Linda Humphrey

Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis.

BACKGROUNDPeriodontal disease is common among adults in the US and is a potential source of chronic inflammation. Recent data have suggested an important role for chronic inflammation in the development of coronary heart disease (CHD).OBJECTIVETo aid the United States Preventive Services Task Force (USPSTF) in evaluating whether periodontal disease is an independent novel risk factor for incident CHD.METHODSStudies were identified by searching Medline (1966 through March 2008) and reviewing prior systematic reviews, reference lists, and consulting experts. Prospective cohort studies that assessed periodontal disease, Framingham risk factors, and coronary heart disease incidence in the general adult population without known CHD were reviewed and quality rated using criteria developed by the USPSTF. Meta-analysis of good and fair quality studies was conducted to determine summary estimates of the risk of CHD events associated with various categories of periodontal disease.RESULTSWe identified seven articles of good or fair quality from seven cohorts. Several studies found periodontal disease to be independently associated with increased risk of CHD. Summary relative risk estimates for different categories of periodontal disease (including periodontitis, tooth loss, gingivitis, and bone loss) ranged from 1.24 (95% CI 1.01–1.51) to 1.34 (95% CI 1.10–1.63). Risk estimates were similar in subgroup analyses by gender, outcome, study quality, and method of periodontal disease assessment.CONCLUSIONPeriodontal disease is a risk factor or marker for CHD that is independent of traditional CHD risk factors, including socioeconomic status. Further research in this important area of public health is warranted.

Screening for Lung Cancer With Low-Dose Computed Tomography: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation

BACKGROUND Lung cancer is the leading cause of cancer-related death in the United States. Because early-stage lung cancer is associated with lower mortality than late-stage disease, early detection and treatment may be beneficial. PURPOSE To update the 2004 review of screening for lung cancer for the U.S. Preventive Services Task Force, focusing on screening with low-dose computed tomography (LDCT). DATA SOURCES MEDLINE (2000 to 31 May 2013), the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth quarter of 2012), Scopus, and reference lists. STUDY SELECTION English-language randomized, controlled trials or cohort studies that evaluated LDCT screening for lung cancer. DATA EXTRACTION One reviewer extracted study data about participants, design, analysis, follow-up, and results, and a second reviewer checked extractions. Two reviewers rated study quality using established criteria. DATA SYNTHESIS Four trials reported results of LDCT screening among patients with smoking exposure. One large good-quality trial reported that screening was associated with significant reductions in lung cancer (20%) and all-cause (6.7%) mortality. Three small European trials showed no benefit of screening. Harms included radiation exposure, overdiagnosis, and a high rate of false-positive findings that typically were resolved with further imaging. Smoking cessation was not affected. Incidental findings were common. LIMITATIONS Three trials were underpowered and of insufficient duration to evaluate screening effectiveness. Overdiagnosis, an important harm of screening, is of uncertain magnitude. No studies reported results in women or minority populations. CONCLUSION Strong evidence shows that LDCT screening can reduce lung cancer and all-cause mortality. The harms associated with screening must be balanced with the benefits. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Homocysteine Level and Coronary Heart Disease Incidence: A Systematic Review and Meta-analysis

OBJECTIVE To determine whether an elevated homocysteine level is an independent risk factor for the development of coronary heart disease (CHD) to aid the US Preventive Services Task Force in its evaluation of novel risk factors for incident CHD. METHODS Studies of homocysteine and CHD were identified by searching MEDLINE (1966 through March 2006). We obtained additional articles by reviewing reference lists from prior reviews, original studies, editorials, and Web sites and by consulting experts. We included prospective cohort studies that measured homocysteine and Framingham risk factors and the incidence of CHD in the general adult population without known CHD. Each study was quality rated using criteria developed by the US Preventive Services Task Force. We conducted a meta-analysis using a random-effects model to determine summary estimates of the risk of major CHD associated with each 5-micromol/L increase in homocysteine level. The systematic review and meta-analysis were conducted between January 25, 2005, and September 17, 2007. RESULTS We identified 26 articles of good or fair quality. Most studies found elevations of 20% to 50% in CHD risk for each increase of 5 micromol/L in homocysteine level. Meta-analysis yielded a combined risk ratio for coronary events of 1.18 (95% confidence interval, 1.10-1.26) for each increase of 5 micromol/L in homocysteine level. The association between homocysteine and CHD was similar when analyzed by sex, length of follow-up, outcome, study quality, and study design. CONCLUSION Each increase of 5 micromol/L in homocysteine level increases the risk of CHD events by approximately 20%, independently of traditional CHD risk factors.

Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians.

DESCRIPTION The American College of Physicians (ACP) developed this guideline to present the evidence for the link between the use of intensive insulin therapy to achieve different glycemic targets and health outcomes in hospitalized patients with or without diabetes mellitus. METHODS Published literature on this topic was identified by using MEDLINE and the Cochrane Library. Additional articles were obtained from systematic reviews and the reference lists of pertinent studies, reviews, and editorials, as well as by consulting experts; unpublished studies on ClinicalTrials.gov were also identified. The literature search included studies published from 1950 through March 2009. Searches were limited to English-language publications. The primary outcomes of interest were short-term mortality and hypoglycemia. This guideline grades the evidence and recommendations by using the ACP clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends not using intensive insulin therapy to strictly control blood glucose in non-surgical intensive care unit (SICU)/medical intensive care unit (MICU) patients with or without diabetes mellitus (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 2: ACP recommends not using intensive insulin therapy to normalize blood glucose in SICU/MICU patients with or without diabetes mellitus (Grade: strong recommendation, high-quality evidence). RECOMMENDATION 3: ACP recommends a target blood glucose level of 7.8 to 11.1 mmol/L (140 to 200 mg/dL) if insulin therapy is used in SICU/MICU patients (Grade: weak recommendation, moderate-quality evidence).

Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians

Description The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on oral pharmacologic treatment of type 2 diabetes in adults. This guideline serves as an update to the 2012 ACP guideline on the same topic. This guideline is endorsed by the American Academy of Family Physicians. Methods This guideline is based on a systematic review of randomized, controlled trials and observational studies published through December 2015 on the comparative effectiveness of oral medications for type 2 diabetes. Evaluated interventions included metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Study quality was assessed, data were extracted, and results were summarized qualitatively on the basis of the totality of evidence identified by using several databases. Evaluated outcomes included intermediate outcomes of hemoglobin A1c, weight, systolic blood pressure, and heart rate; all-cause mortality; cardiovascular and cerebrovascular morbidity and mortality; retinopathy, nephropathy, and neuropathy; and harms. This guideline grades the recommendations by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Target Audience and Patient Population The target audience for this guideline includes all clinicians, and the target patient population includes adults with type 2 diabetes. Recommendation 1 ACP recommends that clinicians prescribe metformin to patients with type 2 diabetes when pharmacologic therapy is needed to improve glycemic control. (Grade: strong recommendation; moderate-quality evidence). Recommendation 2 ACP recommends that clinicians consider adding either a sulfonylurea, a thiazolidinedione, an SGLT-2 inhibitor, or a DPP-4 inhibitor to metformin to improve glycemic control when a second oral therapy is considered. (Grade: weak recommendation; moderate-quality evidence.) ACP recommends that clinicians and patients select among medications after discussing benefits, adverse effects, and costs.

Screening for colorectal cancer: A guidance statement from the american college of physicians

DESCRIPTION Colorectal cancer is the second leading cause of cancer-related deaths for men and women in the United States. The American College of Physicians (ACP) developed this guidance statement for clinicians by assessing the current guidelines developed by other organizations on screening for colorectal cancer. When multiple guidelines are available on a topic or when existing guidelines conflict, ACP believes that it is more valuable to provide clinicians with a rigorous review of the available guidelines rather than develop a new guideline on the same topic. METHODS The authors searched the National Guideline Clearinghouse to identify guidelines developed in the United States. Four guidelines met the inclusion criteria: a joint guideline developed by the American Cancer Society, the U.S. Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology and individual guidelines developed by the Institute for Clinical Systems Improvement, the U.S. Preventive Services Task Force, and the American College of Radiology. GUIDANCE STATEMENT 1: ACP recommends that clinicians perform individualized assessment of risk for colorectal cancer in all adults. GUIDANCE STATEMENT 2: ACP recommends that clinicians screen for colorectal cancer in average-risk adults starting at the age of 50 years and in high-risk adults starting at the age of 40 years or 10 years younger than the age at which the youngest affected relative was diagnosed with colorectal cancer. GUIDANCE STATEMENT 3: ACP recommends using a stool-based test, flexible sigmoidoscopy, or optical colonoscopy as a screening test in patients who are at average risk. ACP recommends using optical colonoscopy as a screening test in patients who are at high risk. Clinicians should select the test based on the benefits and harms of the screening test, availability of the screening test, and patient preferences. GUIDANCE STATEMENT 4: ACP recommends that clinicians stop screening for colorectal cancer in adults over the age of 75 years or in adults with a life expectancy of less than 10 years.

Lung Cancer Screening with Sputum Cytologic Examination, Chest Radiography, and Computed Tomography: An Update for the U.S. Preventive Services Task Force

No major medical professional organization currently recommends screening for lung cancer. The U.S. Preventive Services Task Force (USPSTF) gave lung cancer screening a grade D recommendation in both 1985 and 1996, meaning that there were fair-quality data to recommend against screening for lung cancer (1) based largely on 3 negative trials conducted in the United States in the 1970s. Since the last Task Force review, several new studies of lung cancer screening have been reported, and greater attention has been directed toward the limitations of existing literature. This review was conducted to aid the current USPSTF in updating its lung cancer screening recommendation. Lung cancer is the leading cause of cancer-related death among men and women in the United States; in 2003, approximately 171 900 new cases and 157 200 lung cancerassociated deaths were predicted (2). Worldwide, lung cancer and lung cancerrelated deaths have been increasing in epidemic proportions (3, 4), with an estimated 1 million deaths in the year 2000 (5). Although there are other important risk factors for lung cancer (3, 6-10), cigarette smoking is the major risk factor. Approximately 87% of all lung, bronchial, and tracheal cancer is attributed to smoking (3). Consequently, the most important public health intervention that could reduce lung cancer incidence and deaths is changing smoking habits. Unfortunately, although overall prevalence rates of smoking in the United States have decreased over the past 2 decades, the prevalence of current adult smokers remains high at 24% (10, 11). In the clinical setting, smoking cessation programs, even in conjunction with drug therapy, have long-term smoking cessation rates of only 20% to 35% at 1 year among motivated volunteers in good-quality studies (12-14). In addition, in 1999, approximately 45.7 million adults (23.1%) were former smokers. Currently a high percentage of lung cancer cases occur in former smokers, since the risk for lung cancer does not decrease for many years after smoking cessation (15-17). Household exposure to secondhand smoke is substantial and is also associated with lung cancer (18). These smoking exposure rates, combined with large numbers of individuals with past or passive exposure to smoking, indicate that lung cancer will continue to be a major public health problem in the United States and worldwide. Lung cancer is fatal in more than 90% of affected persons (19). Survival is directly related to the stage of lung cancer at the time of diagnosis, ranging from 70% for stage I disease to less than 5% for stage IV disease (20, 21). Seventy-five percent of patients with lung cancer present with symptoms related to incurable advanced local or metastatic disease (19). Since lung cancer mortality is closely associated with disease stage at the time of diagnosis, it is believed (primarily on the basis of indirect evidence) (22-28) that early surgical resection is associated with better outcomes. Therefore, the current standard of practice is to resect most nonsmall-cell lung cancer without evidence of metastatic spread. For many of these reasons, screening for and treating early lung cancer is intuitively appealing. Methods This review discusses studies of chest radiography, sputum cytologic examination, and low-dose computed tomography (CT) for lung cancer screening and focuses on the outcomes of screening in populations. We reviewed the MEDLINE and Cochrane databases from their inception through January 2003 using the search terms lung neoplasms, lung cancer, and any screening. The search strategy is detailed in Appendix Table 1. To ensure complete ascertainment, we reviewed the bibliographies of reviews, editorials, book chapters, and letters discussing lung cancer screening, as well as a recent Cochrane review and analysis (29). We sought studies evaluating screening in the general population, as well as in high-risk populations, and included observational studies and clinical trials. Observational studies with control groups and controlled trials evaluating disease-specific mortality were evaluated for quality according to criteria created by the USPSTF (30) (Appendix). For the purposes of this review, high-risk persons are those who currently smoke or have ever smoked and low-risk persons are those who have never smoked. To rate each of the studies, we reviewed all original articles discussing the studys methods or findings. We also used studies of the various screening methods to estimate the screening test characteristics of chest radiography and low-dose CT. Finally, we used data from screening studies (when available), as well as clinical series, to evaluate the harms associated with screening and treatment. For completeness, all studies are described in the tables; however, only studies rated as fair or better quality are described in the text. Methodologic issues relevant to understanding screening studies include lead-time bias (when the time of diagnosis is advanced by screening but the time of death is unchanged), length bias (bias toward detecting less aggressive tumors in a periodically screened sample) (31), and volunteer bias (a type of selection bias in which volunteers are compared with nonvolunteers) (32). Overdiagnosis occurs when cancer that would never have been important during an individuals lifetime is diagnosed and treated. These biases can be eliminated only in randomized, controlled trials that include death as an outcome. Therefore, public health guidelines and this review place the most emphasis on information from randomized, controlled trials. This research was funded by the Agency for Healthcare Research and Quality. Agency staff and USPSTF members reviewed interim analyses and the final report. Before preparation of this manuscript, the full report was reviewed by 17 content experts in lung cancer screening and was revised accordingly. Data Synthesis In our searches, we identified 809 citations and abstracts; 149 full-text papers were reviewed. Of these, 1 randomized trial of chest radiography in conjunction with a multiphasic screening program (33, 34) and 5 randomized, controlled trials of chest radiography, sputum cytologic examination, or both as screening for lung cancer (35-40) were reviewed. In addition, 6 casecontrol studies (41-46), 1 nonrandomized, controlled trial (47), and 4 older cohort studies (48-52) were reviewed (Appendix Table 2). We also reviewed 6 recent cohort studies of lung cancer screening with CT (53-62). Lung Cancer Screening with Chest Radiography with or without Sputum Cytologic Examination Controlled Trials The methods and quality of the 6 randomized, controlled trials and the single nonrandomized, controlled trial of lung cancer screening (33-40, 47, 63-85) are shown in Tables 1 and 2. The Figure shows the relative risks and 95% CIs of these randomized trials. In the 1960s, the Northwest London Mass Radiography Service conducted a cluster randomized trial of chest radiography screening in approximately 55 000 men older than 40 years of age (35, 36). In this trial, 29 723 male factory workers from 75 randomly identified firms were offered chest radiography every 6 months and were compared with 25 300 controls from other factories who were offered screening at baseline and at 3 years. After 3 years, the annual mortality rate from lung cancer was 0.7 per 1000 person-years in the intervention group and 0.8 per 1000 person-years in the control group, not a statistically significant difference. Table 1. Controlled Trials of Lung Cancer Screening with Chest Radiography with or without Sputum Cytologic Examination Table 2. Methods and Quality of Controlled Trials of Lung Cancer Screening Figure. Mortality in randomized, controlled trials of lung cancer screening with chest radiography with or without sputum cytologic examination. The National Cancer Institute sponsored 3 randomized, controlled trials of lung cancer screening in male smokers in the United States in the 1970s (37-39, 63, 64, 68, 73-75, 80). The Memorial Sloan-Kettering Study (37, 63-67) and the Johns Hopkins Study (38, 68-72) were identical in design and were conducted to evaluate the incremental benefit of adding sputum cytologic examination to annual chest radiography. Of the 20 427 male smokers ( 20 pack-years of smoking) age 45 years or older who volunteered for these 2 studies, 10 234 were randomly assigned to a dual-screening group that was offered screening with chest radiography annually and sputum cytologic examination every 4 months for 5 years; 10 233 were assigned to a chest radiography group that was offered annual screening for 5 years. Each group was followed for 5 to 8 years. In the Memorial Sloan-Kettering Study, baseline screening identified 30 (6.0 per 1000) malignant tumors in the dual-screening group and 23 (4.6 per 1000) in the chest radiography group (63). After prevalence screening, 114 subsequent (incident) cases of lung cancer were identified in the dual-screening group and 121 were identified in the annual radiography group during the screening period. Thirty-three and 32 cases, respectively, were diagnosed in the 2 years following screening. When the incidence and prevalence tumors are combined, 144 cases of lung cancer were detected in each group during the study (37, 64, 67); 40% of all lung cancer detected was stage I. The mortality rate was 2.7 per 1000 person-years in both the chest radiography and dual-screening groups. In the Johns Hopkins Study, prevalence screening identified 39 malignant tumors in the dual-screening group and 40 in the chest radiography group (38, 71). After 8 years of follow-up, 194 incident cases of cancer were identified in the dual-screening group and 202 were identified in the chest radiography group. The mortality rates were 3.4 per 1000 person-years in the dual-screening group and 3.8 per 1000 person-years in the control group (not statistically significant differences) and were similar t

Appropriate Use of Screening and Diagnostic Tests to Foster High-Value, Cost-Conscious Care

Unsustainable rising health care costs in the United States have made reducing costs while maintaining high-quality health care a national priority. The overuse of some screening and diagnostic tests is an important component of unnecessary health care costs. More judicious use of such tests will improve quality and reflect responsible awareness of costs. Efforts to control expenditures should focus not only on benefits, harms, and costs but on the value of diagnostic tests-meaning an assessment of whether a test provides health benefits that are worth its costs or harms. To begin to identify ways that practicing clinicians can contribute to the delivery of high-value, cost-conscious health care, the American College of Physicians convened a workgroup of physicians to identify, using a consensus-based process, common clinical situations in which screening and diagnostic tests are used in ways that do not reflect high-value care. The intent of this exercise is to promote thoughtful discussions about these tests and other health care interventions to promote high-value, cost-conscious care.

Venous Thromboembolism Prophylaxis in Hospitalized Patients: A Clinical Practice Guideline From the American College of

DESCRIPTION The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on prophylaxis of venous thromboembolism for hospitalized nonsurgical patients (medical patients and patients with acute stroke). METHODS This guideline is based on published literature on the topic from 1950 through April 2011 that was identified by using MEDLINE, the Cochrane Library, and reference lists of pertinent randomized trials and systematic reviews to identify additional reports. Searches were limited to randomized trials and English-language publications. The primary outcome for this guideline was total mortality up to 120 days after randomization. Secondary outcomes included symptomatic deep venous thrombosis; all pulmonary embolisms; fatal pulmonary embolism; all bleeding events; major bleeding events; and, for mechanical prophylaxis, effects on skin. This guideline grades the evidence and recommendations by using the ACPs clinical practice guidelines grading system. RECOMMENDATION 1 ACP recommends assessment of the risk for thromboembolism and bleeding in medical (including stroke) patients prior to initiation of prophylaxis of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 2 ACP recommends pharmacologic prophylaxis with heparin or a related drug for venous thromboembolism in medical (including stroke) patients unless the assessed risk for bleeding outweighs the likely benefits (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 3 ACP recommends against the use of mechanical prophylaxis with graduated compression stockings for prevention of venous thromboembolism (Grade: strong recommendation, moderate-quality evidence). POLICY IMPLICATION ACP does not support the application of performance measures in medical (including stroke) patients that promotes universal venous thromboembolism prophylaxis regardless of risk.

Treatment of Anemia in Patients With Heart Disease: A Clinical Practice Guideline From the American College of Physicians

DESCRIPTION The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the treatment of anemia and iron deficiency in adult patients with heart disease. METHODS This guideline is based on published literature in the English language on anemia and iron deficiency from 1947 to July 2012 that was identified using MEDLINE and the Cochrane Library. Literature was reassessed in April 2013, and additional studies were included. Outcomes evaluated for this guideline included mortality; hospitalization; exercise tolerance; quality of life; and cardiovascular events (defined as myocardial infarction, congestive heart failure exacerbation, arrhythmia, or cardiac death) and harms, including hypertension, venous thromboembolic events, and ischemic cerebrovascular events. The target audience for this guideline includes all clinicians, and the target patient population is anemic or iron-deficient adult patients with heart disease. This guideline grades the evidence and recommendations using the ACPs clinical practice guidelines grading system. RECOMMENDATION 1 ACP recommends using a restrictive red blood cell transfusion strategy (trigger hemoglobin threshold of 7 to 8 g/dL compared with higher hemoglobin levels) in hospitalized patients with coronary heart disease. (Grade: weak recommendation; low-quality evidence) RECOMMENDATION 2 ACP recommends against the use of erythropoiesis-stimulating agents in patients with mild to moderate anemia and congestive heart failure or coronary heart disease. (Grade: strong recommendation; moderate-quality evidence).