Ilaria Bossi

Syncope risk stratification tools vs clinical judgment: An individual patient data meta-analysis

BACKGROUND There have been several attempts to derive syncope prediction tools to guide clinician decision-making. However, they have not been largely adopted, possibly because of their lack of sensitivity and specificity. We sought to externally validate the existing tools and to compare them with clinical judgment, using an individual patient data meta-analysis approach. METHODS Electronic databases, bibliographies, and experts in the field were screened to find all prospective studies enrolling consecutive subjects presenting with syncope to the emergency department. Prediction tools and clinical judgment were applied to all patients in each dataset. Serious outcomes and death were considered separately during emergency department stay and at 10 and 30 days after presenting syncope. Pooled sensitivities, specificities, likelihood ratios, and diagnostic odds ratios, with 95% confidence intervals, were calculated. RESULTS Thirteen potentially relevant papers were retrieved (11 authors). Six authors agreed to share individual patient data. In total, 3681 patients were included. Three prediction tools (Osservatorio Epidemiologico sulla Sincope del Lazio [OESIL], San Francisco Syncope Rule [SFSR], Evaluation of Guidelines in Syncope Study [EGSYS]) could be assessed by the available datasets. None of the evaluated prediction tools performed better than clinical judgment in identifying serious outcomes during emergency department stay, and at 10 and 30 days after syncope. CONCLUSIONS Despite the use of an individual patient data approach to reduce heterogeneity among studies, a large variability was still present. Current prediction tools did not show better sensitivity, specificity, or prognostic yield compared with clinical judgment in predicting short-term serious outcome after syncope. Our systematic review strengthens the evidence that current prediction tools should not be strictly used in clinical practice.

Priorities for emergency department syncope research

STUDY OBJECTIVES There is limited evidence to guide the emergency department (ED) evaluation and management of syncope. The First International Workshop on Syncope Risk Stratification in the Emergency Department identified key research questions and methodological standards essential to advancing the science of ED-based syncope research. METHODS We recruited a multinational panel of syncope experts. A preconference survey identified research priorities, which were refined during and after the conference through an iterative review process. RESULTS There were 31 participants from 7 countries who represented 10 clinical and methodological specialties. High-priority research recommendations were organized around a conceptual model of ED decisionmaking for syncope, and they address definition, cohort selection, risk stratification, and management. CONCLUSION We convened a multispecialty group of syncope experts to identify the most pressing knowledge gaps and defined a high-priority research agenda to improve the care of patients with syncope in the ED.

Quality of Life and Everyday Activities in Patients with Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is generally a slowly progressive disease that may lead to cirrhosis and liver failure. However, patients with PBC often suffer from a variety of symptoms long before the development of cirrhosis that include issues of daily living that have an impact on their work environment and their individual quality of life. We therefore examined multiple parameters by taking advantage of the database of our cohort of 1032 patients with PBC and 1041 matched controls. The data were obtained from patients from 23 tertiary referral centers throughout the United States and from rigorously matched controls by age, sex, ethnicity, and random‐digit dialing. The data showed that patients with PBC were more likely than controls to have significant articular symptoms, a reduced ability to perform household chores, and the need for help with routine activities. Patients with PBC rated their overall activity similar or superior to that of controls; however, more of them reported limitations in their ability to carry out activities at work or at home and difficulties in everyday activities. PBC cases also more frequently reported limitations in participating in certain sports or exercises and pursuing various hobbies; however, they did not report significant limitations in social activities. In a multivariable analysis, household income, a diagnosis of systemic lupus erythematosus, limitations in work activities, a reduction in work secondary to disability, and church attendance were independently increased in PBC cases with respect to controls. Conclusion: Our data indicate that the quality of life of patients with PBC in the United States is generally well preserved. Nevertheless, patients with PBC suffer significantly more than controls from a variety of symptoms that are beyond the immediate impact of liver failure and affect their lifestyle, personal relationships, and work activities. (HEPATOLOGY 2008.)

Lung ultrasound and short-term prognosis in heart failure patients.

BACKGROUND Heart failure (HF) is the leading cause of hospitalization for patients older than 65years, with a 30-day readmission rate of 20-25%. Although several markers have been evaluated to stratify timing of follow-up after an acute decompensation is mostly based on clinical judgment. Lung ultrasound (LUS) has been demonstrated to be a valid tool for the assessment and monitoring of pulmonary congestion. Aim of our study was to evaluate if LUS performed in HF patients at discharge could predict 100-day hospital readmission or death. METHODS One-hundred fifty patients were enrolled. The anterolateral chest was scanned to evaluate the presence of B-lines. A sonographic score was calculated attributing 1 to each positive (≥3 B-lines) sector. Clinical, biochemical and echocardiographic data were recorded. A Cox proportional hazard regression analysis was performed to evaluate the association between variables and 100-day events. RESULTS Follow-up was obtained in 149 patients. Thirty-four events were recorded. Sonographic score was significantly associated with events (HR 1.19; CI 1.05 to 1.34; p=0.005). On average, the increase of 1 point in the sonographic score was associated with an increase of approximately 24% in the risk of event within 100days. At multivariate analysis NTproBNP remained the only independent prognostic factor. CONCLUSIONS We confirmed that B-lines at discharge are a prognostic marker for hospital readmission and death at 100days in HF patients. Nevertheless, further randomized clinical studies are needed to definitely support the routine use of LUS in the clinical management of HF patients, in combination or not with NT-proBNP.

Long-term prophylaxis in hereditary angio-oedema: a systematic review

Objective To systematically review the evidence regarding long-term prophylaxis in the prevention or reduction of attacks in hereditary angio-oedema (HAE). Design Systematic review and meta-analysis. Data sources Electronic databases were searched up to April 2011. Two reviewers selected the studies and extracted the study data, patient characteristics and outcomes of interest. Eligibility criteria for selected studies Controlled trials for HAE prophylaxis. Results 7 studies were included, for a total of 73 patients and 587 HAE attacks. Due to the paucity of studies, a meta-analysis was not possible. Since two studies did not report the number of HAE attacks, five studies (52 patients) were finally included in the summary analysis. Four classes of drugs with at least one controlled trial have been proposed for HAE prophylaxis. All those drugs, except heparin, were found to be more effective than placebo. In the absence of direct comparisons, the relative efficacies of these drugs were determined by calculating a RR of attacks (drug vs placebo). The results were as follows: danazol (RR=0.023, 95% CI 0.003 to 0.162), methyltestosterone (RR=0.054, 95% CI 0.013 to 0.163), ɛ-aminocaproic acid (RR=0.095, 95% CI 0.025 to 0.356), tranexamic acid (RR=0.308, 95% CI 0.195 to 0.479) and C1-INH 0.491 (95% CI 0.395 to 0.607). Conclusions Few trials have evaluated the benefits of HAE prophylaxis, and all drugs but heparin seem to be effective in this setting. Since there are no direct comparisons of HAE drugs, it was not possible to draw definitive conclusions on the most effective one. Thus, to accumulate evidence for HAE prophylaxis, further studies are needed that consider the dose–efficacy relationship and include a head-to-head comparison between drugs, with the active group, rather than placebo, as the control.

Factors Associated with ICU Admission following Blunt Chest Trauma

Background. Blunt chest wall trauma accounts for over 10% of all trauma patients presenting to emergency departments worldwide. When the injury is not as severe, deciding which blunt chest wall trauma patients require a higher level of clinical input can be difficult. We hypothesized that patient factors, injury patterns, analgesia, postural condition, and positive airway pressure influence outcomes. Methods. The study population consisted of patients hospitalized with at least 3 rib fractures (RF) and at least one pulmonary contusion and/or at least one pneumothorax lower than 2 cm. Results. A total of 140 patients were retrospectively analyzed. Ten patients (7.1%) were admitted to intensive care unit (ICU) within the first 72 hours, because of deterioration of the clinical conditions and gas exchange with worsening of chest X-ray/thoracic ultrasound/chest computed tomography. On univariable analysis and multivariable analysis, obliged orthopnea (p = 0.0018) and the severity of trauma score (p < 0.0002) were associated with admission to ICU. Conclusions. Obliged orthopnea was an independent predictor of ICU admission among patients incurring non-life-threatening blunt chest wall trauma. The main therapeutic approach associated with improved outcome is the prevention of pulmonary infections due to reduced tidal volume, namely, upright postural condition and positive airway pressure.

Is there a benefit for a care protocol in the treatment of septic shock

Severe sepsis and septic shock have a short-term mortality in excess of 20 % [1]. In 2001, a single-center ED-based study of a 6-hour early goal-directed therapy (EGDT) protocol reported a significant reduction in in-hospital mortality (30.5 vs 46.5 %) [2]. This EGDT protocol mandated early central venous catheterization to monitor central venous pressure, central venous oxygen saturation, and to guide use of intravenous fluids, vasopressors and packed red cell transfusions. Many trials have been published in the subsequent decade raising the question of whether all elements of the protocol are necessary.

An atypical case of typical chest pain

A 68-year-old woman presented to emergency department (ED) for a 2-week history of fatigue and recurrent episodes of chest pain on exertion described as constrictive and associated with dyspnea. The duration of each episode of pain was about 30 min. To relieve her symptoms, she used transdermic and sublingual nitrates with no benefit. The past medical history revealed primary biliary cirrhosis diagnosed in 1994, a celiac syndrome and a nonsteroidal antiinflammatory-induced gastropathy. She had also a long-standing history of Raynaud’s phenomenon, arthritis, sclerodactily and positive anticentromere antibodies. There was no history of coronary artery disease and no risk factor for cardiovascular diseases. Home medication were omeprazole, NSAID, and ursodeoxycholic acid. On general examination the patient was afebrile and mildly bradycardic (56 beats/min). The blood pressure was 110/60 torr. Pulmonary, cardiac, and abdominal examinations revealed no abnormalities. No oedema was observed in the lower limbs. An enlarged thyroid was palpable. The differential diagnosis of chest pain in a patient with known connective tissue disorder is extensive, ranging from benign to life-threatening etiologies. Musculoskeletal chest wall pain is a common etiology, particularly in rheumatic diseases due to frequent involvement of thoracic joints. This kind of pain is often localized and positional; it may be exacerbated by deep breathing, turning, and arm movement. Ischemic pain due to coronary artery disease has to be carefully considered as a cause of chest discomfort in patients with connective tissue disorders. This issue was emphasized in previous studies [1, 2] that show increased risk of cardiovascular events in connective tissue disorders, particularly in rheumatoid arthritis and erythematosus systemic lupus. The ischemic disease does not appear to be mediated through traditional risk factors, but may be the result of chronic inflammation associated with endothelial dysfunction and a hypercoagulable state [3]. The presence of a pleuritis or a pericarditis has to be excluded in our patient, since serositis is common in connective tissue disorders. Pericardial pain is typically sudden in onset, and occurs over the anterior chest. It may be exacerbated by inspiration, and may decrease in intensity when the patients sits up and leans forward. Also the presence of pulmonary hypertension has to be ruled out in initial evaluation of chest pain. This chronic condition is due to abnormalities in pulmonary vessels that are frequent in patients with rheumatoid arthritis, systemic erythematosus lupus, and systemic sclerosis. In this setting, chest pain is typically associated with exertional dyspnea and seems to be related both to pulmonary artery stretching and to right ventricular ischemia. The chest pain may also be related to an esophageal disease, particularly in our patient who had clinical features of limited cutaneous systemic sclerosis. Esophageal hypomotility and reduction in the lower-esophageal sphincter tone are common in patients with systemic sclerosis [4]. These motility abnormalities may result in gastroesophageal reflux and reflux esophagitis. Gastroesophageal reflux disease may cause symptoms similar to angina pectoris, including a sensation of chest pressure radiating to the neck and arms, which can be triggered by physical exercise and emotions, and relieved by nitrate F. Casella (&) I. Bossi G. Pisano N. Montano Department of Clinical Science, Division of Internal Medicine II, Luigi Sacco Hospital, University of Milan, Via GB Grassi 74, 20157 Milan, Italy e-mail: case.5@libero.it

AN ATYPICAL CASE OF TYPICAL CHEST PAIN

A 68-year-old woman presented to emergency department(ED) for a 2-week history of fatigue and recurrent episodesof chest pain on exertion described as constrictive andassociated with dyspnea. The duration of each episode ofpain was about 30 min. To relieve her symptoms, she usedtransdermic and sublingual nitrates with no benefit.The past medical history revealed primary biliarycirrhosis diagnosed in 1994, a celiac syndrome and anonsteroidal antiinflammatory-induced gastropathy. Shehad also a long-standing history of Raynaud’s phenome-non, arthritis, sclerodactily and positive anticentromereantibodies. There was no history of coronary artery diseaseand no risk factor for cardiovascular diseases. Homemedication were omeprazole, NSAID, and ursodeoxy-cholic acid.On general examination the patient was afebrile andmildly bradycardic (56 beats/min). The blood pressure was110/60 torr. Pulmonary, cardiac, and abdominal examina-tions revealed no abnormalities. No oedema was observedin the lower limbs. An enlarged thyroid was palpable.The differential diagnosis of chest pain in a patient withknown connective tissue disorder is extensive, rangingfrom benign to life-threatening etiologies.Musculoskeletal chest wall pain is a common etiology,particularly in rheumatic diseases due to frequentinvolvement of thoracic joints. This kind of pain is oftenlocalized and positional; it may be exacerbated by deepbreathing, turning, and arm movement.Ischemic pain due to coronary artery disease has to becarefully considered as a cause of chest discomfort inpatients with connective tissue disorders. This issue wasemphasized in previous studies [1, 2] that show increasedrisk of cardiovascular events in connective tissue disorders,particularly in rheumatoid arthritis and erythematosussystemic lupus. The ischemic disease does not appear to bemediated through traditional risk factors, but may be theresult of chronic inflammation associated with endothelialdysfunction and a hypercoagulable state [3].The presence of a pleuritis or a pericarditis has to beexcluded in our patient, since serositis is common in con-nective tissue disorders. Pericardial pain is typically suddenin onset, and occurs over the anterior chest. It may beexacerbated by inspiration, and may decrease in intensitywhen the patients sits up and leans forward.Also the presence of pulmonary hypertension has to beruled out in initial evaluation of chest pain. This chroniccondition is due to abnormalities in pulmonary vessels thatare frequent in patients with rheumatoid arthritis, systemicerythematosus lupus, and systemic sclerosis. In this setting,chest pain is typically associated with exertional dyspneaand seems to be related both to pulmonary artery stretchingand to right ventricular ischemia.The chest pain may also be related to an esophagealdisease, particularly in our patient who had clinical featuresof limited cutaneous systemic sclerosis. Esophagealhypomotility and reduction in the lower-esophagealsphincter tone are common in patients with systemicsclerosis [4]. These motility abnormalities may result ingastroesophageal reflux and reflux esophagitis. Gastro-esophageal reflux disease may cause symptoms similar toangina pectoris, including a sensation of chest pressureradiating to the neck and arms, which can be triggered byphysical exercise and emotions, and relieved by nitrate