Microbial aetiology, outcomes, and costs of hospitalisation for community-acquired pneumonia; an observational analysis

BACKGROUND: The aim of this study was to investigate the clinical outcome and especially costs of hospitalisation for community-acquired pneumonia (CAP) in relation to microbial aetiology. This knowledge is indispensable to estimate cost-effectiveness of new strategies aiming to prevent and/or improve clinical outcome of CAP. METHODS: We performed our observational analysis in a cohort of 505 patients hospitalised with confirmed CAP between 2004 and 2010. Hospital administrative databases were extracted for all resource utilisation on a patient level. Resource items were grouped in seven categories: general ward nursing, nursing on ICU, clinical chemistry laboratory tests, microbiology exams, radiology exams, medication drugs, and other.linear regression analyses were conducted to identify variables predicting costs of hospitalisation for CAP. RESULTS: Streptococcus pneumoniae was the most identified causative pathogen (25%), followed by Coxiella burnetii (6%) and Haemophilus influenzae (5%). Overall median length of hospital stay was 8.5 days, in-hospital mortality rate was 4.8%. Total median hospital costs per patient were €3,899 (IQR 2,911-5,684). General ward nursing costs represented the largest share (57%), followed by nursing on the intensive care unit (16%) and diagnostic microbiological tests (9%). In multivariate regression analysis, class IV-V Pneumonia Severity Index (indicative for severe disease), Staphylococcus aureus, or Streptococcus pneumonia as causative pathogen, were independent cost driving factors. Coxiella burnetii was a cost-limiting factor. CONCLUSIONS: Median costs of hospitalisation for CAP are almost €4,000 per patient. Nursing costs are the main cause of these costs.. Apart from prevention, low-cost interventions aimed at reducing length of hospital stay therefore will most likely be cost-effective

Advanced glycation end products, measured in skin, vs. HbA1c in children with type 1 diabetes mellitus

Background and objective: Advanced glycation end products (AGEs) are considered major contributors to microvascular and macrovascular complications in adult patients with diabetes mellitus. AGEs can be measured non-invasively with skin autofluorescence (sAF). The primary aim was to determine sAF values in children with type 1 diabetes mellitus and to study correlations between sAF values and HbA1c and mean HbA1c over the year prior to measurement Research design and methods: In children with type 1 diabetes mellitus, sAF values were measured using the AGE Reader®. Laboratory and anthropometric values were extracted from medical charts. Correlations were studied using Pearson's correlation coefficient. Multivariable linear regression analysis was conducted to evaluate the effect of multiple study parameters on sAF values. Results: The mean sAF value was 1.33±0.36arbitrary units (AU) in children with type 1 diabetes mellitus (n=144). sAF values correlated positively with HbA1c measured at the same time (r=0.485;

Durvalumab after chemoradiotherapy in patients with stage III non-small-cell lung cancer: real-world outcomes versus clinical trial results

Aim: We investigated the effectiveness of durvalumab post-concurrent CRT (cCRT) and post-sequential CRT (sCRT) versus cCRT and sCRT alone and compared these outcomes with the PACIFIC trial. Methods: Four cohorts of stage III NSCLC patients who received CRT were included: cCRT with and without durvalumab, sCRT with and without durvalumab. PFS and OS were analyzed using Cox regression. Results: Durvalumab improved PFS (cCRT: aHR = 0.69, sCRT: aHR = 0.71) and OS (cCRT: aHR = 0.71, sCRT: aHR = 0.32), although not all results were significant. PFS was longer in the real-world than in the trial, while OS did not differ. Conclusion: Durvalumab after CRT improved the survival outcomes. The difference between PFS in our study and the trial may be due to differences in follow-up methods. Plain language summary We assessed a medicine called durvalumab on patients with non-small cell lung cancer who received chemoradiotherapy in a real-world setting. We compared their outcomes with those from a clinical trial. Patients who received two types of chemoradiotherapy with or without durvalumab were included, and their progression-free survival (PFS) and overall survival (OS) outcomes were analyzed. We found that patients treated with durvalumab had better PFS and OS than those treated without durvalumab. PFS was longer in the real-world than in the clinical trial, but OS was similar. The difference in PFS may be due to differences in measuring PFS

Prior outpatient antibiotic use as predictor for microbial aetiology of community-acquired pneumonia: hospital-based study

Objective: The causative micro-organism in community-acquired pneumonia (CAP) is often difficult to predict. Different studies have examined chronic morbidity and clinical symptoms as predictors for microbial aetiology of pneumonia. The aim of our study was to assess whether prior outpatient antimicrobial treatment is predictive for determining the microbial aetiology of CAP. Methods: This was a hospital-based prospective observational study including all patients admitted with CAP between 1 October 2004 and 1 August 2006. Microbial investigations included sputum, blood culture, sputum PCR, antigen testing and serology. Exposure to antimicrobial drugs prior to hospital admission was ascertained through community pharmacy dispensing records. Multivariate logistic regression analysis was conducted to assess whether prior outpatient antimicrobial treatment is a predictor of microbial aetiology. Patient demographics, co-morbidities and pneumonia severity were considered to be other potential predictors. Results: Overall, 201 patients were included in the study. The microbial aetiology was determined in 64% of the patients. The five most prevalent pathogens were Streptococcus pneumoniae, Heamophilus influenzae, Legionella spp., Mycoplasma pneumoniae and Influenza virus A+B. Forty-seven of the patients (23%) had received initial antimicrobial treatment as outpatients. Multivariate analyses revealed that initial outpatient beta-lactam treatment was associated with a threefold increased chance of finding atypical pathogens and a threefold decreased probability of pneumococcal infection; the corresponding odds ratios were 3.51 (95% CI 1.25-9.99) and 0.30 (95% CI 0.10-0.90), respectively. Patients who received macrolides prior to hospitalisation had an increased probability of viral pneumonia. Conclusion: Prior outpatient antimicrobial therapy has a predictive value in the diagnostic workup aimed at identifying the causative pathogen and planning corresponding antimicrobial treatment in patients hospitalised for pneumonia

Intravitreal aflibercept versus intravitreal ranibizumab in patients with age-related macular degeneration: a comparative effectiveness study

AIM: A hospital-wide, unselected switch of ranibizumab to aflibercept in treatment of age-related macular degeneration (AMD) allowed us to compare the clinical effectiveness of these agents. METHOD: In a single-center before-after, observational study design new AMD-patients started with aflibercept treatment in 2013-2014 were compared with a control group of AMD-patients on ranibizumab before the switch. RESULTS: The mean difference in visual acuity (in logMAR units) after 1 year was comparable (+0.012 [aflibercept, n = 37] vs +0.17 [ranibizumab, n = 30], p = 0.154). However, the aflibercept-group did receive more intravitreal injections (5.8 vs 4.7 injections, p = 0.004) and were treated longer (265.7 vs 197.7 days; p = 0.011). CONCLUSION: With no difference in clinical effectiveness, longer treatment intervals for aflibercept should be investigated

Real-World Effectiveness of Palbociclib Versus Clinical Trial Results in Patients With Advanced/Metastatic Breast Cancer That Progressed on Previous Endocrine Therapy

Objective: The aim of this study was to assess the real-world effectiveness and tolerability of palbociclib combined with endocrine therapy for the treatment of hormone receptor positive (HR-positive), human epidermal growth factor receptor 2 negative (HER2-negative), advanced/metastatic breast cancer that progressed on previous endocrine therapy, and to compare these results with the outcomes of the PALOMA-3 clinical trial. Methods: This study was a retrospective observational cohort study including all patients who started with palbociclib in the St. Antonius Hospital between September 1, 2016 and April 1, 2018 for the treatment of HR-positive, HER2-negative advanced/metastatic breast cancer that progressed on previous endocrine therapy. Individual patient data were collected from electronic medical records. Primary study outcomes were progression-free survival (PFS) and the number of permanent treatment discontinuations before disease progression due to adverse events (AEs). Secondary outcomes were the frequency of all (serious) AEs and the frequency of and reasons for dose reductions, -interruptions and cycle delays. Results: A total of 46 patients were studied with a median follow-up of 13.0 months. Overall, the median PFS in real-world clinical practice was 10.0 months (95% confidence interval (CI) 4.9-15.1), compared with 9.5 months in PALOMA-3 (95% CI 9.2-11.0). Two patients discontinued treatment because of AEs. Neutropenia was the most frequent grade 3-4 AE, but with no febrile neutropenia events. Most AEs were managed with palbociclib dose modifications. Regarding these modifications, more cycle delays, less dose reductions, and less dose interruptions occurred in clinical practice compared with PALOMA-3 (59 vs 36%, 22 vs 34%, and 9 vs 54%, respectively). Patients who did not meet the PALOMA-3 study eligibility criteria (n = 16) showed a lower median PFS of 5.5 months (95% CI 4.7-6.4). Conclusions: The effectiveness and tolerability of palbociclib in real-world clinical practice corresponded well with the results obtained in the PALOMA-3 clinical trial. Despite the differences in dose modifications, this study suggests that there is no efficacy-effectiveness gap in this patient population

Intravitreal aflibercept versus intravitreal ranibizumab in patients with age-related macular degeneration: a comparative effectiveness study

AIM: A hospital-wide, unselected switch of ranibizumab to aflibercept in treatment of age-related macular degeneration (AMD) allowed us to compare the clinical effectiveness of these agents. METHOD: In a single-center before-after, observational study design new AMD-patients started with aflibercept treatment in 2013-2014 were compared with a control group of AMD-patients on ranibizumab before the switch. RESULTS: The mean difference in visual acuity (in logMAR units) after 1 year was comparable (+0.012 [aflibercept, n = 37] vs +0.17 [ranibizumab, n = 30], p = 0.154). However, the aflibercept-group did receive more intravitreal injections (5.8 vs 4.7 injections, p = 0.004) and were treated longer (265.7 vs 197.7 days; p = 0.011). CONCLUSION: With no difference in clinical effectiveness, longer treatment intervals for aflibercept should be investigated

[89Zr]Zr-rituximab PET/CT activity in patients with therapy refractory interstitial pneumonitis: a feasibility study

Recent studies on immune-mediated inflammatory lung diseases show encouraging treatment results with rituximab, a monoclonal antibody (mAb) against CD20-expressing B lymphocytes. The present pilot study aimed to explore the possibility to image CD20-expression in the lungs as future early predictor of treatment response. We describe a series of 10 patients with therapy refractory interstitial pneumonitis who were treated with rituximab (1000 mg at day 0 and day 14) and underwent PET/CT after the administration of [89Zr]Zr-N-suc-DFO-rituximab abbreviated as [89Zr]Zr-rituximab. [89Zr]-rituximab PET/CT of the chest was performed on day 3 and 6. [89Zr]Zr-rituximab PET/CT showed visual and quantifiable increased pulmonary activity in four patients. Other patients demonstrated no increased activity in the lungs. One patient developed a severe allergic reaction during infusion of the first 10% unlabeled rituximab after which rituximab infusion was ceased. Subsequent administration of [89Zr]Zr-rituximab, however, did not result in any adverse reaction. This patient demonstrated the highest uptake of [89Zr]Zr-rituximab in mediastinal lymph nodes and lung parenchyma compared to the other 9 patients who did receive the full dose rituximab before [89Zr]Zr-rituximab. This pilot study demonstrates that [89Zr]Zr-rituximab PET/CT imaging in patients with therapy refractory interstitial pneumonitis is feasible and shows lung-specific uptake in some patients. Further research with larger sample size should establish if the [89Zr]Zr-rituximab uptake correlates with treatment response to rituximab. The higher uptake in the absence of a full 1000 mg rituximab preload may suggest that future studies should consider [89Zr]Zr-rituximab imaging at low mAb dose before treatment with rituximab

Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab: could this indicate a splenic immune-mediated mechanism?

Rituximab (RTX) for immune-mediated inflammatory disease (IMID) with interstitial pneumonitis (IP) results in non-response in about a third of patients for reasons not well understood. Complete peripheral B-cell depletion in IMID-IP does not seem to correlate with successful treatment outcome. A hypothesis is that splenic B cells might play a role in B-cell recovery and attraction of naïve B cells in non-responsive patients. The aim of this post hoc analysis of clinical trial data is to search for indicators in [89Zr]Zr-rituximab PET/CT data from the spleen that might explain non-responsiveness. PET/CT data of 20 patients with IMID-IP, who were enrolled in a phase II trial and treated with RTX were analyzed. Clinical outcome was categorized into responders (RSP) and non-responders (NR) after 6 months of initial RTX by two independent pulmonologists. Patients were examined separately to search for associations between clinical outcome, splenic activity on PET/CT, lymphocyte counts and other biomarkers. Treatment failure was found in 6/20 patients (30%) while all patients exhibited B-cell depletion from the circulation. NR patients demonstrated significantly higher splenic activity than RSP patients (non-preload protocol: SUV 4.9±1.96 and SUV 2.3±1.08 respectively, P=0.025). No correlations between treatment outcome and serum lymphocyte subsets were found. Our findings suggest a potential splenic mechanism in IMID-IP patients non-responding to RTX and warrant further consideration and investigation