Pamela B. Landsman

A randomized, controlled trial of a clinical pharmacist intervention to improve inappropriate prescribing in elderly outpatients with polypharmacy

PURPOSE To evaluate the effect of sustained clinical pharmacist interventions involving elderly outpatients with polypharmacy and their primary physicians. PATIENTS AND METHODS Randomized, controlled trial of 208 patients aged 65 years or older with polypharmacy (> or = 5 chronic medications) from a general medicine clinic of a Veterans Affairs Medical Center. A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians. Outcome measures were prescribing appropriateness, health-related quality of life, adverse drug events, medication compliance and knowledge, number of medications, patient satisfaction, and physician receptivity. RESULTS Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months (decrease 24% versus 6%, respectively; P = 0.0006) and was sustained at 12 months (decrease 28% versus 5%, respectively; P = 0.0002). There was no difference between groups at closeout in health-related quality of life (P = 0.99). Fewer intervention than control patients (30.2%) versus 40.0%; P = 0.19) experienced adverse drug events. Measures for most other outcomes remained unchanged in both groups. Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients (55.1% versus 19.8%; P <0.001). CONCLUSIONS This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life.

Adverse drug events in high risk older outpatients.

OBJECTIVE: To describe the prevalence, types, and consequences of adverse drug events (ADEs) in older outpatients with polypharmacy.

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.

The Role of Antineutrophil Cytoplasmic Antibody (c-ANCA) Testing in the Diagnosis of Wegener Granulomatosis: A Literature Review and Meta-analysis

Wegener granulomatosis is a serious systemic vasculitis that is uniformly fatal if untreated. In 1983, Fauci and colleagues [1] reported their success with a combination of corticosteroid and cyclophosphamide therapy in 85 patients with Wegener granulomatosis. Since then, the recognition among clinicians of Wegener granulomatosis and its expanded clinical spectrum has improved, making early diagnosis and treatment possible. Patients with the classic Wegener triad have necrotizing granulomatous vasculitis of the upper and lower respiratory tract associated with glomerulonephritis; patients with limited Wegener granulomatosis may have vasculitis limited to the respiratory tract [2]. Because of the potential clinical overlap with other diseases, the diagnostic algorithm for patients with suspected Wegener granulomatosis has traditionally included biopsy of the upper airway, lung, or kidney to confirm the diagnosis and to rule out other entities, such as systemic infections and malignancies, that may respond adversely to cyclophosphamide therapy [3]. Antineutrophil cytoplasmic antibody (ANCA), first described in 1982 in patients with systemic vasculitis and glomerulonephritis, has emerged as a new diagnostic tool and marker of disease activity for vasculitis [4, 5]. Originally thought to be a response to arboviral infection, ANCA was later identified as a seromarker for Wegener granulomatosis [4, 6]. It is currently believed that the presence of ANCA is an important factor in the pathogenesis of this disease [5]. Two ANCA patterns may be seen with indirect immunofluorescence of ethanol-fixed neutrophils: a cytoplasmic pattern (c-ANCA) and the artifactual perinuclear pattern (p-ANCA) [7, 8]. The major antigen for c-ANCA is a 29-kd serine protease, known as proteinase 3, which is found within the azurophilic granules of the neutrophil [9]. The major antigen for p-ANCA is myeloperoxidase, a lysosomal enzyme found in neutrophils [7, 10]. Some clinical overlap has been seen, but the two patterns have different disease associations. The c-ANCA pattern has predominantly been associated with Wegener granulomatosis, and p-ANCA has been associated with microscopic polyarteritis, other vasculitides, idiopathic necrotizing and crescentic glomerulonephritis, and other diseases [7, 11-13]. Early studies of c-ANCA in patients with Wegener granulomatosis, especially those with active disease, have been promising. Reported sensitivities and specificities have exceeded 90% [10-12, 14-18]. Because of the morbidity and expense associated with biopsy, c-ANCA has attracted interest as a rapid and noninvasive way to diagnose Wegener granulomatosis. In fact, some investigators advocate immunosuppressive therapy for patients with positive c-ANCA test results and symptoms compatible with Wegener granulomatosis, even in the absence of biopsy results [19-21]. The history of c-ANCA testing appears to mirror the natural history of many new diagnostic tests. Important and early pioneering studies of new tests are typically done in highly selected patients with confirmed disease to determine the tests operating characteristics. However, when the new test is subsequently applied to unselected populations, clinical experience and additional studies often provide a less optimistic picture of its diagnostic power. Several recent reports [22-27] document false-positive c-ANCA test results in patients with tuberculosis, Hodgkin lymphoma, human immunodeficiency virus infection, nasal septal perforation, monoclonal gammopathies, and drug-induced Wegener-like disease. Similarly, additional reports [28, 29] describe negative c-ANCA test results in patients with Wegener granulomatosis, even those with active disease. Given the current enthusiasm for a serologic diagnosis of Wegener granulomatosis, underrecognition of the rate of false-positive c-ANCA test results may lead to inappropriate immunosuppressive therapy in some patients who do not have Wegener granulomatosis. Conversely, underappreciation of the frequency of false-negative c-ANCA test results may delay therapy for patients who have clinical features compatible with Wegener granulomatosis. We did a literature review and meta-analysis to assess the utility of c-ANCA as a diagnostic marker for Wegener granulomatosis overall and in relation to disease activity. Methods As noted above, two ANCA patterns have been described in the literature, and each has separate disease associations. Patients with Wegener granulomatosis often have c-ANCA, whereas p-ANCA is found in patients with various syndromes with and without vasculitis [7, 30, 31]. Because c-ANCA is thought to have a higher test sensitivity than p-ANCA for the diagnosis of Wegener granulomatosis, we focused only on c-ANCA. Search Strategy We could not determine a systematic approach for identifying unpublished data on c-ANCA, and thus we selected only published articles for our literature review. We did a MEDLINE search for English-language studies done in humans and published between 1966 and June 1993. Three searches were done: 1) a textword and registry search for antineutrophil cytoplasmic antibody [ANCA], anticytoplasmic antibody, and antineutrophil antibody; 2) a combination of search terms antibodies, neutrophils and keywords such as pulmonary-renal syndrome, or Wegener granulomatosis, or vasculitis, or glomerulonephritis; and 3) a search using the keyword pulmonary-renal syndrome alone. Using this initial search strategy, we identified 720 citations. Manual examination of the reference lists of included articles and the bibliographies of review articles and standard texts yielded an additional 27 studies, for a total of 747. Article Selection To be included in the analysis, all articles had to pass through a four-stage review (Table 1). First, the titles and abstracts of the 747 articles were independently examined by two reviewers. One reviewer was a rheumatologist, and the other was a health services researcher with a PhD who had experience in the critical appraisal of medical literature. Articles were excluded at this stage if they were not pertinent to the topic (for example, if they addressed antineutrophil antibodies and malignancy) or if they did not present patient-level data (for example, if they were reports of tissue culture experiments). If a cited article did not have a published abstract but appeared to be relevant, or if either reviewer included it, it was retained for further review. Of the original 747 articles, 407 were excluded and 340 were retained for second-level review. Table 1. Summary of the Results of Protocol for Selection of Articles for Meta-analysis In stage 2 of the review process, the complete articles were photocopied and reviewed by a rheumatologist. Articles were excluded if they were case reports (n = 64), reviews (n = 75), or letters to the editor (n = 58), or if they were irrelevant to our topic (n = 81). Sixty-two of the 340 articles remained for potential inclusion. In stage 3, a rheumatologist (JKR) and an investigator with a PhD reviewed the methods section of each article in detail. The methodologic criteria required for inclusion at this stage were specification of the patient selection method and the use of standard reference criteria to define Wegener granulomatosis. For casecontrol and cohort studies, the authors had to have described a systematic method of patient selection (for example, consecutive patients or a random sample based on prespecified criteria) [32]. Thus, case-series studies (such as those defining persons with a common feature nonsystematically without the presence of a control group) were excluded. Authors also had to specify standard reference criteria for establishing Wegener granulomatosis exclusive of the c-ANCA test result. Acceptable reference criteria included the Ear, Nose, Throat, Lung, and Kidney staging system [2], the Fauci criteria [1], and the American College of Rheumatology criteria [33]. The Ear, Nose, Throat, Lung, and Kidney system and the American College of Rheumatology criteria require biopsy confirmation of Wegener granulomatosis, and the Fauci criteria are clinicopathologic in nature. Thirty-nine articles were excluded at this stage for the following reasons: case-series design (n = 24); the method of patient selection was not clearly stated (n = 4); a reference standard was not specified (n = 7); or the article was irrelevant to our review (n = 4). If either reader included an article, it was retained for further review. In stage 4, three physicians each independently read the remaining 23 articles. Articles were excluded at this stage if a 2 2 contingency table, needed to calculate the operating characteristics, could not be constructed from the results (n = 8). Thus, 15 articles remained for detailed review [10, 11, 14, 15, 28, 34-43]. For these 15 articles, 2 2 contingency tables were constructed for patients with and without Wegener granulomatosis compared with patients with and without positive c-ANCA test results. Disagreements between reviewers were resolved by consensus. Definition of Wegener Granulomatosis We included only those studies that specified standard reference criteria for defining Wegener granulomatosis independent of the patients c-ANCA test result [1, 2, 33]. Patients with Wegener granulomatosis can be further divided into two subtypes: those with classic and those with limited disease [2]. In classic Wegener granulomatosis, glomerulonephritis and inflammation of the upper or lower respiratory tract, or both, are present. In limited disease, the kidneys are not involved, but inflammation of the upper or lower respiratory tract, or both, is present. Only 6 of the 15 studies separated patients by subtype. Furthermore, 2 of these 6 studies did not separate the c-ANCA test results by Wegener granulomatosis subtype. Because of these inconsistencies, we considered a single classification (overall Wegener granulomatosis) to repres

Similar motor recovery of upper and lower extremities after stroke.

Background and Purpose This study examined the validity of the clinical tenet that poststroke recovery of the upper extremity is less rapid and complete than poststroke recovery of the lower extremity. Previous studies comparing upper and lower extremity recovery have evaluated disability rather than motor impairment. Individuals with lower extremity impairments may be more functional and appear less disabled than individuals with upper extremity impairments. Function of the upper extremity requires finer motor control, for which the patient can less readily compensate. Therefore, impairments and disability would predictably be more highly correlated in this area. We tested the hypothesis that upper and lower extremity motor recovery are similar. Methods The 95 patients selected for this study were enrolled in the Durham County Stroke Study and had been diagnosed with anterior circulation ischemic stroke. Each subject received Fugl-Meyer assessments within 24 hours of admission and then 5, 30, 90, and 180 days after stroke. We used these assessments to compare the time course and patterns of motor function of the upper and lower extremities. Results Repeated-measures ANOVA revealed that percent maximal motor recovery was significantly (P<.001) affected by time after stroke but not by extremity (upper extremity versus lower extremity) (P=32). When stroke severity level is controlled, the upper and lower extremities continue to show no difference in percent motor recovery (P=.19). Conclusions In patients with anterior circulation ischemic stroke, the severity of motor impairment and the patterns of motor recovery are similar for the upper and lower extremities. The most rapid recovery for both extremities occurs within 30 days.

A summated score for the medication appropriateness index: development and assessment of clinimetric properties including content validity.

Inappropriate medication prescribing is an important problem in the elderly, but is difficult to measure. As part of a randomized controlled trial to evaluate the effectiveness of a pharmacist intervention among elderly veterans using many medications, we developed the Medication Appropriateness Index (MAI), which uses implicit criteria to measure elements of appropriate prescribing. This paper describes the development and validation of a weighting scheme used to produce a single summated MAI score per medication. Using this weighting scheme, two clinical pharmacists rated 105 medications prescribed to 10 elderly veterans from a general medicine clinic. The summated score demonstrated acceptable reliability (intraclass correlation co-efficient = 0.74). In addition, the summated MAI adequately reflected the putative heterogeneity in prescribing appropriateness among 1644 medications prescribed to 208 elderly veterans in the same general medicine clinic. These data support the content validity of the summated MAI. The MAI appears to be a relatively reliable, valid measure of prescribing appropriateness and may be useful for research studies, quality improvement programs, and patient care.

Are Health&Related Quality-of-life Measures Affected by the Mode of Administration?

While measures of health-related quality of life (HRQOL) are increasingly being used as outcomes in clinical trials, it is unknown whether HRQOL assessments are influenced by the method of administration. We compared telephone, face-to-face, and self-administration of a commonly-used HRQOL measure, the SF-36. Veterans (N = 172) receiving care in the General Medicine Clinic were randomized into groups differing only in order of administration. All patients were asked to complete the SF-36 three times over a 4-week period. The SF-36 demonstrated high internal consistency, regardless of mode of administration, but showed large variation over short intervals. This variation may: (1) increase dramatically sample size requirements to detect between-group differences in randomized trials and (2) reduce the SF-36s usefulness for clinicians wishing to follow individual patients over time.

Predicting complications of carotid endarterectomy.

BACKGROUND AND PURPOSE Carotid endarterectomy has been shown to be beneficial in patients with high-grade carotid stenosis and ipsilateral transient ischemic attack or stroke. This benefit will be realized only if the operation is performed safely. We sought to determine the extent to which clinically significant adverse events occurring after carotid endarterectomy can be predicted from clinical data available before surgery. METHODS Eleven hundred sixty patients were randomly selected from all patients who underwent carotid endarterectomy and were discharged during the calendar years 1988, 1989, and 1990 in 12 academic medical centers in 10 states. Clinical data abstracted from hospital charts were analyzed retrospectively. A model was developed and validated to predict the occurrence of stroke, myocardial infarction, or death during the postoperative period of hospitalization. RESULTS Eight patients (6.9%) suffered at least one adverse event. Rates for individual complications were as follows: death, 1.4%; nonfatal stroke, 3.4%; nonfatal myocardial infarction, 2.1%; and nonfatal stroke or death, 4.8%. Significant predictors of adverse events were age 75 years or older, symptom status (ipsilateral symptoms versus asymptomatic or nonipsilateral symptoms), severe hypertension (preoperative diastolic blood pressure of greater than 110 mm Hg), carotid endarterectomy performed in preparation for coronary artery bypass surgery, history of angina, evidence of internal carotid artery thrombus, and internal carotid artery stenosis near the carotid siphon. The presence of two or more of these risk factors was associated with a nearly twofold increase in risk of an adverse event (relative risk, 1.7; 95% confidence interval, 1.0 to 3.0). CONCLUSIONS Clinical data can be used to stratify patients undergoing carotid endarterectomy according to risk of postoperative in-hospital stroke, myocardial infarction, or death.

Race, treatment, and survival among colorectal carcinoma patients in an equal‐access medical system

The aim of this study was to assess the influence of race on the treatment and survival of patients with colorectal carcinoma.

Multicenter review of preoperative risk factors for carotid endarterectomy in patients with ipsilateral symptoms.

Background and Purpose Randomized clinical trials have shown that carotid endarterectomy decreases the risk of subsequent stroke in patients with high-grade carotid stenosis and ipsilateral transient ischemic attack or minor stroke. The benefit of surgery is highly dependent on surgical risk. We previously found that patients with ipsilateral hemispheric symptoms were at greater risk of carotid endarterectomy complications compared with those who were asymptomatic or had nonipsilateral symptoms. The goals of the present study were (1) to identify preoperative clinical factors that may increase the risk of complications after carotid endarterectomy in patients with ipsilateral hemispheric symptoms and (2) to develop a risk index based on this patient-level data. Methods Records from 1160 carotid endarterectomies performed at 12 academic medical centers composed the primary data set. Hospital charts for the admission during which carotid endarterectomy was performed were systematically reviewed by abstractors using a defined protocol. The present analysis was carried out on data from the subset of patients who had carotid endarterectomy for ipsilateral hemispheric symptoms. Candidate variables were identified based on univariate Fishers exact tests or x2 tests. A risk index was then developed using those variables with a greater than 90% probability of being associated with adverse outcomes. Results Of the 697 patients with ipsilateral symptoms, 8.5% had either stroke, myocardial infarction, or died during the postoperative period of hospitalization. Those over the age of 75 had a greater risk of myocardial infarction (6.6% versus 2.3%, P=.024) but not of stroke or death (P<.10). The overall frequencies of adverse outcomes were also higher in the 5 patients with complete ipsilateral carotid occlusions (40% versus 8.2%, p<.01), the 28 patients with ipsilateral intraluminal thrombus (17.9% versus 8.1%, P=.01), and the 65 patients with ipsilateral carotid siphon stenosis (13.9% versus 7.9%, P=.10). There were no differences in adverse outcomes among those with different degrees of ipsilateral stenosis (30% to 49%, 50% to 69%, and 70% to 99%). Adverse outcome rates were similar regardless of the type of symptom (transient ischemic attack, recent ipsilateral minor stroke, remote ipsilateral minor stroke). There were no significant differences in adverse outcome rates based on sex, race, history of angina, recent myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease, hypertension, degree of stenosis of the contralateral carotid artery, or presence of ulceration in the ipsilateral artery (Fishers exact tests, P>.10). A count of variables with greater than 90% probability of being associated with adverse outcomes (age ≤75 years or angiographic evidence of ipsilateral carotid occlusion, stenosis in the region of the carotid siphon, or intraluminal thrombus) was used to form a simple risk index. “High-risk” patients (one or more risk factors) had more than two times the risk of complications compared with “low-risk” patients who had no risk factors (odds ratio, 2.18; 95% confidence interval, 1.25 to 3.81). Conclusions Certain preoperative clinical variables may place patients with ipsilateral symptoms at greater risk of perioperative complications after carotid endarterectomy. Prospective validation of a simple risk index would provide an additional method for assessing preoperative risk in endarterectomy candidates.