Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.
BACKGROUND AND OBJECTIVES Studies of diagnostic accuracy most often report pairs of sensitivity and specificity. We demonstrate the advantage of using bivariate meta-regression models to analyze such data. METHODS We discuss the methodology of both the summary Receiver Operating Characteristic (sROC) and the bivariate approach by reanalyzing the data of a published meta-analysis. RESULTS The sROC approach is the standard method for meta-analyzing diagnostic studies reporting pairs of sensitivity and specificity. This method uses the diagnostic odds ratio as the main outcome measure, which removes the effect of a possible threshold but at the same time loses relevant clinical information about test performance. The bivariate approach preserves the two-dimensional nature of the original data. Pairs of sensitivity and specificity are jointly analyzed, incorporating any correlation that might exist between these two measures using a random effects approach. Explanatory variables can be added to the bivariate model and lead to separate effects on sensitivity and specificity, rather than a net effect on the odds ratio scale as in the sROC approach. The statistical properties of the bivariate model are sound and flexible. CONCLUSION The bivariate model can be seen as an improvement and extension of the traditional sROC approach.
The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed.
BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy, as for randomized trials. We investigate limitations of standard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods. METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy. RESULTS Type I error rates for the Begg, Egger, and Macaskill tests are inflated for typical diagnostic odds ratios (DOR), when disease prevalence differs from 50% and when thresholds favor sensitivity over specificity or vice versa. Regression and correlation tests based on functions of effective sample size are valid, if occasionally conservative, tests for sample size effects. Empirical evidence suggests that they have adequate power to be useful tests. When DORs are heterogeneous, however, all tests of funnel plot asymmetry have low power. CONCLUSION Existing tests that use standard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy. The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects.
Prevalence of Attention-De fi cit/ Hyperactivity Disorder: A Systematic Review and Meta-analysis
BACKGROUND AND OBJECTIVE: Overdiagnosis and underdiagnosis of attention-de fi cit/hyperactivity disorder (ADHD) are widely debated, fueled by variations in prevalence estimates across countries, time, and broadening diagnostic criteria. We conducted a meta-analysis to: establish a benchmark pooled prevalence for ADHD; examine whether estimates have increased with publication of different editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM); and explore the effect of study features on prevalence. METHODS: Medline, PsycINFO, CINAHL, Embase, and Web of Science were searched for studies with point prevalence estimates of ADHD. We included studies of children that used the diagnostic criteria from DSM-III, DSM-III-R and DSM-IV in any language. Data were extracted on sampling procedure, sample characteristics, assessors, measures, and whether full or partial criteria were met. RESULTS: The 175 eligible studies included 179 ADHD prevalence estimates with an overall pooled estimate of 7.2% (95% con fi dence interval: 6.7 to 7.8), and no statistically signi fi cant difference between DSM editions. In multivariable analyses, prevalence estimates for ADHD were lower when using the revised third edition of the DSM compared with the fourth edition ( P = .03) and when studies were conducted in Europe compared with North America ( P = .04). Few studies used population sampling with random selection. Most were from single towns or regions, thus limiting generalizability. CONCLUSIONS: Our review provides a benchmark prevalence estimate for ADHD. If population estimates of ADHD diagnoses exceed our estimate, then overdiagnosis may have occurred for some children. If fewer, then underdiagnosis may have occurred.
Imputing missing standard deviations in meta-analyses can provide accurate results.
BACKGROUND AND OBJECTIVES Many reports of randomized controlled trials (RCTs) fail to provide standard deviations (SDs) of their continuous outcome measures. Some meta-analysts substitute them by those reported in other studies, either from another meta-analysis or from other studies in the same meta-analysis. But the validity of such practices has never been empirically examined. METHODS We compared the actual standardized mean difference (SMD) of individual RCTs and the meta-analytically pooled SMD of all RCTs against those based on the above-mentioned two imputation methods in two meta-analyses of antidepressants. RESULTS Two meta-analyses included 39 RCTs of fluoxetine (n = 3,681) and 25 RCTs of amitriptyline (n = 1,832), which had actually reported means and SDs of the Hamilton Rating Scale for Depression. According to either of the two proposed imputation methods, the agreement between actual SMDs and imputed SMDs for individual RCTs was very good with ANOVA intraclass correlation coefficients between 0.61 and 0.97. The agreement between the actual pooled SMD and the imputed one was even better, with minimal differences in both their point estimates and 95% confidence intervals. CONCLUSION For a systematic review where some of the identified trials do not report SDs, it appears safe to borrow SDs from other studies.
Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype.
BACKGROUND AND OBJECTIVES Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Most childhood cases are caused by Shiga toxin-producing bacteria. The other form, atypical HUS (aHUS), accounts for 10% of cases and has a poor prognosis. Genetic complement abnormalities have been found in aHUS. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS We screened 273 consecutive patients with aHUS for complement abnormalities and studied their role in predicting clinical phenotype and response to treatment. We compared mutation frequencies and localization and clinical outcome in familial (82) and sporadic (191) cases. RESULTS In >70% of sporadic and familial cases, gene mutations, disease-associated factor H (CFH) polymorphisms, or anti-CFH autoantibodies were found. Either mutations or CFH polymorphisms were also found in the majority of patients with secondary aHUS, suggesting a genetic predisposition. Familial cases showed a higher prevalence of mutations in SCR20 of CFH and more severe disease than sporadic cases. Patients with CFH or THBD (thrombomodulin) mutations had the earliest onset and highest mortality. Membrane-cofactor protein (MCP) mutations were associated with the best prognosis. Plasma therapy induced remission in 55 to 80% of episodes in patients with CFH, C3, or THBD mutations or autoantibodies, whereas patients with CFI (factor I) mutations were poor responders. aHUS recurred frequently after kidney transplantation except for patients with MCP mutations. CONCLUSIONS Results underline the need of genetic screening for all susceptibility factors as part of clinical management of aHUS and for identification of patients who could safely benefit from kidney transplant.
Design and Methods
BACKGROUND AND OBJECTIVES The aim of this study was to evaluate the incidence and outcome of invasive fungal infections (IFI) in patients with hematologic malignancies. DESIGN AND METHODS This was a retrospective cohort study of patients admitted between 1999 and 2003 to 18 hematology wards in Italy. Each participating center provided information on all patients with newly diagnosed hematologic malignancies admitted during the survery period and on all episodes of IFI experienced by these patients. RESULTS The cohort was formed of 11,802 patients with hematologic malignacies: acute leukemia (myeloid 3012, lymphoid 1173), chronic leukemia (myeloid 596, lymphoid 1104), lymphoma (Hodgkin's 844, non-Hodgkin's 3457), or multiple myeloma (1616). There were 538 proven or probable IFI (4.6%); 373 (69%) occurred in patients with acute myeloid leukemia. Over half (346/538) were caused by molds (2.9%), in most cases Aspergillus spp. (310/346). The 192 yeast infections (1.6%) included 175 cases of candidemia. Overall and IFI-attributable mortality rates were 2% (209/11802) and 39% (209/538), respectively. The highest IFI-attributable mortality rates were associated with zygomycosis (64%) followed by fusariosis (53%), aspergillosis (42%), and candidemia (33%). INTERPRETATION AND CONCLUSIONS Patients with hematologic malignancies are currently at higher risk of IFI caused by molds than by yeasts, and the incidence of IFI is highest among patients with acute myeloid leukemia. Aspergillus spp are still the most common pathogens, followed by Candida spp. Other agents are rare. The attributable mortality rate for aspergillosis has dropped from 60-70% to approximately 40%. Candidemia-related mortality remains within the 30-40% range reported in literature although the incidence has decreased.
Heparin-induced thrombocytopenia.
BACKGROUND AND OBJECTIVE There are two types of heparin-induced thrombocytopenia (HIT). HIT I is characterized by a transitory, slight and asymptomatic reduction in platelet count, occurring in the first 1-2 days of therapy, that resolves spontaneously; in contrast, HIT II, which has an immunologic origin, is characterized by a significant thrombocytopenia generally after the fifth day of therapy that usually resolves in 5-15 days only after therapy withdrawal. HIT II is the most frequent and dangerous side-effect of heparin therapy; in fact, in spite of thrombocytopenia, it can be complicated by venous and arterial thrombosis. Therefore, the recognition of HIT II may be difficult due to the underlying thrombotic symptoms for which heparin is administered. The aim of this article is to review the most recent advances in the field and to give critical guidelines for the clinical diagnosis and treatment of HIT II. STATE OF THE ART The prevalence of HIT II, as confirmed by laboratory tests, seems to be about 2% in patients receiving unfractionated heparin (UH), while it is much lower in those receiving low molecular weight heparin (LMWH). The immunologic etiology of HIT II is largely accepted. Platelet factor 4 (PF4) displaced from endothelial heparan sulphate or directly from the platelets, binds to the heparin molecule to form an immunogenic complex. The anti-heparin/ PF4 IgG immunocomplexes activate platelets and provoke an immunologic endothelial lesion with thrombocytopenia and/or thrombosis. The IgG anti-heparin/PF4 immunocomplex activates platelets mainly through binding with the FcgRIIa (CD32) receptor. The onset of thrombocytopenia is independent of the dosage, schedule and route of administration of heparin. Orthopedic and cardiovascular surgery patients receiving post-surgical prophylaxis or treatment for deep venous thrombosis are at higher risk of HIT II. Besides thrombocytopenia, cutaneous allergic manifestations and skin necrosis may be present. Hemorrhagic events are not frequent, while the major clinical complications in 30% of patients are both arterial and venous thromboses which carry a 20% mortality. The diagnosis of HIT II should be formulated on the basis of clinical criteria and in vitro demonstration of heparin-dependent antibodies. Functional tests, such as platelet aggregation and (14)C-serotonin release assay and immunologic tests, such as the search for anti-PF4/heparin complex antibodies by an ELISA method are available. If HITT II is probable, heparin must be immediately suspended and an alternative anticoagulant therapy should be initiated before resolution of thrombocytopenia and the following treatment with a vitamin K antagonist. The general opinion is to administer low molecular weight heparin (in the absence of in vitro cross-reactivity with the antibodies), heparinoids such as Orgaran or direct thrombin inhibitors such as hirudin. PERSPECTIVES Further studies are required to elucidate the pathogenesis of HIT II and especially to discover the clinical and immunologic factors that induce the occurrence of thrombotic complications. The best therapeutic strategy remains to be confirmed in larger clinical trials.
Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study.
BACKGROUND AND OBJECTIVES The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, 196 children undergoing CPB were prospectively enrolled and serial urine NGAL measurements obtained by ARCHITECT assay. The primary outcome was AKI, defined as a > or = 50% increase in serum creatinine. RESULTS AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death. CONCLUSIONS Accurate measurements of urine NGAL are obtained using the ARCHITECT platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.
Using the outcome for imputation of missing predictor values was preferred.
BACKGROUND AND OBJECTIVE Epidemiologic studies commonly estimate associations between predictors (risk factors) and outcome. Most software automatically exclude subjects with missing values. This commonly causes bias because missing values seldom occur completely at random (MCAR) but rather selectively based on other (observed) variables, missing at random (MAR). Multiple imputation (MI) of missing predictor values using all observed information including outcome is advocated to deal with selective missing values. This seems a self-fulfilling prophecy. METHODS We tested this hypothesis using data from a study on diagnosis of pulmonary embolism. We selected five predictors of pulmonary embolism without missing values. Their regression coefficients and standard errors (SEs) estimated from the original sample were considered as "true" values. We assigned missing values to these predictors--both MCAR and MAR--and repeated this 1,000 times using simulations. Per simulation we multiple imputed the missing values without and with the outcome, and compared the regression coefficients and SEs to the truth. RESULTS Regression coefficients based on MI including outcome were close to the truth. MI without outcome yielded very biased--underestimated--coefficients. SEs and coverage of the 90% confidence intervals were not different between MI with and without outcome. Results were the same for MCAR and MAR. CONCLUSION For all types of missing values, imputation of missing predictor values using the outcome is preferred over imputation without outcome and is no self-fulfilling prophecy.
World incidence of AKI: a meta-analysis.
BACKGROUND AND OBJECTIVES The burden of AKI around the globe has not been systematically examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A systematic review (2004-2012) of large cohort studies was conducted to estimate the world incidence of AKI and its stages of severity and associated mortality, and to describe geographic variations according to countries, regions, and their economies. AKI definitions were reclassified according to the Kidney Disease Improving Global Outcomes (KDIGO) staging system. Random-effects model meta-analyses and meta-regressions were used to generate summary estimates and explore sources of heterogeneity. RESULTS There were 312 studies identified (n=49,147,878) , primarily in hospital settings. Most studies originated from North America, Northern Europe, and Eastern Asia, from high-income countries, and from nations that spent ≥5% of the gross domestic product on total health expenditure. Among the 154 studies (n=3,585,911) that adopted a KDIGO-equivalent AKI definition, the pooled incidence rates of AKI were 21.6% in adults (95% confidence interval [95% CI], 19.3 to 24.1) and 33.7% in children (95% CI, 26.9 to 41.3). The pooled AKI-associated mortality rates were 23.9% in adults (95% CI, 22.1 to 25.7) and 13.8% in children (95% CI, 8.8 to 21.0). The AKI-associated mortality rate declined over time, and was inversely related to income of countries and percentage of gross domestic product spent on total health expenditure. CONCLUSIONS Using the KDIGO definition, 1 in 5 adults and 1 in 3 children worldwide experience AKI during a hospital episode of care. This analysis provides a platform to raise awareness of AKI with the public, government officials, and health care professionals.
Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study.
BACKGROUND AND OBJECTIVES The authors have previously shown that urine neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA, is an early predictive biomarker of acute kidney injury (AKI) after cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay developed for a standardized clinical platform (ARCHITECT analyzer, Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after CPB was tested. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In a pilot study with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, 196 children undergoing CPB were prospectively enrolled and serial urine NGAL measurements obtained by ARCHITECT assay. The primary outcome was AKI, defined as a > or = 50% increase in serum creatinine. RESULTS AKI developed in 99 patients (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25-fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels correlated with severity and duration of AKI, length of stay, dialysis requirement, and death. CONCLUSIONS Accurate measurements of urine NGAL are obtained using the ARCHITECT platform. Urine NGAL is an early predictive biomarker of AKI severity after CPB.
A Large Outbreak of Clostridium difficile–Associated Disease with an Unexpected Proportion of Deaths and Colectomies at a Teaching Hospital Following Increased Fluoroquinolone Use
Background and Objective: Fluoroquinolones have not been frequently implicated as a cause of Clostridium difficile outbreaks. Nosocomial C. difficile infections increased from 2.7 to 6.8 cases per 1,000 discharges (P < .001). During the first 2 years of the outbreak, there were 253 nosocomial C. difficile infections; of these, 26 resulted in colectomy and 18 resulted in death. We conducted an investigation of a large C. difficile outbreak in our hospital to identify risk factors and characterize the outbreak. Methods: A retrospective case-control study of case-patients with C. difficile infection from January 2000 through April 2001 and control-patients matched by date of hospital admission, type of medical service, and length of stay; an analysis of inpatient antibiotic use; and antibiotic susceptibility testing and molecular subtyping of isolates were performed. Results: On logistic regression analysis, clindamycin (odds ratio [OR], 4.8; 95% confidence interval [CI95], 1.9-12.0), ceftriaxone (OR, 5.4; CI95, 1.8-15.8), and levofloxacin (OR, 2.0; CI95, 1.2-3.3) were independently associated with infection. The etiologic fractions for these three agents were 10.0%, 6.7%, and 30.8%, respectively. Fluoroquinolone use increased before the onset of the outbreak (P < .001); 59% of case-patients and 41% of control-patients had received this antibiotic class. The outbreak was polyclonal, although 52% of isolates belonged to two highly related molecular subtypes. Conclusions: Exposure to levofloxacin was an independent risk factor for C. difficile-associated diarrhea and appeared to contribute substantially to the outbreak. Restricted use of levofloxacin and the other implicated antibiotics may be required to control the outbreak.
The key informant technique.
BACKGROUND AND OBJECTIVE This article considers the role of the key informant technique as a qualitative research method and examines the potential contribution of the approach to health care research. METHOD The principles underlying the technique and the advantages and disadvantages are considered, illustrated with examples from a range of social science studies. RESULTS AND CONCLUSION An example of the author's own use of key informants in a study of the professional relationship between general practitioners and specialists is described.
Imputation of missing values is superior to complete case analysis and the missing-indicator method in multivariable diagnostic research: a clinical example.
BACKGROUND AND OBJECTIVES To illustrate the effects of different methods for handling missing data--complete case analysis, missing-indicator method, single imputation of unconditional and conditional mean, and multiple imputation (MI)--in the context of multivariable diagnostic research aiming to identify potential predictors (test results) that independently contribute to the prediction of disease presence or absence. METHODS We used data from 398 subjects from a prospective study on the diagnosis of pulmonary embolism. Various diagnostic predictors or tests had (varying percentages of) missing values. Per method of handling these missing values, we fitted a diagnostic prediction model using multivariable logistic regression analysis. RESULTS The receiver operating characteristic curve area for all diagnostic models was above 0.75. The predictors in the final models based on the complete case analysis, and after using the missing-indicator method, were very different compared to the other models. The models based on MI did not differ much from the models derived after using single conditional and unconditional mean imputation. CONCLUSION In multivariable diagnostic research complete case analysis and the use of the missing-indicator method should be avoided, even when data are missing completely at random. MI methods are known to be superior to single imputation methods. For our example study, the single imputation methods performed equally well, but this was most likely because of the low overall number of missing values.
External validation is necessary in prediction research: a clinical example.
BACKGROUND AND OBJECTIVES Prediction models tend to perform better on data on which the model was constructed than on new data. This difference in performance is an indication of the optimism in the apparent performance in the derivation set. For internal model validation, bootstrapping methods are recommended to provide bias-corrected estimates of model performance. Results are often accepted without sufficient regard to the importance of external validation. This report illustrates the limitations of internal validation to determine generalizability of a diagnostic prediction model to future settings. METHODS A prediction model for the presence of serious bacterial infections in children with fever without source was derived and validated internally using bootstrap resampling techniques. Subsequently, the model was validated externally. RESULTS In the derivation set (n=376), nine predictors were identified. The apparent area under the receiver operating characteristic curve (95% confidence interval) of the model was 0.83 (0.78-0.87) and 0.76 (0.67-0.85) after bootstrap correction. In the validation set (n=179) the performance was 0.57 (0.47-0.67). CONCLUSION For relatively small data sets, internal validation of prediction models by bootstrap techniques may not be sufficient and indicative for the model's performance in future patients. External validation is essential before implementing prediction models in clinical practice.
Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential.
BACKGROUND AND OBJECTIVES We previously found that human fetal lung is a rich source of mesenchymal stem cells (MSC). Here we characterize and analyze the frequency and function of MSC in other second-trimester fetal tissues. DESIGN AND METHODS Single cell suspensions of fetal bone marrow (BM), liver, lung, and spleen were made and analyzed by flow cytometry for the expression of CD90, CD105, CD166, SH3, SH4, HLA-ABC, HLA-DR, CD34 and CD45. We assessed the frequency of MSC by limiting dilution assay. RESULTS The frequency of MSC in BM was significantly higher than in liver, lung, and spleen (p<0.05). On primary non-expanded cells from fetal liver, lung and spleen the number of cells positive for mesenchymal markers was significantly higher within the CD34 positive population than within the CD34 negative population. The phenotype of the culture-expanded MSC was similar for all fetal tissues, i.e. CD90, CD105, CD166, SH3, SH4 and HLA-ABC positive and CD34, CD45 and HLA-DR negative. Culture-expanded cells from all tissues were able to differentiate along adipogenic and osteogenic pathways. However, adipogenic differentiation was less in MSC derived from spleen, and osteogenic differentiation was reduced in liver-derived MSC (p<0.05). INTERPRETATION AND CONCLUSIONS Our results indicate that culture-expanded MSC derived from second-trimester fetal tissues, although phenotypically similar, exhibit heterogeneity in differentiating potential. We speculate that these differences may be relevant for the clinical application of MSC.
Short term effects of air pollution on health: a European approach using epidemiologic time series data: the APHEA protocol.
BACKGROUND AND OBJECTIVES: Results from several studies over the past five years have shown that the current levels of pollutants in Europe and North America have adverse short term effects on health. The APHEA project aims to quantifying these in Europe, using standardised methodology. The project protocol and analytical methodology are presented here. DESIGN: Daily time series data were gathered for several air pollutants (sulphur dioxide; particulate matter, measured as total particles or as the particle fraction with an aerodynamic diameter smaller than a certain cut off, or as black smoke; nitrogen dioxide; and ozone) and health outcomes (the total and cause specific number of deaths and emergency hospital admissions). The data included fulfilled the quality criteria set by the APHEA protocol. SETTING: Fifteen European cities from 10 different countries with a total population over 25 million. METHODOLOGY: The APHEA collaborative group decided on a specific methodological procedure to control for confounding effects and evaluate the hypothesis. At the same time there was sufficient flexibility to allow local characteristics to be taken into account. The procedure included modelling of all potential confounding factors (that is, seasonal and long term patterns, meteorological factors, day of the week, holidays, and other unusual events), choosing the "best" air pollution models, and applying diagnostic tools to check the adequacy of the models. The final analysis used autoregressive Poisson models allowing for overdispersion. Effects were reported as relative risks contrasting defined increases in the corresponding pollutant levels. Each participating group applied the analyses to their own data. CONCLUSIONS: This methodology enabled results from many different European settings to be considered collectively. It represented the best available compromise between feasibility, comparability, and local adaptibility when using aggregated time series data not originally collected for the purpose of epidemiological studies.
The role of health literacy in patient-physician communication.
BACKGROUND AND OBJECTIVES Patients' health literacy is increasingly recognized as a critical factor affecting patient-physician communication and health outcomes. We reviewed research on health literacy, examined its impact on patient-physician communication, and offer recommendations to enhance communication with patients who have poor health literacy. METHODS We conducted a literature review using the MEDLINE database for January 1966 through July 2001. The keywords "literacy" and "health literacy" were searched independently and in combination with the medical subject headings (MeSH) "physician-patient communication," "communication," and "reading." RESULTS Poor health literacy is common, especially among elderly patients. More than 33% of patients ages 65 and older have inadequate or marginal health literacy, as do up to 80% of patients in public hospital settings. Patients with poor health literacy have a complex array of communication difficulties, which may affect health outcomes. Such patients report worse health status and have less understanding about their medical conditions and treatment; they may have increased hospitalization rates. Professional and public awareness of the health literacy issue must be increased, beginning with education of medical students and physicians and improved patient-physician communication skills. CONCLUSIONS Future research needs to address identification of optimal methods for communicating with patients who have low literacy skills. This should focus on the effect of poor health literacy on patients' ability to communicate their history and physicians' ability to solicit information, as well as identifying the most-effective techniques to educate patients.
Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size.
BACKGROUND AND OBJECTIVES We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measurement using (125)I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS For people who previously underwent a GFR measurement, bias, precision, and accuracies between measured and estimated kidney functions were calculated within strata of the variables. The relation between the absolute bias and the variables was tested with linear regression analysis. RESULTS Overall (n = 271, 44% male, mean measured GFR 72.6 ml/min per 1.73 m(2) [SD 30.4 ml/min per 1.73 m(2)]), mean bias was smallest for MDRD (P < 0.01). CKD-EPI had highest accuracy (P < 0.01 compared with Cockcroft-Gault), which did not differ from MDRD (P = 0.14). The absolute bias of all formulas was related to age. For MDRD and CKD-EPI, absolute bias was also related to the GFR; for Cockcroft-Gault, it was related to body weight and BMI as well. In all extreme subgroups, MDRD and CKD-EPI provided highest accuracies. CONCLUSIONS The absolute bias of all formulas is influenced by age; CKD-EPI and MDRD are also influenced by GFR. Cockcroft-Gault is additionally influenced by body weight and BMI. In general, CKD-EPI gives the best estimation of GFR, although its accuracy is close to that of the MDRD.
A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis.
BACKGROUND AND OBJECTIVES Studies of the impact of systemic lupus erythematosus (SLE) and its pregnancy complications have yielded conflicting results. Major limitations of these studies relate to their small numbers of patients and retrospective designs. The aim of this study was to perform a systematic literature review of pregnancy outcomes in women with SLE and a meta-analysis of the association of lupus nephritis with adverse pregnancy outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We searched electronic databases from 1980 to 2009 and reviewed papers with validity criteria. Random-effects analytical methods were used to evaluate pregnancy complications rates. RESULTS Thirty-seven studies with 1842 patients and 2751 pregnancies were included. Maternal complications included lupus flare (25.6%), hypertension (16.3%), nephritis (16.1%), pre-eclampsia (7.6%), and eclampsia (0.8%). The induced abortion rate was 5.9%, and when excluded, fetal complications included spontaneous abortion (16.0%), stillbirth (3.6%), neonatal deaths (2.5%), and intrauterine growth retardation (12.7%). The unsuccessful pregnancy rate was 23.4%, and the premature birth rate was 39.4%. Meta-regression analysis showed statistically significant positive associations between premature birth rate and active nephritis and increased hypertension rates in subjects with active nephritis or a history of nephritis. History of nephritis was also associated with pre-eclampsia. Anti-phospholipid antibodies were associated with hypertension, premature birth, and an increased rate of induced abortion. CONCLUSIONS In patients with SLE, both lupus nephritis and anti-phospholipid antibodies increase the risks for maternal hypertension and premature births. The presented evidence further supports timing of pregnancy relative to SLE activity and multispecialty care of these patients.
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