation. We retrospectively evaluated the diagnostic accuracy and clinical utility of 16S/18S tNGS, routinely used in the North Denmark Region between 2017 and 2021. METHODS: We retrieved 544 tNGS results from 491 patients hospitalised with suspected infection (e.g. meningitis, pneumonia, intraabdominal abscess, osteomyelitis and joint infection). The tNGS assays was performed using the Illumina MiSeq desktop sequencer, and BION software for annotation. The patients' diagnosis and clinical management was evaluated by medical chart review. We calculated sensitivity and specificity, and determined the diagnostic accuracy of tNGS by defining results as true positive, true negative, false positive, and false negative. RESULTS: Overall, tNGS had a sensitivity of 56% and a specificity of 97%. tNGS was more frequently true positive compared to culture (32% vs 18%), and tNGS detected a greater variety of bacteria and fungi, and was more frequently polymicrobial. However, the total diagnostic turnaround time was 16 days, and although 73% of tNGS results were true positive or true negative, only 4.4% of results led to changes in clinical management. CONCLUSIONS: As a supplement to culture, tNGS improves identification of pathogenic microorganisms in a broad range of clinical specimens. However, the long turnaround time of tNGS in our setting may have contributed to a limited clinical utility. An improved turnaround time can be the key to improved clinical utility in a future setting.

Recurrence of bacteremia and infective endocarditis according to bacterial species of index endocarditis episode.

PURPOSE: In patients surviving infective endocarditis (IE) recurrence of bacteremia or IE is feared. However, knowledge is sparse on the incidence and risk factors for the recurrence of bacteremia or IE. METHODS: Using Danish nationwide registries (2010-2020), we identified patients with first-time IE which were categorized by bacterial species (Staphylococcus aureus, Enterococcus spp., Streptococcus spp., coagulase-negative staphylococci [CoNS], 'Other' microbiological etiology). Recurrence of bacteremia (including IE episodes) or IE with the same bacterial species was estimated at 12 months and 5 years, considering death as a competing risk. Cox regression models were used to compute adjusted hazard ratios of the recurrence of bacteremia or IE. RESULTS: We identified 4086 patients with IE; 1374 (33.6%) with S. aureus, 813 (19.9%) with Enterococcus spp., 1366 (33.4%) with Streptococcus spp., 284 (7.0%) with CoNS, and 249 (6.1%) with 'Other'. The overall 12-month incidence of recurrent bacteremia with the same bacterial species was 4.8% and 2.6% with an accompanying IE diagnosis, while this was 7.7% and 4.0%, respectively, with 5 years of follow-up. S. aureus, Enterococcus spp., CoNS, chronic renal failure, and liver disease were associated with an increased rate of recurrent bacteremia or IE with the same bacterial species. CONCLUSION: Recurrent bacteremia with the same bacterial species within 12 months, occurred in almost 5% and 2.6% for recurrent IE. S. aureus, Enterococcus spp., and CoNS were associated with recurrent infections with the same bacterial species.

Brain Abscess and Risk of Cancer: A Nationwide Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Underlying occult cancer could potentially explain some of the observed increased long-term mortality among patients with brain abscess. METHODS: Nationwide, population-based health care registries were used to examine long-term risks of cancer in patients with brain abscess from 1982 to 2016 compared with a population comparison cohort individually matched (10:1) on age, sex, and residence. Cumulative incidences and adjusted cause-specific hazard rate ratios (HRRs) with 95% CIs for cancer were computed. Potential confounding by family-related factors was explored by comparing cumulative incidences of cancer among siblings of both groups. RESULTS: Among 1,384 patients with brain abscess (37% female, median age 50 years, interquartile ranges [IQR] 33-63), cancer was observed in 218 (16%) compared with 1,657 of 13,838 (12%) in the comparison cohort yielding an adj. HRR of 2.09 (95% CI 1.79-2.45). The median time to diagnosis of cancer was 1.8 years (IQR 0.02-9.1) in patients with brain abscess and 8.6 years (IQR 3.9-15.9) in comparison cohort. Among patients with brain abscess, CNS and eye cancer was diagnosed in 59 (4.3%), of which 47 of 59 (80%) occurred within 90 days of the admission date, metastasizing cancer in 54 (3.9%), respiratory tract cancer in 48 (3.5%), and gastrointestinal cancer in 36 (2.6%). Results remained consistent in almost all subgroups and in sensitivity analyses. Accounting for competing risk of death, the 1-, 5-, 10-, and 35-year cumulative incidence of cancer was 7% (95% CI 6-8), 11% (95% CI 9-12), 13% (95% CI 11-15), and 24% (95% CI 20-27) in patients with brain abscess compared with 0.7% (95% CI 0.6-0.9), 4% (95% CI 4-5), 8% (95% CI 8-9), and 25% (95% CI 23-27) in the comparison cohort, respectively. The cumulative incidences of cancer among siblings of patients with brain abscess were 10% and 12% among siblings of the comparison cohort. DISCUSSION: Brain abscess was associated with substantially increased risk of cancer during the first 10 years after diagnosis.

Do we need blood culture stewardship programs? A quality control study and survey to assess the appropriateness of blood culture collection and the knowledge and attitudes among physicians in Swiss hospitals.

BACKGROUND: Guidance for blood culture (BC) collection is limited. Inappropriate BC collection may be associated with potentially harmful consequences for the patient such as unnecessary laboratory testing, treatment and additional costs. The aim of the study was to assess the appropriateness of BC collection and related knowledge and attitude of precribers. MATERIALS: We conducted a single-center quality control study to assess the appropriateness of BC collection according to the local guidelines in a Swiss university hospital in 2020 by combining three different approaches: point prevalence, patient-individual longitudinal and diseases-related analysis. Second, we conducted a survey regarding BC collection practices and knowledge among physicians in two non-university and one university hospital using an 18-item electronic questionnaire. RESULTS: We analyzed 1114 BC collected in 344 patients. Approximately 40% of the BCs were collected inappropriately, in particular in diseases with low pretest probability of bacteremia such as non-severe community acquired pneumonia (CAP). Follow-up blood culture (FUBC) collection was inappropriate in 60%. Growth of a relevant pathogen was more frequently observed in appropriately than in inappropriately collected BCs (18% vs. 3%, p < 0.001). In the survey, uncertainty concerning the need of index BC collection was high in non-severe CAP and uncomplicated cellulitis. CONCLUSIONS: Almost half of the BCs was not collected according to the guidelines, especially in non-severe CAP and in case of FUBCs. Substantial uncertainty among physicians regarding BC ordering practices was identified. The implementation of diagnostic stewardship programs may improve BC collection practices, increase adherence to local guidelines, and may help reducing unnecessary diagnostics and treatment.

Acute Pericarditis and Cancer Risk: A Matched Cohort Study Using Linked UK Primary and Secondary Care Data.

Background We aimed to examine whether acute pericarditis is an indicator of undetected cancer and identify patient-level factors associated with high cancer risk among patients presenting with pericarditis. Methods and Results A population-based matched cohort study was conducted using primary care data from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics. Patients with acute pericarditis (n=6530) were matched to a comparison cohort (n=26 111) on age, sex, calendar time, and general practice. We estimated cumulative cancer incidences, and calculated hazard ratios using Cox regression. Effect modification by patients' characteristics and lifestyle factors was examined, and we fitted a parsimonious model to evaluate absolute excess risk of later cancer among pericarditis patients by key patient-level factors. We identified 728 and 1379 incidents of cancer among pericarditis patients and the comparison cohort (median follow-up, 2.8 and 3.5 years). Pericarditis was associated with an elevated subsequent risk of any cancer (hazard ratio=3.03; 95% confidence interval, 2.74-3.36). The association was particularly pronounced 0 to 3 months after pericarditis (hazard ratio=23.56; 95% confidence interval, 18.00-30.83), but a more-modest association remained thereafter (hazard ratio=1.95; 95% confidence interval, 1.48-2.57 after 3-12 months, and hazard ratio=1.40; 95% confidence interval, 1.21-1.62 after >12 month). Older individuals hospitalized with pericarditis and with combinations of obesity and smoking were at the highest excess risk of having a cancer diagnosis 3 to 12 months later, reaching 4.8%. Conclusions Occult cancers may be going undiagnosed during the acute episode of pericarditis. Patients presenting with pericarditis and combinations of older age, obesity, smoking, and a need for hospitalization might warrant targeted investigations for cancer.

Risk of bleeding and arterial cardiovascular events in patients with splanchnic vein thrombosis in Denmark: a population-based cohort study.

BACKGROUND: Little is known about adverse events following splanchnic vein thrombosis. Venous thromboembolism has been associated with increased risks of bleeding and arterial cardiovascular events. To learn more about the clinical course of splanchnic vein thrombosis, we examined the risks of bleeding and arterial cardiovascular events in patients with the disease, and compared them with the risks in patients with deep vein thrombosis (DVT) or pulmonary embolism (PE) and individuals from the general population. METHODS: In this population-based cohort study, we used data for all patients with a diagnosis of splanchnic vein thrombosis recorded in the Danish National Patient Registry (DNPR) between Jan 1, 1994, and Nov 30, 2013 (cumulative source population 7 310 450 individuals). We created two comparison cohorts using data from the DNPR and the Civil Registration System for the same period: one of patients with DVT or PE and another of individuals from the general population. Comparison cohorts (ten comparators per patient with splanchnic vein thrombosis) were matched on sex, age, and calendar year of diagnosis. We calculated absolute risks and used proportional hazard regression to calculate adjusted hazard ratios (HRs) for the primary outcomes of bleeding and arterial cardiovascular events after splanchnic vein thrombosis diagnosis (or the index date for comparison cohorts). FINDINGS: 1915 patients with splanchnic vein thrombosis, 18 373 patients with DVT or PE, and 19 150 individuals from the general population were included in the study. Patients with splanchnic vein thrombosis were followed up for a median of 1 year (IQR 0·1-3·9). These patients had a high risk of bleeding in the 30 days after diagnosis, both in absolute terms (4·3% [95% CI 3·5-5·3]) and in adjusted models (HR 9·64 [95% CI 6·46-14·40] vs DVT or PE; 39·79 [19·44-81·46] vs general population). Bleeding risk was still significantly increased in patients with splanchnic vein thrombosis up to 1 year after diagnosis (HR 3·01 [95% CI 2·28-3·97] vs DVT or PE; 6·83 [4·83-9·65] vs general population), and remained elevated for up to 10 years compared with patients with DVT or PE (1·93 [1·12-3·34]) and for up to 19 years compared with the general population (5·90 [2·22-15·64]). The risk of arterial cardiovascular events in patients with splanchnic vein thrombosis was high in the year after diagnosis (absolute risk 3·3% [95% CI 2·6-4·2] up to 30 days; 7·0% [5·8-8·4] up to 31-365 days), and in adjusted models was significantly higher than in patients with DVT or PE (HR 7·05 [95% CI 4·74-10·48] up to 30 days; 2·10 [1·62-2·72] up to 31-365 days) and individuals from the general population (15·75 [9·26-26·79] and 3·17 [2·34-4·27], respectively). However, this risk did not remain significantly elevated above that of patients with DVT or PE after 1 year or the general population after 5 years. INTERPRETATION: Patients with splanchnic vein thrombosis are at increased risk of adverse outcomes, particularly bleeding but also arterial cardiovascular events, for years after diagnosis compared with patients with DVT or PE and the general population. Physicians should be cognisant of these risks in patients with splanchnic vein thrombosis. FUNDING: The Program for Clinical Research Infrastructure (PROCRIN), established by the Lundbeck Foundation and the Novo Nordisk Foundation.

Pericarditis as a Marker of Occult Cancer and a Prognostic Factor for Cancer Mortality.

BACKGROUND: Pericarditis may be a serious complication of malignancy. Its significance as a first symptom of occult cancer and as a prognostic factor for cancer survival is unknown. METHODS: Using Danish medical databases, we conducted a nationwide cohort study of all patients with a first-time diagnosis of pericarditis during 1994 to 2013. We excluded patients with previous cancer and followed up the remaining patients for subsequent cancer diagnosis until November 30, 2013. We calculated risks and standardized incidence ratios of cancer for patients with pericarditis compared with the general population. We assessed whether pericarditis predicts cancer survival by the Kaplan-Meier method and Cox regression using a matched comparison cohort of cancer patients without pericarditis. RESULTS: Among 13 759 patients with acute pericarditis, 1550 subsequently were diagnosed with cancer during follow-up. The overall cancer standardized incidence ratio was 1.5 (95% confidence interval [CI], 1.4-1.5), driven predominantly by increased rates of lung, kidney, and bladder cancer, lymphoma, leukemia, and unspecified metastatic cancer. The <3-month cancer risk among patients with pericarditis was 2.7%, and the standardized incidence ratio was 12.4 (95% CI, 11.2-13.7). The 3- to <12-month standardized incidence ratio of cancer was 1.5 (95% CI, 1.2-1.7), subsequently decreasing to 1.1 (95% CI, 1.0-1.2). Three-month survival after the cancer diagnosis was 80% and 86% among those with and without pericarditis, respectively, and the hazard ratio was 1.5 (95% CI, 1.3-1.8). One-year survival was 65% and 70%, respectively, corresponding to a 3- to <12-month hazard ratio of 1.3 (95% CI, 1.1-1.5). CONCLUSIONS: Pericarditis may be a marker of occult cancer and augurs increased mortality after a cancer diagnosis.

Positive predictive value of peptic ulcer diagnosis codes in the Danish National Patient Registry.

BACKGROUND: Diagnoses of peptic ulcer are registered in the Danish National Patient Registry (DNPR) for administrative as well as research purposes, but it is unknown whether the coding validity depends on the location of the ulcer. OBJECTIVE: To validate the International Classification of Diseases, 10th revision diagnosis codes of peptic ulcer in the DNPR by estimating positive predictive values (PPVs) for gastric and duodenal ulcer diagnoses. METHODS: We identified all patients registered with a hospital discharge diagnosis of peptic ulcer from Aarhus University Hospital, Denmark, in 1995-2006. Among them, we randomly selected 200 who had an outpatient gastroscopy at the time of ulcer diagnosis. We reviewed the findings from these gastroscopies to confirm the presence of peptic ulcer and its location. We calculated PPVs and corresponding 95% confidence intervals (CIs) of gastric and duodenal ulcer diagnoses, using descriptions from the gastroscopic examinations as standard reference. RESULTS: In total, 182 records (91%) were available for review. The overall PPV of peptic ulcer diagnoses in DNPR was 95.6% (95% CI 91.5-98.1), with PPVs of 90.3% (95% CI 82.4-95.5) for gastric ulcer diagnoses, and 94.4% (95% CI 87.4-98.2) for duodenal ulcer diagnoses. PPVs were constant over time. CONCLUSION: The PPV of uncomplicated peptic ulcer diagnoses in the DNPR is high, and the location of the ulcers is registered correctly in most cases, indicating that the diagnoses are useful for research purposes.

Pneumonia diagnosis in childhood and incidence of leukaemia, lymphoma and brain cancer: a Danish nationwide cohort study.

OBJECTIVES: There is an ongoing debate on the possible association between infections in early childhood and subsequent cancer risk, but it remains unclear if a hospital admission for infection is associated with risk of childhood cancer diagnosis. We examined if a hospital-based diagnosis of pneumonia was a clinical marker of the three most common childhood cancers. DESIGN: Population-based cohort study. SETTING: Denmark, hospital diagnoses, 1994-2013. METHODS: Using national health registries, we compared the observed incidence of leukaemia, lymphoma and brain cancer among 83 935 children with a hospital-based pneumonia diagnosis with that expected among children in the general population. We calculated absolute cancer risks and standardised incidence ratios (SIRs) as a measure of relative risk. RESULTS: The cancer SIRs were substantially increased during the first 6 months of follow-up; lymphoid leukaemia: 6.2 (95% CI 3.5 to 10.3); myeloid leukaemia: 14.8 (95% CI 6.0 to 30.6); Hodgkin's lymphoma: 60.8 (95% CI 26.2 to 120), non-Hodgkin's lymphoma: 15.9 (95% CI 5.2 to 37.2) and brain cancer: 4.4 (95% CI 1.9 to 8.7). The 6-month absolute risks of leukaemia, lymphoma and brain cancer were all low, reaching 0.05% when combined. An increased risk persisted beyond 5 years for non-Hodgkin's lymphoma and brain cancer. However, the 5-year absolute cancer risk was 0.14%. CONCLUSIONS: The short-term incidence of leukaemia, lymphoma and brain cancer was higher than expected and persisted beyond 5 years for non-Hodgkin's lymphoma and brain cancer. However, the absolute cancer risk was low.

Differences in reported sepsis incidence according to study design: a literature review.

BACKGROUND: Sepsis and severe sepsis are common conditions in hospital settings, and are associated with high rates of morbidity and mortality, but reported incidences vary considerably. In this literature review, we describe the variation in reported population-based incidences of sepsis and severe sepsis. We also examine methodological and demographic differences between studies that may explain this variation. METHODS: We carried out a literature review searching three major databases and reference lists of relevant articles, to identify all original studies reporting the incidence of sepsis or severe sepsis in the general population. Two authors independently assessed all articles, and the final decision to exclude an article was reached by consensus. We extracted data according to predetermined variables, including study country, sepsis definition, and data source. We then calculated descriptive statistics for the reported incidences of sepsis and severe sepsis. The studies were classified according to the method used to identify cases of sepsis or severe sepsis: chart-based (i.e. review of patient charts) or code-based (i.e. predetermined International Classification of Diseases [ICD] codes). RESULTS: Among 482 articles initially screened, we identified 23 primary publications reporting incidence of sepsis and/or severe sepsis in the general population. The reported incidences ranged from 74 to 1180 per 100,000 person-years and 3 to 1074 per 100,000 person-years for sepsis and severe sepsis, respectively. Most chart-based studies used the Bone criteria (or a modification hereof) and Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study criteria to identify cases of sepsis and severe sepsis. Most code-based studies used ICD-9 codes, but the number of codes used ranged from 1 to more than 1200. We found that the incidence varied according to how sepsis was identified (chart-based vs. code-based), calendar year, data source, and world region. CONCLUSION: The reported incidences of sepsis and severe sepsis in the general population varied greatly between studies. Such differences may be attributable to differences in the methods used to collect the data, the study period, or the world region where the study was undertaken. This finding highlights the importance of standardised definitions and acquisition of data regarding sepsis and severe sepsis.

Lower Gastrointestinal Bleeding And Risk of Gastrointestinal Cancer.

OBJECTIVES: Lower gastrointestinal (GI) bleeding is a well-known symptom of colorectal cancer (CRC). Whether incident GI bleeding is also a marker of other GI cancers remains unclear. METHODS: This nationwide cohort study examined the risk of various GI cancer types in patients with lower GI bleeding. We used Danish medical registries to identify all patients with a first-time hospital diagnosis of lower GI bleeding during 1995-2011 and followed them for 10 years to identify subsequent GI cancer diagnoses. We computed absolute risks of cancer, treating death as a competing risk, and calculated standardized incidence ratios (SIRs) by comparing observed cancer cases with expected cancer incidence rates in the general population. RESULTS: Among 58,593 patients with lower GI bleeding, we observed 2,806 GI cancers during complete 10-year follow-up. During the first year of follow-up, the absolute GI cancer risk was 3.6%, and the SIR of any GI cancer was 16.3 (95% confidence interval (CI): 15.6-17.0). Colorectal cancers accounted for the majority of diagnoses, but risks of all GI cancers were increased. During 1-5 years of follow-up, the SIR of any GI cancer declined to 1.36 (95% CI: 1.25-1.49), but risks remained increased for several GI cancers. Beyond 5 years of follow-up, the overall GI cancer risk was close to unity, with reduced risk of rectal cancer and increased risk of liver and pancreatic cancers. CONCLUSIONS: A hospital-based diagnosis of lower GI bleeding is a strong clinical marker of prevalent GI cancer, particularly CRC. It also predicts an increased risk of any GI cancer beyond 1 year of follow-up.

Survival after splanchnic vein thrombosis: A 20-year nationwide cohort study.

INTRODUCTION: Splanchnic vein thrombosis (SVT) is a rare condition with a poorly understood prognosis. MATERIALS AND METHODS: We conducted a population-based cohort study (1994-2013), using data from Danish nationwide medical registries, to examine the short- and long-term prognosis of SVT. We identified 1915 incident cases of SVT and a matched comparison cohort of 18,267 persons without SVT (matched by cancer, cirrhosis, pancreatitis, alcohol-related disease, atrial fibrillation/flutter, venous thromboembolism, heart failure, and inflammatory bowel disease). We used the Kaplan-Meier method to calculate absolute risk of death. Using stratified Cox regression, we computed mortality rate ratios (MRRs) with 95% confidence intervals (CIs), comparing SVT patients with the comparison cohort. RESULTS: We identified 1,500 (78%) patients with portal vein thrombosis, 204 (11%) with hepatic vein thrombosis, and 211 (11%) with mesenteric vein thrombosis. The mortality risks were markedly higher for SVT patients than for the comparison cohort during the first 5years of follow-up (30-day risk: 20.6% vs. 0.7%; 31-364-day risk: 21.7% vs. 4.7%; and 1-5-year risk: 25.4% vs. 17.7%). The corresponding MRRs were 40.7 (95% CI: 32.4-51.1), 7.4 (95% CI: 6.4-8.6), and 2.4 (95% CI: 2.1-2.8), respectively. The 30-day mortality was higher after mesenteric vein thrombosis than portal and hepatic vein thrombosis, whereas portal vein thrombosis had a stronger impact on mortality after 30days than hepatic and mesenteric vein thrombosis. CONCLUSIONS: Splanchnic vein thrombosis has a poor short- and long-term prognosis that varies according to subtype of thrombosis. Reasons for the increased mortality in patients with SVT need further clarification.

Venous thromboembolism and subsequent risk of cancer in patients with liver disease: a population-based cohort study.

OBJECTIVE: Venous thromboembolism (VTE) may be a marker of occult cancer in the general population. While liver disease is known to increase the risk of VTE and cancer, it is unclear whether VTE in patients with liver disease is also a marker of occult cancer. DESIGN: A population-based cohort study. SETTING: Denmark. PARTICIPANTS: We used population-based health registries to identify all patients with liver disease in Denmark with a first-time diagnosis of VTE (including superficial or deep venous thrombosis and pulmonary embolism) during 1980-2010. Patients with non-cirrhotic liver disease and patients with liver cirrhosis were followed as two separate cohorts from the date of their VTE. MEASURES: For each cohort, we computed the absolute and relative risk (standardised incidence ratio; SIR) of cancer after VTE. RESULTS: During the study period, 1867 patients with non-cirrhotic liver disease and 888 with liver cirrhosis were diagnosed with incident VTE. In the first year following VTE, the absolute risk of cancer was 2.7% among patients with non-cirrhotic liver disease and 4.3% among those with liver cirrhosis. The SIR for the first 90 days of follow-up was 9.96 (95% CI 6.85 to 13.99) among patients with non-cirrhotic liver disease and 13.11 (95% CI 8.31 to 19.67) among patients with liver cirrhosis. After 1 year of follow-up, SIRs declined, but remained elevated in patients with non-cirrhotic liver disease (SIR=1.50, 95% CI 1.23 to 1.81) and patients with liver cirrhosis (SIR=1.95, 95% CI 1.45 to 2.57). CONCLUSIONS: VTE may be a marker of occult cancer in patients with liver disease.

Cirrhosis is Associated with an Increased 30-Day Mortality After Venous Thromboembolism.

OBJECTIVES: Patients with cirrhosis are at increased risk of venous thromboembolism (VTE), but the impact of cirrhosis on the clinical course following VTE is unclear. In a nationwide cohort study, we examined 30-day mortality among patients with cirrhosis and VTE. METHODS: We used Danish population-based health-care databases (1994-2011) to identify patients with incident VTE, i.e., deep venous thrombosis (DVT), pulmonary embolism (PE), and portal vein thrombosis (PVT). Among these, we identified 745 patients with cirrhosis and 3647 patients without cirrhosis (matched on gender, year of birth, calendar year of VTE diagnosis and VTE type). We assessed the 30-day mortality risk among VTE patients with and without cirrhosis, and the mortality rate ratios (MRRs), using an adjusted Cox model with 95% confidence interval. We obtained information on immediate cause of death for patients who died within 30 days after VTE. RESULTS: The 30-day mortality risk for DVT was 7% for patients with cirrhosis and 3% for patients without cirrhosis. Corresponding PE-related mortality risks were 35% and 16%, and PVT-related mortality risks were 19% and 15%, respectively. The adjusted 30-day MRRs were 2.17 (1.24-3.79) for DVT, 1.83 (1.30-2.56) for PE, and 1.30 (0.80-2.13) for PVT. Though overall mortality was higher in patients with cirrhosis than patients without cirrhosis, the proportions of deaths due to PE were similar among patients (25% and 24%, respectively). CONCLUSIONS: Cirrhosis is a predictor for increased short-term mortality following VTE, with PE as the most frequent cause of death.

Positive predictive values of the International Classification of Diseases, 10th revision diagnoses of Gram-negative septicemia/sepsis and urosepsis for presence of Gram-negative bacteremia.

BACKGROUND: Health care databases are a valuable resource for infectious disease epidemiology if diagnoses are accurately coded. We examined the ability of diagnostic coding to accurately identify Gram-negative bacteremia. METHODS: We randomly selected 100 patients among 1,703 patients recorded in the Danish National Patient Register with a diagnosis of either "septicemia/sepsis due to other Gram-negative organisms" (International Classification of Diseases, 10th revision [ICD-10] code A41.5) or "urosepsis" (ICD-10 code A41.9B) who had been admitted at Aalborg University Hospital, Denmark between 1994 and 2012. We estimated the positive predictive value (PPV) of these diagnoses for presence of Gram-negative bacteremia, using microbiological results from blood cultures as standard reference. Complementary clinical information was obtained from the medical records. RESULTS: Of the 100 patients registered with Gram-negative septicemia/sepsis or urosepsis, 72 had blood culture confirmed Gram-negative bacteremia, four patients had monomicrobial Gram-positive bacteremia, 21 patients had a negative blood culture, and three had no blood culture taken. The overall PPV of a blood culture confirmed Gram-negative bacteremia diagnosis was 72% (95% confidence interval [CI]: 62%-81%); for ICD-10 code A41.5 it was 86% (95% CI: 74%-94%) and for ICD-10 code A41.9B it was 55% (95% CI: 39%-70%). The highest PPV was achieved for diagnoses registered in the most recent calendar period (2009-2012) and for secondary discharge diagnoses. CONCLUSION: Our findings indicated good agreement between ICD-10 code A41.5 "septicemia/sepsis due to other Gram-negative organisms" and Gram-negative bacteremia, whereas ICD-10 code A41.9B "urosepsis" was not suited for identification of Gram-negative bacteremia.