Treatment Patterns and Characteristics of Individuals Initiating High-Dose Insulin for Type 2 Diabetes Mellitus.

BACKGROUND: Few studies have examined patient characteristics and treatment patterns of high-dose insulin therapy (> 200 units/day) among patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: To understand patient characteristics, dosing, adherence, and persistence related to high-dose insulin therapy. METHODS: This was a retrospective observational study that used administrative claims from a large national health plan. Patients were identified who had been diagnosed with T2DM and who were aged 18-89 years, enrolled in a commercial or Medicare Advantage Prescription Drug plan, newly initiated on a total daily dose (TDD) > 200 units of insulin between January 2011 and August 2015. Patients were required to be enrolled 6 months before and 12 months after the index date. Patients were categorized to Regimen-100 if treated with U-100 insulin only or Regimen-500 if treated with U-500R with or without U-100. Baseline demographic and clinical characteristics were evaluated. An adjustment factor for the days supply was calculated as the ratio of median time between insulin claims, and median pharmacy reported days supply for each insulin prescription. Adjusted days supply, quantity, and concentration were used to calculate TDD for each quarter after the index date. Adherence was measured as the proportion of days covered (PDC) for each regimen. Persistence was measured in 2 ways: the percentage of patients remaining on index medications in each quarter and the proportion of patients who maintained TDD > 200 units during all 4 quarters of the 12-month post-index period. RESULTS: We identified 2,339 patients newly titrated up to TDD > 200 units on either Regimen-100 (2,062, 88.2%) or Regimen-500 (277, 11.8%). Patients on Regimen-500 were slightly younger with higher prevalence of comorbidities. The mean TDD (SD) for Regimen-100 decreased from 228.6 (36.0) units during the first quarter to 194.2 (181.4) units during the last quarter. The mean TDD (SD) for Regimen-500 increased from 294.2 (102.2) units in the first quarter to 304.8 (281.6) units in last quarter. The average adherence to the high-dose insulin regimen was 68.2% (30.7; median 72.6%) for the Regimen-100 cohort and 75.5% (27.0; median 85.2%) for the Regimen-500 cohort. In the Regimen-100 and Regimen-500 cohorts, 45.3% and 55.2% had a PDC ≥ 80%, respectively. Only 23.0% and 51.6% of patients maintained TDD > 200 units for the Regimen-100 and Regimen-500 cohorts, respectively, throughout the 4 quarters after the index date. CONCLUSIONS: We observed that many patients did not maintain high-dose insulin use over time, especially those on standard U-100 insulin only. This dosing pattern appears to reflect the differences in patient characteristics, insulin needs, and adherence/persistence behavior between those on Regimen-100 and those on Regimen-500. DISCLOSURES: This study was supported by funding from Eli Lilly and Company to Humana as a collaborative research project involving employees of both companies. Chen, Brown, Fan, Taylor, and He are employees of Eli Lilly and Company. Nair and Meah are employees of Humana, which received funding to complete this research. Siadaty was an employee of Humana at the time of this study.

Retrospective assessment of patient characteristics and healthcare costs prior to a diagnosis of Alzheimer's disease in an administrative claims database.

BACKGROUND: The objective of this study was to examine patient characteristics and health care resource utilization (HCRU) in the 36 months prior to a confirmatory diagnosis of Alzheimer's disease (AD) compared to a matched cohort without dementia during the same time interval. METHODS: Patients newly diagnosed with AD (with ≥2 claims) were identified between January 1, 2013 to September 31, 2015, and the date of the second claim for AD was defined as the index date. Patients were enrolled for at least 36 months prior to index date. The AD cohort was matched to a cohort with no AD or dementia codes (1:3) on age, gender, race/ethnicity, and enrollment duration prior to the index date. Descriptive analyses were used to summarize patient characteristics, HCRU, and healthcare costs prior to the confirmatory AD diagnosis. The classification and regression tree analysis and logistic regression were used to identify factors associated with the AD diagnosis. RESULTS: The AD cohort (N = 16,494) had significantly higher comorbidity indices and greater odds of comorbid mental and behavioral diagnoses, including mild cognitive impairment, mood and anxiety disorders, behavioral disturbances, and cerebrovascular disease, heart disease, urinary tract infections, and pneumonia than the matched non-AD or dementia cohort (N = 49,482). During the six-month period before the confirmatory AD diagnosis, AD medication use and diagnosis of mild cognitive impairment, Parkinson's disease, or mood disorder were the strongest predictors of a subsequent confirmatory diagnosis of AD. Greater HCRU and healthcare costs were observed for the AD cohort primarily during the six-month period before the confirmatory AD diagnosis. CONCLUSION: The results of this study demonstrated a higher comorbidity burden and higher costs for patients prior to a diagnosis of AD in comparison to the matched cohort. Several comorbidities were associated with a subsequent diagnosis of AD.

Pacifiers and breastfeeding: a systematic review.

OBJECTIVE: To summarize current evidence on the association between infant pacifier use and breastfeeding. DATA SOURCES: MEDLINE, CINAHL, the Cochrane Library, EMBASE, POPLINE, and bibliographies of identified articles. STUDY SELECTION: A search for English-language records (from January 1950 through August 2006) containing the Medical Subject Heading terms pacifiers and breastfeeding was conducted, resulting in 1098 reports. Duplicate and irrelevant studies were excluded, yielding 29 studies that fit inclusion criteria for the review (4 randomized controlled trials, 20 cohort studies, and 5 cross-sectional studies). Two independent reviewers abstracted data and scored these studies for quality; disagreements were settled through consensus with a third investigator. MAIN EXPOSURE: Pacifier use. MAIN OUTCOME MEASURES: Breastfeeding duration or exclusivity. RESULTS: Results from 4 randomized controlled trials revealed no difference in breastfeeding outcomes with different pacifier interventions (pacifier use during tube feeds, pacifier use at any time after delivery, an educational program for mothers emphasizing avoidance of pacifiers, and a UNICEF [United Nations Children's Fund]/World Health Organization Baby Friendly Hospital environment). Most observational studies reported an association between pacifier use and shortened duration of breastfeeding. CONCLUSIONS: The highest level of evidence does not support an adverse relationship between pacifier use and breastfeeding duration or exclusivity. The association between shortened duration of breastfeeding and pacifier use in observational studies likely reflects a number of other complex factors, such as breastfeeding difficulties or intent to wean. Ongoing quantitative and qualitative research is needed to better understand the relationship between pacifier use and breastfeeding.

Impact of lifestyle intervention on lost productivity and disability: improving control with activity and nutrition.

OBJECTIVE: To evaluate the effectiveness of a lifestyle intervention (LI) in reducing work loss and disability days. METHODS: One year randomized controlled trial of health plan members (n = 147) with type 2 diabetes and obesity. Members were randomized to modest-cost LI or usual care (UC). Outcomes were group differences in cumulative days either missed at work or with disability using Mann-Whitney U-tests and Poisson regression models. RESULTS: LI reduced the risk of workdays lost by 64.3% (P

Multi-database mining.

Biomedical data useful for data mining are often distributed across multiple databases. These databases may be aggregated using several techniques to create single data sets that may be mined using standard approaches; however, separate databases may, in their design or data representation, capture information that is analytically useful and that is lost on integration. Recent techniques for mining multiple databases simultaneously but separately may preserve and leverage the unique perspectives within each database. This article presents an example, "dual mining," in which concurrent analysis of a target database with a related knowledge base can improve the identification of association patterns in the target most likely to be of interest for further analysis.

Effects of lifestyle intervention on health care costs: Improving Control with Activity and Nutrition (ICAN).

OBJECTIVE: To evaluate program and health care costs of a lifestyle intervention in a high-risk obese population. DESIGN: Twelve-month randomized controlled trial comparing lifestyle case management to usual care. SUBJECTS/SETTING: Health plan members (n=147) with obesity (body mass index >/=27) and type 2 diabetes. INTERVENTION: Lifestyle case management entailed individual and group education, support, and referrals by registered dietitians. Those in the usual-care group received educational material. MAIN OUTCOME MEASURES: Medical and pharmaceutical health care costs reimbursed by the participant's primary insurance company. STATISTICAL ANALYSIS: Total costs were modeled using the four-equation model using previous year cost as a predictor. RESULTS: Net cost of the intervention was $328 per person per year. After incorporating program costs, mean health plan costs were $3,586 (95% confidence interval [CI]: -$8,036, -$25, P<0.05) lower in case management compared to usual care. The difference was driven by group differences in medical (-$3,316, 95% CI: -$7,829 to -$320, P<0.05) but not pharmaceutical costs (-$239, 95% CI: -$870 to $280, not statistically significant), with fewer inpatient admissions and costs among case management compared with usual care (admission prevalence: 2.8% vs 22.5% respectively, P<0.001). CONCLUSION: Addition of a modest-cost, registered dietitian-led lifestyle case-management intervention to usual medical care did not increase health care costs and suggested modest cost savings among obese patients with type 2 diabetes. Larger trials are needed to determine whether these results can be replicated in a broader population. The findings can be judiciously applied to support that the addition of a registered dietitian-led lifestyle case-management program to medical care does not increase health care costs.

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.

Relemed: sentence-level search engine with relevance score for the MEDLINE database of biomedical articles.

BACKGROUND: Receiving extraneous articles in response to a query submitted to MEDLINE/PubMed is common. When submitting a multi-word query (which is the majority of queries submitted), the presence of all query words within each article may be a necessary condition for retrieving relevant articles, but not sufficient. Ideally a relationship between the query words in the article is also required. We propose that if two words occur within an article, the probability that a relation between them is explained is higher when the words occur within adjacent sentences versus remote sentences. Therefore, sentence-level concurrence can be used as a surrogate for existence of the relationship between the words. In order to avoid the irrelevant articles, one solution would be to increase the search specificity. Another solution is to estimate a relevance score to sort the retrieved articles. However among the >30 retrieval services available for MEDLINE, only a few estimate a relevance score, and none detects and incorporates the relation between the query words as part of the relevance score. RESULTS: We have developed "Relemed", a search engine for MEDLINE. Relemed increases specificity and precision of retrieval by searching for query words within sentences rather than the whole article. It uses sentence-level concurrence as a statistical surrogate for the existence of relationship between the words. It also estimates a relevance score and sorts the results on this basis, thus shifting irrelevant articles lower down the list. In two case studies, we demonstrate that the most relevant articles appear at the top of the Relemed results, while this is not necessarily the case with a PubMed search. We have also shown that a Relemed search includes not only all the articles retrieved by PubMed, but potentially additional relevant articles, due to the extended 'automatic term mapping' and text-word searching features implemented in Relemed. CONCLUSION: By using sentence-level matching, Relemed can deliver higher specificity, thus eliminating more false-positive articles. By introducing an appropriate relevance metric, the most relevant articles on which the user wishes to focus are listed first. Relemed also shrinks the displayed text, and hence the time spent scanning the articles.

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.

Locating previously unknown patterns in data-mining results: a dual data- and knowledge-mining method.

BACKGROUND: Data mining can be utilized to automate analysis of substantial amounts of data produced in many organizations. However, data mining produces large numbers of rules and patterns, many of which are not useful. Existing methods for pruning uninteresting patterns have only begun to automate the knowledge acquisition step (which is required for subjective measures of interestingness), hence leaving a serious bottleneck. In this paper we propose a method for automatically acquiring knowledge to shorten the pattern list by locating the novel and interesting ones. METHODS: The dual-mining method is based on automatically comparing the strength of patterns mined from a database with the strength of equivalent patterns mined from a relevant knowledgebase. When these two estimates of pattern strength do not match, a high "surprise score" is assigned to the pattern, identifying the pattern as potentially interesting. The surprise score captures the degree of novelty or interestingness of the mined pattern. In addition, we show how to compute p values for each surprise score, thus filtering out noise and attaching statistical significance. RESULTS: We have implemented the dual-mining method using scripts written in Perl and R. We applied the method to a large patient database and a biomedical literature citation knowledgebase. The system estimated association scores for 50,000 patterns, composed of disease entities and lab results, by querying the database and the knowledgebase. It then computed the surprise scores by comparing the pairs of association scores. Finally, the system estimated statistical significance of the scores. CONCLUSION: The dual-mining method eliminates more than 90% of patterns with strong associations, thus identifying them as uninteresting. We found that the pruning of patterns using the surprise score matched the biomedical evidence in the 100 cases that were examined by hand. The method automates the acquisition of knowledge, thus reducing dependence on the knowledge elicited from human expert, which is usually a rate-limiting step.

Spatial analysis of prostate cancer incidence and race in Virginia, 1990-1999.

BACKGROUND: Racial disparities exist in prostate cancer incidence. An important contributor to these disparities may be socioeconomic status. METHODS: Virginia Cancer Registry data, 1990-1999 (37,373 cases) were geocoded to the Census tract and county level. The annualized, age-adjusted incidence rates for African Americans and whites were calculated, and crude and smoothed maps of these rates were produced. Statistical tests for clustering of cases were conducted. Prostate cancer incidence was statistically modeled as a function of area-based measures of poverty, median household income, education, rural status, ratio of physicians to population in each county, percentage of men in each county obtaining prostate cancer screening with the prostate-specific antigen (PSA) test, and percent of households headed by females. RESULTS: Prostate cancer incidence was elevated in the eastern and central portions of the state. Statistical tests for clustering were highly significant (Tango's test, p<0.008; spatial scan statistic, p<0.001). Poverty and lower education were associated with a decreased incidence among whites but not African Americans. Median household income and urban status were positively associated with incidence for both populations. Among whites, increased percent of female heads of households and ratio of physicians per population were associated with increased incidence. Associations between predictor variables and prostate cancer incidence were seen only in the census tract level analyses. CONCLUSIONS: Overall, the findings support the argument that area measures of poverty and education do not explain the increased incidence of prostate cancer among African Americans. Other factors, such as dietary practices, may help explain racial disparities in prostate cancer incidence. Because of the large differences between tract and county level results, the time and expense of obtaining data geocoded to the tract level seems worthwhile.

Data mining and clinical data repositories: Insights from a 667,000 patient data set.

Clinical repositories containing large amounts of biological, clinical, and administrative data are increasingly becoming available as health care systems integrate patient information for research and utilization objectives. To investigate the potential value of searching these databases for novel insights, we applied a new data mining approach, HealthMiner, to a large cohort of 667,000 inpatient and outpatient digital records from an academic medical system. HealthMiner approaches knowledge discovery using three unsupervised methods: CliniMiner, Predictive Analysis, and Pattern Discovery. The initial results from this study suggest that these approaches have the potential to expand research capabilities through identification of potentially novel clinical disease associations.

Geographic bias related to geocoding in epidemiologic studies.

BACKGROUND: This article describes geographic bias in GIS analyses with unrepresentative data owing to missing geocodes, using as an example a spatial analysis of prostate cancer incidence among whites and African Americans in Virginia, 1990-1999. Statistical tests for clustering were performed and such clusters mapped. The patterns of missing census tract identifiers for the cases were examined by generalized linear regression models. RESULTS: The county of residency for all cases was known, and 26,338 (74%) of these cases were geocoded successfully to census tracts. Cluster maps showed patterns that appeared markedly different, depending upon whether one used all cases or those geocoded to the census tract. Multivariate regression analysis showed that, in the most rural counties (where the missing data were concentrated), the percent of a county's population over age 64 and with less than a high school education were both independently associated with a higher percent of missing geocodes. CONCLUSION: We found statistically significant pattern differences resulting from spatially non-random differences in geocoding completeness across Virginia. Appropriate interpretation of maps, therefore, requires an understanding of this phenomenon, which we call "cartographic confounding."

Do pacifiers reduce the risk of sudden infant death syndrome? A meta-analysis.

OBJECTIVE: Pacifier use has been reported to be associated with a reduced risk of sudden infant death syndrome (SIDS), but most countries around the world, including the United States, have been reluctant to recommend the use of pacifiers because of concerns about possible adverse effects. This meta-analysis was undertaken to quantify and evaluate the protective effect of pacifiers against SIDS and to make a recommendation on the use of pacifiers to prevent SIDS. METHODS: We searched the Medline database (January 1966 to May 2004) to collect data on pacifier use and its association with SIDS, morbidity, or other adverse effects. The search strategy included published articles in English with the Medical Subject Headings terms "sudden infant death syndrome" and "pacifier" and the keywords "dummy" and "soother." Combining searches resulted in 384 abstracts, which were all read and evaluated for inclusion. For the meta-analysis, articles with data on the relationship between pacifier use and SIDS risk were limited to published original case-control studies, because no prospective observational reports were found; 9 articles met these criteria. Two independent reviewers evaluated each study on the basis of the 6 criteria developed by the American Academy of Pediatrics Task Force on Infant Positioning and SIDS; in cases of disagreement, a third reviewer evaluated the study, and a consensus opinion was reached. We developed a script to calculate the summary odds ratio (SOR) by using the reported ORs and respective confidence intervals (CI) to weight the ORs. We then pooled them together to compute the SOR. We performed the Breslow-Day test for homogeneity of ORs, Cochran-Mantel-Haenszel test for the null hypothesis of no effect (OR = 1), and the Mantel-Haenszel common OR estimate. The consistency of findings was evaluated and the overall potential benefits of pacifier use were weighed against the potential risks. Our recommendation is based on the taxonomy of the 5-point (A-E) scale adopted by the US Preventive Services Task Force. RESULTS: Seven studies were included in the meta-analysis. The SOR calculated for usual pacifier use (with univariate ORs) is 0.90 (95% confidence interval [CI]: 0.79-1.03) and 0.71 (95% CI: 0.59-0.85) with multivariate ORs. For pacifier use during last sleep, the SORs calculated using univariate and multivariate ORs are 0.47 (95% CI: 0.40-0.55) and 0.39 (95% CI: 0.31-0.50), respectively. CONCLUSIONS: Published case-control studies demonstrate a significant reduced risk of SIDS with pacifier use, particularly when placed for sleep. Encouraging pacifier use is likely to be beneficial on a population-wide basis: 1 SIDS death could be prevented for every 2733 (95% CI: 2416-3334) infants who use a pacifier when placed for sleep (number needed to treat), based on the US SIDS rate and the last-sleep multivariate SOR resulting from this analysis. Therefore, we recommend that pacifiers be offered to infants as a potential method to reduce the risk of SIDS. The pacifier should be offered to the infant when being placed for all sleep episodes, including daytime naps and nighttime sleeps. This is a US Preventive Services Task Force level B strength of recommendation based on the consistency of findings and the likelihood that the beneficial effects will outweigh any potential negative effects. In consideration of potential adverse effects, we recommend pacifier use for infants up to 1 year of age, which includes the peak ages for SIDS risk and the period in which the infant's need for sucking is highest. For breastfed infants, pacifiers should be introduced after breastfeeding has been well established.

Hypothermia is a bedside predictor of imminent death in patients with congestive heart failure.

BACKGROUND: Most studies on predictors of mortality for patients with congestive heart failure (CHF) have described predictors that are either difficult to measure in routine practice or are only modestly sensitive and specific. Having observed 3 patients whose body temperature decreased shortly before death, we hypothesized that hypothermia may predict inhospital mortality. METHODS: The medical records of 291 patients with a primary discharge diagnosis of CHF were selected from 423 admissions to Memorial Hermann Hospital, Houston, Tex, 1998, after excluding patients with comorbidities that confound body temperature, deaths for causes other than progressive pump failure, and readmissions except the last. Three groups were defined on the basis of admission body temperature (T adm): hypothermia groups T adm (95.5 degrees F-96.5 degrees F) and T adm < 95.5 degrees F, and reference group T adm > or = 96.6 degrees F. Several other known CHF risk factors were studied for confounding, and adjusted hazard ratios were calculated using Cox regression. RESULTS: Of the 291 patients (mean age 73 years, 47% men), 17 (6%) had hypothermia on admission. Mean hospital stay was 5 days. Of the 17 (6%) patients who died of pump failure, 5 had been hypothermic on admission. Hypothermia was significantly associated with survival, and after adjusting for New York Heart Association functional class, hazard ratio for T adm < 95.5 degrees F was 4.46 (95% confidence interval 1.38-14.3) (P trend = .0283). CONCLUSIONS: Hypothermia predicted inhospital death in these patients with CHF. If confirmed by future studies, this finding could prove useful, because temperature can be measured continuously, rapidly, and inexpensively, in or out of the hospital.

Papaverine prolongs patency of peripheral arterial catheters in neonates.

OBJECTIVE: To test the hypothesis that the continuous infusion of papaverine-containing solutions in peripheral arterial catheters would decrease the catheter failure rate and increase the functional duration of the catheter in neonates. STUDY DESIGN: In a prospective, randomized, placebo-controlled, masked trial, 82 catheters were placed in 70 neonates in the papaverine group and 98 catheters were placed in 71 neonates in the placebo group. RESULTS: The catheters in the papaverine group remained functional for a significantly longer duration than those in the placebo group. The median (25th%, 75th%) time before catheter failure was 16.6 (9.5, 24.3) days in the papaverine group and 12 days (6.1, 18.2) in the placebo group ( P = .023; Cox proportional hazards model). There was no significant difference in the incidence of intraventricular hemorrhage (IVH) between groups, and there was no evidence of hepatic toxicity. CONCLUSIONS: The continuous infusion of papaverine-containing fluids prolongs the patency of peripheral arterial catheters in neonates. In this small number of infants, we found no difference in the incidence of IVH or hepatic toxicity.

Proportional odds ratio model for comparison of diagnostic tests in meta-analysis.

BACKGROUND: Consider a meta-analysis where a 'head-to-head' comparison of diagnostic tests for a disease of interest is intended. Assume there are two or more tests available for the disease, where each test has been studied in one or more papers. Some of the papers may have studied more than one test, hence the results are not independent. Also the collection of tests studied may change from one paper to the other, hence incomplete matched groups. METHODS: We propose a model, the proportional odds ratio (POR) model, which makes no assumptions about the shape of ORp, a baseline function capturing the way OR changes across papers. The POR model does not assume homogeneity of ORs, but merely specifies a relationship between the ORs of the two tests. One may expand the domain of the POR model to cover dependent studies, multiple outcomes, multiple thresholds, multi-category or continuous tests, and individual-level data. RESULTS: In the paper we demonstrate how to formulate the model for a few real examples, and how to use widely available or popular statistical software (like SAS, R or S-Plus, and Stata) to fit the models, and estimate the discrimination accuracy of tests. Furthermore, we provide code for converting ORs into other measures of test performance like predictive values, post-test probabilities, and likelihood ratios, under mild conditions. Also we provide code to convert numerical results into graphical ones, like forest plots, heterogeneous ROC curves, and post test probability difference graphs. CONCLUSIONS: The flexibility of POR model, coupled with ease with which it can be estimated in familiar software, suits the daily practice of meta-analysis and improves clinical decision-making.

The effect of physician feedback and an action checklist on diabetes care measures.

The objective was to evaluate whether physician feedback accompanied by an action checklist improved diabetes care process measures. Eighty-three physicians in an academic general medicine clinic were provided a single feedback report on the most recent date and result of diabetes care measures (glycosylated hemoglobin [A1c], urine microalbumin, serum creatinine, lipid levels, retinal examination) as well as recent diabetes medication refills with calculated dosing and adherence on 789 patients. An educational session regarding the feedback and adherence information was provided. The physicians were asked to complete a checklist accompanying the feedback on each of their patients, indicating requested actions with respect to follow-up, testing, and counseling. The physicians completed 82% of patient checklists, requesting actions consistent with patient needs on the basis of the feedback. Of the physicians, 93% felt the patient information and intervention format to be useful. The odds of urine microalbumin testing, serum creatinine, lipid profile, A1c, and retinal examination increased in the 6 months after the feedback. The increase was sustained at 1 year only for microalbumin and retinal exams. There was no significant change in refill adherence for the group overall after the feedback, although adherence did improve among patients of physicians attending the educational session. No significant change was noted in lipid or A1c levels during the study period. In conclusion, a simple physician feedback tool with action checklist can be both helpful and popular for improving rates of diabetes care guideline adherence. More complex interventions are likely required to improve diabetes outcomes.

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.