Brian P. Schmitt

Does hypogonadism contribute to the occurrence of a minimal trauma hip fracture in elderly men

The risk of MTHF in hypogonadal elderly men was investigated with a case‐control model. Cases and controls were selected from males age 65 years and older residing in the 120‐bed McGuire Veterans Affairs Medical Center Nursing Home Care Unit over a 5‐day interval. Historical data and serum free testosterone (fTe) were available on 17 subjects with MTHF and 61 controls. When groups were compared for differences in age, race, alcohol abuse, cigarette abuse, and diseases or drugs that may be associated with MTHF, only race was significantly different. Although 25.6% of residents were black, 100% of MTHF subjects were white (P = 0.004). Hypogonadism was defined as a random fTe <9 pg/mL (normal 9 to 46 pg/mL) and was found in 21 subjects (26.9%). Of cases with a MTHF, 58.8% were hypogonadal compared with only 18.0% of controls. Utilizing logistic regression, a highly significant association was found between hypogonadism and MTHF (P = 0.008), and using the odds ratio, subjects with hypogonadism were 6.5 times more likely to have a MTHF (95% CI 2.0 to 20.6). To adjust for race, the odds ratio was repeated excluding black subjects, and the results remained highly significant (4.6, 95% CI 1.3 to 16.2). We conclude that hypogonadal elderly white men may be at increased risk for MTHF.

Health Care Provider-Directed Intervention to Increase Colorectal Cancer Screening Among Veterans: Results of a Randomized Controlled Trial

PURPOSE Colorectal cancer screening is the most underused cancer screening tool in the United States. The purpose of this study was to test whether a health care provider-directed intervention increased colorectal cancer screening rates. PATIENTS AND METHODS The study was a randomized controlled trial conducted at two clinic firms at a Veterans Affairs Medical Center. The records of 5,711 patients were reviewed; 1,978 patients were eligible. Eligible patients were men aged 50 years and older who had no personal or family history of colorectal cancer or polyps, had not received colorectal cancer screening, and had at least one visit to the clinic during the study period. Health care providers in the intervention firm attended a workshop on colorectal cancer screening. Every 4 to 6 months, they attended quality improvement workshops where they received group screening rates, individualized confidential feedback, and training on improving communication with patients with limited literacy skills. Medical records were reviewed for colorectal cancer screening recommendations and completion. Literacy level was assessed in a subset of patients. RESULTS Colorectal cancer screening was recommended for 76.0% of patients in the intervention firm and for 69.4% of controls (P = .02). Screening tests were completed by 41.3% of patients in the intervention group versus 32.4% of controls (P = .003). Among patients with health literacy skills less than ninth grade, screening was completed by 55.7% of patients in the intervention group versus 30% of controls (P < .01). CONCLUSION A provider-directed intervention with feedback on individual and firm-specific screening rates significantly increased both recommendations and colorectal cancer screening completion rates among veterans.

Clopidogrel-Associated TTP: An Update of Pharmacovigilance Efforts Conducted by Independent Researchers, Pharmaceutical Suppliers, and the Food and Drug Administration

Background and Purpose— Since the 1999 identification of clopidogrel-associated thrombotic thrombocytopenic purpura (TTP) through independent active surveillance, subsequent cases have been identified by pharmaceutical suppliers of clopidogrel and the Food and Drug Administration (FDA). For cases of clopidogrel-associated TTP reported between 1998 to 2002, we evaluated the quality and timeliness of data from 3 reporting systems-independent active surveillance (n=13), pharmaceutical suppliers (n=24), and the FDA (n=13)—and identified prognostic factors associated with mortality. Methods— This study assessed the completeness of information on TTP diagnosis, treatment response, and causality from the 3 reporting systems. In addition, predictors of mortality were identified through classification tree analysis. Results— Completeness, timeliness, and certainty of diagnosis were best for cases obtained by active surveillance, intermediate for cases reported to the pharmaceutical supplier, and poorest for cases reported directly to the FDA. Clopidogrel had been used for ≤2 weeks by 65%. The survival rate for patients with clopidogrel-associated TTP was 71.2%. Receipt of therapeutic plasma exchange within 3 days of onset of TTP increased the likelihood of survival (100% versus 27.3%, P <0.001). Conclusions— Compared with reports submitted by suppliers or the FDA, reports obtained through active surveillance provided timelier and more complete information. Clopidogrel-associated TTP often occurs within 2 weeks of drug initiation, occasionally relapses, and has a high mortality if not treated promptly.

Screening Primary Care Patients for Hereditary Hemochromatosis with Transferrin Saturation and Serum Ferritin Level: Systematic Review for the American College of Physicians

Hereditary hemochromatosis is a genetic disorder of iron metabolism resulting in excessive iron overload and is associated with clinically significant morbid and fatal complications related to tissue iron deposition (1). It is an autosomal recessive disorder linked to a mutation of the HFE gene on the short arm of chromosome 6. This gene is the result of a single base change in which tyrosine is substituted for cysteine at position 282 of the HFE protein (C282Y). Available evidence strongly supports an association of the C282Y mutation with hereditary hemochromatosis, although other mutations in HFE have been identified. The substitution of aspartic acid for histidine at position 63 (H63D) has been observed but has limited clinical effect (2). Several genetic mutations are also linked to juvenile hereditary hemochromatosis (3, 4). The C282Y mutation is variably and unpredictably associated with phenotypic changes of iron overload that include elevated transferrin saturation and serum ferritin levels. An increasing transferrin saturation is the earliest detectable biochemical abnormality in hereditary hemochromatosis and is attributed to increased intestinal iron absorption (4). Enterocytes aberrantly continue to transfer iron from the gut into the bloodstream rather than store the iron as ferritin. The role of HFE in this pathophysiologic process is not fully clear. Some patients with the HFE gene never progress beyond this biochemical abnormality. However, progressive iron overload occurs in others. Marked elevation of serum ferritin level has been associated with histologic evidence of iron deposition (5). The morbid complications of hereditary hemochromatosis are the result of tissue deposition, and they develop late in its course. They include arthritis, diabetes mellitus, congestive heart failure, cirrhosis, and hepatocellular carcinoma (6). Liver iron deposition with cirrhosis is associated with reduced survival (7). The estimated prevalence of hereditary hemochromatosis is 1 in 200 persons to 1 in 250 persons in the general population, making hereditary hemochromatosis one of the most common genetic disorders (8). However, the prevalence of hereditary hemochromatosis varies depending on the case definition of disease (9). With genetic testing of populations originating in northern Europe, approximately 0.5% is homozygous for the C282Y mutation (10). With phenotypic screening, 1% to 6% of the U.S. population have elevated transferrin saturation levels, and 11% to 22% of them have concomitant elevations of their serum ferritin levels (11). Over the past decade, interest in promoting general population screening for hereditary hemochromatosis has increased (12, 13). Advances in genetic testing, changing definitions of the disease that include earlier stages of iron overload, increased appreciation of the prevalence and importance of the disease, and the presumed effectiveness of a simple intervention (phlebotomy) have prompted a debate on the benefits and risks of a screening intervention program in the United States. The use of genetic testing to screen family members of individuals identified with hereditary hemochromatosis seems to be cost-effective (14). The benefit in primary care is less clear. In 1997, the Centers for Disease Control and Prevention and the National Institutes of Health sponsored a meeting on iron overload, public health, and genetics (15). A result of the conference was a published review of the evidence for hemochromatosis screening (13). Evidence for screening was evaluated against the U.S. Preventive Services Task Force criteria (16). Little evidence was available to support the efficacy of genetic testing, and there were substantial ethical, legal, and social concerns. Likewise, evidence was insufficient to support the use of transferrin saturation, and few comparative data were available to establish the magnitude and clinical significance of risk in patients with various levels of iron overload. However, others argued for expanded screening and have targeted primary care physicians for educational intervention to improve awareness of the disease (12, 17). The Working Group on Research Priorities identified the evidence that is most needed to provide a scientific basis for population screening (18). They identified the need for research to characterize the natural history of the relationship between genotype and phenotype in hereditary hemochromatosis and other iron overload disorders. They also identified 3 additional priorities: 1) development of an optimal approach for screening for iron overload; 2) analyses of the cost-effectiveness of screening; and 3) assessment of the ethical, legal, and social implications of screening. Given this background, we must examine the current evidence and determine whether it now supports general population screening for hereditary hemochromatosis. To promote screening within the primary care setting, one must demonstrate that the disease is common, the burden is substantial, the treatment is efficacious, the screening tests are accurate, the screening is effective, and the benefits of screening outweigh the risks (16). We evaluate the evidence to support screening within the primary care setting. Because of the controversy surrounding genetic testing as a screening tool (low penetrance of hereditary hemochromatosis and lack of complete identification of genetic mutations associated with hereditary hemochromatosis), our review focuses on the phenotypic measures that are most likely to be useful in primary care: transferrin saturation and serum ferritin level. To evaluate the evidence, we address each key question that is relevant to a screening intervention. Methods We conducted a systematic review for each question in MEDLINE for papers published from 1966 through April 2004 by using PubMed Clinical Queries filters for a sensitive search of prognosis, diagnosis, etiology, or treatment depending on the question. We included only English-language studies. Two reviewers independently reviewed all abstracts. A third reviewer resolved conflicts about inclusion of an article. We also manually searched references from included studies. The Appendix includes details for conducting the search for each subquestion. We assessed methodologic quality of studies for a specific question by using accepted epidemiologic criteria (19). We did not use any formal method of quality assessment or scoring. This paper was written under contract with the American College of Physicians. The funding source had no role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results Subquestion 1: What Is the Prevalence of Hereditary Hemochromatosis in the Primary Care Setting? We identified 3 prevalence studies in primary care settings (Table 1) and 12 studies in various general population settings (Table 2) (Appendix Figure 1). Because of variability among studies, we examined the prevalence data in 3 ways: use of the strict definition recommended in the Hemochromatosis and Iron Overload Screening (HEIRS) study (34); use of the prevalence reported by the investigator(s); and use of a ceiling estimate, which assumed that the many study participants with elevated transferrin saturation and serum ferritin levels who declined liver biopsy or therapeutic phlebotomy had the same probability of primary iron overload as those who were actually evaluated. Table 1. Prevalence of Hereditary Hemochromatosis in Primary Care Settings Table 2. Prevalence of Hereditary Hemochromatosis in Various General Population Settings Appendix Figure 1. The selection and exclusion of articles to address subquestion 1 about the prevalence of hereditary hemochromatosis. Using strict criteria, we found that the prevalence of hereditary hemochromatosis within a primary care setting was 0.18% to 0.59% (1 in 169 patients screened to 1 in 556 patients screened). The prevalence reported by the investigators was 0.2% to 1.8% (1 in 56 patients screened to 1 in 500 patients screened). We estimated the ceiling prevalence of hereditary hemochromatosis to be 0.37% to 0.79% (1 in 127 patients screened to 1 in 270 patients screened). Most patients with hereditary hemochromatosis did not have concomitant cirrhosis. Using the HEIRS study definition, we found that hereditary hemochromatosis prevalence was higher in white men (0.37% to 0.46%) than nonwhite men (0% to 0.17%) and was higher in men than women. Using strict criteria, we estimated the prevalence of hereditary hemochromatosis from the 2 general population studies (23, 24) to be 0.16% to 0.28% (1 in 357 patients screened to 1 in 625 patients screened). The investigators reported higher ratesas high as 0.74% in Norwegian men. In screening employees or blood donors, the prevalence of hereditary hemochromatosis was higher in men than women and, when demographic data were available, was higher in white men than nonwhite men (Table 2). Within the primary care setting (n= 23055) and using strict criteria, we identified hereditary hemochromatosis in 59 patients (0.13%) (equivalent to 1 in 795 screened patients). Of these 59 patients, 55 patients (93%) were 40 years of age or older, 46 patients (78%) were men, and 38 patients (93%) in the 2 studies that provided racial characteristics were white. Fifty-two of 59 patients (88%) did not have cirrhosis. These data demonstrate that the prevalence of hereditary hemochromatosis varies across different subgroups determined by race, sex, and age. The highest prevalence of hereditary hemochromatosis detected by screening within primary care seems to be in white men, probably ranging between 1 of 185 screened patients and 1 of 219 screened patients (20, 21). Screening that targeted white men 40 years of age or older would further increase the prevalence of hereditary hemochromatosis. Subquestion 2: In Asymptomatic Patients with Hereditary Hemochromatosis, Wh

The diagnostic usefulness of the history of the patient with dyspnea

The diagnostic usefulness of the medical history may depend on the type of problem confronted. It has been suggested that dyspnea is an example of a condition the causes of which cannot be easily distinguished based on identification in the history of stereotypical disease patterns presented in standard texts. To evaluate this assertion, faculty members independently interviewed 146 consecutively admitted patients with dyspnea, and following the history of the present illness, made a diagnosis. After discharge of the patients, another faculty member, using preselected criteria, independently reviewed each record to make a final diagnosis. History-based diagnoses predicted final diagnoses 74% of the time. Therefore, the history appeared to be useful in identifying the primary diagnosis for most dyspneic patients admitted to the hospital. However, it is not known whether this identification provides sufficient rationale for therapy or leads to more efficient use of laboratory tests.

Heart failure between 1986 and 1994: Temporal trends in drug-prescribing practices, hospital readmissions, and survival at an academic medical center

Since 1987, publications in widely circulated medical journals have reported improved survival and lower hospital readmission rates when patients with heart failure and systolic dysfunction are treated with angiotensin-converting enzyme (ACE) inhibitors. We describe changes in ACE inhibitor use among patients hospitalized with heart failure between 1986 and 1993. Simultaneous trends in readmissions and survival rates are reported. Subjects were 612 consecutive patients hospitalized with a principal diagnosis of heart failure at an academic medical center during the period of Sept. 1, 1986, to Dec. 31, 1987 (interval I) or during the period Aug. 1, 1992, to Nov. 30, 1993 (interval II). Medical records were reviewed for 434 patients, consisting of all patients hospitalized with heart failure during interval II and a randomly selected 50% subset of patients hospitalized during interval I. Among 145 patients with systolic dysfunction whose medical records were reviewed, ACE inhibitor prescriptions significantly increased between interval I and interval II (43% vs 71%, p < 0.01, odds ratio 3.22, 95% confidence interval 1.62 to 6.42). Prescriptions of ACE inhibitors combined with digoxin and a diuretic also increased (37% vs 56%, p = 0.02, odds ratio 2.22, 95% confidence interval 1.14 to 4.32). Among all 612 patients, 6-month heart failure readmission rates increased from 13% to 21% (p = 0.02, odds ratio 1.79, 95% confidence interval 1.10 to 2.82). There was no significant change in survival rate between interval I and interval II, however, survival rate was marginally significantly improved among patients with systolic dysfunction. Our results suggest that drug-prescribing practices have significantly changed between 1986 and 1993. The absence of observed improvement in outcomes may result from changes in hospital admission criteria for heart failure.

Encephalopathy Complicating Whipple's Disease: Failure to Respond to Antibiotics

Progressive dementia, vertical ophthalmoplegia, and prominent hypothalamic dysfunction developed in one patient with documented intestinal Whipples disease despite ongoing antibiotic therapy with intestinal remission. A clinical diagnosis of central nervous Whipples disease was made on the basis of the patients presentation. High-dose parenteral penicillin and chloramphenicol were administered for 4 1/2 weeks. There was no improvement in results of daily mental status examination or neuropsychologic testing. Deterioration was noted in the electroencephalographic findings after therapy. Vigorous antibiotic therapy with agents that cross the blood-brain barrier had no immediate beneficial effect. Irreversible neurologic damage or a slow, delayed response may account for this observation.

Process Evaluation in an Intervention Designed to Improve Rates of Colorectal Cancer Screening in a VA Medical Center

Colorectal cancer (CRC) is the third most common cancer in the United States. Although CRC screening is recommended for individuals 50 years and older, screening completion rates are low. This can be attributed to provider and patient barriers. We developed an intervention to improve provider recommendation and patient screening among noncompliant male veterans in a 2-year randomized controlled trial and examined the relationship between participation and study outcomes among patients and providers. Overall, providers who attended intervention sessions recommended CRC screening during 64% of patient visits and providers who did not attend any intervention sessions recommended screening during 54% of visits (p < .01). Patients of providers who attended intervention sessions also were more likely to be screened (42% versus 29%, p < .05). The patient intervention did not have the desired impact. The subgroup of patients in the patient intervention was not more likely to complete CRC screening.

Derivation of a Triage Algorithm for Chest Radiography of Community-acquired Pneumonia Patients in the Emergency Department

BACKGROUND Community-acquired pneumonia (CAP) accounts for 1.5 million emergency department (ED) patient visits in the United States each year. OBJECTIVES To derive an algorithm for the ED triage setting that facilitates rapid and accurate ordering of chest radiography (CXR) for CAP. METHODS The authors conducted an ED-based retrospective matched case-control study using 100 radiographic confirmed CAP cases and 100 radiographic confirmed influenzalike illness (ILI) controls. Sensitivities and specificities of characteristics assessed in the triage setting were measured to discriminate CAP from ILI. The authors then used classification tree analysis to derive an algorithm that maximizes sensitivity and specificity for detecting patients with CAP in the ED triage setting. RESULTS Temperature greater than 100.4 degrees F (likelihood ratio = 4.39, 95% confidence interval [CI] = 2.04 to 9.45), heart rate greater than 110 beats/minute (likelihood ratio = 3.59, 95% CI = 1.82 to 7.10), and pulse oximetry less than 96% (likelihood ratio = 2.36, 95% CI = 1.32 to 4.20) were the strongest predictors of CAP. However, no single characteristic was adequately sensitive and specific to accurately discriminate CAP from ILI. A three-step algorithm (using optimum cut points for elevated temperature, tachycardia, and hypoxemia on room air pulse oximetry) was derived that is 70.8% sensitive (95% CI = 60.7% to 79.7%) and 79.1% specific (95% CI = 69.3% to 86.9%). CONCLUSIONS No single characteristic adequately discriminates CAP from ILI, but a derived clinical algorithm may detect most radiographic confirmed CAP patients in the triage setting. Prospective assessment of this algorithm will be needed to determine its effects on the care of ED patients with suspected pneumonia.

Using Patient Traffic Control to Reduce Treatment Delays for High-Risk Patients at a VA Hospital

BACKGROUND For patients at high risk of function-limiting or life-limiting disease, the time elapsed between first clinical presentation, diagnosis, and treatment can influence the likelihood of treatment success. METHODS A systematic change in the management of high-risk patients was undertaken. This approach includes identifying primary provider responsibility, establishing communication expectations between providers, developing a tracking system to actively monitor patients (patient traffic control), and using a time guideline to assess patient progression. A 60-day time frame was established for the time from first clinical presentation to diagnostic exclusion or treatment initiation. RESULTS In a one-year period, 288 high-risk patients were entered into patient traffic control, 211 (73%) of whom were monitored in the primary care setting. The median time to diagnostic exclusion or treatment was 43 days (mean, 58.5 days). Sixty-six percent of all patients achieved diagnostic exclusion or treatment by 60 days. Of the 95 patients monitored for > 60 days, 56% had delays caused by patient noncompliance or because of the appropriate need for long-term serial radiographic monitoring. Thirty-eight patients (13.1%) demonstrated problems with appointment nonadherence. None were lost to follow-up. DISCUSSION The patient traffic control approach enabled the management of the majority of high-risk patients within 60 days of presentation.