Paul S. Frame

Screening adults for type 2 diabetes: A review of the evidence for the U.S. Preventive Services Task Force

The prevalence of type 2 diabetes mellitus (diabetes) in the United States is growing (1, 2); the burden of suffering caused by its complications is heavy (3) and may also be growing. These complications include increased risk for cardiovascular disease (CVD) (4), end-stage renal disease (ESRD) (5, 6), blindness (7), and amputation of the lower extremities (8, 9). The magnitude of the risk for these complications varies among persons with a new clinical diagnosis of diabetes. After 10 years, more than 20% of such persons will have had a major cardiovascular event (for example, myocardial infarction [MI], stroke, heart failure, or sudden death), fewer than 5% will have developed blindness, and fewer than 2% will have developed ESRD or had lower-extremity amputation (10). Three general approaches to reducing the complications of diabetes are 1) preventing the occurrence of diabetes in the first place, 2) improving care for persons who have already received a diagnosis, and 3) screening asymptomatic persons for diabetes (11). By asymptomatic, we mean persons without both the direct symptoms of hyperglycemia (for example, polyuria) and the symptoms of associated conditions (for example, infections or angina pectoris). We distinguish between detection of diabetes due to the presence of these symptoms and detection of diabetes by screening, either systematic screening or the haphazard screening that occurs with frequent use of multichannel chemistry profiles. Our review focuses on the evidence for the effectiveness of systematic screening for diabetes as opposed to no screening. Interest in screening has been prompted by research showing that approximately one third of persons who meet criteria for diabetes have not received a diabetes diagnosis (12). In 1996, the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for diabetes (13). Since that USPSTF review, new evidence concerning the effectiveness of various treatments to prevent complications has fueled continued controversy about the effectiveness of screening (14-22). To assist the USPSTF in updating its recommendation, we performed a systematic review of the evidence concerning screening adults for diabetes. Methods To guide our literature search, we used USPSTF methods to develop an analytic framework with linkages that represent five key questions in a logical chain between screening and health outcomes (23). We developed eligibility criteria for admissible evidence for each key question, focusing on screening strategies that are feasible in a primary care environment and on high-quality evidence about health outcomes (as contrasted with intermediate outcomes) of treatment for newly diagnosed diabetes. We examined the critical literature from the 1996 USPSTF review and searched MEDLINE and the Cochrane Library for reviews and relevant studies published in English between 1 January 1994 and 30 July 2002. We also examined key articles published before 1994 and articles found by examining the reference lists of pertinent reviews or suggested by experts. The first author and at least one coauthor or trained assistant reviewed abstracts and articles to find those that met eligibility criteria (Appendix Table 1). For included studies, two reviewers abstracted relevant information using standardized abstraction forms and graded the quality of the study according to USPSTF criteria (23). Important articles on which a recommendation could rest were examined and discussed by all authors. We distributed a draft systematic evidence review for external peer review, soliciting comments from experts, relevant professional organizations, and federal agencies, and made revisions based on feedback. A more complete account of the methods used in this review can be found in the Appendix. The complete systematic evidence review is available on the Agency for Healthcare Research and Quality Web site (www.ahrq.gov) (24). This evidence report was funded through a contract to the Research Triangle InstituteUniversity of North Carolina Evidence-based Practice Center from the Agency for Healthcare Research and Quality. Staff of the funding agency and members of the USPSTF contributed to the study design, reviewed draft and final manuscripts, and made editing suggestions. Results For the USPSTF to conclude that screening reduces diabetic complications, the evidence must demonstrate that feasible screening tests can detect diabetes during a preclinical phase and that the knowledge of the diagnosis of diabetes in this phase will lead to earlier treatment that will reduce complications more than would treatment begun after clinical detection. Furthermore, the magnitude of this additional benefit (that is, the reduction in complications from initiation of treatment in the preclinical phase minus the reduction in complications from starting treatment after clinical diagnosis) must be great enough to outweigh the harms and effort of screening. Does Diabetes Have an Asymptomatic Preclinical Phase, and How Long Is It? The natural history of diabetes includes an asymptomatic preclinical phase. Many people who meet criteria for diabetes have not received a diabetes diagnosis. In the third National Health and Nutrition Examination Study (NHANES III), conducted between 1988 and 1994, the prevalence of diagnosed diabetes among persons 20 years of age and older was 5.1%; the prevalence of previously undiagnosed diabetes was 2.7% (12). Rates of diagnosed diabetes for non-Hispanic black and Mexican-American persons were 1.6 and 1.9 times the rate for non-Hispanic white persons, and the rates of undiagnosed diabetes were similarly higher. The length of this asymptomatic period is less clear. No study has compared a screened with a comparable unscreened sample to determine the difference in the time at which diabetes is diagnosed. One group used an indirect approach to calculate this interval. After making assumptions about the rate of development of diabetic retinopathy early in diabetes, Harris and colleagues (25, 26) estimated that the preclinical period lasted between 10 and 12 years. According to this calculation, screening a previously unscreened population would detect diabetes an average of 5 to 6 years before clinical diagnosis. Even if this estimate is accurate, however, it represents a mean value. Some people will have a longer and some a shorter asymptomatic period. The true mean length of this period and the distribution of its length are unknown. How Accurate Are the Screening Tests? Determining the accuracy of screening tests for diabetes is complicated by uncertainty about the most appropriate reference standard. Two standards of diagnosis are in general use: one based on the 2-hour postload plasma glucose test and the other based on the fasting plasma glucose (FPG) test (27-29). The standard cut-point for the 2-hour postload plasma glucose test is 11.1 mmol/L (200 mg/dL); the FPG cut-point is 7.0 mmol/L (126 mg/dL). Both tests require a second confirmation. Hemoglobin A1c, using various cut-points, is a third test that has been proposed as a standard reference for diagnosing diabetes (30-32). It is not clear which of these tests and cut-points most closely predict diabetic complications (33). The cut-point for the 2-hour postload plasma glucose test was based on a threshold that predicted retinopathy prevalence in several studies (27, 28). The FPG cut-point was chosen to correspond to that for the 2-hour postload plasma glucose test (27, 28). All three tests (2-hour postload plasma glucose, FPG, and hemoglobin A1c) are associated with future cardiovascular events in a linear fashion both above and below the present diabetes cut-points, with no obvious threshold (34-39). However, experts have set the point at which hyperglycemia is termed diabetes without considering CVD prediction. When a 2-hour postload glucose level of at least 11.1 mmol/L ( 200 mg/dL) is used as the reference standard, the specificity of an FPG level with a cut-point of 7.0 mmol/L (126 mg/dL) is greater than 95%; the sensitivity is about 50% and may be lower for persons older than 65 years of age (40). Among a general, previously nondiabetic sample of persons 40 to 74 years of age, a person with an FPG level of 7.8 mmol/L or greater ( 140 mg/dL) has a 91% probability of having a 2-hour postload plasma glucose level at least 11.1 mmol/L ( 200 mg/dL). For an FPG level between 7.0 mmol/L (126 mg/dL) and 7.8 mmol/L (140 mg/dL), the probability is 47% (41). Hemoglobin A1c level is more closely related to FPG than to 2-hour postload plasma glucose level (42), but it is not sensitive to low levels of hyperglycemia (30). Reliability is higher for FPG than for hemoglobin A1c or 2-hour postload plasma glucose level (43-45). Although the reliability of the hemoglobin A1c assay has been a concern, it is now not as grave a problem (43). In clinical practice, requiring a screening test to be fasting (as with the FPG) or postload (as with the 2-hour plasma glucose test) presents logistical problems. In a recent study in primary care settings, random capillary blood glucose with a cut-point of 6.7 mmol/L (120 mg/dL) had a sensitivity of 75% and a specificity of 88% for detecting persons who have positive results on FPG assay or on 2-hour postload plasma glucose assay (46). Does Earlier Knowledge of Diabetes after Screening Lead to Better Treatment and Improved Health Outcomes? We examine here the extent to which earlier application of available treatments for diabetes would improve health outcomes. Tight Glycemic Control Five randomized, controlled trials (RCTs) have compared health outcomes in groups that differ with respect to glycemic control (10, 47-57) (Table 1). Four of these studies (48-56), although generally well conducted, were small and lacked power to detect clinically important differences between groups. The longest and largest study was the United Kingdom Pr

Screening for Abdominal Aortic Aneurysm in Men Ages 60 to 80 Years: A Cost-Effectiveness Analysis

Rupture of abdominal aortic aneurysms causes 1.2% of male deaths and 0.6% of female deaths of persons older than 65 years in the United States [1]. Risk factors for abdominal aortic aneurysm (AAA) include increasing age, male sex, tobacco use, family history, and, probably, hypertension [2]. If emergent surgery is not possible, a rupture usually causes rapid death. Only 21% to 66% of patients with a ruptured aneurysm survive to surgery [3], and death following emergency surgery is about 50% [4]. No prospective or retrospective controlled trials of screening for AAA that include outcome data have been reported. It would be difficult to do a prospective, randomized trial including outcome measures because of the difficulty of identifying all deaths caused by AAA [5]. Many patients die unexpectedly of a ruptured aneurysm outside the hospital, and the cause of death is either not known or attributed to other causes. Considerable data are available from several sources about the natural history of AAA, the cost, sensitivity and specificity of screening tests, and the effectiveness and costs of surgical treatment. The quality of this data ranges from excellent to speculative. Several authorities have made recommendations regarding screening for abdominal aortic aneurysms. The current recommendation of the Canadian Task Force on the Periodic Health Examination [6] states: There is poor evidence to support the inclusion or exclusion of screening by physical examination or ultrasound for abdominal aortic aneurysm in the periodic health examination of asymptomatic individuals (C recommendation based on grade II-2 and III-3 evidence). The U.S. Preventive Services Task Force did not consider screening for AAA in its initial report [7] but has recently endorsed the recommendation of the Canadian Task Force. Oboler and LaForce [8] recommend that abdominal examination to detect the presence of an abdominal aortic aneurysm be done yearly in all men older than 60 years. Bengtsson and colleagues [9] recommend screening men at ages 60, 67, and 74 years by abdominal ultrasonography. We will try to resolve the uncertainty and controversy caused by the intuitive appeal of screening for AAA contrasted with the lack of direct experimental evidence of benefit from screening. We have created a computer model of screening for AAA by abdominal ultrasound or abdominal palpation with ultrasound confirmation of positive results. The model allows us to use the scattered data from many sources to create a range of predictions of the potential benefit of screening. Parameters Relevant to Screening Most studies of AAA have been done in the high-risk population of men ages 60 to 80 years. Estimates of prevalence in this population range from 2% to 7.8% [10, 11]. Groups with additional risk factors including smoking, hypertension, or atherosclerotic vascular disease have a higher prevalence [2]. The prevalence of AAA is much less in younger adults. The male-to-female ratio for death from AAA is 11:1 between ages 60 to 64 years and narrows to 3:1 between ages 85 to 90 years [12]. Few aneurysms less than 4 cm in diameter will rupture [13, 14]. The rate of rupture of untreated aneurysms larger than 4 cm is directly related to the size of the aneurysm. The rate of AAA rupture as a continuous function of size, however, is not known precisely [15]. Therefore it is difficult to compare the benefits from screening using different aneurysm sizes at which surgery would be offered. Overall, 3% to 6% of aneurysms greater than 4 cm in diameter will rupture annually [14, 16]. Without surgical intervention, rupture of an aortic aneurysm is invariably fatal. Three percent to 5% of initially small (< 4 cm) aneurysms will progress to a potentially operable size each year [9, 17]. No direct data exist on the annual incidence of new aneurysms in a previously screened population; however, an estimate of 0.1% has been made [9]. Screening Tests Two tests, ultrasonography and palpation of the abdomen by physical examination, have been advocated as screening tests for AAA. Other tests that can detect aneurysms, including plain radiographs of the abdomen, computed tomographic scanning, and magnetic resonance imaging, are either not sensitive enough or are too expensive to warrant serious consideration. The accuracy of physical examination in detecting AAA is not completely known. Larger aneurysms are easier to detect than small ones, and it is easier to detect aneurysms in thin people. Estimates of the sensitivity of physical examination in detecting AAA, using surgical measurement or abdominal ultrasound as the gold standard, range from 22% to 96% [18, 19]. Higher sensitivities are obtained in studies of surgical candidates for resection, a group with a high prevalence of large aneurysms. Collin and associates [20] reported a sensitivity rate of 34.8%, a specificity rate of 97%, and a positive predictive value of 36% in a community-based population with a 5.4% prevalence of AAA. Lederle and colleagues [21] observed a sensitivity rate of 50% and a positive predictive value of 35% in a high-risk group with a prevalence of AAA of 9% screened in an internal medicine clinic. Four of five aneurysms larger than 5 cm in diameter in this series were detected by palpation. In contrast, Allen and coworkers [18] reported a 22% sensitivity rate and a 94% specificity rate with a positive predictive value of 17% in a sample of a population with a 5% prevalence of aneurysm. No large-scale, community-based studies of screening for AAA by physical examination have been reported. Ultrasonography is an extremely sensitive and specific test for AAA of all sizes, at least in cases in which the diagnosis and size of the aneurysm can be confirmed at surgery. Reported sensitivity rates range from 82% to 99%, with sensitivity approaching 100% in some series of patients with a pulsatile mass [3, 6]. Based on Medicare reimbursement rates, abdominal ultrasonography costs about

Preventive dentistry: practitioners’ recommendations for low-risk patients compared with scientific evidence and practice guidelines

150 in the United States. It should be possible to do screening ultrasound scans for much lessperhaps as little as

Implementing Asthma Guidelines Using Practice Facilitation and Local Learning Collaboratives: A Randomized Controlled Trial

50. Data from other countries [9] have reported ultrasound costs as low as

Determinants of cancer screening frequency: the example of screening for cervical cancer.

35 in 1989. Effectiveness of Treatment Surgical resection and repair with an artificial graft is an effective treatment for AAA. If the patient survives the immediate postoperative period, long-term survival is comparable to that in persons who never had an AAA. The elective surgical mortality rate is about 5%. The mortality rate during emergency surgery for rupture is much higher, ranging from 21% to 76% [22, 23]. There is considerable debate about whether patients with aneurysms measuring between 4 and 5 cm in diameter should be observed or offered surgery [2, 13, 22]. Several studies are in progress to resolve this issue [2]; however, results will not be available for several years. A recent decision analysis [15] concluded that in the majority of scenarios. early surgery is preferred to watchful waiting for patients with AAAs less than 5 cm in diameter. Reported prevalence data use 4 cm to divide small and large aneurysms. Prevalence data using 5 cm as the dividing line between large and small aneurysms are not available. For this reason we have used 4 cm as the cutoff point above which surgery might be offered. The analysis recognizes that not all patients with an aneurysm larger than 4 cm will be offered or elect to have surgery. Changing the proportion of patients undergoing surgery allows consideration of only operating on larger aneurysms in the analysis (Table 1). Table 1. Variables in the Screening Model for Abdominal Aortic Aneurism Methods A systematic review of the literature was done as part of work carried out for the Canadian Task Force on the Periodic Health Examination and the United States Preventive Services Task Force. The resulting background papers were reviewed for accuracy and completeness by outside experts. Data relevant to screening for AAA were obtained from this review (Table 1). A range of possible values is shown for most variables as well as a value considered most probable by the authors. Some of these data can be accepted with a high degree of confidence whereas others are speculative. The Simulation Model We used a computer spreadsheet program (Quattro Pro 4.0; Borland International, Inc.; Scotts Valley, California) to simulate possible AAA screening programs for a cohort of 10 000 men ages 60 to 79 years at the initiation of screening and followed for 20 years. The initial distribution of ages in the cohort was presumed to be that of the U.S. male population in this age range: 60 to 64 years, 35%; 65 to 69 years, 29%; 70 to 74 years, 22%; and 75 to 79 years, 14%. The cohort is presumed to be unscreened until the first year of the simulation. The model simulates several processes affecting this cohort simultaneously over time: onset and growth of AAAs; clinical surfacing of AAAs in the absence of screening; rupture and death from AAAs; aging and death from causes other than AAA rupture or surgical complication; case finding by screening; and repair by elective or emergency surgery. Members of the cohort are considered to be in one of seven states at any given time: 1) alive without AAA; 2) having an AAA less than 4 cm in diameter that has not been discovered; 3) having an AAA greater than 4 cm in diameter that has not been discovered; 4) having an AAA less than 4 cm that has been discovered; 5) having an AAA greater than 4 cm, previously discovered when less than 4 cm and not re-examined since; 6) having an AAA greater than 4 cm, known to the medical system; 7) dead. Because we used deterministic calculations in a simplified model, these processes were represented as sequential events occurring each year in the cohort. The status of men in the cohort is represented as transitions among the seven states as the result of the events occurring. The sequence in each year is presumed as follows: Day 1. If

Use of Colchicine to Treat Severe Constipation in Developmentally Disabled Patients

INTRODUCTION The purpose of this article is to compare published evidence supporting procedures to prevent dental caries and periodontal disease, in low-risk patients, with the actual preventive recommendations of practicing dentists. METHODS Methods included (1) a survey questionnaire of general dentists practicing in western New York State concerning the preventive procedures they would recommend and at what intervals for low-risk children, young adults, and older adults; and (2) review of the published, English-language literature for evidence supporting preventive dental interventions. RESULTS The majority of dentists surveyed recommended semiannual visits for visual examination and probing to detect caries (73% to 79%), and scaling and polishing to prevent periodontal disease (83% to 86%) for low-risk patients of all ages. Bite-wing radiographs were recommended for all age groups at annual or semiannual intervals. In-office fluoride applications were recommended for low-risk children at intervals of 6 to 12 months by 73% of dentists but were recommended for low-risk older persons by only 22% of dentists. Application of sealants to prevent pit and fissure caries was recommended for low-risk children by 22% of dentists. Literature review found no studies comparing different frequencies of dental examinations and bite-wing radiographs to determine the optimal screening interval in low-risk patients. Two studies of the effect of scaling and polishing on the prevention of periodontal disease found no benefit from more frequent than annual treatments. Although fluoride is clearly a major reason for the decline in the prevalence of dental caries, there are no studies of the incremental benefit of in-office fluoride treatments for low-risk patients exposed to fluoridated water and using fluoridated toothpaste. CONCLUSIONS Comparative studies using outcome end points are needed to determine the optimal frequency of dental examinations and bite-wing radiographs for the early detection of caries, and of scaling and polishing to prevent periodontal disease in low-risk persons. There is no scientific evidence that dental examinations, including scaling and polishing, at 6 month intervals, as recommended by the dentists surveyed in this study, is superior to annual or less frequent examinations for low-risk populations. There is also no evidence that in-office fluoride applications offer incremental benefit over less costly methods of delivering fluoride for low-risk populations.

Can computerized reminder systems have an impact on preventive services in practice

PURPOSE Guideline implementation in primary care has proven difficult. Although external assistance through performance feedback, academic detailing, practice facilitation (PF), and learning collaboratives seems to help, the best combination of interventions has not been determined. METHODS In a cluster randomized trial, we compared the independent and combined effectiveness of PF and local learning collaboratives (LLCs), combined with performance feedback and academic detailing, with performance feedback and academic detailing alone on implementation of the National Heart, Lung and Blood Institute’s Asthma Guidelines. The study was conducted in 3 primary care practice-based research networks. Medical records of patients with asthma seen during pre- and postintervention periods were abstracted to determine adherence to 6 guideline recommendations. McNemar’s test and multivariate modeling were used to evaluate the impact of the interventions. RESULTS Across 43 practices, 1,016 patients met inclusion criteria. Overall, adherence to all 6 recommendations increased (P ≤.002). Examination of improvement by study arm in unadjusted analyses showed that practices in the control arm significantly improved adherence to 2 of 6 recommendations, whereas practices in the PF arm improved in 3, practices in the LLCs improved in 4, and practices in the PF + LLC arm improved in 5 of 6 recommendations. In multivariate modeling, PF practices significantly improved assessment of asthma severity (odds ratio [OR] = 2.5, 95% CI, 1.7–3.8) and assessment of asthma level of control (OR = 2.3, 95% CI, 1.5–3.5) compared with control practices. Practices assigned to LLCs did not improve significantly more than control practices for any recommendation. CONCLUSIONS Addition of PF to performance feedback and academic detailing was helpful to practices attempting to improve adherence to asthma guidelines.

Surgery for low back pain

Background: Cancer screening frequency should be based on the rate of progression of the disease and the sensitivity of the screening test. A common misconception is that a persons risk of getting the disease determines how often they should be screened. Methods: We describe algebraically the theoretical interaction of disease progression rate and screening test sensitivity determining the portion of invasive cancers prevented by screening. After discussing the assumptions and limitations of the model, we apply this model to the example of screening for cervical cancer. Actual data from large screening programs assembled by the International Agency for Research on Cancer (IARC) are used to test the assumptions of the model. Results: A simple formula can express the relation between disease progression rate, sensitivity of the screening test, screening frequency, and screening error. Disease prevalence does not figure in this equation. The IARC data suggest that, at least for cervical cancer, as screening frequency increases, incremental sensitivity of the test decreases or remaining undetected cases progress more rapidly so that anticipated benefits from more frequent screening are not realized. Conclusions: Rate of disease progression and sensitivity of the screening test are the proper determinants of cancer screening frequency. Because these factors can vary depending on screening frequency, however, the optimal screening interval for a particular cancer must be determined by clinical trials.

Computerized health maintenance tracking systems: a clinician's guide to necessary and optional features. A report from the American Cancer Society Advisory Group on Preventive Health Care Reminder Systems.

Background: Patients with severe developmental disabilities often have concurrent decreased neuromuscular tone of the gastrointestinal tract, which can lead to a weak gag reflex, esophageal reflux, aspiration, and severe intractable constipation. High doses of multiple laxatives are frequently needed to maintain bowel motility in these patients. Colchicine, a natural alkaloid that is primarily used for the treatment of acute attacks of gout, causes an increase in gastrointestinal motility by neurogenic stimulation. The purpose of this study was to determine whether daily colchicine administration can improve bowel function and reduce laxative use in profoundly disabled patients with severe, intractable constipation who currently require large doses of multiple laxatives. Methods: Twelve developmentally disabled patients who required three or more different laxatives to manage their chronic constipation were selected to participate in a double-blind, crossover study. Eleven patients who completed the study received placebo treatment for 8 weeks and colchicine treatment for 8 weeks. The total number of bowel movements and the total number of laxatives used during each of the two 8-week periods were compared. Results: Eight of 11 patients experienced an improved bowel pattern while on colchicine compared with placebo, as defined by an increase in total number of bowel movements or a decrease in total number of rectal laxatives used. No clinically important complications were related to use of colchicine. Conclusions: Colchicine appears to be a valuable adjunct in the management of severe intractable constipation. Larger, long-term studies are needed to confirm these preliminary results.

How primary health care providers can integrate cancer prevention into practice

This report reviews computerized reminder systems for tracking health maintenance in clinical practice and discusses the features of a useful, cost-effective system. Systems presently available are predominantly designed for large groups. The primary product of these systems is a health maintenance status report for the provider that is generated at each patient visit. Systems for smaller groups that will generate reminders for providers and patients at specified appropriate intervals and will easily send reminders to patients who do not have appointments or are inactive are not available. Necessary features of such “ideal” computerized tracking systems include: 1) Demographic data must be obtainable from the practice’s billing system and not require separate data entry. 2) Data entry must be quick, preferably single-screen. 3) Multiple-entry options must be available for each procedure. 4) The system must generate reminders regardless of whether a patient has an appointment. 5) Providers must be able to specify or cancel patient reminders. 6) A status report must be created for the chart at specified intervals. 7) The frequency and description of indicated procedures must be modifiable without programmer assistance.