Michael K. Gould

Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND This article addresses the treatment of VTE disease. METHODS We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence. RESULTS For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C). CONCLUSION Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences.

International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.

Introduction: Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods: An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results: The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. Conclusions: This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression-free survival with EGFR tyrosine kinase inhibitors in advanced lung adenocarcinoma, we recommend that patients with advanced adenocarcinomas be tested for EGFR mutation. This has implications for strategic management of tissue, particularly for small biopsies and cytology samples, to maximize high-quality tissue available for molecular studies. Potential impact for tumor, node, and metastasis staging include adjustment of the size T factor according to only the invasive component (1) pathologically in invasive tumors with lepidic areas or (2) radiologically by measuring the solid component of part-solid nodules.

Benefits and Harms of CT Screening for Lung Cancer: A Systematic Review

CONTEXT Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer. OBJECTIVE To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline. DATA SOURCES MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012). STUDY SELECTION Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation. DATA EXTRACTION Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus. RESULTS Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 274 vs 309 events per 100,000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare. CONCLUSION Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

Parenteral Anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This chapter describes the pharmacology of approved parenteral anticoagulants, including the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin factor Xa and other clotting factors. Heparin also binds to cells and other plasma proteins, endowing it with unpredictable pharmacokinetic and pharmacodynamic properties, and can lead to nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and have a lower risk of nonhemorrhagic side effects. LMWHs can be administered once or twice daily by subcutaneous injection, without anticoagulant monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin; therefore, HIT and osteoporosis are unlikely to occur. Fondaparinux has excellent bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without anticoagulant monitoring. Three parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in HIT patients.

Test Performance of Positron Emission Tomography and Computed Tomography for Mediastinal Staging in Patients with Non–Small-Cell Lung Cancer: A Meta-Analysis

Context Is computed tomography (CT) or positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) better for mediastinal staging of nonsmall-cell lung cancer? Contribution This synthesis of 39 studies found that FDG-PET was more accurate than CT for identifying lymph node involvement. Positron emission tomography with 18-fluorodeoxyglucose was more sensitive but less specific when CT showed enlarged nodes than when CT showed no node enlargement. Implications Positron emission tomography with 18-fluorodeoxyglucose is more accurate than CT for mediastinal staging. Because FDG-PET has more true-positive and false-positive findings in patients with enlarged nodes, positive findings warrant biopsy confirmation. Interpretation of negative FDG-PET findings should rely heavily on pretest probability of metastasis regardless of CT findings. The Editors Accurate mediastinal staging is crucial in managing patients with nonsmall-cell lung cancer. Regional lymph node status is an important determinant of prognosis, and decisions about treatment depend critically on tumor stage. Conventional methods for mediastinal staging include computed tomography (CT) and various biopsy procedures. However, CT has poor sensitivity and specificity for identifying mediastinal metastases (1-3), and biopsy procedures are inconvenient and potentially risky. Positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) is a promising but expensive functional imaging test that is rapidly gaining acceptance as a tool for lung cancer staging (4, 5). Positron emission tomography with 18-fluorodeoxyglucose identifies malignant cells in tumors and lymph nodes on the basis of their increased metabolic rate (6). In the past decade, several studies of PET imaging for mediastinal staging were published. These studies suggested that FDG-PET is more accurate than CT for identifying mediastinal metastases. However, most were small and potentially limited by other methodologic shortcomings. In addition, previous studies have not systematically addressed the conditional test performance of FDG-PET and CT. Conditional test performance refers to the possibility that the sensitivity and specificity of 1 test might differ depending on the results of the other test (7). The results of FDG-PET and CT might be mutually dependent, despite the fact that they identify malignant lymph nodes by different mechanisms. In a preliminary analysis, we found that FDG-PET was more sensitive but less specific in patients with lymph node enlargement on CT (8). If confirmed, this finding has important implications for selecting and interpreting tests in mediastinal staging. For example, if FDG-PET is more sensitive when lymph node enlargement is present on CT, then a negative PET result would rule out disease more reliably (because its negative predictive value would be higher). Consequently, confirmatory mediastinal biopsy might not be necessary in some of these patients, especially when pretest probability is low. We performed this meta-analysis to compare the accuracy of FDG-PET and CT for identifying mediastinal metastasis in patients with nonsmall-cell lung cancer. We also aimed to determine whether the results of FDG-PET and CT are conditionally dependent, that is, whether the sensitivity and specificity of FDG-PET depend on the presence or absence of lymph node enlargement on CT. Finally, we explored whether various aspects of study methods affected diagnostic accuracy. Methods We used systematic review methods to identify potentially relevant studies, assess studies for eligibility, evaluate study quality, and derive summary estimates of diagnostic test performance (9-12). We previously used similar methods to evaluate the accuracy of FDG-PET imaging for diagnosis of pulmonary nodules and mass lesions (13). Additional details about our methods can be found in the Appendix. Study Identification We attempted to identify all published studies that examined FDG-PET imaging for mediastinal staging in patients with known or suspected nonsmall-cell lung cancer. We sought studies that evaluated both FDG-PET and CT, but we did not attempt to identify studies that examined only CT for mediastinal staging. An investigator and a professional librarian searched MEDLINE, CancerLit, and EMBASE databases in August 2001 and repeated searches in June 2002 (Appendix Table 1). We updated the literature search in MEDLINE, EMBASE, Current Contents, and BIOSIS through 27 March 2003 as part of a technology assessment performed for the U.S. Department of Veterans Affairs (Appendix Table 2). We augmented our computerized literature searches by manually reviewing the reference lists of identified studies and review articles. We included studies published in any language but did not include abstracts. For English-language studies, 2 investigators independently evaluated studies for inclusion, rated the methodologic quality of included studies, and abstracted relevant data. Disagreements were resolved by discussion. One reviewer performed these tasks for non-English-language studies. Reviewers were blinded to journal, author, institutional affiliation, and date of publication. Study Eligibility We included studies that examined FDG-PET imaging for mediastinal lymph node staging in patients with known or suspected nonsmall-cell lung cancer; enrolled at least 10 participants, including at least 5 participants with lymph node metastases; and provided enough data to permit calculation of sensitivity and specificity for identifying malignant lymph node involvement. Study Quality We adapted an existing instrument (11, 13) to examine 7 aspects of study quality: technical quality of the index tests, technical quality and application of the reference test, independence of test interpretation, description of the study population, cohort assembly, sample size, and unit of analysis (Appendix Table 3). Data Abstraction We abstracted data about the demographic characteristics of participants, the prevalence of malignant lymph node involvement, and the sensitivity and specificity of CT and FDG-PET for identifying malignant lymph nodes. For studies that reported results by using the patient as the unit of analysis, we determined the ability of CT and FDG-PET to distinguish ipsilateral or contralateral mediastinal lymph node involvement (N2 or N3) from hilar, intrapulmonary, or no lymph node involvement (N0 or N1). This distinction is critical because involvement of N2 or N3 nodes usually indicates non-surgically treatable disease. When it was not possible to make this distinction, we determined test sensitivity and specificity for distinguishing N0 lymph node status from N1, N2, or N3 lymph node status. For studies in which the individual patient was not the unit of analysis, we determined the test sensitivity and specificity for identifying malignant lymph nodes or lymph node stations. Because observations are not independent when several lymph nodes from the same patient are analyzed separately, these studies may yield biased estimates of diagnostic test performance. Therefore, we analyzed data from these studies separately. To determine whether the sensitivity and specificity of FDG-PET depended on the presence or absence of enlarged nodes on CT, we recorded the results of FDG-PET, CT, and the reference test or tests for each patient. This enabled us to derive separate estimates for the sensitivity and specificity of FDG-PET in patients with and without lymph node enlargement on CT. Data Synthesis and Statistical Analysis For each study, we constructed 2 2 contingency tables in which all participants were classified as having positive (N2 or N3) or negative (N0 or N1) results and as having or not having mediastinal lymph node involvement as determined by the reference test or tests. We calculated the true-positive rate (true-positive rate = sensitivity), the false-positive rate (false-positive rate = 1 specificity), and the log odds ratio (log odds true-positive rate log odds false-positive rate) for CT and FDG-PET. The log odds ratio is a measure of diagnostic test performance that accounts for the correlation between the true-positive rate and the false-positive rate. We calculated exact 95% CIs for the true-positive rate and the false-positive rate on the basis of the binomial distribution (14). To derive summary estimates of diagnostic test performance, we constructed summary receiver-operating characteristic (ROC) curves by using the method of Moses (12, 13, 15, 16), which confirmed that the curves were symmetrical and could be described by a single parameter, the summary log odds ratio. Because this method requires the use of a correction factor when the reported sensitivity or specificity is 100%, we calculated the summary diagnostic odds ratios by using a fixed-effects model (17), or a random-effects model when there was evidence of heterogeneity (18), and reported results derived from these models. Because the summary log odds ratio is difficult to interpret clinically, we express our results in terms of the maximum joint sensitivity and specificity (12), a transformation of the summary log odds ratio that is a global measure of diagnostic accuracy, similar to the area under the ROC curve. The maximum joint sensitivity and specificity is the point on the summary ROC curve at which sensitivity and specificity are equal. It varies from 0.5 for a test that provides no diagnostic information to 1.0 for a test that is perfect. We used meta-regression to make all statistical comparisons (19), with 1 exception. To compare the sensitivity and specificity of FDG-PET in patients with and without lymph node enlargement, we used discriminant function analysis (20) and a nonparametric permutation test (21). We considered a 2-sided P value less than 0.05 to be significant for all statistical tests. Sensitivity Analysis In prespecified analyses, we examined the effect of year of publication, language, and

Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND VTE is a common cause of preventable death in surgical patients. METHODS We developed recommendations for thromboprophylaxis in nonorthopedic surgical patients by using systematic methods as described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS We describe several alternatives for stratifying the risk of VTE in general and abdominal-pelvic surgical patients. When the risk for VTE is very low (< 0.5%), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation. For patients at low risk for VTE (∼1.5%), we suggest mechanical prophylaxis, preferably with intermittent pneumatic compression (IPC), over no prophylaxis (Grade 2C). For patients at moderate risk for VTE (∼3%) who are not at high risk for major bleeding complications, we suggest low-molecular-weight heparin (LMWH) (Grade 2B), low-dose unfractionated heparin (Grade 2B), or mechanical prophylaxis with IPC (Grade 2C) over no prophylaxis. For patients at high risk for VTE (∼6%) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or low-dose unfractionated heparin (Grade 1B) over no prophylaxis. In these patients, we suggest adding mechanical prophylaxis with elastic stockings or IPC to pharmacologic prophylaxis (Grade 2C). For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer, we recommend extended-duration, postoperative, pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B). For patients at moderate to high risk for VTE who are at high risk for major bleeding complications or those in whom the consequences of bleeding are believed to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C). For patients in all risk groups, we suggest that an inferior vena cava filter not be used for primary VTE prevention (Grade 2C) and that surveillance with venous compression ultrasonography should not be performed (Grade 2C). We developed similar recommendations for other nonorthopedic surgical populations. CONCLUSIONS Optimal thromboprophylaxis in nonorthopedic surgical patients will consider the risks of VTE and bleeding complications as well as the values and preferences of individual patients.

Methods for Staging Non-small Cell Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

BACKGROUND Correctly staging lung cancer is important because the treatment options and prognosis differ significantly by stage. Several noninvasive imaging studies and invasive tests are available. Understanding the accuracy, advantages, and disadvantages of the available methods for staging non-small cell lung cancer is critical to decision-making. METHODS Test accuracies for the available staging studies were updated from the second iteration of the American College of Chest Physicians Lung Cancer Guidelines. Systematic searches of the MEDLINE database were performed up to June 2012 with the inclusion of selected meta-analyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables. RESULTS The sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were approximately 55% and 81%, respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For PET scanning, estimates of sensitivity and specificity for identifying mediastinal metastasis were approximately 77% and 86%, respectively. These findings demonstrate that PET scanning is more accurate than CT scanning, but tissue biopsy is still required to confirm PET scan findings. The needle techniques endobronchial ultrasound-needle aspiration, endoscopic ultrasound-needle aspiration, and combined endobronchial ultrasound/endoscopic ultrasound-needle aspiration have sensitivities of approximately 89%, 89%, and 91%, respectively. In direct comparison with surgical staging, needle techniques have emerged as the best first diagnostic tools to obtain tissue. Based on randomized controlled trials, PET or PET-CT scanning is recommended for staging and to detect unsuspected metastatic disease and avoid noncurative resections. CONCLUSIONS Since the last iteration of the staging guidelines, PET scanning has assumed a more prominent role both in its use prior to surgery and when evaluating for metastatic disease. Minimally invasive needle techniques to stage the mediastinum have become increasingly accepted and are the tests of first choice to confirm mediastinal disease in accessible lymph node stations. If negative, these needle techniques should be followed by surgical biopsy. All abnormal scans should be confirmed by tissue biopsy (by whatever method is available) to ensure accurate staging. Evidence suggests that more complete staging improves patient outcomes.

Catheter-directed Therapy for the Treatment of Massive Pulmonary Embolism: Systematic Review and Meta-analysis of Modern Techniques

PURPOSE Systemic thrombolysis for the treatment of acute pulmonary embolism (PE) carries an estimated 20% risk of major hemorrhage, including a 3%-5% risk of hemorrhagic stroke. The authors used evidence-based methods to evaluate the safety and effectiveness of modern catheter-directed therapy (CDT) as an alternative treatment for massive PE. MATERIALS AND METHODS The systematic review was initiated by electronic literature searches (MEDLINE, EMBASE) for studies published from January 1990 through September 2008. Inclusion criteria were applied to select patients with acute massive PE treated with modern CDT. Modern techniques were defined as the use of low-profile devices (< or =10 F), mechanical fragmentation and/or aspiration of emboli including rheolytic thrombectomy, and intraclot thrombolytic injection if a local drug was infused. Relevant non-English language articles were translated into English. Paired reviewers assessed study quality and abstracted data. Meta-analysis was performed by using random effects models to calculate pooled estimates for complications and clinical success rates across studies. Clinical success was defined as stabilization of hemodynamics, resolution of hypoxia, and survival to hospital discharge. RESULTS Five hundred ninety-four patients from 35 studies (six prospective, 29 retrospective) met the criteria for inclusion. The pooled clinical success rate from CDT was 86.5% (95% confidence interval [CI]: 82.1%, 90.2%). Pooled risks of minor and major procedural complications were 7.9% (95% CI: 5.0%, 11.3%) and 2.4% (95% CI: 1.9%, 4.3%), respectively. Data on the use of systemic thrombolysis before CDT were available in 571 patients; 546 of those patients (95%) were treated with CDT as the first adjunct to heparin without previous intravenous thrombolysis. CONCLUSIONS Modern CDT is a relatively safe and effective treatment for acute massive PE. At experienced centers, CDT should be considered as a first-line treatment for patients with massive PE.

Sociodemographic characteristics of members of a large, integrated health care system: comparison with US Census Bureau data.

BACKGROUND Data from the memberships of large, integrated health care systems can be valuable for clinical, epidemiologic, and health services research, but a potential selection bias may threaten the inference to the population of interest. METHODS We reviewed administrative records of members of Kaiser Permanente Southern California (KPSC) in 2000 and 2010, and we compared their sociodemographic characteristics with those of the underlying population in the coverage area on the basis of US Census Bureau data. RESULTS We identified 3,328,579 KPSC members in 2000 and 3,357,959 KPSC members in 2010, representing approximately 16% of the population in the coverage area. The distribution of sex and age of KPSC members appeared to be similar to the census reference population in 2000 and 2010 except with a slightly higher proportion of 40 to 64 year olds. The proportion of Hispanics/Latinos was comparable between KPSC and the census reference population (37.5% vs 38.2%, respectively, in 2000 and 45.2% vs 43.3% in 2010). However, KPSC members included more blacks (14.9% vs 7.0% in 2000 and 10.8% vs 6.5% in 2010). Neighborhood educational levels and neighborhood household incomes were generally similar between KPSC members and the census reference population, but with a marginal underrepresentation of individuals with extremely low income and high education. CONCLUSIONS The membership of KPSC reflects the socioeconomic diversity of the Southern California census population, suggesting that findings from this setting may provide valid inference for clinical, epidemiologic, and health services research.

Accuracy of transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: a meta-analysis

Background: The reported accuracy of transbronchial needle aspiration (TBNA) for mediastinal staging in non-small cell lung cancer (NSCLC) varies widely. We performed a meta-analysis to estimate the accuracy of TBNA for mediastinal staging in NSCLC. Methods: Medline, Embase, and the bibliographies of retrieved articles were searched for studies evaluating TBNA accuracy with no language restriction. Meta-analytical methods were used to construct summary receiver-operating characteristic curves and to pool sensitivity and specificity. Results: Thirteen studies met inclusion criteria, including six studies that surgically confirmed all TBNA results and enrolled at least 10 patients with and without mediastinal metastasis (tier 1). Methodological quality varied but did not affect diagnostic accuracy. In tier 1 studies the median prevalence of mediastinal metastasis was 34%. Using a random effects model, the pooled sensitivity and specificity were 39% (95% CI 17 to 61) and 99% (95% CI 96 to 100), respectively. Compared with tier 1 studies, the median prevalence of mediastinal metastasis (81%; p = 0.002) and pooled sensitivity (78%; 95% CI 71 to 84; p = 0.009) were higher in non-tier 1 studies. Sensitivity analysis confirmed that the sensitivity of TBNA depends critically on the prevalence of mediastinal metastasis. The pooled major complication rate was 0.3% (95% CI 0.01 to 4). Conclusions: When properly performed, TBNA is highly specific for identifying mediastinal metastasis in patients with NSCLC, but sensitivity depends critically on the study methods and patient population. In populations with a lower prevalence of mediastinal metastasis, the sensitivity of TBNA is much lower than reported in recent lung cancer guidelines.