Evaluation of an integrated care pathway for out-of-hospital treatment of older adults with an acute moderate-to-severe lower respiratory tract infection or pneumonia: protocol of a mixed methods study.

INTRODUCTION: Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagnostic and treatment possibilities in primary care, and the presence of financial barriers. We will evaluate the implementation of an integrated regional care pathway ('The Hague RTI Care Bridge') developed with the aim to treat and coordinate care for these patients outside the hospital. METHODS AND ANALYSIS: This is a prospective mixed methods study. Participants will be older adults (age≥65 years) with an acute moderate-to-severe LRTI or pneumonia treated outside the hospital (care pathway group) versus those treated in the hospital (control group). In addition, patients, their informal caregivers and treating physicians will be asked about their experiences with the care pathway. The primary outcome of this study will be the feasibility of the care pathway, which is defined as the percentage of patients treated outside the hospital, according to the care pathway, whom fully complete their treatment without the need for hospitalisation within 30 days of follow-up. Secondary outcomes include the safety of the care pathway (30-day mortality and occurrence of complications (readmissions, delirium, falls) within 30 days); the satisfaction, usability and acceptance of the care pathway; the total number of days of bedridden status or hospitalisation; sleep quantity and quality; functional outcomes and quality of life. ETHICS AND DISSEMINATION: The Medical Research Ethics Committee Leiden The Hague Delft (reference number N22.078) has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. The results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN68786381.

Risk of atherothrombotic events in patients after proximal deep-vein thrombosis.

Several studies have shown high incidence of atherothrombotic events (ATEs) in patients with unprovoked pulmonary embolism. This association remains understudied in patients presenting with deep-vein thrombosis (DVT). We evaluated the risk factors for and the incidence of ATEs in patients with unprovoked proximal DVT, and compared it to patients with provoked DVT and reference patients without DVT. Patients with compression ultrasonography (CUS)-proven unprovoked proximal DVT, provoked DVT, and symptomatic patients in whom DVT was excluded by CUS were followed and scored for the occurrence of ATEs. A total of 1235 patients were enrolled: 170 patients with provoked, 74 patients with unprovoked DVT, and 991 patients without DVT. During follow-up, 128 ATEs occurred (incidence 6.5/100 patient-years). Adjusted hazard ratio was not different between patients with DVT and without DVT [hazard ratio 1.4; 95% confidence interval (CI) 0.76-2.4]. In contrast, patients with unprovoked DVT suffered from ATEs more frequently than provoked DVT patients (hazard ratio 3.16; 95% CI 1.1-9.1) and reference patients (hazard ratio 2.8; 95% CI 1.3-5.7). Notably, when fully adjusted for the known ATE risk factors, the risk differences between references, provoked, and unprovoked DVT patients diminished: hazard ratio 1.1 (95% CI 0.47-2.5) and 1.7 (95% CI 0.80-3.6), respectively. Our study confirms that the risk of ATEs in patients with unprovoked DVT was higher than in those with provoked DVT or reference patients. Interestingly, our results raise the question whether the known risk factors for ATE and venous thromboembolism attribute equally in pulmonary embolism and DVT patients, and contradict a causal relation between ATE and proximal DVT.

NT-pro-BNP levels in patients with acute pulmonary embolism are correlated to right but not left ventricular volume and function.

N-terminal pro-Brain Natriuretic Peptide (NT-pro-BNP) is primarily secreted by left ventricular (LV) stretch and wall tension. Notably, NT-pro-BNP is a prognostic marker in acute pulmonary embolism (PE), which primarily stresses the right ventricle (RV). We sought to evaluate the relative contribution of the RV to NT-pro-BNP levels during PE. A post-hoc analysis of an observational prospective outcome study in 113 consecutive patients with computed tomography (CT)-proven PE and 226 patients in whom PE was clinically suspected but ruled out by CT. In all patients RV and LV function was established by assessing ECG-triggered-CT measured ventricular end-diastolic-volumes and ejection fraction (EF). NT-pro-BNP was assessed in all patients. The correlation between RV and LV end-diastolic-volumes and systolic function was evaluated by multiple linear regression corrected for known confounders. In the PE cohort increased RVEF (ß-coefficient (95% confidence interval [CI]) -0.044 (± -0.011); p<0.001) and higher RV end-diastolic-volume (ß-coefficient 0.005 (± 0.001); p<0.001) were significantly correlated to NT-pro-BNP, while no correlation was found with LVEF (ß-coefficient 0.005 (± 0.010); p=0.587) and LV end-diastolic-volume (ß-coefficient -0.003 (± 0.002); p=0.074). In control patients without PE we found a strong correlation between NT-pro-BNP levels and LVEF (ß-coefficient -0.027 (± -0.006); p<0.001) although not LV end-diastolic-volume (ß-coefficient 0.001 (± 0.001); p=0.418). RVEF (ß-coefficient -0.002 (± -0.006); p=0.802) and RV end-diastolic-volume (ß-coefficient <0.001 (± 0.001); p=0.730) were not correlated in patients without PE. In PE patients, lower RVEF and higher RV end-diastolic-volume were significantly correlated to NT-pro-BNP levels as compared to control patients without PE. These observations provide pathophysiological ground for the well-known prognostic value of NT-pro-BNP in acute PE.

Meta-analysis: serum creatinine changes following contrast enhanced CT imaging.

PURPOSE: Contrast induced nephropathy (CIN) is defined as a decrease in renal function following administration of contrast media. The aim of this meta-analysis was to asses the overall risk of CIN, chronic loss of kidney function and the need for renal replacement therapy (RRT) after intravenous contrast enhanced CT-scan. Secondly, we aimed to identify subgroups at increased risk for CIN. MATERIALS AND METHODS: A literature search in Pubmed, Medline, Embase and Cochrane databases was performed. Data extraction was carried out independently by two reviewers. Meta-analysis and meta-regression were performed using an exact likelihood approach. RESULTS: Forty studies evaluating the incidence of CIN after CT were included. The pooled incidence of CIN was 6.4% (95% CI 5.0-8.1). The risk of RRT after CIN was low, 0.06% (95% CI 0.01-0.4). The decline in renal function persisted in 1.1% of patients (95% CI 0.6-2.1%). Patients with chronic kidney disease (odds ratio 2.26, p<0.001) or diabetes mellitus (odds ratio 3.10, p<0.001) were at increased risk for the development of CIN. CONCLUSION: CIN occurred in 6% of patients after contrast enhanced CT. In 1% of all patients undergoing contrast enhanced CT the decline in renal function persisted.

Blood pressure class and carotid artery intima-media thickness in a population at the secondary epidemiological transition.

OBJECTIVES: Data relating blood pressure (BP) class to subclinical organ damage are infrequently reported in populations with a traditional 'nonwestern' lifestyle. As the relevance of BP stratification to cardiovascular prognosis has not been elucidated in these low-income countries at the second epidemiological transition, we aimed to study the effect of BP class on carotid artery intima-media thickness (IMT) in Flores Island, Indonesia. METHODS: A cross-sectional study was performed in 476 inhabitants (men/women) of Flores. BP was classified using the European Society of Hypertension/European Society of Cardiology classification. The primary endpoint was mean carotid-IMT measured by ultrasonography in classes of BP. Covariate analysis was performed adjusting for conventional cardiovascular risk factors. RESULTS: BP ranged from 94 to 250 mmHg systolic and 50 to 125 mmHg diastolic, 35% of the population had 'grade-I hypertension' or higher, 1.7% of the population was short-term treated with antihypertensive therapy. IMT significantly differed for BP classes (P < 0.001). Mean (± SEM) IMT was 587.8 (± 9.3) µm, 621.5 (± 7.6) µm, 653.6 (± 10.5) µm, 717.9 (± 14.0) µm, and 750.1 (± 21.8) µm for 'optimal', '(high) normal', 'grade-I, grade-II, and grade-III hypertension' classes, respectively. After adjustment for cardiovascular risk factors, similar results were obtained. CONCLUSION: A strong association was found between BP class and carotid artery IMT in treatment-naive participants of a population with a traditional lifestyle, at the second epidemiological transition. Intriguingly, the increase of IMT was already observed at the 'high normal' BP class. This study may help to prioritize preventive and therapeutic measures to lower BP in countries at the second epidemiological transition.

Time-dependent effects of low-dose aspirin on plasma renin activity, aldosterone, cortisol, and catecholamines.

Studies have shown that aspirin may decrease blood pressure when given at bedtime but not when administered on awakening. However, until now, a biologically plausible mechanism of this striking phenomenon was not revealed. We investigated the effect of 100 mg of aspirin administered at bedtime compared with administration on awakening on plasma renin activity and aldosterone levels over 24 hours and excretion of cortisol and catecholamines in 24-hour urine samples. A randomized, placebo-controlled, double-blind, crossover trial was performed in 16 grade 1 hypertensive subjects. During 2 periods of 2 weeks separated by a 4-week washout period, participants used aspirin both at morning and at night, which was blinded with placebo. After both periods, subjects were admitted for 24 hours to measure the aforementioned parameters. Aspirin intake at bedtime compared with on awakening reduced average (24-hour) plasma renin activity by 0.08 microg/L per hour (95% CI: 0.03 to 0.13 microg/L per hour; P=0.003) without affecting aldosterone levels (95% CI: -0.01 to 0.01 nmol/L; P=0.93). Cortisol excretion in 24-hour urine was 52 nmol/24 hours (95% CI: 5 to 99 nmol/24 hours; P=0.05) lower, and dopamine and norepinephrine excretions were 0.25 micromol/24 hours (95% CI: 0.01 to 0.48 micromol/24 hours; P=0.04) and 0.22 micromol/24 hours (95% CI: -0.03 to 0.46 micromol/24 hours; P=0.02) lower in patients treated with bedtime aspirin. In conclusion, aspirin taken at bedtime compared with on awakening significantly diminished 24-hour plasma renin activity and excretion of cortisol, dopamine, and norepinephrine in 24-hour urine. Decreased activity of these pressor systems forms a biologically plausible explanation for the finding that aspirin at night may reduce blood pressure, whereas aspirin at morning does not.