Highlights from the I international symposium of thrombosis and anticoagulation in internal medicine, October 23-25, 2008, Sao Paulo, Brazil.

The importance of thrombosis and anticoagulation in clinical practice is rooted firmly in several fundamental constructs that can be applied both broadly and globally. Awareness and the appropriate use of anticoagulant therapy remain the keys to prevention and treatment. However, to assure maximal efficacy and safety, the clinician must, according to the available evidence, choose the right drug, at the right dose, for the right patient, under the right indication, and for the right duration of time. The first International Symposium of Thrombosis and Anticoagulation in Internal Medicine was a scientific program developed by clinicians for clinicians. The primary objective of the meeting was to educate, motivate and inspire internists, cardiologists and hematologists by convening national and international visionaries, thought-leaders and dedicated clinician-scientists in Sao Paulo, Brazil. This article is a focused summary of the symposium proceedings.

Risk-assessment algorithm and recommendations for venous thromboembolism prophylaxis in medical patients.

UNLABELLED: The risk for venous thromboembolism (VTE) in medical patients is high, but risk assessment is rarely performed because there is not yet a good method to identify candidates for prophylaxis. PURPOSE: To perform a systematic review about VTE risk factors (RFs) in hospitalized medical patients and generate recommendations (RECs) for prophylaxis that can be implemented into practice. DATA SOURCES: A multidisciplinary group of experts from 12 Brazilian Medical Societies searched MEDLINE, Cochrane, and LILACS. STUDY SELECTION: Two experts independently classified the evidence for each RF by its scientific quality in a standardized manner. A risk-assessment algorithm was created based on the results of the review. DATA SYNTHESIS: Several VTE RFs have enough evidence to support RECs for prophylaxis in hospitalized medical patients (eg, increasing age, heart failure, and stroke). Other factors are considered adjuncts of risk (eg, varices, obesity, and infections). According to the algorithm, hospitalized medical patients > or =40 years-old with decreased mobility, and > or =1 RFs should receive chemoprophylaxis with heparin, provided they don't have contraindications. High prophylactic doses of unfractionated heparin or low-molecular-weight-heparin must be administered and maintained for 6-14 days. CONCLUSIONS: A multidisciplinary group generated evidence-based RECs and an easy-to-use algorithm to facilitate VTE prophylaxis in medical patients.

Risk of venous thromboembolism and efficacy of thromboprophylaxis in hospitalized obese medical patients and in obese patients undergoing bariatric surgery.

BACKGROUND: Obesity is considered a highly prevalent risk factor for venous thromboembolism (VTE) in hospitalized patients. However, recommendations for VTE prophylaxis in obese patients are not clear. METHODS: To evaluate obesity as a risk factor for VTE in medical and bariatric patients and the efficacy of VTE prophylaxis, we performed a systematic review in MEDLINE, Cochrane Database of Systematic Reviews and LILACS from 1976 to 2006. Evidence was evaluated independently by 2 authors and presented descriptively. RESULTS: Of the 124 studies found, 87 were excluded based on predefined criteria. There is no consensus among studies, but prospective cohorts show that obesity is associated with a higher risk of VTE in medical patients. There is evidence that the risk of VTE exceeds that attributable to the surgical procedure alone in bariatric surgery. Only 6 studies evaluated prophylactic methods (unfractionated heparin, low molecular weight heparin and sequential compression devices) in obese patients. Although these studies have some methodological flaws, they suggest efficacy of VTE prophylaxis in medical and surgical obese patients. CONCLUSIONS: Obesity is a risk factor for VTE in obese medical patients and patients undergoing bariatric surgery. Obesity appears to play an adjuvant role for the development of VTE in hospitalized patients with other risk factors. The small number of prospective trials in this population prevents a definite conclusion about the most effective and safe VTE prophylactic method for obese patients. Thus, randomized clinical trials to compare VTE prophylactic methods in obese patients are still highly warranted.

Association between lower lobe location and upstaging for early-stage non-small cell lung cancer.

STUDY OBJECTIVE: To identify factors associated with a misclassification of the true disease stage by comparing the differences between the clinical and pathologic stage of patients with early-stage non-small cell lung cancer (NSCLC). DESIGN: A prospective cohort study. SETTING: A multidisciplinary thoracic oncology clinic at a university-affiliated Veterans Affairs medical center. PATIENT POPULATION: One hundred nine male veterans with clinical stage I/II NSCLC who had undergone thoracotomy with systematic lymph node dissection. METHODS: Prospective data were collected on all patients between September 1997 and April 2002. Logistic regression analysis was used to establish the odds ratio (OR) for predictors of changes in stage. RESULTS: A stage misclassification was found in 35.8% of patients (39 of 109 patients) after thoracotomy with lymph node dissection, and all but one patient were upstaged. Unsuspected nodal involvement (N stage) resulted in the upstaging of 16.5% of the patients, a change in tumor stage (T stage) resulted in the upstaging of 13.8% of the patients, a change in both stages resulted in the upstaging of 2.7% of patients, and the designation of metastatic disease resulted in the upstaging of 1.9% of the patients. The rate of unsuspected mediastinal lymph node involvement (pathologic stage N2) was 8.3% (9 of 109 patients), despite negative mediastinoscopy findings. Complete anatomic resection was performed in all patients. Advanced disease was found in 8.3% of the patients (9 of 109 patients) [stage IIIB or IV]. Having the primary tumor in a lower lobe location was the only statistically significant factor associated with upstaging (OR, 3.56; 95% confidence interval, 1.4 to 9.1). The effect of location was robust after controlling for tumor size and the prior performance of mediastinoscopy. Patient age, smoking history, weight loss, tumor size, and tumor histology were all found not to be associated with upstaging. CONCLUSION: A lower lobe tumor location in patients with early-stage NSCLC appears to be associated with upstaging after surgery. We conclude that a tumor location in a lower lobe deserves special attention.

Venous thromboembolism in intensive care patients.

Venous thromboembolism frequently complicates the management of patients with severe medical and surgical illnesses. Because the diagnosis of VTE is especially challenging in critically ill patients, the focus of intensivists should be on characterization of risk factors and the appropriate choice of VTE prophylaxis. LDUH or LMHW is the preferred choice for VTE prophylaxis in ICU patients. Mechanical methods of prophylaxis should be reserved for patients with a high risk for bleeding. The effectiveness of mechanical methods and of combined strategies of prevention and the clinically important outcomes of therapy need to be explored further in critically ill patients. Few diagnostic strategies have been assessed in ICU patients with suspected PE. Ventilation-perfusion lung scans remain a pivotal diagnostic test but retain the same limitations in critically ill patients as seen in other patient populations. Newer noninvasive techniques, such as spiral CT associated with imaging of the extremities, are gaining more wide-spread use, but, thus far, pulmonary angiography remains the most reliable technique to confirm or exclude PE in patients with respiratory failure. A consensus must be reached regarding the most appropriate combination of tests for adequate and cost-effective diagnosis of VTE. Further investigation of diagnostic strategies that include adequate consideration of clinical diagnosis using standardized models and noninvasive imaging are warranted.

Miltefosine in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil: a randomized and controlled trial.

BACKGROUND: Cutaneous leishmaniasis (CL) is treated with parenteral drugs for decades with decreasing rate cures. Miltefosine is an oral medication with anti-leishmania activity and may increase the cure rates and improve compliance. METHODOLOGY/PRINCIPAL FINDINGS: This study is a randomized, open-label, controlled clinical trial aimed to evaluate the efficacy and safety of miltefosine versus pentavalent antimony (Sb(v)) in the treatment of patients with CL caused by Leishmania braziliensis in Bahia, Brazil. A total of 90 patients were enrolled in the trial; 60 were assigned to receive miltefosine and 30 to receive Sb(v). Six months after treatment, in the intention-to-treat analyses, the definitive cure rate was 53.3% in the Sb(v) group and 75% in the miltefosine group (difference of 21.7%, 95% CI 0.08% to 42.7%, p = 0.04). Miltefosine was more effective than Sb(v) in the age group of 13-65 years-old compared to 2-12 years-old group (78.9% versus 45% p = 0.02; 68.2% versus 70% p = 1.0, respectively). The incidence of adverse events was similar in the Sb(v) and miltefosine groups (76.7% vs. 78.3%). Vomiting (41.7%), nausea (40%), and abdominal pain (23.3%) were significantly more frequent in the miltefosine group while arthralgias (20.7%), mialgias (20.7%) and fever (23.3%) were significantly more frequent in the Sb(v) group. CONCLUSIONS: This study demonstrates that miltefosine therapy is more effective than standard Sb(v) and safe for the treatment of CL caused by Leishmania braziliensis in Bahia, Brazil. TRIAL REGISTRATION: Clinicaltrials.gov Identifier NCT00600548.

[How to implement a guideline from theory to practice: the example of the venous thromboembolism prophylaxis]. / Como implementar uma diretriz da teoria à prática: exemplo da profilaxia para tromboembolismo venoso.

The objective of this manuscript is to discuss the existing barriers for the dissemination of medical guidelines, and to present strategies that facilitate the adaptation of the recommendations into clinical practice. The literature shows that it usually takes several years until new scientific evidence is adopted in current practice, even when there is obvious impact in patients' morbidity and mortality. There are some examples where more than thirty years have elapsed since the first case reports about the use of a effective therapy were published until its utilization became routine. That is the case of fibrinolysis for the treatment of acute myocardial infarction. Some of the main barriers for the implementation of new recommendations are: the lack of knowledge of a new guideline, personal resistance to changes, uncertainty about the efficacy of the proposed recommendation, fear of potential side-effects, difficulties in remembering the recommendations, inexistence of institutional policies reinforcing the recommendation and even economical restrains. In order to overcome these barriers a strategy that involves a program with multiple tools is always the best. That must include the implementation of easy-to-use algorithms, continuous medical education materials and lectures, electronic or paper alerts, tools to facilitate evaluation and prescription, and periodic audits to show results to the practitioners involved in the process. It is also fundamental that the medical societies involved with the specific medical issue support the program for its scientific and ethical soundness. The creation of multidisciplinary committees in each institution and the inclusion of opinion leaders that have pro-active and lasting attitudes are the key-points for the program's success. In this manuscript we use as an example the implementation of a guideline for venous thromboembolism prophylaxis, but the concepts described here can be easily applied to any other guideline. Therefore, these concepts could be very useful for institutions and services that aim at quality improvement of patient care. Changes in current medical practice recommended by guidelines may take some time. However, if there is a broader participation of opinion leaders and the use of several tools listed here, they surely have a greater probability of reaching the main objectives: improvement in provided medical care and patient safety.

Acute renal failure after lung transplantation: incidence, predictors and impact on perioperative morbidity and mortality.

The incidence, predictors and clinical significance of acute renal failure (ARF) after lung transplantation are not well described. We retrospectively collected data on 296 patients transplanted at our center between April 1992 and December 2000; follow-up was extended until December 2002. Patients were initially divided into two groups: ARF (doubling of baseline creatinine within 2 weeks after surgery) and NoARF. The ARF group was subdivided into ARFD (dialyzed) and ARFnD (not dialyzed). The incidence of ARF was 56% (166/296), but most cases were ARFnD (n = 143). Independent predictors of ARFD (n = 23) were: baseline GFR (OR 0.98, CI 0.96-0.99, p = 0.012), pulmonary diagnosis other than COPD (OR 6.80, CI 1.5-30.89, p = 0.013), mechanical ventilation > 1 d (OR 6.16, CI 1.70-22.24, p = 0.006) and parenteral amphotericin B use (OR 3.04, CI 1.03-8.98, p = 0.045). Both ARFnD and ARFD were associated with longer duration of mechanical ventilation, increased hospital stay and increased early mortality. One-year patient survival was 92.3%, 81.8% and 21.7% in the NoARF, ARFnD and ARFD groups, respectively (p < 0.0001). After controlling for important covariates, ARFD remained associated with an increased hazard of dying (HR 6.77, CI 4.00-11.44, p < 0.0001). In conclusion, ARF occurs commonly after lung transplantation and affects important clinical outcomes, especially when dialysis is required.

Contraindications and safety of transbronchial lung biopsy via flexible bronchoscopy. A survey of pulmonologists and review of the literature.

BACKGROUND: Transbronchial lung biopsy (TBLB) via flexible bronchoscopy is a common procedure performed by pulmonologists. Limited scientific data exist concerning the risk of this procedure in patients with conditions that may adversely affect the rate of procedural complications. OBJECTIVES: To evaluate the current practice pattern and attitude of pulmonologists toward the performance of TBLB in the presence of high-risk conditions. METHODS: A survey was constructed and distributed at the American College of Chest Physicians annual meeting, held in Philadelphia, USA, in November of 2001. RESULTS: A total of 227 surveys were distributed with a return of 158 (69.6%). Anticoagulation medications are temporarily held prior to TBLB by the majority of our survey respondents (98.7% for intravenous heparin, 90.5% for warfarin, and 87.3% for low-molecular-weight heparin). Medications with effect on platelet function are held by fewer pulmonologists. There is a wide variation in the pulmonologists' perception of the risk of performing TBLB when certain medical conditions coexist: pulmonary hypertension [absolute contraindication (AC), 28.7%; relative contraindication (RC) 58.6%], superior vena cava syndrome (AC 19.6%, RC 51%), mechanical ventilation (AC 17.8%, RC 58.6%) and lung cavity/abscess (AC 7%, RC 44.9%). A significant percentage of pulmonologists (55%) do not regard an elevated serum creatinine at any level as AC to TBLB. Thirty-eight percent of the survey participants administer desmopressin prior to TBLB in uremic patients to prevent excessive bleeding. CONCLUSIONS: Prior to performing bronchoscopic TBLB, the majority of pulmonologists temporarily holds anticoagulation medications. However, there is a lack of agreement in relation to perceived contraindications and safety of TBLB.