David L. Simel

A nurse-coordinated intervention for primary care patients with non-insulin-dependent diabetes mellitus: impact on glycemic control and health-related quality of life

AbstractOBJECTIVE: To examine the impact of a nurse-coordinated intervention delivered to patients with non-insulin-dependent diabetes mellitus between office visits to primary care physicians. DESIGN: Randomized, controlled trial. SETTING: Veterans Affairs general medical clinic. PATIENTS: 275 veterans who had NIDDM and were receiving primary care from general internists. INTERVENTION: Nurse-initiated contacts were made by telephone at least monthly to provide patient education (with special emphasis on regimens and significant signs and symptoms of hyperglycemia and hypoglycemia), reinforce compliance with regimens, monitor patients’ health status, facilitate resolution of identified problems, and facilitate access to primary care. MEASUREMENTS: Glycemic control was assessed using glycosylated hemoglobin (GHb) and fasting blood sugar (FBS) levels. Health-related quality of life (HRQOL) was measured with the Medical Outcomes Study SF-36, and diabetes-related symptoms were assessed using patients’ self-reports of signs and symptoms of hyper- and hypoglycemia during the previous month. MAIN RESULTS: At one year, between-group differences favored intervention patients for FBS (174.1 mg/dL vs 193.1 mg/dL, p=0.011) and GHb (10.5% vs 11.1%, p=0.046). Statistically significant differences were not observed for either SF-36 scores (p=0.66) or diabetes-related symptoms (p=0.23). CONCLUSIONS: The intervention, designed to be a pragmatic, low-intensity adjunct to care delivered by physicians, modestly improved glycemic control but not HRQOL or diabetes-related symptoms.

Does This Patient Have a Torn Meniscus or Ligament of the Knee?: Value of the Physical Examination

ment, using the anterior drawer test, were 3.8 (95% confidence interval [CI], 0.7-22.0) for a positive examination and 0.30 (95% CI, 0.05-1.50) for a negative examination; the Lachman test, 25.0 (95% CI, 2.7-651.0) and 0.1 (95% CI, 0.0-0.4); and the composite assessment, 25.0 (95% CI, 2.1-306.0) and 0.04 (95% CI, 0.01-0.48), respectively. The LRs could not be generated for any specific examination maneuver for a posterior cruciate ligament tear, but the composite assessment had an LR of 21.0 (95% CI, 2.1-205.0) for a positive examination and 0.05 (95% CI, 0.01-0.50) for a negative examination. Determination of meniscal lesions, using McMurray test, had an LR of 1.3 (95% CI, 0.9-1.7) for a positive examination and 0.8 (95% CI, 0.6-1.1) for a negative examination; joint line tenderness, 0.9 (95% CI, 0.8-1.0) and 1.1 (95% CI, 1.0-1.3); and the composite assessment, 2.7 (95% CI, 1.4-5.1) and 0.4 (95% CI, 0.2-0.7), respectively. Conclusion The composite examination for specific meniscal or ligamentous injuries of the knee performed much better than specific maneuvers, suggesting that synthesis of a group of examination maneuvers and historical items may be required for adequate diagnosis.

Clinical evaluation for sinusitis : making the diagnosis by history and physical examination

OBJECTIVE To identify the most useful clinical examination findings for the diagnosis of acute and subacute sinusitis. DESIGN Prospective comparison of clinical findings with radiographs. SETTING General medicine clinics at a university-affiliated Veterans Affairs Medical Center. PATIENTS Two hundred forty-seven consecutive adult men with rhinorrhea (51%), facial pain (22%) , or self-suspected sinusitis (27%) (median age, 50 years; median duration of symptoms, 11.5 days). MEASUREMENTS Patients were examined by a principal investigator (86%) or by a staff general internist, internal medicine resident (postgraduate year 2 or 3), or physician assistant, all blinded to radiographic results. All examiners recorded the presence or absence of 16 historical items, 5 physical examination items, and the clinical impression for sinusitis (high, intermediate, or low probability). The criterion standard was paranasal sinus radiographs (4 views), which were interpreted by radiologists blinded to clinical findings. RESULTS Thirty-eight percent of patients meeting entrance criteria had sinusitis. Sensitivity, specificity, and likelihood ratios were measured for clinical items. Logistic regression analysis showed five independent predictors of sinusitis: maxillary toothache (odds ratio, 2.9), transillumination (odds ratio, 2.7), poor response to nasal decongestants or antihistamines (odds ratio, 2.4), colored nasal discharge reported by the patient (odds ratio, 2.2), or mucopurulence seen during examination (odds ratio, 2.9). THe overall clinical impression was more accurate than any single finding: high probability (likelihood ratio, 4.7, intermediate (likelihood ratio, 1.4), low probability (likelihood ratio, 0.4). CONCLUSIONS General internists, focusing on five clinical findings and their overall clinical impression, can effectively stratify male patients with sinus symptoms as having a high, intermediate, or low probability of sinusitis.

Noninvasive Carotid Artery Testing: A Meta-analytic Review

An estimated 500 000 people in the United States have a new or recurrent stroke each year; there are currently approximately 3 million stroke survivors, many of whom have a substantial disability [1]. Most strokes occur in the carotid distribution [2]. Among patients with carotid territory symptoms or a high degree of stenosis (70% or more on carotid angiography), endarterectomy has been shown to effectively reduce strokes [3-5]. Noninvasive tests are often used for preliminary screening before carotid endarterectomy. The value of these tests rests largely in their ability to accurately identify patients with high-grade stenosis. An earlier comparison of the various noninvasive imaging tests of the carotid arteries indicated that carotid duplex and carotid Doppler ultrasonography were superior [6]. However, new studies of older technologies and the emergence of new noninvasive tests justify a re-evaluation of published data about noninvasive testing of the carotid arteries. Our purpose was to estimate the sensitivity and specificity of noninvasive carotid artery tests using formal meta-analysis and to determine which tests are the most discriminating in the detection of carotid artery occlusion and severe disease (defined as >70% stenosis) using composite receiver operating characteristic (ROC) analysis and a summary measure of test effectiveness. Methods Noninvasive Tests Selected for Study The six noninvasive tests we selected assess carotid artery stenosis either by detecting the carotid artery, the flow within it, or both (direct tests) or by evaluating flow through collateral vessels (indirect tests). Carotid Doppler ultrasonography assesses the velocity changes in blood flow associated with stenosis in the carotid arteries using either a continuous wave, a single-gated pulsed wave, or directional color modes [7-33]. Real-time B-mode ultrasonographic imaging allows for direct visualization of the carotid artery and calculation of the widths of obstructed and unobstructed arteries and of the lesions themselves; thus, investigators can determine the percentage of stenosis [34, 35]. Duplex ultrasonography combines the direct visualization capabilities of B-mode ultrasonography and the blood-flow velocity measurements of Doppler ultrasonography [26-28, 31, 36-56]. Magnetic resonance angiography is a relatively new technique that directly assesses both carotid and intracranial arterial stenosis by building up images from many thin-layer, two-dimensional slices or from a smaller quantity of three-dimensional volumes [29-31, 55-67]. The tests that indirectly assess the carotid artery include supraorbital Doppler ultrasonography and oculoplethysmography. Supraorbital Doppler ultrasonography was the first noninvasive technology available to evaluate carotid artery stenosis; it indirectly assesses blood flow from collateral branches of the internal carotid artery through the supraorbital vessels. The test is done by placing a directional Doppler probe over a supraorbital artery and observing the flow with and without compression of neighboring arteries [32, 68-71]. Oculoplethysmography indirectly evaluates the patency of the internal carotid artery by graphically recording ocular pulses obtained from corneal cups held in place by mild suction. Concomitant ear-lobe pulses are also recorded for timing comparison [33, 51, 70, 71]. The results of these studies can be translated into estimates of carotid patency. Identification of Articles We searched the MEDLINE database for English-language articles about the diagnostic testing of extracranial carotid artery disease that were published between 1977 and 1993. The keywords used were oculoplethysmography, ultrasonography, digital subtraction angiography, cerebral angiography, and magnetic resonance imaging (as they relate to disease involving the cerebral arteries); and vertebral arteries, basilar arteries, and carotid arteries in humans. Additional articles listed in the bibliographies of standard neurology texts and references cited in accepted articles were also included among the articles considered. All articles passed through a multilevel, systematic review by teams of nurses and physicians (Figure 1). Articles were excluded if 1) results from the test used were not compared with the results of conventional carotid angiography or intra-arterial digital subtraction carotid angiography; 2) the angiographic results were not separated to allow for specific identification of occluded arteries; or 3) the reference standard test results could not be classified into a contingency table according to degree of stenosis. Through the MEDLINE, textbook reference, and bibliography searches, we initially identified 568 articles, 354 of which were initially rejected, either because the noninvasive test was not compared with carotid angiography or because carotid artery occlusion was not reported as a separate category. The remaining 214 articles were then analyzed by one of four physicians. An additional 110 of these articles were eliminated, most because the reported data were not sufficient to permit construction of contingency tables. When an article was included, data about patient demographics, study design, sites of patient enrollment, blinding of reviewers to test outcomes, and specific results were abstracted. The reliability of the first exclusion was assessed by randomly selecting 22 (10%) of the rejected articles and submitting them to another physician for a second review. Agreement about the appropriateness of the exclusions was 100%. Figure 1. Article review flow chart. The 104 articles initially included by the first physician reviewers were then examined and abstracted by second physician reviewers. Discrepancies between the two reviews were resolved by discussions. As a result of these discussions, 34 additional articles were rejected, 15 because contingency tables could not be reliably constructed from the reported data and 18 because of overlapping populations (in these cases, the most recently reported of the studies or the study with the larger population was included). One article was rejected because the diagnostic test reports were given as a single result that reflected the output of many concurrent tests. Therefore, the results of 70 studies form the basis of this review. Quality Criteria for Evaluating Study Methods Criteria used to rate the quality of the study methods were based on previously defined standards [72]. Each article was rated on the methods used by the investigators, the site of patient enrollment, the degree of blinding between interpretation of the noninvasive test and the reference standard, and the disease spectrum of the patients enrolled. In most studies, the site of patient enrollment was the radiology or surgery unit. Methods of patient enrollment were specified or implied in all 70 articles: Forty-one percent used consecutive series and 59% used convenience or retrospective samples. Blinding of the reviewers was rarely mentioned in any study; because of the sequence of enrollment, we speculated that the reviewers interpreting noninvasive tests were blinded to the results of invasive tests in 84% of the studies. The indications for the testing of patients were listed in 53% of the studies and included recent stroke or transient ischemic attack and asymptomatic carotid bruits. In a secondary analysis, we examined the results of the meta-analysis by comparing studies in which the reviewers interpreting the noninvasive tests were blinded to the angiograms with those in which they were not blinded and by comparing studies in which patients were enrolled consecutively with those in which another method of patient enrollment was used. Statistical Analysis Results from angiographic and noninvasive tests were classified into as many of the following categories as possible: carotid artery occlusion, 99% to 70% stenosis, 70% to 50% stenosis, and 50% to 0% stenosis. Sensitivity and specificity were the primary measures of test performance; carotid angiography was the reference standard. To facilitate comparisons among noninvasive tests, values for sensitivity and specificity (with CIs) were calculated by classifying all lesions above a given cut-point as positive. For the purposes of this comparison, occlusion was considered positive [6]. Articles relating to one particular test type were summarized by pooling estimates of sensitivity and specificity [73]. Confidence intervals were derived using exact methods for proportions [74]. A chi-square test for homogeneity was done on the data from each study at the 100%, 70% (or equivalent), and 50% stenosis cut-points. Sensitivity and specificity were estimated using a random-effects or a fixed-effects model according to the homogeneity of the test results [73, 75]: When the pooled estimate was heterogeneous, a random-effects model was used. Composite ROC curves were constructed; the reference standard of carotid angiography was defined as positive at 70% stenosis. This cut-point was chosen because of the entry criteria for the North American Symptomatic Carotid Endarterectomy Trial (NASCET) [3]. Noninvasive tests were then selected as positive at 50% stenosis, 70% stenosis, or carotid artery occlusion, and true-positive and false-positive rates were calculated because these distinctions provide the most information for clinicians who choose to refer patients for angiography at different thresholds. The tests for homogeneity and methods of meta-analytic combination mentioned earlier were then used to derive the pooled true-positive and false-positive rates for each test type [75, 76]. These were plotted as ROC curves, and the points were connected using a nonparametric assumption [77]. Areas under the ROC curves were derived using a trapezoidal method [77, 78]. We also calculated a new measure for diagnostic tests termed test effectiveness, which attempts to avert the forced tradeoffs between sensi

The relationship between glycemic control and health-related quality of life in patients with non-insulin-dependent diabetes mellitus.

The relationship between glycemic control and health-related quality of life was examined in patients with non-insulin-dependent diabetes mellitus (NIDDM). Within the context of a randomized controlled trial, 275 patients with NIDDM receiving primary care from a Veterans Administration general medical clinic were enrolled and monitored for 1 year. Glycemic control (glycosylated hemoglobin levels) and health-related quality of life (Medical Outcomes Study Short-Form 36-item Health Survey [SF-36]) were assessed at baseline and at 1 year. Multivariate regression modeling using baseline and change scores during a 1− year period did not find a linear or curvilinear relationship between glycosylated hemoglobin and SF-36 scores (P = .15); this was true even after controlling for five covariates identified a priori (insulin use, number of diabetic complications, duration of diabetes, education, number of hyper-, or hypoglycemic episodes during the preceding month). Health services researchers and clinicians alike need to be aware that these two important outcomes may not be directly related. This lack of association could contribute to the high noncompliance rates observed among patients prescribed complex diabetic regimens. Unless patients perceive a benefit from following such regimens, good glycemic control may continue to be an elusive therapeutic goal, especially in patients with long-standing disease.

Clinical examination for the detection of protective sensation in the feet of diabetic patients

AbstractOBJECTIVE: We compared the reproducibility and accuracy of conventional clinical examination of the diabetic foot to monofilament examination. We also sought to simplify the monofilament examination by reducing it to fewer touch points. METHODS: In a cross-sectional study at 10 centers in the United States, Canada, and Switzerland, general internists and residents performed a structured history and physical examination for neuropathy on the feet of diabetic patients. Independent examination by two observers included monofilament sensation, pinprick, vibration, position sense, and ankle reflexes. MAIN RESULTS: A total of 304 patients were examined by at least one practitioner, and 200 received duplicate examinations. Monofilament examination and ankle reflexes had the best reproducibility, with moderate agreement (κ=0.59); pinprick, position, and vibration sense had fair agreement (κ=0.28–0.36). No component of the history or physical examination, singly or in aggregate, was both sensitive and specific for identifying a patient with an abnormal monofilament examination. A simplified monofilament examination using only 4 sites per foot (total 8 sites) detected 90% of patients with an abnormal 16-site monofilament evaluation. CONCLUSIONS: Conventional clinical examination had low reproducibility and correlated poorly with monofilament examination for the identification of the at-risk patient. The Semmes-Weinstein monofilament examination, a reproduible, valid, and generalizable test of foot sensation, is recommended as the screening procedure of choice for examining diabetic feet.

Intermediate, Indeterminate, and Uninterpretable Diagnostic Test Results

Diagnostic tests do not always yield positive or negative results; sometimes the results are intermediate, indeterminate, or uninterpretable. No consensus exists for the incorporation of such results into data assessment. Conventional Bayesian analysis leads investigators to either exclude patients with non-positive, non-negative results from their studies or categorize such results into inappropriate cells of the standard four-cell decision matrix. The authors propose a standardized method for reporting results in studies dealing with diagnostic test use and discuss how researchers should expand the four-cell matrix to six cells when non- positive, non-negative results occur. They suggest that the six-cell matrix with new operational definitions of sensitivity, specificity, likelihood ratios, and test yield should be adopted rou tinely. In addition, they define the different types of non-positive, non-negative results and demonstrate how clinicians can use tree-structured decision analysis from the six-cell matrix. While their method does not solve all problems posed by non-positive, non-negative results, it does suggest a standard method for reporting these results and utilizing all the data in decision making. Key words: diagnostic tests, Bayes theorem, decision analysis. (Med Decis Making 7:107-114, 1987)

Meta-Analyses of Septal Reduction Therapies for Obstructive Hypertrophic Cardiomyopathy Comparative Rates of Overall Mortality and Sudden Cardiac Death After Treatment

Background—Septal reduction for obstructive hypertrophic cardiomyopathy may be performed by surgical myectomy or alcohol septal ablation (ASA). Unlike surgical myectomy, ASA creates an intramyocardial scar that may potentiate the risk of ventricular arrhythmias and sudden cardiac death (SCD). Methods and Results—Systematic reviews for ASA and surgical myectomy were performed. Study selection and data extraction were completed independently by 2 investigators. Comparative data analyses were completed using a random effects model and regression analysis. Kappa statistics for agreement on initial study inclusion were high for both ASA (0.78; 95% CI, 0.68 to 0.88) and surgical myectomy studies (0.95; 95% CI, 0.84 to 1.0). Nineteen ASA studies (2207 patients) and 8 surgical myectomy studies (1887 patients) were included. Median follow-up was shorter for ASA than for myectomy studies (51 versus 1266 patient-years; P<0.001). For ASA and surgical myectomy, unadjusted rates (events/patient-years) of all-cause mortality (0.021 versus 0.018, respectively; P=0.37) and SCD (0.004 versus 0.003, respectively; P=0.36) were similar. Patients treated with ASA were older (weighted mean, 55 versus 44 years; P<0.001) and had less septal hypertrophy (weighted mean, 21 versus 23 mm; P<0.001) compared with those treated with myectomy. After adjustment for available baseline characteristics, odds ratios for treatment effect on all-cause mortality and SCD were 0.28 (95% CI, 0.16 to 0.46) and 0.32 (95% CI, 0.11 to 0.97), respectively, favoring ASA. Conclusions—Rates of all-cause mortality and SCD after both ASA and surgical myectomy were similarly low. Adjusted for baseline characteristics, the odds ratios for treatment effect on all-cause mortality and SCD were lower in ASA cohorts compared with surgical myectomy cohorts.Background— Septal reduction for obstructive hypertrophic cardiomyopathy may be performed by surgical myectomy or alcohol septal ablation (ASA). Unlike surgical myectomy, ASA creates an intramyocardial scar that may potentiate the risk of ventricular arrhythmias and sudden cardiac death (SCD). Methods and Results— Systematic reviews for ASA and surgical myectomy were performed. Study selection and data extraction were completed independently by 2 investigators. Comparative data analyses were completed using a random effects model and regression analysis. Kappa statistics for agreement on initial study inclusion were high for both ASA (0.78; 95% CI, 0.68 to 0.88) and surgical myectomy studies (0.95; 95% CI, 0.84 to 1.0). Nineteen ASA studies (2207 patients) and 8 surgical myectomy studies (1887 patients) were included. Median follow-up was shorter for ASA than for myectomy studies (51 versus 1266 patient-years; P <0.001). For ASA and surgical myectomy, unadjusted rates (events/patient-years) of all-cause mortality (0.021 versus 0.018, respectively; P =0.37) and SCD (0.004 versus 0.003, respectively; P =0.36) were similar. Patients treated with ASA were older (weighted mean, 55 versus 44 years; P <0.001) and had less septal hypertrophy (weighted mean, 21 versus 23 mm; P <0.001) compared with those treated with myectomy. After adjustment for available baseline characteristics, odds ratios for treatment effect on all-cause mortality and SCD were 0.28 (95% CI, 0.16 to 0.46) and 0.32 (95% CI, 0.11 to 0.97), respectively, favoring ASA. Conclusions— Rates of all-cause mortality and SCD after both ASA and surgical myectomy were similarly low. Adjusted for baseline characteristics, the odds ratios for treatment effect on all-cause mortality and SCD were lower in ASA cohorts compared with surgical myectomy cohorts. Received October 15, 2009; accepted January 8, 2010. # CLINICAL PERSPECTIVE {#article-title-2}

A Telephone-Delivered Intervention for Patients With NIDDM: Effect on coronary risk factors

OBJECTIVE To examine whether a telephone-delivered intervention (TDI), designed to improve glycemie control in patients with non-insulin-dependent diabetes mellitus (N1DDM), improved coronary risk factors in high-risk patients. RESEARCH DESIGN AND METHODS This randomized controlled trial involved 275 veterans with N1DDM followed in a general medical clinic. Intervention (TDI) patients were telephoned at least monthly by a nurse. Calls emphasized compliance with the medical regimen (diet, medications, and exercise), encouraged behavioral changes, and facilitated referrals to a dietitian or smoking cessation clinic. Control patients received no such calls. Baseline and 12-month follow-up measurements included fasting lipid profiles, weight, smoking status (self-reported; cessation verified by measurement of exhaled CO), adherence to diet and exercise (self-reported), appointments, and medications (hospital computerized data base). RESULTS After 12 months, equal numbers of obese patients in the two groups reported adhering to a diabetic diet and exercising, although more obese TDI patients had seen a dietitian (30 vs. 7%, P = 0.003). Weight loss was not seen in either group (—0.9 ± 5.3 vs. —0.1 ± 3.6 kg, P = 0.202). Hyperlipidemic TDI patients were more likely to see a dietitian (31 vs. 6%, P = 0.003) and receive lipid-lowering medications (22 vs. 9%, P = 0.096), but serum cholesterol reduction was similar between groups (–11.7 ± 33.4 vs. –4.3 ± 32.7 mg/dl, P = 0.270); comparable results were seen for high-density lipoprotein, low-density lipoprotein, and triglyceride levels. More TDI group smokers reported quitting (26 vs. 0%, P = 0.033), but the difference was not significant for CO-verified abstention (10 vs. 0%, P = 0.231). CONCLUSIONS The TDI improved self-reported adherence to regimens that might reduce coronary risk, but had little effect on objective measures of risk.

Does This Patient Have Obstructive Sleep Apnea?: The Rational Clinical Examination Systematic Review

IMPORTANCE Obstructive sleep apnea is a common disease, responsible for daytime sleepiness. Prior to referring patients for definitive testing, the likelihood of obstructive sleep apnea should be established in the clinical examination. OBJECTIVE To systematically review the clinical examination accuracy in diagnosing obstructive sleep apnea. DATA SOURCES MEDLINE and reference lists from articles were searched from 1966 to June 2013. Titles and abstracts (n = 4449) were reviewed for eligibility and appraised for evidence levels. STUDY SELECTION For inclusion, studies must have used full, attended nocturnal polysomnography for the reference standard (n = 42). MAIN OUTCOMES AND MEASURES Community and referral-based prevalence of obstructive sleep apnea; accuracy of symptoms and signs for the diagnosis of obstructive sleep apnea. RESULTS The prevalence of sleep apnea in community-screened patients is 2% to 14% (sample sizes 360-1741) and 21% to 90% (sample sizes 42-2677) for patients referred for sleep evaluation. The prevalence varies based on the apnea-hypopnea index (AHI) threshold used for the evaluation (≥5 events/h, prevalence 14%; ≥15/h, prevalence 6%) and whether the disease definition requires symptoms in addition to an abnormal AHI (≥5/h with symptoms, prevalence 2%-4%). Among patients referred for sleep evaluation, those with sleep apnea weighed more (summary body mass index, 31.4; 95% CI, 30.5-32.2) than those without sleep apnea (summary BMI, 28.3; 95% CI, 27.6-29.0; P < .001 for the comparison). The most useful observation for identifying patients with obstructive sleep apnea was nocturnal choking or gasping (summary likelihood ratio [LR], 3.3; 95% CI, 2.1-4.6) when the diagnosis was established by AHI ≥10/h). Snoring is common in sleep apnea patients but is not useful for establishing the diagnosis (summary LR, 1.1; 95% CI, 1.0-1.1). Patients with mild snoring and body mass index lower than 26 are unlikely to have moderate or severe obstructive sleep apnea (LR, 0.07; 95% CI, 0.03-0.19 at threshold of AHI ≥15/h). CONCLUSIONS AND RELEVANCE Nocturnal gasping or choking is the most reliable indicator of obstructive sleep apnea, whereas snoring is not very specific. The clinical examination of patients with suspected obstructive sleep apnea is useful for selecting patients for more definitive testing.