Delirium, a Symptom of UTI in the Elderly: Fact or Fable? A Systematic Review.

BACKGROUND: In geriatrics, delirium is widely viewed as a consequence of and, therefore, a reason to initiate workup for urinary tract infection (UTI). There is a possibility that this association is overestimated. To determine the evidence behind this clinical practice, we undertook a systematic review of the literature linking delirium with UTI. METHODS: A MEDLINE search was conducted from 1966 through 2012 using the MESH terms "urinary tract infection" and "delirium", limited to humans, age 65 and older. The search identified 111 studies. Of these, five met our inclusion criteria of being primary studies that addressed the association of UTI and delirium. The studies were four cross-sectional observational studies and one case series. No randomized control trials were identified. All studies were published between 1988 and 2011. Four collected data retrospectively and one prospectively, with study sizes ranging from 14 to 1,285. The methodological strength of the studies was evaluated using six standards adapted from a previous systematic review. RESULTS: Only two of the five studies adequately matched or statistically adjusted for differences in comparison groups. None of the studies evaluated subjects with equal intensity for the presence of delirium and UTI, nor did they have objective criteria for either diagnosis. In subjects with delirium, UTI rates ranged from 25.9% to 32% compared to 13% in those without delirium. In subjects with UTI, delirium rates ranged from 30% to 35%, compared to 7.7% to 8% in those without UTI. CONCLUSIONS: Few studies have examined the association between UTI and delirium. Though the studies examined conclude that there is an association between UTI and delirium, all of them had significant methodological flaws that likely led to biased results. Therefore, it is difficult to ascertain the degree to which urinary tract infections cause delirium. More research is needed to better define the role of UTI in delirium etiology.

Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis.

PURPOSE: Women at high risk of breast cancer face the complex decision of whether to take tamoxifen or raloxifene for breast cancer chemoprevention. We investigated what is known about decisions of women regarding chemoprevention. METHODS: Using MEDLINE, CINAHL, and PSYCINFO, plus reviewing reference lists of relevant articles, in December 2009 we identified 13 studies that addressed patient decisions about breast cancer chemoprevention, were published in 1995 or later, were peer-reviewed primary clinical studies, and reported rates at which participants showed interest in (hypothetical uptake) or accepted (real uptake) chemoprevention medications. RESULTS: Nine studies provided information about hypothetical breast cancer chemoprevention decisions (mean uptake rate, 24.7%) and five provided information about real decisions (mean uptake rate, 14.8%). The range of rates was wide, and each of the hypothetical uptake studies assessed interest differently. A logistic regression model found significant correlation with uptake of decision type (hypothetical versus real, odds ratio [OR] = 1.65; 95% CI, 1.26 to 2.16), educational or decision support intervention (provided v not, OR = 0.21; 95% CI, 0.17 to 0.27), and cohort risk for breast cancer (high-risk v general population, OR = 0.65; 95% CI, 0.56 to 0.75). Perceived vulnerability to breast cancer was consistently correlated with increased uptake, and concern for adverse effects was correlated with reduced uptake. All studies used a correlational/descriptive design, and most studies used convenience sampling strategies. CONCLUSION: Breast cancer chemoprevention uptake rates are low and variation is wide. Hypothetical uptake rates are higher than real uptake, and interventions markedly reduce uptake. Research is needed that uses reproducible sampling methods and examines decision support strategies that lead to quality decisions.

Air travel and venous thromboembolism: a systematic review.

CONTEXT: Despite multiple attempts to document and quantify the danger of venous thromboembolism (VTE) following prolonged travel, there is still uncertainty about the magnitude of risk and what can be done to lower it. OBJECTIVES: To review the methodologic strength of the literature, estimate the risk of travel-related VTE, evaluate the efficacy of preventive treatments, and develop evidence-based recommendations for practice. DATA SOURCES: Studies identified from MEDLINE from 1966 through December 2005, supplemented by a review of the Cochrane Central Registry of Controlled Trials, the Database of Abstracts of Reviews of Effects, and relevant bibliographies. STUDY SELECTION: We included all clinical studies that either reported primary data concerning travel as a risk factor for VTE or tested preventive measures for travel-related VTE. DATA EXTRACTION AND ANALYSIS: Two reviewers reviewed each study independently to assess inclusion criteria, classify research design, and rate methodologic features. The effect of methodologic differences, VTE risk, and travel duration on VTE rate was evaluated using a logistic regression model. DATA SYNTHESIS: Twenty-four published reports, totaling 25 studies, met inclusion criteria (6 case-control studies, 10 cohort studies, and 9 randomized controlled trials). Method of screening for VTE [screening ultrasound compared to usual clinical care, odds ratio (OR) 390], outcome measure [all VTE compared to pulmonary embolism (PE) only, OR 21], duration of travel (<6 hours compared to 6-8 hours, OR 0.011), and clinical risk ("higher" risk travelers compared to "lower," OR 3.6) were significantly related to VTE rate. Clinical VTE after prolonged travel is rare [27 PE per million flights diagnosed through usual clinical care, 0.05% symptomatic deep venous thrombosis (DVT) diagnosed through screening ultrasounds], but asymptomatic thrombi of uncertain clinical significance are more common. Graduated compression stockings prevented travel-related VTE (P < 0.05 in 4 of 6 studies), aspirin did not, and low-molecular-weight heparin (LMWH) showed a trend toward efficacy in one study. CONCLUSIONS: All travelers, regardless of VTE risk, should avoid dehydration and frequently exercise leg muscles. Travelers on a flight of less than 6 hours and those with no known risk factors for VTE, regardless of the duration of the flight, do not need DVT prophylaxis. Travelers with 1 or more risk factors for VTE should consider graduated compression stockings and/or LMWH for flights longer than 6 hours.

Uptake rates for breast cancer genetic testing: a systematic review.

PURPOSE: Individuals and families dealing with the possibility of hereditary cancer risk face numerous decisions, including whether to obtain genetic testing. The purpose of this article is to determine what is known about the rate at which people obtain cancer genetic testing. METHODS: Using MEDLINE, CINAHL, and PSYCHINFO plus reviewing reference lists of relevant articles, we identified 40 studies in May 2002 that addressed breast cancer-related decisions, enrolled adult participants, were published in 1990 or more recently, were peer-reviewed primary clinical studies, addressed genetic testing either alone or in combination with genetic counseling, and reported rates at which participants showed interest in and/or underwent cancer genetic testing. Information regarding study design, participants, and genetic testing uptake rates was recorded. Each article was reviewed for methodologic quality using a flexible quality review system applicable to all study types. RESULTS: Of the 40 studies, 25 provided information about hypothetical genetic testing decisions, 14 about real decisions, and 1 about both. Mean hypothetical uptake was 66% (range, 20-96%) and real uptake was 59% (range, 25-96%). Multivariate logistic regression analyses found that decision type (real/hypothetical), personal and family history of breast cancer, and variability in sampling strategy, recruitment setting, and criteria for real and hypothetical uptake were independently associated with uptake. Our systematic review identified additional explanations for uptake variability (investigator influences, small sample sizes, variability in target populations, lack of clearly described sampling strategies, sampling methods open to bias, and variability in reporting associated risk factors). CONCLUSION: In addition to clinical characteristics, research methodologic issues are likely to be major determinants of variability in published breast cancer genetic testing uptake rates. An understanding of these issues will clarify to clinicians why their clinical experience may not be congruent with published rates and help guide future research.

Free clinics: a national survey.

OBJECTIVES: To describe the scope and value of services provided by free clinics across the United States. METHODS: Mail survey of directors of free clinics registered in the Free Clinic Directory of the Free Clinic Foundation of America, November 2001, concerning the calendar year 2001. RESULTS: Eighty two percent (281/355) of clinics responded. Seventy five percent of clinics described their target population as the "uninsured" and 23% as "low income". Fifty five percent had income based eligibility criteria of 200% Federal poverty level or less. Clinics provided a mean of 5,989 patient visits/year and 11,202 prescriptions/year to 2,311 unique patients. 61.8% of patients were female, 80.4% between ages 19 to 64, 55.1% white, 21.8% black, and 18.7% Hispanic. Clinics were open 29.7 hours/week, 4.1 days/week, and 32.9% had a licensed pharmacy. The mean annual budget was $458,028 and clinics were staffed by 156.7 volunteers and 6.9 paid employees per clinic. CONCLUSIONS: Free clinics have become an established part of the safety net for the uninsured. The differences among the clinics are striking, supporting the conclusion that a variety of approaches to the care of the underserved can be used. However, despite their efforts, the responding free clinics manage to provide care to only 650,000 of the nation's 41 million uninsured.

Repeated-measures modeling improved comparison of diagnostic tests in meta-analysis of dependent studies.

OBJECTIVE: Current methods for meta-analysis of diagnostic tests do not allow utilizing all the information from papers in which several tests have been studied on the same patient sample. We demonstrate how to combine several studies of diagnostic tests, where each study reports on more than one test and some tests (but not necessarily all of them) are shared with other papers selected for the meta-analysis. We adopt statistical methodology for repeated measurements for the purpose of meta-analysis of diagnostic tests. STUDY DESIGN AND SETTING: The method allows for missing values of some tests for some papers, takes into account different sample sizes of papers, adjusts for background and confounding factors including test-specific covariates and paper-specific covariates, and accounts for correlations of the repeated measurements within each paper. It does not need individual-level data, although it can be modified to use them, and uses the two-by-two table of test results vs. gold standard. RESULTS: The results are translated from diagnostic odds ratios (DOR) to more clinically useful measures such as predictive values, post-test probabilities, and likelihood ratios. Models to capture between-study variation are introduced. The fit and influence of specific studies on the regression can be evaluated. Furthermore, model-based tests for homogeneity of DORs across papers are presented. CONCLUSION: The use of this new method is illustrated using a recent meta-analysis of the D-dimer test for the diagnosis of deep venous thrombosis.

D-dimer testing for deep venous thrombosis: a metaanalysis.

BACKGROUND: The use of D-dimer assays as a rule-out test for deep venous thrombosis (DVT) is controversial. To clarify this issue we performed a systematic review of the relevant literature. METHODS: We identified eligible studies, using MEDLINE entries from February 1995 through October 2003, supplemented by a review of bibliographies of relevant articles. Studies reporting accuracy evaluations comparing D-dimer test results with lower extremity ultrasound or venography in symptomatic patients with suspected acute DVT were selected for review. Two reviewers critically appraised each study independently according to previously established methodologic standards for diagnostic test research. Those studies judged to be of highest quality were designated Level 1. RESULTS: The 23 Level 1 studies reported data on 21 different D-dimer assays. There was wide variation in assay sensitivity, specificity, and negative predictive values, and major differences in methodology of reviewed studies. A multivariate analysis of assay performance, controlling for sample size, DVT prevalence, reference standard, and patient mix, found few differences among the assays in effect on test performance as measured by diagnostic odds ratio. Increasing prevalence of DVT was associated with poorer test performance (P = 0.01), whereas the choice of venography as the reference standard was associated with better test performance (P <0.005). CONCLUSIONS: Explanations for the wide variation in assay performance include differences in biochemical and technical characteristics of the assays, heterogeneity and small size of patient groups, and bias introduced by choice of reference standards. Assay sensitivity and negative predictive value were frequently <90%, uncharacteristic of a good rule-out test. General use of D-dimer assays as a stand-alone test for the diagnosis of DVT is not supported by the literature.

The d-dimer test for deep venous thrombosis: gold standards and bias in negative predictive value.

BACKGROUND: Because venous ultrasound (US) fails to fully image the calf veins, there is the potential for US gold standard studies to classify patients with calf deep venous thrombosis (DVT) in the nondiseased category, causing bias in test index calculations. A false increase in negative predictive value (NPV) is especially likely because calf DVT false-negative tests will be counted in the numerator along with the true-negative tests in NPV calculations. We verified the presence and magnitude of this bias for the d-dimer test. METHODS: We abstracted data on overall (calf and thigh) and thigh-only test sensitivity, specificity, and NPV from the six English language studies published between March 1995 and October 2001 that compared d-dimer to a gold standard (GS) capable of imaging both thigh and calf veins and that also stratified results by thigh and calf location. Thigh specificity and NPV were calculated classifying calf DVT patients as free of disease. RESULTS: The six studies included 81-214 participants and provided 26 comparisons of 16 different d-dimer assays to the GS. Thigh sensitivity was higher than overall sensitivity in 22 of 26 comparisons (range, -0.3 to 8.6); thigh specificity was lower than overall specificity in all comparisons (range, -0.7 to -7.8); and thigh NPV was higher than overall NPV in 22 of 26 comparisons and unchanged in 4 comparisons (range, 0.0-9.2). NPV was >95% in 20 of the thigh results but >95% in only 8 of the overall results. CONCLUSIONS: Different GS can produce clinically significant differences in test indices. Care must be taken in interpreting DVT studies that evaluate d-dimer as a rule-out test and that use US as a GS, because missed calf DVT can falsely increase the NPV.