Simone Birocchi

Standard and pocket-size lung ultrasound devices can detect interstitial lung disease in rheumatoid arthritis patients

OBJECTIVES Interstitial lung disease (ILD) is a frequent extra-articular manifestation of RA associated with increased mortality. High-resolution CT (HRCT) is used for diagnosis and follow-up, but its accuracy is counterbalanced by high costs and radiological risk. In the presence of ILD, lung US (LUS) detects vertical artefacts called B-lines. The aims of the present study were to evaluate the accuracy of LUS in the diagnosis of ILD in RA and to validate the use of a pocket-size US device (PS-USD) as a screening tool. METHODS LUS was performed with standard equipment by a trained physician through longitudinal scans following anatomical lines: 72 segments were considered (28 anteriorly and 44 posteriorly) and B-lines were counted in each segment. A B-lines score >10 identified a positive examination (presence of ILD). A second LUS session for positive/negative judgment was performed by a short-trained physician using a PS-USD. RESULTS Thirty-nine patients were studied. The sensitivity and specificity of standard LUS vs HRCT were 92% and 56%, respectively. The B-line score was significantly correlated with HRCT score (r = 0.806). A total of 29 patients were studied with a PS-USD. Sensitivity and specificity for PS-USD vs HRCT were 89% and 50%. CONCLUSION The sensitivity of LUS in the detection of ILD supports its use as a screening test for ILD in RA patients, even in the ambulatory setting with a PS-USD. The strong correlation between echographic and HRCT scores indicates LUS is a valid tool for grading and follow-up of ILD.

Aspirin in the secondary prevention of unprovoked thromboembolism: the WARFASA and ASPIRE studies

The treatment of unprovoked venous thromboembolism (VTE) is anticoagulant therapy for at least 3 months [1]. As VTE recurs frequently and about 20 % of the patients with an unprovoked VTE develop recurrence within the first 2 years [2], extended vitamin K antagonist (VKA) treatment is often considered. The decision to prolong VKA therapy after the initial treatment period is a dilemma, since longer term therapy reduces the risk of recurrent thromboembolism, but increases the risk of bleeding. The last American College of Chest Physicians (ACCP) EvidenceBased Clinical guidelines suggest a strategy to balance the benefits and risks of different durations of anticoagulant therapy; in unprovoked VTE, ACCP guidelines suggest extended anticoagulant therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high. When extended anticoagulant therapy is contraindicated, aspirin might be appealing. In fact the annual risk of major bleeding is only 0.1 % in patients on long-term low-dose aspirin therapy, thus lower than VKA therapy [3]. A large meta-analysis by the Antiplatelet Trialists’ Collaboration shows that antiplatelet therapy significantly reduces the risk of fatal or non-fatal pulmonary embolism (PE) by 25 % [3]. Moreover, a large trial involving patients undergoing surgery for hip fracture shows a 36 % risk reduction in VTE in the aspirin therapy group, [4] suggesting that antiplatelet therapy may be an alternative to prolonged VKA therapy. Two randomized controlled studies were conducted to evaluate the use of ASA for the prevention of venous thromboembolism recurrence: the Aspirin for the Prevention of Recurrent Venous Thromboembolism (Warfarin and Aspirin [WARFASA]) [5] and the Aspirin to Prevent Recurrent Venous Thromboembolism (ASPIRE) study [6].

To anticoagulate or not to anticoagulate? That is the question: A Medline-based quantitative approach to share evidence on common clinical problems

Mr. P.C., an 81-year-old man, was admitted to our hospital for worsening of anemia of unknown origin (hemoglobin 7 g/dl, while the previous value was 10 g/dl 4 months earlier, recent negative gastroduodenoscopy and colonoscopy) and congestive heart failure. The medical history was significant for permanent atrial fibrillation, hypertension, ischemic stroke, peptic ulcer disease 10 years before and chronic renal failure (serum creatinine 2 mg/dl). The patient’s medication included warfarin, atorvastatin, omeprazole, amlodipine, furosemide and lorazepam. Considering the worsening of anemia on one hand and atrial fibrillation and comorbid conditions on the other, the clinical dilemma was to continue warfarin, to substitute warfarin with an antiplatelet drug such as aspirin or withdraw warfarin without taking any antithrombotic therapy [1]. How could we know which one is the best choice (Fig. 1)? Dr. Costantino First of all, we have to estimate the risk of cardio-embolic stroke in Mr. P.C., considering atrial fibrillation and the additional risk factors. In order to answer this question, I performed a search on PubMed to find a clinical risk score that was validated and userfriendly. The key words for this search were: [(scale) OR (rule) OR (risk prediction) OR (score)] AND (atrial fibrillation) AND (stroke). Every term was searched as text word or Medical Subject Headings (MeSH). 572 results were retrieved. I tried to limit to systematic reviews, but I obtained only 21 results, none of which regarded the validation of a clinical score. 572 results were then analyzed. Among them 16 were about the validation of at least one clinical risk score. 14 considered CHADS2 score, 2 CHADSVASC score, 2 NICE scale, 2 ACCP scale [1–16]. I decided to use the CHADS2 score [2] that is the most commonly used and validated score, granting a good prediction of the risk of cardio-embolic stroke in single patients. Moreover Poli et al. [11] have compared different risk scores and CHADS2 was the most accurate. This stroke risk scheme is based on five risk factors, assigning to each of them a score (1 point for Congestive heart failure, Hypertension, Age, Diabetes, 2 points for previous Stroke or transient ischemic attack). A CHADS2 score between 0 and 6 is computed for each patient, and a high score corresponds to a greater annual risk of stroke, while a low score corresponds to a lower annual risk of stroke. In our patient the result of the score was 5, and it was associated with an estimated annual risk of 12.5 % without antithrombotic therapy. Such a high risk virtually excludes the no antithrombotic therapy option (Table 1). Dr. Podda An integral part of anticoagulation treatment decision-making is the estimation of the risk of bleeding in a patient on anticoagulants, with iron deficiency anemia and other risk factors. I performed a search on PubMed similar to the previous one, to find a hemorrhagic prediction clinical score that could be applied to our patient. The keywords for my search were: (anticoagulants) AND [(scale) OR (rule) OR (risk prediction) OR (score)] On behalf of Gruppo di Autoformazione Metodologica (GrAM).

Eplerenone, an aldosterone antagonist, reduces hospitalization and death in heart failure patients with nyha class II and an ejection fraction of less than 30%

BackgroundThe renin-angiotensin-aldosterone system (RAAS) playsan important role in pathophysiology of heart failure (HF).RAAS blockade with angiotensin converting (ACE)inhibitor slows the progression of HF and improves thesurvival [1]. However, ACE inhibitors do not block themineralocorticoid receptors, which are usually overexpressed in patients with heart failure, and promote car-diac fibrosis in experimental models [2]. The latter hasbeen confirmed by clinical trials that show a reduction inmortality and hospitalization of patients with severe heartfailure in New York Heart Association class III–IV(NYHA III–IV) treated with spironolactone [3], or inpatients after a myocardial infarction complicated by areduced systolic function treated with eplerenone [4].Thus, it is reasonable to suppose that the use of aldoste-rone antagonists might also delay the progression of heartfailure in patients with mild failure symptoms (NYHA II).SummaryThe Eplerenone in Mild Patients Hospitalization and Sur-vival Study in Heart Failure (EMPHASIS-HF) trial [5]randomized 2,737 patients aged more than 55 years withNYHA II heart failure and an ejection fraction of not morethan 35%, to receive either eplerenone (up to 50 mg daily)or placebo, in addition to recommended therapy. The pri-mary outcome was a composite of death from cardiovas-cular causes or a first hospitalization for heart failure. Deathand hospitalization for any cause were secondary outcomes.The trial was planned to last 48 months, but it wasstopped prematurely, after a median follow-up period of21 months, because of an overwhelming benefit in theeplerenone group. The primary outcome occurred in 18.3%of patients in the eplerenone group as compared with25.9% in the placebo group (hazard ratio, 0.63, 95% con-fidence interval (CI), 0.54–0.74, P\0.001). A total of12.5% of patients receiving eplerenone and 15.5% of thosereceiving placebo died (hazard ratio, 0.76, 95% CI,0.62–0.93, P = 0.008); hospitalizations for heart failureand any other cause were also reduced with eplerenone.Among adverse events, only hyperkalemia showed a sig-nificant difference between the two groups: serum potas-sium level exceeding 5.5 mmol per litre occurred in 11.8%of patients in the eplerenone group and in 7.2% of those inthe placebo group (P\0.001). The estimated number ofpatients who would need to be treated to prevent one pri-mary outcome per year was 19 (95% CI 15–27), and theestimated number needed to treat to postpone one death peryear, was 51 (95% CI 32–180).Strength of the study– It addresses a relevant clinical issue (it’s the first trialconducted among the patients in class NYHA II).– Rationale of the study: there is a strong pathophysio-logic background for the utility of aldosterone antag-onists in heart failure patients, and the previous studyalready confirms this observation [3, 4];

Oral anticoagulants for stroke prevention in patients with atrial fibrillation and previous intracranial hemorrhage

Intracerebral hemorrhage (ICH) affects up to 0.6–1% of patients per year, and is the most feared and lethal complication of anticoagulant therapy, with high in-hospital mortality (22%) and disability rate (61% of cases) [1]. The incidence of anticoagulant-associated ICH varies by ethnicity, being highest in Asians. Survivors of ICH frequently have ongoing risks for thrombosis, in particular atrial fibrillation (AF) that is the most frequent cause of cardioembolism. The dilemma for these patients is whether to start, restart or withhold oral anticoagulation, depending on the balance between the ischemic risk and the risk of recurrent ICH [2, 3]. High-quality evidence is lacking. In small observational studies that have addressed the use of oral anticoagulants after ICH, the risk of recurrence appears to be related to the presence of hypertension and pre-existing vascular damage; it has also been reported that ICH recurrence is [5-fold higher in lobar compared with deep ICHs. Kuramatsu and co-workers retrospectively analyzed data of 719 patients that experienced warfarin associated ICH, and observed a reduction in ischemic strokes without a significant increment in ICH in patients who resume oral anticoagulant (OAC) therapy [3]. Summary of the study

Adjunct prednisone therapy for patients with community-acquired pneumonia

Pneumonia is one of the principal causes of morbidity and mortality worldwide, despite the advances in antibiotic therapies and in preventive measures [1]. The intense inflammatory response that was of fundamental importance in the pre-antibiotics era nowadays might be excessive. In fact, it can lead to multiple organ failure, thus causing more harm than benefit [2]. Corticosteroids have a strong antiinflammatory effect; therefore, their use in pneumonia has been studied for a long time. One of the most important trials was recently published by Meijvis [3]. A 4-day course of 5 mg of dexamethasone was compared to placebo, showing a 1-day reduction in hospital stay, but no difference in mortality. A meta-analysis by Nie [4] does not find any significant reduction in pneumonia overall mortality; however, a subgroup analysis shows a significant reduction in mortality in both studies considering patients with severe pneumonias and treating subjects for more than 5 days. Therefore, the authors conclude that adequately powered double-blind randomized controlled trials (RCTs) are warranted to give recommendations for the use of steroids in pneumonia. Summary

Is a liberal transfusion strategy better than a symptomatic strategy in patients with cardiovascular disease undergoing surgical hip fracture repair

In patients with hip fracture, anemia may result as a direct consequence of the injury or surgery. Red blood cell transfusions are commonly administered to surgical patients in response to operative hemorrhage, and to treat anemia. However, the impact of transfusions on mortality and morbidity in patients with hip fracture is still unclear. A large observational study finds no beneficial effect of transfusion on mortality regardless of the presence of preexisting cardiovascular disease [1]. Other studies suggest that anemia decreases physical performance and postoperative rehabilitation in patients with hip fracture, and red blood cell transfusions improve short-term functional outcomes [2, 3]. To date, there are few randomized clinical trials (RCT) assessing the clinical impact of different transfusion thresholds. A large study involving patients in intensive care units shows that a restrictive strategy of redcell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients [4]. However, there are no RCTs evaluating the safety of withholding transfusion until symptoms of anemia develop in patients with hip fracture. Furthermore, the safety of symptomatic transfusion in patients with cardiovascular disease and the impact of a lower transfusion threshold on functional recovery after surgical hip repair have not been studied. Summary