Kim Oren Gradel

Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with ulcerative colitis - a nationwide cohort study

It is still controversial whether pre‐operative anti‐tumour necrosis factor‐alpha (anti‐TNF‐α) agents increase post‐operative complications in patients with ulcerative colitis (UC).

Pre‐operative use of anti‐TNF‐α agents and the risk of post‐operative complications in patients with Crohn's disease – a nationwide cohort study

A possible negative role of pre‐operative use of antitumour necrosis factor‐alpha (anti‐TNF‐α) agents on post‐operative outcomes in Crohns disease (CD) patients is still debated.

Epidemiology of Haemophilus influenzae bacteremia: A multi-national population-based assessment

OBJECTIVES Haemophilus influenzae is an important cause of invasive infection but contemporary data in non-selected populations is limited. METHODS Population-based surveillance for Haemophilus influenzae bacteremia was conducted in seven regions in Australia, Canada, and Denmark during 2000-2008. RESULTS The overall annual incidence rate was 1.31 per 100,000 population and type specific rates were 0.08 for H. influenzae serotype b (Hib), 0.22 for H. influenzae serotypes a, c-f (Hiac-f), and 0.98 per 100,000 for non-typeable H. influenzae (NTHi). Very young and old patients were at highest risk. The serotypes causing disease varied according to age with nearly all cases in the elderly due to NTHi. The presence of comorbid medical illness was common with 14%, 16%, and 29% patients having Charlson comorbidity scores of 1, 2, and ≥ 3, respectively. The 30-day all-cause case-fatality rate was 18%. Factors independently associated with death at 30-days in logistic regression analysis included male gender, hospital-onset disease, older age, and lower respiratory tract, central nervous system, or unknown focus of infection. CONCLUSIONS Haemophilus influenzae is an important cause of morbidity and mortality particularly with NTHi in the elderly. These data serve as a baseline to assess the future effectiveness of new preventative interventions.

Classification of positive blood cultures: computer algorithms versus physicians' assessment - development of tools for surveillance of bloodstream infection prognosis using population-based laboratory databases

BackgroundInformation from blood cultures is utilized for infection control, public health surveillance, and clinical outcome research. This information can be enriched by physicians’ assessments of positive blood cultures, which are, however, often available from selected patient groups or pathogens only. The aim of this work was to determine whether patients with positive blood cultures can be classified effectively for outcome research in epidemiological studies by the use of administrative data and computer algorithms, taking physicians’ assessments as reference.MethodsPhysicians’ assessments of positive blood cultures were routinely recorded at two Danish hospitals from 2006 through 2008. The physicians’ assessments classified positive blood cultures as: a) contamination or bloodstream infection; b) bloodstream infection as mono- or polymicrobial; c) bloodstream infection as community- or hospital-onset; d) community-onset bloodstream infection as healthcare-associated or not. We applied the computer algorithms to data from laboratory databases and the Danish National Patient Registry to classify the same groups and compared these with the physicians’ assessments as reference episodes. For each classification, we tabulated episodes derived by the physicians’ assessment and the computer algorithm and compared 30-day mortality between concordant and discrepant groups with adjustment for age, gender, and comorbidity.ResultsPhysicians derived 9,482 reference episodes from 21,705 positive blood cultures. The agreement between computer algorithms and physicians’ assessments was high for contamination vs. bloodstream infection (8,966/9,482 reference episodes [96.6%], Kappa = 0.83) and mono- vs. polymicrobial bloodstream infection (6,932/7,288 reference episodes [95.2%], Kappa = 0.76), but lower for community- vs. hospital-onset bloodstream infection (6,056/7,288 reference episodes [83.1%], Kappa = 0.57) and healthcare-association (3,032/4,740 reference episodes [64.0%], Kappa = 0.15). The 30-day mortality in the discrepant groups differed from the concordant groups as regards community- vs. hospital-onset, whereas there were no material differences within the other comparison groups.ConclusionsUsing data from health administrative registries, we found high agreement between the computer algorithms and the physicians’ assessments as regards contamination vs. bloodstream infection and monomicrobial vs. polymicrobial bloodstream infection, whereas there was only moderate agreement between the computer algorithms and the physicians’ assessments concerning the place of onset. These results provide new information on the utility of computer algorithms derived from health administrative registries.

Decreasing incidence rates of bacteremia: A 9-year population-based study

BACKGROUND Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS We conducted a population-based study among adults with first-time bacteremia in Funen County, Denmark, during 2000-2008 (N = 7786). We reported mean and annual incidence rates (per 100,000 person-years), overall and by place of acquisition. Trends were estimated using a Poisson regression model. RESULTS The overall incidence rate was 215.7, including 99.0 for community-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p < .001), the incidence rate of community-acquired bacteremia decreased by 25.6% from 119.0 to 93.8 (3.7% annually, p < .001) and the incidence rate of nosocomial bacteremia decreased by 28.9% from 82.2 to 56.0 (4.2% annually, p < .001). The incidence rate of healthcare-associated bacteremia remained stable. The most common microorganisms were Escherichia coli (28.3%), Staphylococcus aureus (12.3%), coagulase-negative staphylococci (10.0%) and Streptococcus pneumoniae (9.1%). Regardless of place of acquisition, the proportion of bacteremias caused by enterococci increased (p < .05) and the proportion caused by coagulase-negative staphylococci decreased (p < .05). CONCLUSIONS The incidence rates of community-acquired and nosocomial bacteremia decreased substantially over time.

Baseline C‐reactive protein level as a predictor of mortality in bacteraemia patients: a population‐based cohort study

We examined the association between C-reactive protein (CRP) level at time of blood culture (BC) draw and mortality following bacteraemia. Our population-based cohort study comprised all first-time monomicrobial bacteraemia episodes in adults in a Danish county during 1996-2004 (n = 5267). CRP was measured within 24 h of the first positive BC draw. Cox regression was used to compute mortality rate ratios (MRRs) associated with CRP level quartiles (10-64 (reference), 65-143, 144-240 and 241-688 mg/L), controlling for age, gender, comorbidity, specialty, acquisition of infection, and infection focus. We also looked for a biological interaction between CRP level and high magnitude of bacteraemia (three of three culture bottles positive). Thirty-day mortality increased with higher CRP level: adjusted 0-30-day MRRs for patients in the second, third and fourth CRP quartiles were 1.38 (95% CI 1.13-1.69), 1.70 (95% CI 1.40-2.06), and 2.38 (95% CI 1.96-2.87), respectively (p for trend <10(-4)). In contrast, mortality associations with CRP during 31-365 days of follow-up were weak (adjusted MRRs for the second to fourth quartiles ranged from 1.18 to 1.28). A high magnitude of bacteraemia strengthened the association between high CRP level and 30-day mortality. We conclude that the CRP level, measured concurrently with the first positive BC, independently predicted 30-day mortality in adult bacteraemia patients.

Non-typhoidal Salmonella and Campylobacter infections among HIV-positive patients in Denmark

Abstract Non-typhoidal Salmonella (NTS) and Campylobacter are common causes of diarrhoea in human immunodeficiency virus (HIV)-positive patients. To investigate if incidence has changed since the introduction of highly active antiretroviral therapy (HAART), we combined data from The Danish Surveillance Registry for Enteric Pathogens and The Danish National Hospital Registry. We found that the incidences of NTS- and Campylobacter-related illness among HIV-positive patients in Denmark have declined since the introduction of HAART, although the incidences remained higher compared to the background population. Moreover our study suggests that there is an increased incidence of Campylobacter-related illness among homosexual men in the HIV-positive population.

Does C-reactive protein independently predict mortality in adult community-acquired bacteremia patients with known sepsis severity?

We evaluated whether sepsis severity and C‐reactive protein (CRP) level on admission prognostically corroborated or annulled each other in adult patients with incident community‐acquired bacteremia (Funen, Denmark, 2000–2008). We used logistic regression and area under the receiver operating characteristic curve (AUC) to evaluate 30‐day mortality in four models: (i) age, gender, comorbidity, bacteria, and ward. (ii) Model 1 and sepsis severity. (iii) Model 1 and CRP. (iv) Model 1, sepsis severity, and CRP. Altogether, 416 of 1999 patients died within 30 days. CRP independently predicted 30‐day mortality [Model 4, odds ratio (95% CIs) for 100 mg/L: 1.16 (1.06–1.27)], but it did not contribute to the AUC (Model 2 vs Model 4: p = 0.31). In the 963 non‐severe sepsis patients, CRP independently predicted 30‐day mortality [Model 4: 1.42 (1.20–1.69)] and it increased the AUC (Model 2 vs Model 4: p = 0.06), thus CRP contributed as much as sepsis severity to prognosis.

Increased prescription rate of antibiotics prior to non-typhoid Salmonella infections: a one-year nested case-control study.

We conducted a nested case-control study of antibiotic consumption 1 y prior to a non-typhoid Salmonella (NTS) infection. We included all 1882 NTS patients diagnosed in 1994–2003 in North Jutland County, Denmark, and for each case we retrieved 10 controls among all residents in the county, matched for the specimen date, gender, and age. Antibiotic redemptions were retrieved from a countywide prescription database. Being a marker of the infection, redemptions within 1 week before NTS infection were excluded. The subjects last antibiotic redemption, if any, was the binary outcome in a conditional logistic regression model, and we adjusted for comorbidity based on previous hospital discharge diagnoses. In the y up to the NTS episode, 42.0% of cases and 28.5% of controls redeemed antibiotics (adjusted odds ratio (OR) 1.59, 95% confidence intervals 1.43–1.77). The OR was constant up to 20 weeks before the NTS episode and increased continuously thereafter. The higher antibiotic consumption during the entire y may imply that NTS patients are frailer than the general population. The increased OR in the weeks close to the NTS infection are consistent with alterations in the intestinal microflora being involved in acquiring an NTS infection.

No Specific Time Window Distinguishes between Community-, Healthcare-, and Hospital-Acquired Bacteremia, but They Are Prognostically Robust

OBJECTIVE We examined whether specific time windows after hospital admission reflected a sharp transition between community and hospital acquisition of bacteremia. We further examined whether different time windows to distinguish between community acquisition, healthcare association (HCA), and hospital acquisition influenced the results of prognostic models. DESIGN Population-based cohort study. SETTING Hospitals in 3 areas of Denmark (2.3 million inhabitants) during 2000-2011. METHODS We computed graphs depicting proportions of males, absence of comorbidity, microorganisms, and 30-day mortality pertaining to bacteremia 0, 1, 2, …, 30, and 31 days and later after admission. Next, we assessed whether different admission (0-1, 0-2, 0-3, 0-7 days) and HCA (30, 90 days) time windows were associated with changes in odds ratio (OR) and area under the receiver operating characteristic (ROC) curve for 30-day mortality, adjusting for sex, age, comorbidity, and microorganisms. RESULTS For 56,606 bacteremic episodes, no sharp transitions were detected on a specific day after admission. Among the 8 combined time windows, ORs for 30-day mortality varied from 1.30 (95% confidence interval [CI], 1.23-1.37) to 1.99 (95% CI, 1.48-2.67) for HCA and from 1.36 (95% CI, 1.24-1.50) to 2.53 (95% CI, 2.01-3.20) for hospital acquisition compared with community acquisition. Area under the ROC curve changed marginally from 0.684 (95% CI, 0.679-0.689) to 0.700 (95% CI, 0.695-0.705). CONCLUSIONS No time transitions unanimously distinguished between community and hospital acquisition with regard to sex, comorbidity, or microorganisms, and no difference in 30-day mortality was seen for HCA patients in relation to a 30- or 90-day time window. ORs decreased consistently in the order of hospital acquisition, HCA, and community acquisition, regardless of time window combination, and differences in area under the ROC curve were immaterial.