Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial.

RATIONALE: Outpatient treatment of pulmonary embolism (PE) may lead to improved patient satisfaction and reduced healthcare costs. However, trials to assess its safety and the optimal method for patient selection are scarce. OBJECTIVES: To validate the utility and safety of selecting patients with PE for outpatient treatment by the Hestia criteria and to compare the safety of the Hestia criteria alone with the Hestia criteria combined with N-terminal pro-brain natriuretic peptide (NT-proBNP) testing. METHODS: We performed a randomized noninferiority trial in 17 Dutch hospitals. We randomized patients with PE without any of the Hestia criteria to direct discharge or additional NT-proBNP testing. We discharged the latter patients as well if NT-proBNP did not exceed 500 ng/L or admitted them if NT-proBNP was greater than 500 ng/L. The primary endpoint was 30-day adverse outcome defined as PE- or bleeding-related mortality, cardiopulmonary resuscitation, or intensive care unit admission. The noninferiority margin for the primary endpoint was 3.4%. MEASUREMENTS AND MAIN RESULTS: We randomized 550 patients. In the NT-proBNP group, 34 of 275 (12%) had elevated NT-proBNP values and were managed as inpatients. No patient (0 of 34) with an elevated NT-proBNP level treated in hospital (0%; 95% confidence interval [CI], 0-10.2%), versus no patient (0 of 23) with a post hoc-determined elevated NT-proBNP level from the direct discharge group (0%; 95% CI, 0-14.8%), experienced the primary endpoint. In both trial cohorts, the primary endpoint occurred in none of the 275 patients (0%; 95% CI, 0-1.3%) subjected to NT-proBNP testing, versus in 3 of 275 patients (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.25). During the 3-month follow-up, recurrent venous thromboembolism occurred in two patients (0.73%; 95% CI, 0.1-2.6%) in the NT-proBNP group versus three patients (1.1%; 95% CI, 0.2-3.2%) in the direct discharge group (P = 0.65). CONCLUSIONS: Outpatient treatment of patients with PE selected on the basis of the Hestia criteria alone was associated with a low risk of adverse events. Given the low number of patients with elevated NT-proBNP levels, this trial was unable to draw definite conclusions regarding the incremental value of NT-proBNP testing in patients who fulfill the Hestia criteria. Clinical trial registered with www.trialregister.nl/trialreg/admin/rctview.asp?TC=2603 (NTR2603).

Hestia criteria can discriminate high- from low-risk patients with pulmonary embolism.

We investigated whether the clinical criteria used in the Hestia study for selection of pulmonary embolism (PE) patients for outpatient treatment could discriminate PE patients with high and low risk for adverse clinical outcome. We performed a cohort study with PE patients who were triaged with 11 criteria for outpatient treatment. Patients not eligible for outpatient treatment were treated in hospital. Study outcomes were recurrent venous thromboembolism, major bleeding and all-cause mortality during 3 months. In total, 530 patients were included, of which 297 were treated at home. In the outpatient group, six patients (2.0%, 95% CI 0.7-4.3%) had recurrent venous thromboembolism versus nine in-patients (3.9%, 95% CI 1.9-7.0%). Three patients (1.0%, 95% CI 0.2-2.9) died during the 3-months follow-up in the outpatient group versus 22 patients (9.6%, 95% CI 6.3-14) in the in-patient group (p<0.05). None of the outpatients died as a result of fatal PE versus five (2.2%) in-patients (p<0.05). In the outpatient group, 0.7% (95% CI 0.08-2.4) had major bleeding events versus 4.8% (95% CI 2.4-8.4) of in-patients (p<0.05). This study showed that the Hestia criteria can discriminate PE patients with low risk from patients with high risk for adverse clinical outcome. The low-risk patients can safely be treated at home.

Reasons for Hospitalization of Patients with Acute Pulmonary Embolism Based on the Hestia Decision Rule.

BACKGROUND: The Hestia criteria can be used to select pulmonary embolism (PE) patients for outpatient treatment. The subjective Hestia criterion "medical/social reason for admission" allows the treating physician to consider any patient-specific circumstances in the final management decision. It is unknown how often and why this criterion is scored. METHODS: This is a patient-level post hoc analysis of the combined Hestia and Vesta studies. The main outcomes were the frequency of all scored Hestia items in hospitalized patients and the explicit reason for scoring the subjective criterion. Hemodynamic parameters and computed tomography-assessed right ventricular (RV)/left ventricular (LV) ratio of those only awarded with the subjective criterion were compared with patients treated at home. RESULTS: From the 1,166 patients screened, data were available for all 600 who were hospitalized. Most were hospitalized to receive oxygen therapy (45%); 227 (38%) were only awarded with the subjective criterion, of whom 51 because of "intermediate to intermediate-high risk PE." Compared with patients with intermediate risk PE (RV/LV ratio > 1.0) treated at home (179/566, 32%), hospitalized patients with only the subjective criterion had a higher mean RV/LV ratio (mean difference +0.30, 95% confidence interval [CI] 0.19-0.41) and a higher heart rate (+18/min, 95% CI 10-25). No relevant differences were observed for other hemodynamic parameters. CONCLUSION: The most frequent reason for hospital admission was oxygen therapy. In the decision to award the subjective criterion as sole argument for admission, the severity of the RV overload and resulting hemodynamic response of the patient was taken into account rather than just abnormal RV/LV ratio.

Anaemia management with epoetin alfa in lung cancer patients in The Netherlands.

Anaemia seriously threatens the quality of life (QOL) in cancer patients receiving chemotherapy. In this article results are presented on the lung cancer population from a Dutch observational study. This study addressed the real-life situation of recombinant human erythropoietin (r-Hu-EPO or epoetin alfa) treatment in anaemic cancer patients receiving chemotherapy, with a focus on efficacy. In total 781 patients were enrolled in the observational study, including 382 patients with lung cancer. At enrolment patients were receiving epoetin alfa treatment and/or patients had a haemoglobin (Hb) level 11.3g/dl) was especially effective for NSCLC patients where it resulted in a stabilization of Hb at baseline level. For SCLC patients this strategy was less effective. Furthermore, early intervention seemed to diminish the need for a blood transfusion, i.e., the higher the Hb at epoetin initiation the more patients did not receive any blood transfusion. Results from this observational study demonstrate that epoetin alfa treatment corrects chemotherapy-related anaemia in both NSCLC as well as SCLC patients. Early epoetin alfa intervention seems advantageous for lung cancer patients both in terms of maintaining adequate Hb levels during chemotherapy as well as reducing transfusions.

Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH)2 Vitamin D3 Treatment.

BACKGROUND: Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs). Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH)2D3) affects these antimicrobial peptide levels. METHODS: The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 µg 1,25(OH)2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study. RESULTS: Levels of neutrophil α-defensins (human neutrophil peptides 1-3; HNP1-3) and lipocalin 2 (LCN2; also known as NGAL) were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH)2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH)2D3. CONCLUSION: Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D.

Association of lung function measurements and visceral fat in men with metabolic syndrome.

BACKGROUND: Several studies have reported a positive relationship between lung function impairment and the metabolic syndrome. This is most usually explained by abdominal adiposity. We hypothesized that the main determinant of the association between lung function impairment and abdominal obesity is the presence of visceral fat. METHODS: The present study is a cross-sectional analysis of 98 non-diabetic men aged between 50 and 70 years with the metabolic syndrome. The amount of visceral and subcutaneous adipose tissue was determined by an MRI scan. The association between visceral fat and measures of lung function (FEV1, FVC, exhaled and NO) was assessed using linear regression. RESULTS: 98 participants were included in this analysis. There was a linear inverse association between visceral fat and both FEV1 and FVC. None of the other different fat-related measurements (subcutaneous fat, waist circumference and BMI) or features of the metabolic syndrome were found to be associated with these lung function measurements. CONCLUSION: In non-diabetic subjects with the metabolic syndrome and a lung function that is within the normal range, visceral fat is negatively correlated with FEV1 and FVC.

Telepulmonology: effect on quality and efficiency of care.

BACKGROUND: Interpreting spirometry results has proven challenging in primary care practice, among others potentially leading to under- and misdiagnosis of COPD. In telepulmonology a general practitioner (GP) digitally consults a pulmonologist to support the interpretation of spirometry results. This study assessed the effect of telepulmonology on quality and efficiency of care. METHODS: Quality of care was measured by five indicators, among others the percentage of TelePulmonology Consultations (TPCs) sent by GPs for advice, percentage of those TPCs resulting in a physical referral, and educational effect of telepulmonology as experienced by GPs. Efficiency was defined as the percentage of prevented unnecessary physical referrals of patients to the pulmonologist. RESULTS: Between April 2009 and November 2012 1.958 TPCs were sent by 158 GPs to 32 pulmonologists. Sixty-nine percent of the TPCs were sent for advice. Based on the advice of the pulmonologist 18% of these TPCs led to a physical referral of patients who would not have been referred without telepulmonology. Thirty-one percent of the TPCs were intended to prevent a physical referral, 68% of these actually prevented a physical referral to a pulmonologist. CONCLUSION: The results show telepulmonology can contribute to quality of care by supporting GPs and can additionally prevent unnecessary physical referrals.

Telepulmonology in the Netherlands: effect on quality and efficiency of care.

In telepulmonology a general practitioner (GP) digitally consults a local pulmonologist. This study assessed the effect of telepulmonology on quality and efficiency of care. Efficiency of care was measured as the percentage of prevented physical referrals. Quality of care was measured using 5 indicators. Thirty-one percent of the TelePulmonology Consultations (TPCs) were sent to prevent a physical referral, the other TPCs were sent to ask for advice of the pulmonologist. Sixty-eight percent of the TPCs sent to prevent a physical referral indeed prevented a physical referral. Eighteen percent of the TPCs sent for advice resulted in a physical referral on advice of the pulmonologist. These patients would not have been referred without telepulmonology.

Comparison of two methods for selection of out of hospital treatment in patients with acute pulmonary embolism.

The aim of this study is to compare the performance of two clinical decision rules to select patients with acute pulmonary embolism (PE) for outpatient treatment: the Hestia criteria and the simplified Pulmonary Embolism Severity Index (sPESI). From 2008 to 2010, 468 patients with PE were triaged with the Hestia criteria for outpatient treatment: 247 PE patients were treated at home and 221 were treated as inpatients. The outcome of interest was all-cause 30-day mortality. In a post-hoc fashion, the sPESI items were scored and patients were classified according to the sPESI in low and high risk groups. Of the 247 patients treated at home, 189 (77%) patients were classified as low risk according to the sPESI and 58 patients (23%) as high risk. In total, 11 patients died during the first month; two patients treated at home and nine patients treated in-hospital. None of the patients treated at home died of fatal PE. Both the Hestia criteria and sPESI selected >50% of patients as low risk, with good sensitivity and negative predictive values for 30-day mortality: 82% and 99% for the Hestia criteria and 91% and 100% for the sPESI, respectively. The Hestia criteria and the sPESI classified different patients eligible for outpatient treatment, with similar low risks for 30-day mortality. This study suggests that the Hestia criteria may identify a proportion of high risk sPESI patiennts who can be safely treated at home, this however requires further validation.

Evaluation of a treatment strategy for optimising preoperative chemoradiotherapy in stage III non-small-cell lung cancer.

OBJECTIVE: Concurrent chemoradiotherapy is standard of care in stage III non-small-cell lung cancer, although surgery may be beneficial in selected patients in whom induction therapy has achieved 'down-staging' of mediastinal nodal disease. Previous studies incorporated treatment 'splits' for re-evaluation, and such gaps lead to poorer survival in patients undergoing chemoradiotherapy. We describe the outcome of a treatment strategy to limit the duration of treatment splits. METHODS: A prospective database (2003-2007) of stage III non-small-cell lung cancer patients treated with concurrent chemoradiotherapy outwith clinical trials at our centre was reviewed. Preoperative chemoradiotherapy consisted of one induction course of cisplatin-gemcitabine, followed by two courses of cisplatin-etoposide with once-daily thoracic radiotherapy using four-dimensional involved-field treatment planning. After a dose of 46-50 Gy, potentially resectable patients without disease progression underwent immediate planned mediastinal re-staging and patients with persistent N2 disease or who were unfit for surgery continued to full-dose radiotherapy. Effort was made to shorten the treatment split by substituting mediastinoscopy for endoscopic procedures (transbronchial and -oesophageal). RESULTS: A total of 34 patients had potentially resectable disease at the start of treatment. Toxicity of chemoradiotherapy was predominantly leucocytopaenia grade III/IV in 38% of courses and grade III oesophagitis in five patients (15%), but was manageable and reversible. After re-staging, 24 patients (71%) proceeded to surgery. A radical resection was achieved in 23 patients; nine had a complete pathological response. Re-staging was accurate with only one false-negative mediastinoscopy. One patient died 10 days after surgery. Median time from end of induction treatment to re-staging or surgery was 12 (range: 0-51 days) and 35 days (range: 18-63 days), respectively. Median survival for resected patients was not reached. Six patients had persisting N2 disease, of which two continued radiotherapy after a split of 3 and 4 days. CONCLUSIONS: Image-guided, involved-field preoperative chemoradiotherapy can be performed with acceptable toxicity, and the present strategy achieves the goal of limiting splits in treatment delivery that may adversely affect survival in patients who do not undergo down-staging with induction therapy.