Mortality and cause of death in persons with chronic hepatitis B virus infection versus healthy persons from the general population in Denmark.

The study aimed to determine adjusted all-cause mortality and cause of death in persons with chronic hepatitis B virus (HBV) infection compared with age- and sex-matched persons from the general population. We used nationwide registers to identify persons aged ≥18 years with chronic HBV infection in 2002-2017 in Denmark and included 10 age- and sex-matched controls for each. Follow-up was from 6 months after diagnosis until death, emigration, or 31 December 2017. Mortality rate ratios (MRRs) adjusted for age, sex, employment, origin and comorbidity were calculated using Poisson regression. Unadjusted cause-specific mortality rate ratios with 95% confidence intervals were calculated assuming a Poisson distribution. A total of 6988 persons with chronic HBV infection and 69,847 controls were included. During a median follow-up of 7.7 years (range 0.0-15.5), 315 (5%) persons with-and 1525 (2%) without-chronic HBV infection died. The adjusted all-cause MRR was 1.5 (95% CI 1.2-2.0). Persons with chronic HBV infection had increased mortality due to liver disease including hepatocellular carcinoma (MRR 12.3 [8.6-17.7]), external causes (MRR 3.3 [2.5-4.7]), endocrine disease (MRR 3.2 [1.8-5.4]), genitourinary disease (MRR 3.2 [1.2-7.6]) and neoplasms (except hepatocellular carcinoma; MRR 1.6 [1.2-2.0]). In conclusion, this study showed an increased all-cause mortality in persons with chronic HBV infection in comparison with age- and sex-matched persons without chronic HBV infection which remained after adjustment for several confounding factors. Excess mortality was mainly associated with liver disease, but also external factors, endocrine disease, genitourinary disease and neoplasms (excluding hepatocellular carcinoma).

Altered balance between collagen formation and degradation after successful direct-acting antiviral therapy of chronic hepatitis C.

The effect of direct-acting antiviral (DAA) therapy on extracellular matrix (ECM) turnover, a prominent feature of chronic hepatitis C (CHC), is unknown. ECM protein degradation and formation generate fragments reflecting the tissue turnover balance when quantified in the blood. PRO-C3 and PRO-C4 reflect type III and IV collagen formation; C3M and C4M are degradation markers of type III and IV. We aimed to assess the markers' dynamics with DAA therapy in CHC patients. Plasma PRO-C3, PRO-C4, C3M and C4M were assessed before, during and up till one year after 12-24 weeks of DAA therapy in 77 CHC patients with advanced fibrosis (n = 14) or cirrhosis (n = 63). Liver stiffness was evaluated using transient elastography. PRO-C3, C3M and C4M levels decreased significantly (P < .00001) while PRO-C4 was unchanged (P = .20) during the study period. There was a steep decrease in the PRO-C3/C3M ratio during DAA therapy and follow-up (P < .02). The PRO-C4/C4M ratio was unchanged (P > .27). The dynamics of the collagen markers behaved similarly between patients with advanced fibrosis and cirrhosis. However, the cirrhosis patients had >20% higher levels of C3M, PRO-C4 and C4M at all time points (P < .05). The collagen markers correlated with liver stiffness at baseline and follow-up.Markers of type III and IV collagen formation and degradation decreased during and after successful DAA therapy in CHC patients with advanced liver disease, and associated with disease severity. These results indicate an altered balance between collagen formation and degradation after viral clearance suggesting favourable effects on liver fibrosis.

Time-dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct-acting antiviral therapy of chronic hepatitis C.

Sofosbuvir-based direct-acting antiviral (DAA) therapy generally cures chronic hepatitis C (CHC) infections, however, the effects on the underlying liver disease and the potential rate of recovery are unclear. We aimed to investigate the effects of DAA therapy on liver inflammation, fibrosis, metabolic function and cognitive function and the time course in CHC patients with advanced liver disease. Seventy-one CHC patients with advanced liver disease were studied before, during and one year after successful sofosbuvir-based DAA therapy. Liver inflammation was assessed by plasma sCD163 and sMR levels (ELISA), fibrosis by liver stiffness (transient elastography), function by galactose elimination capacity (GEC) and cognitive performance by continuous reaction time (CRT). During DAA therapy, we observed a rapid sCD163 decline from baseline to end of treatment (6.9 vs 3.8 mg/L, P < .0001), whereas the change in sMR was more subtle (0.37 vs 0.30 mg/L, P < .0001). Liver stiffness decreased by 20% at end of treatment (17.8 vs 14.3 kPa, P < .0001), together suggesting rapid resolution of liver inflammation. One year after treatment, liver stiffness decreased by an additional 15% (P < .0001), suggestive of fibrosis regression. The GEC improved at follow-up (all: 1.74 vs 1.98 mmol/min), mainly at 12 weeks post-treatment, both in patients with cirrhosis (n = 56) and those with advanced liver fibrosis (n = 15) (P < .001). The CRT improved at one-year follow-up (1.86 vs 2.09, P = .04). In conclusion, successful DAA therapy of CHC proves beneficial in advanced liver disease, with an initial rapid resolution of liver inflammation and a subsequent gradual but steady improvement in liver fibrosis, metabolic liver function and reaction time.

Coordinating objects of care: Exploring the role of case managers as brokers in cancer patient pathways.

OBJECTIVE: Healthcare systems increasingly make use of case managers to handle organisational complexity. In Danish cancer patient pathways, case managers handle the complexities of cancer diagnostics and treatment while adhering to pathway guidelines. This article explores how case managers handle their various responsibilities and focuses on the micro-politics of case management. METHODS: An ethnographic study was carried out in three Danish cancer patient pathways. Interactions between patients and healthcare professionals were observed, including professionals with case management tasks. We interviewed 13 cancer diagnostic patients in their homes and 26 healthcare professionals during work hours, among other things about case management. RESULTS: We found that the work of case managers differs between cancer patient pathways and settings but overall emphasises coordination of patient trajectories and being contact person. We argue that case managers, embodying the figure of the broker, handle their responsibilities by coordinating the following co-existing objects of care, each with different goals: the diseased body, the person, the organisation and the cancer patient pathway. CONCLUSION: We conclude that case managers, in addition to being a response to the complexity of healthcare services, impact the implementation of cancer patient pathways and influence cancer diagnostic activities.

Rapid and persistent decline in soluble CD163 with successful direct-acting antiviral therapy and associations with chronic hepatitis C histology.

BACKGROUND AND AIM: Soluble CD 163 (sCD163) is released from activated liver macrophages in chronic viral hepatitis C (HCV) and serum levels reflect liver disease severity. The impact of direct-acting antiviral (DAA)-therapy on sCD163-levels and the ability of sCD163 to predict the presence of liver fibrosis remain unclear. In a combined observational and prospective study, we aimed to investigate changes in sCD163 with DAA-treatment, to investigate associations between sCD163 and histopathological activity and fibrosis and to validate the sCD163-based fibrosis score in HCV-patients. METHODS: We examined three groups of patients: an Australian (n = 28) treated with pegylated-interferon and a first-generation DAA, a Danish (n = 38) treated with sofosbuvir-based DAA-regimens and a Japanese (n = 562) assessed for activity and fibrosis (Metavir scoring system) in liver biopsies. Serum sCD163-levels were quantified by ELISA. RESULTS: Thirteen (46%) of the Australian patients achieved sustained virological response (SVR) and only these patients had significant decreases in sCD163-levels (2.7 (95%CI:1.9-3.6) vs. 4.1(2.9-5.7) mg L - 1, p = .008). In the Danish group, 37 (97%) patients achieved SVR at 12-weeks post-treatment with 32% reduction in sCD163-levels (5.0 (4.3-5.8) vs. 7.4 (6.3-8.7), p < .001). The decline was rapid and persisted 12 months after treatment cessation (p < .007). sCD163 levels increased in parallel with inflammatory activity and fibrosis (p < .001). The sCD163-based fibrosis score outperformed established fibrosis scores for significant fibrosis (areas under the receiver operating characteristics curves (AUROCs): 0.79 (0.75-0.83) vs. aspartate aminotransferase to platelet ratio index (APRI) 0.73 (0.69-0.77), Fibrosis-4 (FIB-4) 0.74 (0.70-0.78), p < .001). CONCLUSION: sCD163-levels decline rapidly with successful DAA therapy and are associated with histological inflammatory activity and fibrosis, confirming a key role for macrophages in HCV inflammation and fibrosis and supporting sCD163 as a biomarker of treatment response.

Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark.

OBJECTIVE: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission. MATERIALS AND METHODS: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc. RESULTS: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission. CONCLUSION: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.

Clinical findings in a multi-ethnic adult hepatitis B virus patient population in Denmark with emphasis on genotypic characteristics.

OBJECTIVE: Most knowledge about chronic hepatitis B virus (HBV) infection is based upon studies in high-endemic areas with one or two predominant genotype(s). The aim of the study was to describe clinical characteristics of a heterogeneous genotypic HBV patient population in a low-endemic European country. METHODS: Data from HBV patients currently followed in a Danish university hospital and affiliated regional clinics were reviewed in accordance to genotype status. RESULTS: Of 540 HBV patients, 462 (86%) were of non-Danish ethnicity originating from 43 different countries. HBV genotype was known in 37% of the patients: A (11%), B (25%), C (25%), D (37%) and E (2%). Logistic regression analysis of pre-treatment data among genotype A-D patients receiving nucleos(t)ide analogue (NA) therapy revealed a decreased HBeAg rate by age (OR = 0.93; CI: 0.89-0.97; p < 0.01) and an increased rate in genotype C patients (OR = 20.5; CI: 3.3-129; p < 0.01). Among untreated patients HBeAg rate was also significantly decreased by age (OR = 0.90 (0.85:0.95; p < 0.0001), whereas the rate was increased in both genotype B and C patients (OR = 7.5; CI: 1.8-30.5; p < 0.01 and OR = 12.2; CI: 3.2-46.6; p < 0.001, respectively). No significant variation was found in HBV DNA level in any of the two groups when adjusting for age, gender, genotype and HBeAg. Increased liver pathology prevalence was, irrespectively of treatment status, associated to age and male gender, but not to any genotype. CONCLUSION: In this study population, genotype B and C was found associated with higher HBeAg rate but not with increased liver pathology.

Genetic variants in the apoptosis gene BCL2L1 improve response to interferon-based treatment of hepatitis C virus genotype 3 infection.

Genetic variation upstream of the apoptosis pathway has been associated with outcome of hepatitis C virus (HCV) infection. We investigated genetic polymorphisms in the intrinsic apoptosis pathway to assess their influence on sustained virological response (SVR) to pegylated interferon-α and ribavirin (pegIFN/RBV) treatment of HCV genotypes 1 and 3 infections. We conducted a candidate gene association study in a prospective cohort of 201 chronic HCV-infected individuals undergoing treatment with pegIFN/RBV. Differences between groups were compared in logistic regression adjusted for age, HCV viral load and interleukin 28B genotypes. Four single nucleotide polymorphisms (SNPs) located in the B-cell lymphoma 2-like 1 (BCL2L1) gene were significantly associated with SVR. SVR rates were significantly higher for carriers of the beneficial rs1484994 CC genotypes. In multivariate logistic regression, the rs1484994 SNP combined CC+TC genotypes were associated with a 3.4 higher odds ratio (OR) in SVR for the HCV genotype 3 (p=0.02). The effect estimate was similar for genotype 1, but the association did not reach statistical significance. In conclusion, anti-apoptotic SNPs in the BCL2L1 gene were predictive of SVR to pegIFN/RBV treatment in HCV genotypes 1 and 3 infected individuals. These SNPs may be used in prediction of SVR, but further studies are needed.

Testing for hepatitis B virus and HIV in patients with chronic hepatitis C: screening performance and outcome.

BACKGROUND: Patients infected with hepatitis C virus (HCV) and co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV) are at increased risk for progression of liver disease. The aim of this study was to assess HBV and HIV screening performance and outcome in HCV patients followed at a Danish university hospital and affiliated regional outpatient clinics. METHODS: HBV and HIV serology data were extracted from a quality assurance database for the assessment of screening performance in patients diagnosed with chronic HCV infection during the period 1 January 1996 to 31 December 2011. Patients with incomplete and missing serology data had complementary serology tests performed to assess the prevalence of HBV and HIV co-infection and HBV immune status. RESULTS: Among 624 HCV patients, 10 (2%) were co-infected with chronic HBV and 32 (5%) with HIV. Approximately half of the cohort were non-immune to HBV or had an unknown HBV serology status. Serology results consistent with resolved infection and HBV vaccination were found in 209 (33%) and 65 (10%) patients, respectively. During the 16-y observation period, HBV and HIV screening coverage at HCV diagnosis increased from 23% to 92% and from 38% to 80%, respectively. CONCLUSION: Despite improvements throughout the study period, HBV and HIV serology screening remained incomplete. The majority of patients were either HBV non-immune or had an unknown HBV serology status. These findings thus call for a more proactive screening approach as well as an improved HBV vaccination strategy for patients with chronic HCV infection.

Short-course antibiotic therapy for hospitalized patients with early clinical response in community-acquired pneumonia: a multicentre cohort study.

OBJECTIVES: To explore whether short-course antibiotic therapy is efficient and safe in routine clinical settings among patients hospitalized with community-acquired pneumonia (CAP) who achieve an early clinical response. METHODS: During 2017-2019, we conducted a cohort study of patients admitted with CAP to four hospitals in Denmark. Data were prospectively gathered from medical records and enriched with data from nationwide registries. In the present study, we included patients with early clinical response and divided them into treatment groups based on antibiotic duration, as decided by the attending physician: short-course (4-7 days) or prolonged-course (8-14 days). The primary outcome was post-treatment mortality within 30 days. Secondary outcomes included readmissions or new antibiotics. Logistic regression models were used to estimate ORs with 95% CIs, and inverse probability weighting was applied to adjust for confounding. RESULTS: The study cohort included 1151 patients with a median age of 74 years, predominantly presenting with mild-moderate disease. The 30-day post-treatment mortality was 3.36% (11/327) in the short-course group and 3.40% (28/824) in the prolonged-course group (adjusted OR 1.05, 95% CI 0.38-1.88). Readmission occurred in 15.6% (42/269) vs. 14.0% (102/727) (adjusted OR 1.07, 95% CI 0.75-1.69) and new prescription of antibiotics in 11.9% (32/269) vs. 12.1% (88/727) (adjusted OR 0.99, 95% CI 0.61-1.49). DISCUSSION: In patients hospitalized with CAP and early clinical response, similar outcomes were observed between short-course and prolonged-course therapies. These results support the use of short-course therapy in routine clinical settings.

Association of Self-reported Systemic Reactions Following SARS-CoV-2 Vaccination With Immunological Response in the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE).

Background: Side effects to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are a key concern contributing to vaccine hesitancy, but more individuals may be encouraged if SARS-CoV-2 vaccines were known to lead to a stronger immune response. Methods: Included were adult participants from the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE) who completed a questionnaire to assess systemic reactions following SARS-CoV-2 vaccination (BTN162b2, mRNA-1273, ChAdOx1) and had SARS-CoV-2 spike immunoglobulin G (IgG) levels measured at baseline and post-vaccine. A symptom score was developed to measure severity of systemic adverse reactions (+1 for each moderate, +2 for each severe). Post-vaccination SARS-CoV-2 spike IgG levels were compared between participants with different scores using multivariable linear regression. Results: A total of 6528 participants were included (56.3% females; median age [interquartile range], 64 [54-75] years). After the first vaccination, no association was found between symptom score and post-vaccine dose spike IgG level (P = .575). Following the second vaccination, significantly higher spike IgG levels were observed according to higher symptom scores (P < .001); adjusted geometric mean ratios were 1.16 (95% CI, 1.04-1.30), 1.24 (95% CI, 1.09-1.41), 1.25 (95% CI, 1.06-1.46), and 1.21 (95% CI, 1.08-1.35), for scores of 2, 3, 4, and ≥5, respectively, compared with a score of 0. After adjustment for pre-vaccine dose spike IgG, this association was attenuated. Conclusions: An association was found between more severe adverse reactions and stronger antibody response after the second vaccination but not the first, likely attributed to higher levels of preexisting immunity gained from response to first vaccination. Regardless of side effects, most people experienced an effective immune response following vaccination.

Incidence of Hepatocellular Carcinoma and Decompensated Liver Cirrhosis and Prognostic Accuracy of the PAGE-B HCC Risk Score in a Low Endemic Hepatitis B Virus Infected Population.

Purpose: We aimed to determine incidence of hepatocellular carcinoma (HCC) and decompensated liver cirrhosis in persons with chronic hepatitis B virus (HBV) infection in Denmark stratified by disease phase, liver cirrhosis, and treatment status at baseline. Additionally, we aimed to assess the prognostic value of the PAGE-B HCC risk score in a mainly non-cirrhotic population. Patients and Methods: In this register-based cohort study, we included all individuals over the age of 18, with chronic HBV infection first registered between 2002 and 2016 in at least one of three nationwide registers. The study population was followed until HCC, decompensated liver cirrhosis, death, emigration, or December 31, 2017, which ever came first. Results: Among 6016 individuals included in the study, 10 individuals with and 23 without baseline liver cirrhosis developed HCC during a median follow up of 7.3 years (range 0.0-15.5). This corresponded to five-year cumulative incidences of 7.1% (95% confidence interval (CI) 2.0-12.3) and 0.2% (95% CI 0.1-0.4) in persons with and without baseline liver cirrhosis. The five-year cumulative incidence of decompensated liver cirrhosis was 0.7% (95% CI 0.5-1.0). Among 2038 evaluated for liver events stratified by disease phase, incidence of HCC was low in all who were non-cirrhotic and untreated for HBV at baseline. PAGE-B score was evaluated in 1529 persons. The 5-year cumulative incidence of HCC was 0, 0.8 (95% CI 0.5-1.8), and 8.7 (95% CI 1.0-16.4) in persons scoring <10, 10-17 and >17, respectively (c-statistic 0.91 (95% CI 0.84-0.98)). Conclusion: We found low incidence of HCC and decompensated liver cirrhosis in persons with chronic HBV infection in Denmark. Moreover, the PAGE-B score showed good accuracy for five-year risk of developing HCC in the population with chronic HBV infection in Denmark.

Cohort Profile:The Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE).

PURPOSE: The ENFORCE cohort is a national Danish prospective cohort of adults who received a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination programme. It was designed to investigate the long-term effectiveness, safety and durability of SARS-CoV-2 vaccines used in Denmark. PARTICIPANTS: A total of 6943 adults scheduled to receive a SARS-CoV-2 vaccine in the Danish COVID-19 vaccination programme were enrolled in the study prior to their first vaccination. Participants will be followed for a total of 2 years with five predetermined follow-up visits and additional visits in relation to any booster vaccination. Serology measurements are performed after each study visit. T-cell immunity is evaluated at each study visit for a subgroup of 699 participants. Safety information is collected from participants at visits following each vaccination. Data on hospital admissions, diagnoses, deaths and SARS-CoV-2 PCR results are collected from national registries throughout the study period. The median age of participants was 64 years (IQR 53-75), 56.6% were women and 23% were individuals with an increased risk of a serious course of COVID-19. A total of 340 (4.9%) participants tested positive for SARS-CoV-2 spike IgG at baseline. FINDINGS TO DATE: Results have been published on risk factors for humoral hyporesponsiveness and non-durable response to SARS-CoV-2 vaccination, the risk of breakthrough infections at different levels of SARS-CoV-2 spike IgG by viral variant and on the antibody neutralising capacity against different SARS-CoV-2 variants following primary and booster vaccinations. FUTURE PLANS: The ENFORCE cohort will continuously generate studies investigating immunological response, effectiveness, safety and durability of the SARS-CoV-2 vaccines. TRIAL REGISTRATION NUMBER: NCT04760132.

Ischemic Heart Disease in Chronic Hepatitis B: A Danish Nationwide Cohort Study.

Objective: Data on the risk of ischemic heart disease (IHD) in patients with chronic hepatitis B virus (CHB) are conflicting. Our objective was to address the rate of IHD in patients with CHB compared with individuals without CHB (control-persons) from the general population. Study Design and Setting: We conducted a cohort study of prospectively obtained data from Danish nationwide registries. We produced cumulative incidence curves and calculated the unadjusted incidence rate ratio (IRR) of IHD in persons with and without CHB. The adjusted association between having CHB and developing IHD was examined using a cause-specific Cox regression model. Results: In total, 6472 persons with CHB and 62,251 age- and sex-matched individuals from the general population were followed for 48,840 and 567,456 person-years, respectively, during which 103 (1,59%) with CHB and 1058 (1,70%) control-persons developed IHD. The crude IRR was 1.13 (95% CI: 0.91-1.39). CHB did not have a statistically significant effect on the rate of IHD after adjusting for several confounding factors (adjusted hazard ratio: 0.96, 95% CI: 0.76-1.21). Conclusion: In this nationwide cohort study, we did not find any difference between rate of IHD in persons with CHB in comparison with the general population.

Time to antibiotic administration and patient outcomes in community-acquired pneumonia: results from a prospective cohort study.

OBJECTIVES: Community-acquired pneumonia (CAP) is a frequently occurring disease linked to high mortality and morbidity. Previous studies indicated that the administration of antibiotics within 4 hrs of admission can improve key patient outcomes associated with CAP, such as mortality and time to clinical stability. However, the results have been heterogeneous and may not be applicable to all healthcare settings. Therefore, we designed a cohort study to estimate the impact of timely antibiotic administration on outcomes in patients admitted with CAP. METHODS: The impact of antibiotic administration within 4 hrs of admission and other covariates were estimated for 30-day mortality, stability within 72 hrs, 30-day readmission and time to discharge, using multivariable regression models. Sensitivity analyses were performed on a subset of patients with the most severe CAP and a propensity score matched cohort. RESULTS: In total, 2264 patients were included. Of these, 273 (12.1%) died within 30 days of admission, 1277 (56.4%) were alive and stable within 72 hrs and 334 (14.8%) were discharged alive and readmitted within 30 days. Median length of hospital stay was 5 days (interquartile range 3-8). In all models, the administration of antibiotics within 4 hrs of admission had no significant effect on the outcomes. The adjusted odds ratios (OR) derived from the multivariable models for 30-day mortality, stability within 72 hrs and 30-day readmission were 1.01 (95% confidence interval (CI) 0.76; 1.33), 0.88 (95% CI 0.74; 1.05) and 1.05 (95% CI 0.82; 1.34). The adjusted hazard ratio (HR) for time to discharge was 1.00 (95% CI 0.91; 1.10). DISCUSSION: A strict 4-hr threshold for antibiotic administration in all patients admitted with CAP is not reasonable. Instead, our results suggested that patients should be triaged and prioritized according to age, comorbidities, clinical condition and pneumonia severity.

The impact of a stewardship program on antibiotic administration in community-acquired pneumonia: Results from an observational before-after study.

BACKGROUND: A majority of patients with community-acquired pneumonia (CAP) receive antibiotics. According to the evidence, 5-7 days of treatment should be sufficient for most patients. Many, however, are treated longer than recommended. We have previously conducted a quality improvement study to ensure guideline-conform treatment for CAP. However, the impact of the interventions on antibiotic use has not been investigated. OBJECTIVE: To estimate the impact of an eight-month stewardship program on antibiotic use. METHODS: We conducted a before-after study comparing a four-month baseline period with data from a corresponding follow-up period. We performed univariable and multivariable logistic regression to compare odds for ≤7 days of total antibiotic treatment, ≤3 days of intravenous treatment and the proportion of correct empiric antibiotics. As sensitivity analysis, we repeated the univariable logistic regression on a propensity score-matched cohort by using the same variables we used for adjustments in the multivariable analysis. We also performed subgroup analyses for patients stable ≤72 h of admission. RESULTS: In total, 771 patients were included. Compared to preintervention, the unadjusted odds ratio (OR) for ≤7 days of total antibiotic treatment were 1.84 (95% CI 1.34-2.54) for the whole population and 2.08 (1.41-3.10) for the stable patients. The OR for ≤3 days of intravenous antibiotics were 1.16 (0.87-1.54) and 1.38 (0.87-2.22), respectively. The OR for correct empiric antibiotics were 1.96 (1.45-2.68) and 1.82 (1.23-2.69). Comparable results regarding all outcomes were derived from the other analyses. CONCLUSION: The program resulted in a significantly lower overall antibiotic exposure and a higher proportion of patients treated with the recommended antibiotics without a the reduction of exposure to intravenous antibiotics significantly.

The increasing importance of Haemophilus influenzae in community-acquired pneumonia: results from a Danish cohort study.

BACKGROUND: Numerous studies have shown that the aetiology of community-acquired pneumonia (CAP) varies considerably among different healthcare settings. Because empiric therapies for CAP should cover the major pathogens, reports examining CAP aetiology are considered crucial, particularly in Nordic countries that still rely on penicillin G or V treatments for most patients with CAP. The primary objective of our study was to report CAP aetiology. Secondary objectives included the estimation of positivity rates for different tests and the odds of a positive test for various subgroups. METHODS: In this cohort study, microbiological data were analysed for an overall cohort (variable degree of microbiological testing) and for a subgroup that was tested for both, bacteria, viruses and fungi, using routine methods (defined as extensive testing). RESULTS: The overall cohort comprised 2,264 patients, including 315 who were extensively tested. Bacterial and viral monoinfections were the most commonly identified infections. The dominant pathogen identified among extensively tested patients was Haemophilus influenzae (23.7%), followed by Streptococcus pneumoniae (20.6%). The tests with the highest positivity rates were sputum cultures (34.7%) and viral polymerase chain reaction (PCR, 24.4%). The odds of achieving a microbiological diagnosis increased significantly when extensive testing was performed compared with selective testing (OR 2.86, 95% CI 2.24-3.64). CONCLUSION: Our study indicated that H. influenzae is the dominant responsible pathogen for bacterial CAP in Denmark. Thus, we believe that the current treatment recommendations that encourage the use of penicillin G or V for the majority of patients with CAP need to be revised.

Improved treatment of community-acquired pneumonia through tailored interventions: Results from a controlled, multicentre quality improvement project.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading causes of healthcare utilisation and death worldwide. Treatment according to evidence-based clinical guidelines can reduce mortality, antibiotic exposure and length of hospital stay related to CAP. LOCAL PROBLEM: Several studies, including a pilot study from one of our sites, indicate that physicians show a low grade of guideline adherence when managing patients with CAP. METHODS: To improve the guideline-based treatment of patients with CAP admitted to hospital, we designed a quality improvement study. Four process indicators were combined in a CAP care bundle: chest X-ray, CURB-65 severity score, lower respiratory tract samples and antibiotics within 8 hours from admission. After a 4-month baseline period, we applied multiple interventions at three hospitals during 8 months. Progression in our process indicators was measured continuously and compared with a control site without interventions. After the 8-month intervention period, we continued with a 4-month follow-up period to assess the sustainability of the improvements. RESULTS: The care bundle utilisation rate within 8 hours increased from 11% at baseline to 41% in the follow-up period at the intervention sites, whereas it remained below 3% at the control site. The most considerable improvements have been observed regarding documentation of CURB-65 (34% at baseline, 68% at follow-up) and the collection of lower respiratory tract samples (43% at baseline, 63% at follow-up). CONCLUSION: Our study has demonstrated poor adherence to CAP guidelines at all sites at baseline. After implementing multiple tailored interventions, guideline adherence increased substantially. In conclusion, we recommend that CAP guidelines should be actively adapted in order to be followed in a daily routine.

Hepatosplenic schistosomiasis: playing hide-and-seek with an elusive parasite.

A 27-year-old man of Eritrean origin presented with persistent left-sided abdominal pain. Initial investigation showed signs of liver fibrosis, portal hypertension and splenomegaly. A diagnosis of hepatosplenic schistosomiasis was suspected on grounds of elevated total IgE, grey area antischistosomiasis antibodies and the high endemic status of his native country. However, repeated microscopy of faecal and urine samples, as well as rectal biopsies, failed to demonstrate schistosomal eggs. Finally, the diagnosis of hepatosplenic schistosomiasis was established through demonstration of a Schistosoma mansoni egg in a liver biopsy taken in an attempt to clarify the cause of the above findings. The patient had recently been treated for uncomplicated malaria. Lowered schistosomiasis worm/egg burden and hence reduced sensitivity of classic microscopy-based schistosomiasis testing was attributed to the antischistosomal activity of the antimalarial chemotherapy.