Renda Soylemez Wiener

Benefits and Risks of Tight Glucose Control in Critically Ill Adults: A Meta-analysis

CONTEXT The American Diabetes Association and Surviving Sepsis Campaign recommend tight glucose control in critically ill patients based largely on 1 trial that shows decreased mortality in a surgical intensive care unit. Because similar studies report conflicting results and tight glucose control can cause dangerous hypoglycemia, the data underlying this recommendation should be critically evaluated. OBJECTIVE To evaluate benefits and risks of tight glucose control vs usual care in critically ill adult patients. DATA SOURCES MEDLINE (1950-2008), the Cochrane Library, clinical trial registries, reference lists, and abstracts from conferences from both the American Thoracic Society (2001-2008) and the Society of Critical Care Medicine (2004-2008). STUDY SELECTION We searched for studies in any language in which adult intensive care patients were randomly assigned to tight vs usual glucose control. Of 1358 identified studies, 34 randomized trials (23 full publications, 9 abstracts, 2 unpublished studies) met inclusion criteria. DATA EXTRACTION AND ANALYSIS Two reviewers independently extracted information using a prespecified protocol and evaluated methodological quality with a standardized scale. Study investigators were contacted for missing details. We used both random- and fixed-effects models to estimate relative risks (RRs). RESULTS Twenty-nine randomized controlled trials totaling 8432 patients contributed data for this meta-analysis. Hospital mortality did not differ between tight glucose control and usual care overall (21.6% vs 23.3%; RR, 0.93; 95% confidence interval [CI], 0.85-1.03). There was also no significant difference in mortality when stratified by glucose goal ([1] very tight: < or = 110 mg/dL; 23% vs 25.2%; RR, 0.90; 95% CI, 0.77-1.04; or [2] moderately tight: < 150 mg/dL; 17.3% vs 18.0%; RR, 0.99; 95% CI, 0.83-1.18) or intensive care unit setting ([1] surgical: 8.8% vs 10.8%; RR, 0.88; 95% CI, 0.63-1.22; [2] medical: 26.9% vs 29.7%; RR, 0.92; 95% CI, 0.82-1.04; or [3] medical-surgical: 26.1% vs 27.0%; RR, 0.95; 95% CI, 0.80-1.13). Tight glucose control was not associated with significantly decreased risk for new need for dialysis (11.2% vs 12.1%; RR, 0.96; 95% CI, 0.76-1.20), but was associated with significantly decreased risk of septicemia (10.9% vs 13.4%; RR, 0.76; 95% CI, 0.59-0.97), and significantly increased risk of hypoglycemia (glucose < or= 40 mg/dL; 13.7% vs 2.5%; RR, 5.13; 95% CI, 4.09-6.43). CONCLUSION In critically ill adult patients, tight glucose control is not associated with significantly reduced hospital mortality but is associated with an increased risk of hypoglycemia.

Time Trends in Pulmonary Embolism in the United States: Evidence of Overdiagnosis

BACKGROUND Computed tomographic pulmonary angiography (CTPA) may improve detection of life-threatening pulmonary embolism (PE), but this sensitive test may have a downside: overdiagnosis and overtreatment (finding clinically unimportant emboli and exposing patients to harms from unnecessary treatment). METHODS To assess the impact of CTPA on national PE incidence, mortality, and treatment complications, we conducted a time trend analysis using the Nationwide Inpatient Sample and Multiple Cause-of-Death databases. We compared age-adjusted incidence, mortality, and treatment complications (in-hospital gastrointestinal tract or intracranial hemorrhage or secondary thrombocytopenia) of PE among US adults before (1993-1998) and after (1998-2006) CTPA was introduced. RESULTS Pulmonary embolism incidence was unchanged before CTPA (P = .64) but increased substantially after CTPA (81% increase, from 62.1 to 112.3 per 100,000; P < .001). Pulmonary embolism mortality decreased during both periods: more so before CTPA (8% reduction, from 13.4 to 12.3 per 100,000; P < .001) than after (3% reduction, from 12.3 to 11.9 per 100,000; P = .02). Case fatality improved slightly before (8% decrease, from 13.2% to 12.1%; P = .02) and substantially after CTPA (36% decrease, from 12.1% to 7.8%; P < .001). Meanwhile, CTPA was associated with an increase in presumed complications of anticoagulation for PE: before CTPA, the complication rate was stable (P = .24), but after it increased by 71% (from 3.1 to 5.3 per 100,000; P < .001). CONCLUSIONS The introduction of CTPA was associated with changes consistent with overdiagnosis: rising incidence, minimal change in mortality, and lower case fatality. Better technology allows us to diagnose more emboli, but to minimize harms of overdiagnosis we must learn which ones matter.

Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis*.

Objectives:Trends in severe sepsis mortality derived from administrative data may be biased by changing International Classification of Diseases, 9th Revision, Clinical Modification, coding practices. We sought to determine temporal trends in severe sepsis mortality using clinical trial data that does not rely on International Classification of Diseases, 9th Revision, Clinical Modifications coding and compare mortality trends in trial data with those observed from administrative data. Design:We searched MEDLINE for multicenter randomized trials that enrolled patients with severe sepsis from 1991 to 2009. We calculated standardized mortality ratios for each trial from observed 28-day mortality of usual care participants and predicted mortality from severity-of-illness scores. To compare mortality trends from clinical trials to administrative data, we identified adult severe sepsis hospitalizations in the Nationwide Inpatient Sample, 1993–2009, using two previously validated algorithms. Setting:In-patient. Patients:Patients with severe sepsis or septic shock. Interventions:None. Measurements and Main Results:Of 3,244 potentially eligible articles, we included 36 multicenter severe sepsis trials, with a total of 14,418 participants in a usual care arm. Participants with severe sepsis receiving usual care had a 28-day mortality of 33.2%. Observed mortality decreased 3.0% annually (95% CI, 0.8%–5.0%; p = 0.009), decreasing from 46.9% (standardized mortality ratio 0.94; 95% CI, 0.86–1.03) during years 1991–1995 to 29% (standardized mortality ratio 0.53; 95% CI, 0.50–0.57) during years 2006–2009 (3.0% annual change). Trends in hospital mortality among patients with severe sepsis identified from administrative data (Angus definition, 4.7% annual change; 95% CI, 4.1%–5.3%; p = 0.69 and Martin definition, 3.5% annual change; 95% CI, 3.0%–4.1%; p = 0.97) were similar to trends identified from clinical trials. Conclusion:Since 1991, patients with severe sepsis enrolled in usual care arms of multicenter randomized trials have experienced decreasing mortality. The mortality trends identified in clinical trial participants appear similar to those identified using administrative data and support the use of administrative data to monitor mortality trends in patients with severe sepsis.

Population-Based Risk for Complications After Transthoracic Needle Lung Biopsy of a Pulmonary Nodule: An Analysis of Discharge Records

BACKGROUND Because pulmonary nodules are found in up to 25% of patients undergoing computed tomography of the chest, the question of whether to perform biopsy is becoming increasingly common. Data on complications after transthoracic needle lung biopsy are limited to case series from selected institutions. OBJECTIVE To determine population-based estimates of risks for complications after transthoracic needle biopsy of a pulmonary nodule. DESIGN Cross-sectional analysis. SETTING The 2006 State Ambulatory Surgery Databases and State Inpatient Databases for California, Florida, Michigan, and New York from the Healthcare Cost and Utilization Project. PATIENTS 15 865 adults who had transthoracic needle biopsy of a pulmonary nodule. MEASUREMENTS Percentage of biopsies complicated by hemorrhage, any pneumothorax, or pneumothorax requiring a chest tube, and adjusted odds ratios for these complications associated with various biopsy characteristics, calculated by using multivariate, population-averaged generalized estimating equations. RESULTS Although hemorrhage was rare, complicating 1.0% (95% CI, 0.9% to 1.2%) of biopsies, 17.8% (CI, 11.8% to 23.8%) of patients with hemorrhage required a blood transfusion. In contrast, the risk for any pneumothorax was 15.0% (CI, 14.0% to 16.0%), and 6.6% (CI, 6.0% to 7.2%) of all biopsies resulted in pneumothorax requiring a chest tube. Compared with patients without complications, those who experienced hemorrhage or pneumothorax requiring a chest tube had longer lengths of stay (P < 0.001) and were more likely to develop respiratory failure requiring mechanical ventilation (P = 0.020). Patients aged 60 to 69 years (as opposed to younger or older patients), smokers, and those with chronic obstructive pulmonary disease had higher risk for complications. LIMITATIONS Estimated risks may be inaccurate if coding of complications is incomplete. The analyzed databases contain little clinical detail (such as information on nodule characteristics or biopsy pathology) and cannot indicate whether performing the biopsy produced useful information. CONCLUSION Whereas hemorrhage is an infrequent complication of transthoracic needle lung biopsy, pneumothorax is common and often necessitates chest tube placement. These population-based data should help patients and physicians make more informed choices about whether to perform biopsy of a pulmonary nodule. PRIMARY FUNDING SOURCE Department of Veterans Affairs and National Cancer Institute.

When a test is too good: how CT pulmonary angiograms find pulmonary emboli that do not need to be found

#### Summary box For decades clinicians have been taught that pulmonary embolism—defined by the National Institutes of Health as a “sudden blockage in a lung artery”1—always matters and to be vigilant because a missed embolism can be fatal.2 When a patient presents with shortness of breath, pleuritic chest pain, tachycardia, or signs of right heart strain, clinicians are trained to think “pulmonary embolism.” Because these symptoms and signs are neither sensitive nor specific, scoring systems (such as the Wells criteria) have been developed to help clinicians decide which patients to scan,3 although …

Linezolid vs Glycopeptide Antibiotics for the Treatment of Suspected Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Meta-analysis of Randomized Controlled Trials

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of nosocomial pneumonia. Societal guidelines suggest linezolid may be the preferred treatment of MRSA nosocomial pneumonia. We investigated the efficacy of linezolid compared with glycopeptide antibiotics (vancomycin or teicoplanin) for nosocomial pneumonia. METHODS This was a systematic review and meta-analysis of English language, randomized, controlled trials comparing linezolid to glycopeptide antibiotics for suspected MRSA pneumonia in subjects > 12 years of age. A highly sensitive search of PubMed MEDLINE and Cochrane Central Register of Controlled Trials databases identified relevant studies. RESULTS Eight trials encompassing 1,641 subjects met entry criteria. Linezolid was not superior to glycopeptide antibiotics for end points of clinical success (relative risk [RR] linezolid vs glycopeptide, 1.04; 95% CI, 0.97-1.11; P = .28), microbiologic success (RR, 1.13; 95% CI, 0.97-1.31; P = .12), or mortality (RR, 0.91; 95% CI, 0.69-1.18; P = .47). In addition, clinical success in the subgroup of subjects with MRSA-positive respiratory tract culture (RR, 1.23; 95% CI, 0.97-1.57; P = .09) was not significantly different from those without MRSA (RR, 0.95; 95% CI, 0.83-1.09; P = .48), P for interaction, 0.07. The risk for adverse events was not different between the two antibiotic classes (RR, 0.96; 95% CI, 0.86-1.07; P = .48). CONCLUSION Randomized controlled trials do not support superiority of linezolid over glycopeptide antibiotics for the treatment of nosocomial pneumonia. We recommend that decisions between linezolid or glycopeptide antibiotics for empirical or MRSA-directed therapy of nosocomial pneumonia depend on local availability, antibiotic resistance patterns, preferred routes of delivery, and cost, rather than presumed differences in efficacy.

What Do You Mean, a Spot?: A Qualitative Analysis of Patients’ Reactions to Discussions With Their Physicians About Pulmonary Nodules

BACKGROUND More than 150,000 Americans each year are found to have a pulmonary nodule. Even more will be affected following the publication of the National Lung Screening Trial. Patient-doctor communication about pulmonary nodules can be challenging. Although most nodules are benign, it may take 2 to 3 years to rule out cancer. We sought to characterize patients’ perceptions of communication with their providers about pulmonary nodules. METHODS We conducted four focus groups at two sites with 22 adults with an indeterminate pulmonary nodule. Transcripts were analyzed using principles of grounded theory. RESULTS Patients described conversations with 53 different providers about the pulmonary nodule. Almost all patients immediately assumed that they had cancer when first told about the nodule. Some whose providers did not discuss the actual cancer risk or explain the evaluation plan experienced confusion and distress that sometimes lasted for months. Patients were frustrated when their providers did not address their concerns about cancer or potential adverse effects of surveillance (eg, prolonged uncertainty, radiation exposure), which in some cases led to poor adherence to evaluation plans. Patients found it helpful when physicians used lay terms, showed the CT image, and quantified cancer risk. By contrast, patients resented medical jargon and dismissive language. CONCLUSIONS Patients commonly assume that a pulmonary nodule means cancer. What providers tell (or do not tell) patients about their cancer risk and the evaluation plan can strongly influence patients’ perceptions of the nodule and related distress. We describe simple communication strategies that may help patients to come to terms with an indeterminate pulmonary nodule.

Components Necessary for High-Quality Lung Cancer Screening: American College of Chest Physicians and American Thoracic Society Policy Statement

Lung cancer screening with a low-dose chest CT scan can result in more benefit than harm when performed in settings committed to developing and maintaining high-quality programs. This project aimed to identify the components of screening that should be a part of all lung cancer screening programs. To do so, committees with expertise in lung cancer screening were assembled by the Thoracic Oncology Network of the American College of Chest Physicians (CHEST) and the Thoracic Oncology Assembly of the American Thoracic Society (ATS). Lung cancer program components were derived from evidence-based reviews of lung cancer screening and supplemented by expert opinion. This statement was developed and modified based on iterative feedback of the committees. Nine essential components of a lung cancer screening program were identified. Within these components 21 Policy Statements were developed and translated into criteria that could be used to assess the qualification of a program as a screening facility. Two additional Policy Statements related to the need for multisociety governance of lung cancer screening were developed. High-quality lung cancer screening programs can be developed within the presented framework of nine essential program components outlined by our committees. The statement was developed, reviewed, and formally approved by the leadership of CHEST and the ATS. It was subsequently endorsed by the American Association of Throacic Surgery, American Cancer Society, and the American Society of Preventive Oncology.

Use of Noninvasive Ventilation in Patients with Acute Respiratory Failure, 2000–2009: A Population-Based Study

RATIONALE Although evidence supporting use of noninvasive ventilation (NIV) during acute exacerbations of chronic obstructive pulmonary disease (COPD) is strong, evidence varies widely for other causes of acute respiratory failure. OBJECTIVES To compare utilization trends and outcomes associated with NIV in patients with and without COPD. METHODS We identified 11,659,668 cases of acute respiratory failure from the Nationwide Inpatient Sample during years 2000 to 2009 and compared NIV utilization trends and failure rates for cases with or without a diagnosis of COPD. MEASUREMENTS AND MAIN RESULTS The proportion of patients with COPD who received NIV increased from 3.5% in 2000 to 12.3% in 2009 (250% increase), and the proportion of patients without COPD who received NIV increased from 1.2% in 2000 to 6.0% in 2009 (400% increase). The rate of increase in the use of NIV was significantly greater for patients without COPD (18.1% annual change) than for patients with COPD (14.3% annual change; P = 0.02). Patients without COPD were more likely to have failure of NIV requiring endotracheal intubation (adjusted odds ratio, 1.19; 95% confidence interval, 1.15-1.22; P < 0.0001). Patients in whom NIV failed had higher hospital mortality than patients receiving mechanical ventilation without a preceding trial of NIV (adjusted odds ratio, 1.14; 95% confidence interval, 1.11-1.17; P < 0.0001). CONCLUSION The use of NIV during acute respiratory failure has increased at a similar rate for all diagnoses, regardless of supporting evidence. However, NIV is more likely to fail in patients without COPD, and NIV failure is associated with increased mortality.

An official American Thoracic Society/American College of Chest Physicians policy statement: implementation of low-dose computed tomography lung cancer screening programs in clinical practice.

RATIONALE Annual low-radiation-dose computed tomography (LDCT) screening for lung cancer has been shown to reduce lung cancer mortality among high-risk individuals and is now recommended by multiple organizations. However, LDCT screening is complex, and implementation requires careful planning to ensure benefits outweigh harms. Little guidance has been provided for sites wishing to develop and implement lung cancer screening programs. OBJECTIVES To promote successful implementation of comprehensive LDCT screening programs that are safe, effective, and sustainable. METHODS The American Thoracic Society (ATS) and American College of Chest Physicians (ACCP) convened a committee with expertise in lung cancer screening, pulmonary nodule evaluation, and implementation science. The committee reviewed the evidence from systematic reviews, clinical practice guidelines, surveys, and the experience of early-adopting LDCT screening programs and summarized potential strategies to implement LDCT screening programs successfully. MEASUREMENTS AND MAIN RESULTS We address steps that sites should consider during the main three phases of developing an LDCT screening program: planning, implementation, and maintenance. We present multiple strategies to implement the nine core elements of comprehensive lung cancer screening programs enumerated in a recent ACCP/ATS statement, which will allow sites to select the strategy that best fits with their local context and workflow patterns. Although we do not comment on cost-effectiveness of LDCT screening, we outline the necessary costs associated with starting and sustaining a high-quality LDCT screening program. CONCLUSIONS Following the strategies delineated in this policy statement may help sites to develop comprehensive LDCT screening programs that are safe and effective.