Longitudinal correlation of biomarkers of cardiac injury, inflammation, and coagulation to outcome in hospitalized COVID-19 patients.

BACKGROUND: Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitudinal follow-up of cardiac injury, inflammation and coagulation markers in relation to disease severity and outcome. METHODS: We retrospectively assessed 2068 patients with laboratory-confirmed COVID-19 between January 29 and April 1, 2020 at Tongji Hospital in Wuhan, China. We defined cardiac injury as an increase in high sensitivity cardiac troponin-I (hs-cTnI) above the 99th of the upper reference limit. We explored the dynamics of elevation in hs-cTnI and the relationship with inflammation (interleukin [IL]-6, IL-8, IL-10, IL-2 receptor, tumor necrosis factor-α, C-reactive protein) and coagulation (d-dimer, fibrinogen, international normalized ratio) markers in non-critically ill versus critically ill patients longitudinally and further correlated these markers to survivors and non-survivors. RESULTS: Median age was 63 years (first to third quartile 51-70 years), 51.4% of whom were women. When compared to non-critically ill patients (N = 1592, 77.0%), critically ill (defined as requiring mechanical ventilation, in shock or multiorgan failure) patients (N = 476, 23.0%), had more frequent cardiac injury on admission (30.3% vs. 2.3%, p < 0.001), with increased mortality during hospitalization (38.4% vs. 0%, p < 0.001). Among critically ill patients, non-survivors (N = 183) had a continuous increase in hs-cTnI levels during hospitalization, while survivors (N = 293) showed a decrease in hs-cTnI level between day 4 and 7 after admission. Specifically, cardiac injury is an independent marker of mortality among critically ill patients at admission, day 4-7 and 8-14. Consistent positive correlations between hs-cTnI and interleukin (IL)-6 on admission (r = 0.59), day 4-7 (r = 0.66) and day 8-14 (r = 0.61; all p < 0.001) and d-dimer (at the same timepoints r = 0.54; 0.65; 0.61, all p < 0.001) were observed. A similar behavior was observed between hs-cTnI and most of other biomarkers of inflammation and coagulation. CONCLUSIONS: Cardiac injury commonly occurs in critically ill COVID-19 patients, with increased levels of hs-cTnI beyond day 3 since admission portending a poor prognosis. A consistent positive correlation of hs-cTnI with IL-6 and d-dimer at several timepoints along hospitalization could suggest nonspecific cytokine-mediated cardiotoxicity.

Quality of reporting in abstracts of RCTs published in emergency medicine journals: a systematic survey of the literature suggests we can do better.

OBJECTIVE: We investigated the association between the publication of the Consolidated Standards of Reporting Trials extension for abstracts (CONSORT-EA) and other variables of interest on the quality of reporting of abstracts of randomised controlled trials (RCTs) published in emergency medicine (EM) journals. METHODS: We performed a survey of the literature, comparing the quality of reporting before (2005-2007) with after (2014-2015) the publication of the dedicated CONSORT-EA in 2008. The quality of reporting was measured as the sum of items of the CONSORT-EA checklist reported in each abstract, ranging from 0 to 15. The main explanatory variable was the period of publication: pre-CONSORT-EA versus post-CONSORT-EA public. Other explanatory variables were journal's endorsement of the CONSORT statement, number of centres participating in the study, study's sample size, type of intervention, significance of results, source of funding and study setting. We analysed the data using generalised estimation equations, performing a univariate and a multivariable analysis. RESULTS: We retrieved 844 articles, and randomly selected 60 per period for review, after stratifying for journal. The mean (SD) number of items reported was 6.4 (1.9) in the period before and 6.9 (1.8) in the period after the publication of the CONSORT-EA, with an adjusted mean difference (aMD) of 0.47 (95% CI -0.13 to 1.06). Abstracts of trials of pharmacological interventions had a significantly larger mean number of reported items than those of trials of non-pharmacological interventions (aMD 1.59; 95% CI 0.94 to 2.24). CONCLUSIONS: The quality of reporting in abstracts of RCTs published in EM journals is low and was not significantly impacted by the publication of a dedicated CONSORT-EA.

Single-center outbreak of Pneumocystis jirovecii pneumonia in heart transplant recipients.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) outbreaks are described in solid organ transplant recipients. Few reports suggest interhuman transmission with important infection control implications. We described a large PJP outbreak in heart transplant (HTx) recipients. METHODS: Six cases of PJP occurred in HTx recipients within 10 months in our hospital. Demographics, clinical characteristics, treatment and outcomes were described. To identify contacts among individuals a review of all dates of out-patient visits and patient hospitalizations was performed. Cross exposure was also investigated using genotyping on PJ isolates. RESULTS: At the time of PJP-related hospitalization, patients' mean age was 49 ± standard deviation 4 years, median time from HTx was 8 (25%-75% interquartile range [Q1-Q3] 5-12) months and none of the cases were on prophylaxis. At PJP-related admission, 5 patients had CMV reactivation, of whom 4 were on antiviral preemptive treatment. Median in-hospital stay was 30 (Q1-Q3, 28-48) days; and 2 cases required intensive care unit admission. All patients survived beyond 2 years. Transmission map analysis suggested interhuman transmission in all cases (presumed incubation period, median 90 [Q1-Q3, 64-91] days). Genotyping was performed in 4 cases, demonstrating the same PJ strain in 3 cases. CONCLUSIONS: We described a large PJP cluster among HTx recipients, supporting the nosocomial acquisition of PJP through interhuman transmission. Based on this experience, extended prophylaxis for more than 6 months after HTx could be considered in specific settings. Further work is required to understand its optimal duration and timing based on individual risk factor profiles and to define standardized countermeasures to prevent and limit PJP outbreaks.

Acute and Fulminant Myocarditis: a Pragmatic Clinical Approach to Diagnosis and Treatment.

PURPOSE OF REVIEW: To review the clinical features of acute myocarditis, including its fulminant presentation, and present a pragmatic approach to the diagnosis and treatment, considering indications of American and European Scientific Statements and recent data derived by large contemporary registries. RECENT FINDINGS: Patients presenting with acute uncomplicated myocarditis (i.e., without left ventricular dysfunction, heart failure, or ventricular arrhythmias) have a favorable short- and long-term prognosis: these findings do not support the indication to endomyocardial biopsy in this clinical scenario. Conversely, patients with complicated presentations, especially those with fulminant myocarditis, require an aggressive and comprehensive management, including endomyocardial biopsy and availability of advanced therapies for circulatory support. Although several immunomodulatory or immunosuppressive therapies have been studied and are actually prescribed in the real-world practice, their effectiveness has not been clearly demonstrated. Patients with specific histological subtypes of acute myocarditis (i.e., giant cell and eosinophilic myocarditis) or those affected by sarcoidosis or systemic autoimmune disorders seem to benefit most from immunosuppression. On the other hand, no clear evidence supports the use of immunosuppressive agents in patients with lymphocytic acute myocarditis, even though small series suggest a potential benefit. Acute myocarditis is a heterogeneous condition with distinct pathophysiological pathways. Further research is mandatory to identify factors and mechanisms that may trigger/maintain or counteract/repair the myocardial damage, in order to provide a rational for future evidence-based treatment of patients affected by this condition.

Statin Use and Risk of Atrial Fibrillation or Flutter: A Population-based Case-Control Study.

The pleiotropic effects of statins have been suggested to prevent atrial fibrillation onset. We conducted a population-based case-control study using medical databases from Northern Denmark (population: 1.8 million) to examine the association between statin use and atrial fibrillation or flutter. We identified 51,374 patients with atrial fibrillation or flutter between 1999 and 2010 and 513,670 matched population controls. We collected data on statin prescriptions redeemed within 90 days (current users) or longer (former users) before the diagnosis date of atrial fibrillation or flutter. We stratified statin users by duration of exposure, determined by the number of days between first and last redeemed prescription before the diagnosis date (<365, 365-1094, and ≥1095 days). We used conditional logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs), controlling for potential confounders. We defined people without previous statin use as never users (reference). A total of 7360 (14.3%) cases and 55,699 (10.8%) controls were current statin users. Among current users (adjusted OR: 0.96, 95% CI, 0.93-0.99), the preventive effect of statins on atrial fibrillation or flutter was related to duration of use: adjusted ORs decreased from 1.35 (95% CI, 1.28-1.42) for users who were prescribed statins for <365 days to 0.85 (95% CI, 0.81-0.89) for users who were prescribed statins for ≥1095 days compared with never users. For former users (adjusted OR: 0.94, 95% CI. 0.90-0.98), the ORs did not change with varying lengths of exposure. In conclusion, long-term statin use may reduce the risk of atrial fibrillation or flutter compared with never use.

Immunomodulating Therapies in Acute Myocarditis and Recurrent/Acute Pericarditis.

The field of inflammatory disease of the heart or "cardio-immunology" is rapidly evolving due to the wider use of non-invasive diagnostic tools able to detect and monitor myocardial inflammation. In acute myocarditis, recent data on the use of immunomodulating therapies have been reported both in the setting of systemic autoimmune disorders and in the setting of isolated forms, especially in patients with specific histology (e.g., eosinophilic myocarditis) or with an arrhythmicburden. A role for immunosuppressive therapies has been also shown in severe cases of coronavirus disease 2019 (COVID-19), a condition that can be associated with cardiac injury and acute myocarditis. Furthermore, ongoing clinical trials are assessing the role of high dosage methylprednisolone in the context of acute myocarditis complicated by heart failure or fulminant presentation or the role of anakinra to treat patients with acute myocarditis excluding patients with hemodynamically unstable conditions. In addition, the explosion of immune-mediated therapies in oncology has introduced new pathophysiological entities, such as immune-checkpoint inhibitor-associated myocarditis and new basic research models to understand the interaction between the cardiac and immune systems. Here we provide a broad overview of evolving areas in cardio-immunology. We summarize the use of new imaging tools in combination with endomyocardial biopsy and laboratory parameters such as high sensitivity troponin to monitor the response to immunomodulating therapies based on recent evidence and clinical experience. Concerning pericarditis, the normal composition of pericardial fluid has been recently elucidated, allowing to assess the actual presence of inflammation; indeed, normal pericardial fluid is rich in nucleated cells, protein, albumin, LDH, at levels consistent with inflammatory exudates in other biological fluids. Importantly, recent findings showed how innate immunity plays a pivotal role in the pathogenesis of recurrent pericarditis with raised C-reactive protein, with inflammasome and IL-1 overproduction as drivers for systemic inflammatory response. In the era of tailored medicine, anti-IL-1 agents such as anakinra and rilonacept have been demonstrated highly effective in patients with recurrent pericarditis associated with an inflammatory phenotype.

Update on acute myocarditis.

Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.

Management perspectives from the 2019 Wuhan international workshop on fulminant myocarditis.

Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.

Emergently planned exclusive hub-and-spoke system in the epicenter of the first wave of COVID-19 pandemic in Italy: the experience of the largest COVID-19-free ICU hub for time-dependent diseases.

BACKGROUND: Lombardy was the epicenter in Italy of the first wave of COVID-19 pandemic. To face the contagion growth, from March 8 to May 8, 2020, a regional law redesigned the hub-and-spoke system for time-dependent diseases to better allocate resources for COVID-19 patients. METHODS: We report the reorganization of the major hospital in Lombardy during COVID-19 pandemic, including the rearrangement of its ICU beds to face COVID-19 pandemic and fulfill its role as extended hub for time-dependent diseases while preserving transplant activity. To highlight the impact of the emergently planned hub-and-spoke system, all patients admitted to a COVID-19-free ICU hub for trauma, neurosurgical emergencies and stroke during the two-month period were retrospectively collected and compared to 2019 cohort. Regional data on organ procurement was retrieved. Observed-to-expected (OE) in-ICU mortality ratios were computed to test the impact of the pandemic on patients affected by time-dependent diseases. RESULTS: Dynamic changes in ICU resource allocation occurred according to local COVID-19 epidemiology/trends of patients referred for time-dependent diseases. The absolute increase of admissions for trauma, neurosurgical emergencies and stroke was roughly two-fold. Patients referred to the hub were older and characterized by more severe conditions. An increase in crude mortality was observed, though OE ratios for in-ICU mortality were not statistically different when comparing 2020 vs. 2019. An increase in local organ procurement was observed, limiting the debacle of regional transplant activity. CONCLUSIONS: We described the effects of a regional emergently planned hub-and-spoke system for time-dependent diseases settled in the epicenter of COVID-19 pandemic in Italy.

Outcome of patients on heart transplant list treated with a continuous-flow left ventricular assist device: Insights from the TRans-Atlantic registry on VAd and TrAnsplant (TRAViATA).

BACKGROUND: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. METHODS: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. RESULTS: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. CONCLUSIONS: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU.

Emerging evidence of myocardial injury in COVID-19: A path through the smoke.

Although Coronavirus Disease 2019 (COVID-19) presents primarily as a respiratory condition, a growing body of evidence shows it is a systemic disease. Recently, many authors have described myocardial damage in COVID-19, suggesting various pathophysiological mechanisms. In this issue, Cao et al. demonstrate the prognostic value of cardiac troponin I in patients with COVID-19, showing how even minor elevations in this molecule carry a great impact on patient mortality. In a situation such as the worldwide COVID-19 pandemic, where healthcare resources are placed under enormous stress, readily available tests such as this play an important role in helping clinicians identify patients at greater risk of developing severe forms of the disease, and should be included in the initial triage panel.

Validation of the BAP-65 score for prediction of in-hospital death or use of mechanical ventilation in patients presenting to the emergency department with an acute exacerbation of COPD: a retrospective multi-center study from the Italian Society of Emergency Medicine (SIMEU).

Exacerbations of chronic obstructive pulmonary disease (COPDE) frequently require hospitalizations, may necessitate of invasive mechanical ventilation (IMV), and are associated with a remarkable in-hospital mortality. The BAP-65 score is a risk assessment model (RAM) based on simple variables, that has been proposed for the prediction of these adverse outcomes in patients with COPDE. If showed to be accurate, the BAP-65 RAM might be used to guide the patients management, in terms of destination and treatment. We conducted a retrospective, multicentre, chart-review study, on patients attending the ED for a COPDE during 2014. The aim of the study was the validation of the BAP-65 RAM for the prediction of in-hospital death or use of IMV (composite primary outcome). We assessed the discrimination and the prognostic performance of the BAP-65 RAM. We enrolled 2908 patients from 20 centres across Italy. The mean (standard deviation) age was 76 (11) years, and 38% of patients were female. The composite outcome occurred in 5.3% of patients. The AUROC of BAP-65 for the composite outcome was 0.64 (95%CI 0.59-0.68). The sensitivity of BAP-65 score ≥ 4 to predict in-hospital mortality was 44% (95% CI 34%-55%), the specificity was 84% (95% CI 82%-85%), the positive predictive value was 9% (95% CI 6%-12%), and the negative predictive value was 98% (95% CI 97%-98%). CONCLUSIONS: In patients attending Italian EDs with a COPDE, we found that the BAP-65 score did not have sufficient accuracy to stratify patients upon their risk of severe in-hospital outcomes.

Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction.

BACKGROUND: Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES: This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS: A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. RESULTS: Patients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). CONCLUSIONS: This international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

Fulminant myocarditis: Characteristics, treatment, and outcomes.

Myocarditis is an inflammatory disease of the myocardium with a broad spectrum of clinical presentations, ranging from mild symptoms to severe heart failure. The course of patients with myocarditis is heterogeneous, varying from partial or full clinical recovery in few days to advanced low cardiac output syndrome requiring mechanical circulatory support or heart transplantation. Fulminant myocarditis (FM) is a peculiar clinical condition and is an acute form of myocarditis, whose main characteristic is a rapidly progressive clinical course with the need for hemodynamic support. Despite the common medical belief of the past decades, recent comprehensive data, including a recent registry that compared FM with acute non-FM, highlighted that FM has a poor inhospital outcome, often requires advanced hemodynamic support, and may result in residual left ventricular dysfunction in survivors. This review aimed to provide an updated practical definition of FM, including essentials in the diagnosis and management of the disease. Finally, the outcome of FM was critically revised according to the current published registries focusing on the topic.

COPD exacerbations in the emergency department: Epidemiology and related costs. A retrospective cohort multicentre study from the Italian Society of Emergency Medicine (SIMEU).

Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) frequently cause patients with COPD to access the emergency department and have a negative impact on the course of the disease. The objectives of our study were: 1) describing the socio-demographic and clinical characteristics, and the clinical management, of patients with AECOPD, when they present to the emergency department; and 2) estimating the costs related to the management of these patients. We conducted a retrospective cohort study in Italy, collecting data on 4396 patients, from 34 centres. Patients had a mean (SD) age of 76,6 (10.6) years, and 61.2% of them where males. >70% of the patients had a moderate to very high comorbidity burden, and heart failure was present in 26.4% of the cohort. The 64.6% of patients were admitted to hospital wards, with a mean (SD) length of stay of 10.8 (9.8) days. The estimated cost per patient was 2617 €. CONCLUSIONS: Patients attending the ED for an AECOPD are old and present important comorbidities. The rate of admission is high, and costs are remarkable.

Estimating the risk of severe hypoglycemic event related to glucose-lowering treatment among Italian patients with diabetes: the HYPOTHESIS database.

The primary objective of this study was to estimate 1) the annual risk of undergoing a severe hypoglycemic event in Italian patients with diabetes and 2) the risk of hospitalization following such event. From the HYPOTHESIS database, powered by 46 emergency departments covering a 12-million-odd population, data were extracted of 1,922 hypoglycemic events occurring in patients with diabetes in 2011. The mean age was 71.5 (standard deviation 16.8) years, 50.1% were men, and blood glucose at the time of the event was 44.2 (26.5) mg/dL. Patients were being treated with insulin alone (55%) or in combination with oral hypoglycemic agents (OHA, 15%), or with OHA alone, either in monotherapy (14%) or in multiple therapy (16%). Comorbidities were recorded in 71.8% of the patients. Based on the rates of glucose-lowering drug use in Italian patients with diabetes, the annual risk of undergoing a serious hypoglycemic event was estimated at 1.27% for subjects treated with insulin alone, the highest (p<0.00001) as compared with insulin + OHA (0.41%) or OHA alone, either in monotherapy or in multiple therapy (0.1% and 0.17%, respectively). The risk of being hospitalized following the hypoglycemic event was the least (27.6%) for subjects treated with insulin alone (p<0.0083). Subjects treated with insulin + OHA showed a lower risk (34.2%) as compared with that for subjects treated with OHA (p<0.02). Death occurs in 7% of hospitalized patients. Older age (p<0.0001) and comorbidities (p<0.0001) were risk factors for hypoglycemia-related hospitalization. Treatments with insulin alone (p<0.005) or in combination (p<0.049) were negatively associated with hospital admission. Severe hypoglycemic events associated with the use of oral glucose-lowering agents carry the highest risk of hospital treatment. As such, they are also likely to generate higher tangible and intangible costs.

Assessment of Tobacco Habits, Attitudes, and Education Among Medical Students in the United States and Italy: A Cross-sectional Survey.

OBJECTIVES: Medical students represent a primary target for tobacco cessation training. This study assessed the prevalence of medical students' tobacco use, attitudes, clinical skills, and tobacco-related curricula in two countries, the US and Italy, with known baseline disparities in hopes of identifying potential corrective interventions. METHODS: From September to December 2013, medical students enrolled at the University of Bologna and at Brown University were recruited via email to answer survey questions assessing the prevalence of medical students' tobacco use, attitudes and clinical skills related to patients' smoking, and elements of medical school curricula related to tobacco use. RESULTS: Of the 449 medical students enrolled at Brown and the 1426 enrolled at Bologna, 174 Brown students (38.7%) and 527 Bologna students (36.9%) participated in this study. Italian students were more likely to smoke (29.5% vs. 6.1%; p<0.001) and less likely to receive smoking cessation training (9.4% vs. 80.3%; p<0.001) than their American counterparts, even though the majority of students in both countries desired smoking cessation training (98.6% at Brown, 85.4% at Bologna; p<0.001). Additionally, negative beliefs regarding tobacco usage, the absence of formal training in smoking cessation counseling, and a negative interest in receiving specific training on smoking cessation were associated with a higher risk of not investigating a patient's smoking status during a routine history and not offering tobacco cessation treatment to patients. CONCLUSIONS: Medical curricula on tobacco-related health hazards and on smoking cessation should be mandatory in order to reduce smoking among medical students, physicians, and patients, thereby improving tobacco-related global health.