Short-course antibiotic therapy of 5 days in community-acquired pneumonia (CAP5): study protocol for a randomised controlled trial.

INTRODUCTION: The optimal duration of antibiotic therapy for community-acquired pneumonia (CAP) is unsettled. Short-course therapy has proved successful in clinical trials but is not yet implemented in everyday clinical practice. Validation of results from randomised controlled trials is crucial to evaluate existing evidence and provide clinicians with assurance of using new treatment strategies. In a pragmatic framework, we aim to assess the use of short-course antibiotic therapy guided by the onset of clinical stability in patients hospitalised with CAP. METHODS AND ANALYSIS: This study is a randomised controlled trial with a non-inferiority design that will examine the efficacy of short-course antibiotic therapy in patients hospitalised with CAP. From six hospitals across Denmark, we plan to enrol 564 patients between 2019 and 2024. Within 3-5 days after initiating antibiotic therapy, participants will be randomised 1:1 to parallel treatment arms: (1) short-course antibiotic therapy of 5 days or (2) antibiotic therapy of at least 7 days. The primary outcome will be 90-day readmission-free survival and will be estimated as an absolute risk difference with a predefined non-inferiority margin of -6%. Secondary outcomes will comprise other safety measures including new antibiotics, adverse events, length of hospital stay and postdischarge outpatient visits. Both intention-to-treat and per-protocol analyses will be performed. ETHICS AND DISSEMINATION: This study has been approved by the Health Research Ethics Committee of the Capital Region of Denmark (identifier number: H-19014479). Trial data will be made available in anonymous form when the trial has ended. TRIAL REGISTRATION NUMBER: NCT04089787, ClinicalTrials.Gov.

Excess length of stay and readmission following hospital-acquired bacteraemia: a population-based cohort study applying a multi-state model approach.

OBJECTIVES: Population-based estimates of excess length of stay after hospital-acquired bacteraemia (HAB) are few and prone to time-dependent bias. We investigated the excess length of stay and readmission after HAB. METHODS: This population-based cohort study included the North Denmark Region adult population hospitalized for ≥48 hours, from 2006 to 2018. Using a multi-state model with 45 days of follow-up, we estimated adjusted hazard ratios (aHRs) for end of stay and discharge alive. The excess length of stay was defined as the difference in residual length of stay between infected and uninfected patients, estimated using a non-parametric approach with HAB as time-dependent exposure. Confounder effects were estimated using pseudo-value regression. Readmission after HAB was investigated using the Cox regression. RESULTS: We identified 3457 episodes of HAB in 484 291 admissions in 205 962 unique patients. Following HAB, excess length of stay was 6.6 days (95% CI, 6.2-7.1 days) compared with patients at risk. HAB was associated with decreased probability of end of hospital stay (aHR, 0.60; 95% CI, 0.57-0.62) driven by the decreased hazard for discharge alive; the aHRs ranged from 0.30 (95% CI, 0.23-0.40) for bacteraemia stemming from 'heart and vascular' source to 0.72 (95% CI, 0.69-0.82) for the 'urinary tract'. Despite increased post-discharge mortality (aHR, 2.76; 95% CI, 2.38-3.21), HAB was associated with readmission (aHR, 1.42; 95% CI, 1.31-1.53). CONCLUSION: HAB was associated with considerably excess length of hospital stay compared with hospitalized patients without bacteraemia. Among patients discharged alive, HAB was associated with increased readmission rates.

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.

Risk factors for hospital-acquired bacteraemia - an explorative case-control study of hospital interventions.

BACKGROUND: Knowledge on hospital-related interventions as risk factors for hospital-acquired bacteraemia (HAB) is sparse. AIM: We aimed to investigate hospital interventions as risk factors for HAB. METHODS: Prospectively through one year, we identified episodes of HAB in a single tertiary hospital. We used a matched incidence density sampled case-control design. Matching on sex and age group, we sampled controls (1:2) from the adult hospital population with ongoing hospitalization for ≥48 h. Using conditional logistic regression, we estimated odds ratios (OR) with 95% confidence intervals (CI). For adjusted ORs (aOR), adjustments were made for length of hospital stay, type and urgency of admission, and Charlson Comorbidity Index score level. FINDINGS: From 15th October 2019 through 14th October 2020, we identified 115 incident episodes of HAB and matched them with 230 controls. HAB patients were more often admitted as 'medicine or emergency surgery'-patients (94% vs 87%) and had a longer hospital stay before inclusion (median days 20 vs 12). They were more frequently categorized as having a 'low level comorbidity' (58% vs 39%) but had higher prevalence of haematologic (15% vs 6%) or metastatic cancer (13% vs 10%). Our estimates for central venous catheters were aOR of 3.46 (95% CI 1.92-6.23), haemodialysis; aOR 5.05 (95% CI 1.41-18.06), immunosuppressive treatment including chemotherapy; aOR of 1.72 (95% CI 1.00-2.96). CONCLUSION: Central venous catheters and haemodialysis were the most prominent risk factors. Immunosuppressive treatment including therapy may play an important role in the development of HAB.

Incidence and mortality of hospital-acquired bacteraemia: a population-based cohort study applying a multi-state model approach.

OBJECTIVE: The effect of hospital-acquired bacteraemia on mortality is sparsely investigated. We investigated the incidence and hospital-acquired bacteraemia impact on mortality. METHODS: We conducted a 13-year population-based cohort study using the North Denmark Bacteraemia Research Database and Danish health registries. The population comprised all adult patients with a hospital admission lasting ≥48 hr. We used Poisson regression to estimate trends in incidence. The 30-day mortality of hospital-acquired bacteraemia was estimated using an illness-death multistate model with recovery using the population at risk of hospital-acquired bacteraemia as reference. RESULTS: We identified 3588 episodes of hospital-acquired bacteraemia in 484 264 admissions. The incidence increased proportionally by 1.02 episodes yearly (95% CI 1.01-1.03) between 2006 and 2018. Hospital-acquired bacteraemia was associated with increased mortality (adjusted hazard ratio (aHR) 4.32, 95% CI 3.95-4.72), especially hospital-acquired bacteraemia with unknown source (aHR 6.42 (95% CI 5.67-7.26), "thoracic incl. pneumonia" (aHR 5.89, 95% CI 3.45-10.12) and abdominal source (aHR 4.33, 95% CI 3.27-5.74). The relative impact on mortality diminished with age (aHR 5.66, 95% CI 2.00-16.01 in 18-40 years old vs. 3.69, 95% CI 3.14-4.32 in 81-105 years old) and comorbidity (aHR 5.75, 95% CI 4.45-7.42 in low vs. 3.55, 95% CI 3.16-3.98 in high comorbidity), and was higher in elective admissions (aHR 9.09, 95% CI 7.14-11.57 vs. aHR of 4.03, 95% CI 3.67-4.42). DISCUSSION: Hospital-acquired bacteraemia is associated with high mortality, especially when the source is unknown or originating from the thoracic cavity.

[Ramsay Hunt syndrome can present with vesicular elements on the tongue, facial nerve palsy and meningitis].

Ramsay Hunt syndrome (RHS) is caused by a reactivation of the varicella zoster virus (VZV). It normally involves the triad of earache, peripheral facial nerve palsy and ipsilateral rash but can present without/with minimal visible rashes. In this case report, a 53-year-old male was admitted to hospital after a week-long headache, right-sided earache and peripheral facial nerve palsy. Vesicular elements were observed on the right side of the tongue. Cerebrospinal fluid (CSF) analysis showed 195 monocytes/mm3, and PCR verified VZV in the CSF. To avoid misdiagnosis, early recognition of the symptoms of RHS and diagnostic workup is advised.

Neutrophil-to-lymphocyte ratio, calprotectin and YKL-40 in patients with chronic obstructive pulmonary disease: correlations and 5-year mortality - a cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and progressive decline in pulmonary function. Neutrophil-to-lymphocyte ratio (NLR), YKL-40 and calprotectin are biomarkers of inflammation and predict mortality in patients with different inflammatory diseases. We aimed to investigate the correlation between levels of these three biomarkers and neutrophil granulocyte and lymphocyte count in patients with moderate to very severe COPD stratified by use of systemic glucocorticoids. Furthermore, we studied the ability of these biomarkers to predict all-cause mortality. METHODS: 386 patients with moderate to very severe COPD were followed prospectively for 10 years. Patients were divided into two groups according to systemic glucocorticoid use at baseline. Correlations between biomarkers were assessed by Spearman's Rho, and mortality was evaluated in uni- and multivariate Cox regression analyses with hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Plasma calprotectin was positively correlated with neutrophil granulocyte count and NLR. No significant association was found between plasma YKL-40 and the cellular biomarkers, irrespective of glucocorticoid treatment. In the group not treated with systemic glucocorticoids, plasma calprotectin [HR 1.002 (95% CI 1.000 - 1.004)], NLR [HR 1.090 (1.036 - 1.148)] and lymphocyte count [HR 0.667 (0.522 - 0.851)] were significantly associated with higher mortality. In the group treated with systemic glucocorticoids, higher plasma YKL-40 was significantly associated with mortality in univariate Cox regression analysis [HR 1.006 (1.003 - 1.008)]. CONCLUSIONS: Calprotectin was related to neutrophil granulocyte count and NLR in patients with moderate to very severe COPD in stable phase and not in treatment with systemic glucocorticoids. Lymphopenia, higher plasma calprotectin and higher NLR were independent predictors of increased all-cause mortality in this group. Our data also suggests that treatment with systemic glucocorticoids has a significant impact on the ability of inflammatory biomarkers to predict all-cause mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT00132860.

Serum vitamin D in patients with chronic obstructive lung disease does not correlate with mortality--results from a 10-year prospective cohort study.

BACKGROUND: Recent studies have found vitamin D (25-OHD) deficiency and insufficiency to be common among patients with COPD. Serum level of 25-OHD seems to correlate to pulmonary function, COPD disease staging, and increased susceptibility to respiratory infections. We wanted to investigate whether vitamin D deficiency or insufficiency was associated with mortality rate in patients suffering from advanced COPD. METHODS: 25-OHD serum levels were measured in 462 patients suffering from moderate to very severe COPD. Patients were stratified into three groups according to serum levels of 25-OHD. Outcome measure was mortality in a 10 year follow-up period. Kaplan-Meier curves (KM) were plotted and mortality hazard ratios (HR) were calculated using Cox Proportional Hazard regression (Cox PH). RESULTS: Serum 25-OHD deficiency and insufficiency were prevalent. We were unable to demonstrate any association between baseline serum levels of 25-OHD and mortality rate. We found an association between mortality and age [HR 1.05 (CI 95%: 1.03-1.06)], Charlson score [HR 1.49 (CI 95%: 1.06-2.09)], increasing neutrophil count [HR 1.05 (CI 95%: 1.02-1.09)], severe [HR 1.41 (CI 95%: 1.06-1.86)]/very severe COPD [HR 2.19 (CI 95%: 1.58-3.02)] and a smoking history of more than 40 pack years [HR 1.27 (CI 95%: 1.02-1.70)]. CONCLUSIONS: Serum level of 25-OHD does not seem to be associated with mortality rate, suggesting no or only a minor role of 25-OHD in disease progression in patients with moderate to very severe COPD.