Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study.

BACKGROUND: Clinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population. AIM: To determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands. METHODS: Two large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument. RESULTS: Between 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis. CONCLUSIONS: High-risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.

Patients with CTEPH and mild hemodynamic severity of disease improve to a similar level of exercise capacity after pulmonary endarterectomy compared to patients with severe hemodynamic disease.

The correlation between hemodynamics and degree of pulmonary vascular obstruction (PVO) is known to be poor in chronic thromboembolic pulmonary hypertension (CTEPH), which makes the selection of patients eligible for pulmonary endarterectomy (PEA) challenging. It can be postulated that patients with similar PVO but different hemodynamic severity have different postoperative hemodynamics and exercise capacity. Therefore, we aimed to assess the effects of PEA on hemodynamics and exercise physiology in mild and severe CTEPH patients. We retrospectively studied 18 CTEPH patients with a mild hemodynamic profile (mean pulmonary arterial pressure [mPAP] between 25 and 30 mmHg at rest) and CTEPH patients with a more severe hemodynamic profile (mPAP > 30 mmHg), matched by age, gender, and PVO. Cardiopulmonary exercise testing parameters were evaluated at baseline and 18 months following PEA. At baseline, exercise capacity, defined as oxygen uptake, was less severely impaired in the mild CTEPH group compared to the severe CTEPH group. After PEA, in the mild CTEPH group, ventilatory efficiency and oxygen pulse improved significantly (p < 0.05), however, the change in ventilatory efficiency and oxygen pulse was smaller compared to the severe CTEPH group. Only in the severe CTEPH group exercise capacity improved significantly (p < 0.001). Hence, in the present study, postoperative hemodynamic outcome and the CPET-determined recovery of exercise capacity in mild CTEPH patients did not differ from a matched group of severe CTEPH patients.

Doxycycline for outpatient-treated acute exacerbations of COPD: a randomised double-blind placebo-controlled trial.

BACKGROUND: Antibiotics do not reduce mortality or short-term treatment non-response in patients receiving treatment for acute exacerbations of COPD in an outpatient setting. However, the long-term effects of antibiotics are unknown. The aim of this study was to investigate if the antibiotic doxycycline added to the oral corticosteroid prednisolone prolongs time to next exacerbation in patients with COPD receiving treatment for an exacerbation in the outpatient setting. METHODS: In this randomised double-blind placebo-controlled trial, we recruited a cohort of patients with COPD from outpatient clinics of nine teaching hospitals and three primary care centres in the Netherlands. Inclusion criteria were an age of at least 45 years, a smoking history of at least 10 pack-years, mild-to-severe COPD (Global Initiative of Chronic Obstructive Lung Disease [GOLD] stage 1-3), and at least one exacerbation during the past 3 years. Exclusion criteria were poor mastery of the Dutch language, poor cognitive functioning, known allergy to doxycycline, pregnancy, and a life expectancy of shorter than 1 month. If a participant had an exacerbation, we randomly assigned them (1:1; with permuted blocks of variable sizes [ranging from two to ten]; stratified by GOLD stage 1-2 vs 3) to a 7 day course of oral doxycycline 100 mg daily (200 mg on the first day) or placebo. Exclusion criteria for randomisation were fever, admission to hospital, and current use of antibiotics or use within the previous 3 weeks. Patients in both groups received a 10 day course of 30 mg oral prednisolone daily. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary outcome was time to next exacerbation in all randomly allocated patients except for those incorrectly randomly allocated who did not meet the inclusion criteria or met the exclusion criteria. This trial is registered with the Netherlands Trial Register, number NTR2499. FINDINGS: Between Dec 22, 2010, and Aug 6, 2013, we randomly allocated 305 (34%) patients from the cohort of 887 patients to doxycycline (152 [50%]) or placebo (153 [50%]), excluding four (1%) patients (two [1%] from each group) who were incorrectly randomly allocated from the analysis. 257 (85%) of 301 patients had a next exacerbation (131 [87%] of 150 in the doxycycline group vs 126 [83%] of 151 in the placebo group). Median time to next exacerbation was 148 days (95% CI 95-200) in the doxycycline group compared with 161 days (118-211) in the placebo group (hazard ratio 1·01 [95% CI 0·79-1·31]; p=0·91). We did not note any significant differences between groups in the frequency of adverse events during the first 2 weeks after randomisation (47 [31%] of 150 in the doxycycline group vs 53 [35%] of 151 in the placebo group; p=0·54) or in serious adverse events during the 2 years of follow-up (42 [28%] vs 43 [29%]; p=1). INTERPRETATION: In patients with mild-to-severe COPD receiving treatment for an exacerbation in an outpatient setting, the antibiotic doxycycline added to the oral corticosteroid prednisolone did not prolong time to next exacerbation compared with prednisolone alone. These findings do not support prescription of antibiotics for COPD exacerbations in an outpatient setting. FUNDING: Netherlands Organization for Health Research and Development.

Hemodynamic and ventilatory responses during exercise in chronic thromboembolic disease.

BACKGROUND: Patients with chronic thromboembolic disease (CTED) may suffer from exercise intolerance without pulmonary hypertension at rest. Pulmonary endarterectomy (PEA) for symptomatic CTED results in improvement of symptoms and quality of life. Neither the pathophysiology of the exercise limitation nor the underlying mechanisms of the PEA-induced improvement have been studied previously. OBJECTIVES: We studied hemodynamic and ventilatory responses upon exercise in 14 patients with CTED. After 1 year, we studied the underlying physiologic mechanisms of the PEA-induced symptomatic improvement. METHODS: Cardiopulmonary exercise testing (CPET) was performed during right heart catheterization, and noninvasive CPET was performed 1 year postoperatively. RESULTS: During exercise, we observed abnormal pulmonary vascular responses, that is, a steep mean pulmonary artery pressure/cardiac output (2.7 ± 1.2 mm Hg·min·L(-1)), and low pulmonary vascular compliance (2.8 ± 1.1 mL·mm Hg(-1)); mean pulmonary artery pressure/cardiac output slope correlated with dead-space ventilation (r = 0.586; P = .028) and ventilatory equivalents for carbon dioxide slope (r = .580; P = .030). Postoperatively, the improvement observed in exercise capacity was related to improvements in CPET-derived parameters pointing to restoration of right ventricle stroke volume response (oxygen pulse: 11.7 ± 3.1 to 13.3 ± 3.3; P = .027; heart rate response: 80.9 ± 12.4 to 72.0 ± 5.7; P = .003); and, indicating improved ventilatory efficiency, the ventilatory equivalents for carbon dioxide slope decreased from 38.2 ± 3.6 to 32.8 ± 7.0 (P = .014). CONCLUSIONS: Patients with CTED showed an abnormal pulmonary vascular response to exercise and a decreased ventilatory efficiency. Responses after PEA point to restoration of right ventricle stroke volume response and ventilatory efficiency.

[A paradox: sarcoidosis in an HIV-positive patient]. / Een paradox: sarcoïdose bij een hiv-positieve patiënt.

BACKGROUND: In view of the diminished number of CD4+ lymphocytes, the co-existence of an HIV infection and sarcoidosis seems paradoxical. Immune reconstitution inflammatory syndrome (IRIS) may be observed in response to anti-retroviral therapy (ART). According to the conventional definition, this is caused by an overwhelming immune response to an already present or to a new agent. CASE DESCRIPTION: We describe the case of a 47-year-old HIV-positive patient, who presented with an exacerbation of his sarcoidosis nine months after initiation of ART. Based on the time course and the dynamics of the CD4+ lymphocyte count, this presentation of disease can be placed in the context of IRIS. CONCLUSION: The presentation or exacerbation of sarcoidosis after initiation of antiretroviral therapy in HIV-positive patients with a low CD4+ count at start of therapy can be placed in the context of IRIS.

The effect of different levels of realism of context learning on the prescribing competencies of medical students during the clinical clerkship in internal medicine: an exploratory study.

PURPOSE: The aim of this study is to evaluate the effect of different levels of realism of context learning on the prescribing competencies of medical students during the clinical clerkship in internal medicine. METHODS: Between 2001 and 2007, 164 medical students took part in the prospective explorative study during their clinical clerkship in internal medicine at the VU University Medical Center, Amsterdam, The Netherlands. In a fixed order, each student had to formulate a treatment plan for a real patient in three situations of increasing realism: a minimal level (studying a patient record), medium level (preparing for a therapeutic consultation), and optimal level (preparing for and performing a therapeutic consultation with the patient). RESULTS: In comparison to studying a patient record (minimal context level), preparing a therapeutic consultation (medium context) improved four of the six steps of the WHO six-step plan. Preparing and performing a therapeutic consultation with a real patient (optimal context) further improved three essential prescribing competencies, namely checking for contraindications and interactions, prescription writing, and instructions to the patient. CONCLUSION AND RECOMMENDATIONS: The results of this first explorative study suggest that enrichment of the learning context (responsibility for patient care) might be an important factor to improve the training of rational prescribing skills of medical students during their clinical clerkship in internal medicine. Clinical (pharmacology) teachers should be aware that seemingly small adaptations in the learning context of prescribing training during clinical clerkships (i.e., with or without involvement with and responsibility for patient care) may have relatively large impact on the development of prescribing competencies of our future doctors.

Pulmonary vascular limitation to exercise and survival in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Pulmonary hypertension is frequently observed in advanced idiopathic pulmonary fibrosis (IPF) and is associated with poor prognosis. Cardiopulmonary exercise testing (CPET) can be used to detect less advanced pulmonary vascular impairment, and therefore may be of prognostic use. We studied the predictive value of non-invasive exercise parameters that were associated with elevated systolic pulmonary artery pressure (sPAP) for survival in IPF patients. METHODS: From our interstitial lung disease database, we reviewed records of consecutive patients with IPF in whom CPET and echocardiography were performed within 2 weeks (n = 38). RESULTS: Eleven patients (29%) had increased sPAP (≥40 mm Hg). From all non-invasive CPET parameters, only the ventilatory equivalent for CO2 (V'E /V'CO2 ) at anaerobic threshold differed significantly between patients with and without sPAP ≥ 40 mm Hg. The receiver-operator characteristic curve for V'E /V'CO2 resulted in areas under the curve of 0.77 (95% CI: 0.569-0.970; P = 0.026), with a cut-off value for predicting sPAP ≥ 40 mm Hg of >45.0. Patients with V'E /V'CO2 > 45.0 had significantly worse survival compared with patients with V'E /V'CO2 ≤ 45.0 (P = 0.001). In contrast, sPAP did not predict survival. CONCLUSIONS: V'E /V'CO2 , the only CPET parameter associated with elevated sPAP, appears a potentially useful non-invasive marker for early detection of pulmonary vascular impairment, and therefore may be of use for a more accurate prognostic assessment in IPF patients.