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Impact of a medical back care program on utilization of services and primary care physician satisfaction in a large, multispecialty group practice health maintenance organization.

STUDY DESIGN: Samples of patients with new back pain were compared at two medical centers, one with and one without a medical back care program. OBJECTIVES: To measure the impact of a medical back care program on use of services and physician satisfaction in a health maintenance organization. SUMMARY OF BACKGROUND DATA: A medical back care program is staffed with specially trained primary care physicians and provides consultative and educational services to the medical center. METHODS: Program impact on services was measured by comparing the number of physician office visits, consultations, physical therapy referrals, and imaging procedures provided to a sample of patients with back pain at the two medical centers. Physician satisfaction with care provided to patients with back pain was measured by a survey sent to primary care physicians at both medical centers. RESULTS: At the medical center with a back care program, 42% fewer consultations, 59% fewer physical therapy referrals, and 33% fewer imaging procedures were ordered. Less expensive consultations with back care physicians in medicine or family practice were ordered more frequently than consultations with either neurologists or orthopedists. This change in pattern of care took place without significantly altering clinical course. The effect of the program on the rate of surgery was not measured. CONCLUSIONS: The results of this study support the benefits of an organized medical back care program.

Adolescent↗

Degeneration and aging affect the tensile behavior of human lumbar anulus fibrosus.

STUDY DESIGN: Samples of human lumbar (L3-L4) anulus fibrosus from four different anatomic sites (anterior outer, posterolateral inner), ranging from normal to severely degenerate, were studied in uniaxial tension and measured for water content. OBJECTIVES: To evaluate the effects of aging and degeneration on the tensile properties and hydration of the anulus fibrosus in a site-specific manner. The relationship between hydration and parameters of the tensile behavior were investigated. SUMMARY OF BACKGROUND DATA: Degeneration and aging have been shown to be related to dramatic changes in the composition and structure of the anulus fibrosus. The associated changes in the tensile, compressive, and shear properties of the anulus fibrosus have not been documented. Numerical studies using finite element models have attempted to simulate the degenerative process by incorporating estimated mechanical properties meant to represent the degenerate anulus fibrosus. Their results present findings that suggest that altered material properties of the anulus fibrosus affect the mechanics of the entire intervertebral disc. METHODS: Samples of human lumbar anulus fibrosus were classified by grade of degeneration based on a morphologic grading scheme. Multiple layer anulus specimens from four sites in the disc were tested in uniaxial tension under quasistatic conditions in a physiologic saline bath. The tensile modules, Poisson's ratio, failure stress and strain, the strain energy density to failure, and the corresponding hydration were determined for each sample. RESULTS: The Poisson's ratio, failure stress, and strain energy density of the anulus fibrosus were found to be affected significantly by degeneration, with some evidence of a sensitivity of the tensile modulus to grade of degeneration. All material properties were found to exhibit a significant and greater dependence on site within the disc than on degenerative grade. Weak correlations between aging and the Poisson's ratio and strain energy density were observed. Water content of anulus fibrosus tissue was not affected by degeneration or aging, although correlations with tensile properties were observed. CONCLUSIONS: The dramatic changes in morphology, composition, and structure that occur in anulus fibrosus with aging and degeneration are accompanied by specific variations in the tensile properties, which were generally small in magnitude. Position of the anulus fibrosus within the intervertebral disc, particularly in the radial direction, appeared to be the most important variable affecting anulus fibrosus tensile properties. This dependence on position did not change with either aging or degeneration. Results from the present study may be useful in future finite element models to assess how altered material properties of the anulus fibrosus during degeneration and aging may affect the mechanics of the entire intervertebral disc.

Adolescent↗

The safety and efficacy of laparoscopic live donor nephrectomy: a systematic review.

BACKGROUND: The aim of this systematic review was to compare the safety and efficacy of laparoscopic live donor nephrectomy with the "gold" standard of open live donor nephrectomy. METHODS SEARCH STRATEGY: Three search strategies were devised to enable literature retrieval from the Medline, Current Contents, Embase, and Cochrane Library databases up until, and including, February 2000. STUDY SELECTION: Inclusion of a report was determined on the basis of a predetermined protocol, independent assessment by two reviewers, and a final consensus decision. English language reports were selected and acceptable study designs included randomized-controlled trials, controlled clinical trials, case series, or case reports. Each report was required to provide information on at least one of several safety and efficacy outcomes as detailed in the protocol. DATA COLLECTION AND ANALYSIS: Twenty-five reports met the inclusion criteria. They were tabulated and critically appraised in terms of the methodology and design, sample size, outcomes, and the possible influence of bias, confounding, and chance. RESULTS: High level evidence comparing the safety and efficacy of laparoscopic live donor nephrectomy with open donor nephrectomy was not available at the time of this review. Limited low level evidence suggested that the laparoscopic approach might be advantageous regarding the donor's hospital stay, convalescence, pain, and resumption of employment. CONCLUSIONS: The ASERNIP-S Review Group concluded that the evidence-base for laparoscopic live donor nephrectomy was inadequate to make a safety and efficacy recommendation. Clinical and research recommendations were developed regarding the introduction and current practice of this procedure in Australia.

Australia↗

Lack of correlation between self-reported symptoms of dyspepsia and infection with Helicobacter pylori, in a general population sample.

OBJECTIVE: To investigate any correlation between infection with Helicobacter pylori (H. pylori) and overall symptoms of dyspepsia, in a general population sample. DESIGN: Analysis of test results and questionnaire replies from a population screening study involving subjects registered at a single general practice in Market Harborough, UK. METHODS: H. pylori status was established using a commercial enzyme-linked immunosorbent assay (ELISA), and frequent dyspepsia was assessed using a previously validated self-completion symptom questionnaire. RESULTS: Complete results for dyspepsia and H. pylori status were obtained and analysed for 1524 men and women aged 21-55 years at the start of the study. In those who attended for screening, the prevalence of dyspepsia was 39%, with a 15% prevalence of infection with H. pylori. No significant correlation was found between H. pylori status and frequent dyspepsia, upper abdominal pain or reflux-like symptoms. Adjustment for age, gender, smoking and alcohol consumption did not alter these findings. CONCLUSION: The analysis suggested that H. pylori infection does not play an important role in overall symptoms of non-ulcer dyspepsia in the community, nor is it important in protecting against acid reflux in patients without duodenal ulcer.

Adult↗

Augmentation of electroconvulsive therapy seizures with sleep deprivation.

Electroconvulsive therapy (ECT) is the fastest and most effective treatment for severe or treatment-resistant affective and psychotic disorders. Its therapeutic effect is obtained through a generalized tonic-clonic seizure of adequate duration. Several factors (older age, male gender, and the sessions of ECT themselves) increase seizure threshold and reduce seizure time. In our work, sleep deprivation was used as a strategy to enhance the ECT seizure. A matched sample design was conducted on the basis of the following variables: gender, age range, and seizure threshold. After the first ECT, when the initial seizure threshold was measured, subjects were assigned to ECT (electroconvulsive therapy) or SD+ECT (sleep deprivation + electroconvulsive therapy). Changes in the variable of seizure threshold were studied in both groups during the treatment course. A nonparametric analysis was implemented for 2 independent groups. During the treatment course, the SD+ECT group showed a decreased seizure threshold, from 190.4 mC in the first ECT session to 176.4 mC in the last ECT session, whereas the ECT group showed an increased seizure threshold, increasing from 190.4 mC to 321.91 mC. Sleep deprivation is an effective and safe technique used to lower the seizure threshold of ECT and to obtain an adequate seizure time without increasing the energy applied.

Aged↗

Safety of vaginal birth after cesarean: a systematic review.

OBJECTIVE: To evaluate the benefits and harms of vaginal birth after cesarean compared with repeat cesarean delivery. DATA SOURCES: The computerized databases MEDLINE, EMBASE, HealthSTAR, Cochrane CENTRAL, and National Centre for Reviews and Dissemination Database of Abstracts of Reviews of Effectiveness, along with reference lists and national experts, were used to conduct this review. METHODS OF STUDY SELECTION: All studies that reported data for maternal or infant outcomes in women with prior cesarean delivery were eligible. Methodological quality was evaluated for each study with the criteria of the United States Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination. Twenty of 6,828 potentially relevant articles (55,506 patients) were included in the analysis. TABULATION, INTEGRATION, AND RESULTS: Two authors independently abstracted information on study design, sample size, participant characteristics, and maternal and fetal health outcomes by using a standardized protocol. Rates of vaginal delivery in women undergoing a trial of labor ranged from 60% to 82%. There was no significant difference in maternal deaths or hysterectomy between trial of labor and repeat cesarean. Uterine rupture was more common in the trial-of-labor group, but rates of asymptomatic uterine dehiscence did not differ. Studies conflicted on the effect of induction of labor on these outcomes. Data regarding infant outcomes were poor. CONCLUSION: Safety in childbirth for women with prior cesarean is a major public health concern. Methodological deficiencies in the literature evaluating the relative safety of vaginal birth after cesarean compared with repeat cesarean delivery are striking. The identification of high-risk and low-risk groups of women and settings for morbidity remains a key research priority.

Cesarean Section, Repeat↗

Coding of perineal lacerations and other complications of obstetric care in hospital discharge data.

OBJECTIVE: To assess the validity of obstetric complications, including the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) Core Measure on perineal lacerations, in the California Patient Discharge Data Set. METHODS: We randomly sampled 1,611 deliveries from 52 of the 267 hospitals that performed more than 678 eligible deliveries in California in 1992-1993. We compared hospital-reported complications against our recoding of the same records. RESULTS: Third- and fourth-degree perineal lacerations were reported accurately, with estimated sensitivities exceeding 90% and positive predictive values exceeding 65% (weighted to account for the stratified sampling design) or 85% (unweighted). Based on in-depth review of discrepant cases, we estimate the actual positive predictive value at over 90%. Most coding discrepancies were between no injury and first degree, or between first and second degree. Most postpartum complications, including urinary tract and wound infections, endometritis, anesthesia complications, and postpartum hemorrhage were reported with less than 70% sensitivity, but at least 80% positive predictive value. Composite measures from HealthGrades and Solucient, which include these complication codes, also suffer from high false-negative rates. CONCLUSION: Third- and fourth-degree perineal lacerations are accurately reported on hospital discharge abstracts, confirming the validity of related quality indicators sponsored by the Agency for Healthcare Research and Quality and JCAHO. Administrative data seem less useful for monitoring other in-hospital postpartum complications.

Adult↗

Obstacles and opportunities in meta-analysis of genetic association studies.

Genetic association studies have the potential to advance our understanding of genotype-phenotype relationships, especially for common, complex diseases where other approaches, such as linkage, are less powerful. Unfortunately, many reported studies are not replicated or corroborated. This lack of reproducibility has many potential causes, relating to study design, sample size, and power issues, and from sources of true variability among populations. Genetic association studies can be considered as more similar to randomized trials than other types of observational epidemiological studies because of "Mendelian randomization" (Mendel's second law). The rationale and methodology for synthesizing randomized trials is highly relevant to the meta-analysis of genetic association studies. Nevertheless, there are a number of obstacles to overcome when performing such meta-analyses. In this review, the impacts of Type I error, lack of power, and publication and reporting biases are explored, and the role of multiple testing is discussed. A number of special features of association studies are especially pertinent, because they may lead to true variability among study results. These include population dynamics and structure, linkage disequilibrium, conformity to Hardy-Weinberg Equilibrium, bias, population stratification, statistical heterogeneity, epistatic and environmental interactions, and the choice of statistical models used in the analysis. Approaches to dealing with these issues are outlined. The supreme importance of complete and consistent study reporting and of making data readily available is also highlighted as a prerequisite for sound meta-analysis. We believe that systematic review and meta-analysis has an important role to play in understanding genetic association studies and should help us to separate the wheat from the chaff.

Epistasis, Genetic↗

Effect of dietary fiber intake on blood pressure: a meta-analysis of randomized, controlled clinical trials.

OBJECTIVE: We conducted a meta-analysis of 25 randomized controlled trials published in English-language journals before February 2004, to assess the effect of dietary fiber intake on blood pressure (BP). DESIGN: Using a standardized protocol, information on study design, sample size, participant characteristics, duration of follow-up and change in mean BP, was abstracted. The data from each study were pooled using a random effects model to provide an overall estimate of dietary fiber intake on BP. INTERVENTION: Dietary fiber intake was the only significant intervention difference between the active and control groups. RESULTS: Overall, dietary fiber intake was associated with a significant -1.65 mmHg [95% confidence interval (CI), -2.70 to -0.61] reduction in diastolic BP (DBP) and a non-significant -1.15 mmHg (95% CI, -2.68 to 0.39) reduction in systolic BP (SBP). A significant reduction in both SBP and DBP was observed in trials conducted among patients with hypertension (SBP -5.95 mmHg, 95% CI, -9.50 to -2.40; DBP -4.20 mmHg, 95% CI, -6.55 to -1.85) and in trials with a duration of intervention > or = 8 weeks (SBP -3.12 mmHg, 95% CI, -5.68 to -0.56; DBP -2.57 mmHg, 95% CI, -4.01 to -1.14). CONCLUSIONS: Our results indicate that increased intake of dietary fiber may reduce BP in patients with hypertension and suggests a smaller, non-conclusive, reduction in normotensives. An intervention period of at least 8 weeks may be necessary to achieve the maximum reduction in BP. Our findings warrant conduct of additional clinical trials with a larger sample size and longer period of intervention to examine the effect of dietary fiber intake on BP.

Blood Pressure↗

Gender differences in the presentation and management of acute coronary syndromes: a national sample of 1365 admissions.

BACKGROUND: Gender differences in presentation and management of acute coronary syndromes (ACS) are well established internationally. This study investigated differences in a national Irish sample. DESIGN: Cross-sectional survey. METHODS: All centres (n=39) admitting cardiac patients to intensive/coronary care provided information on 25 consecutive acute myocardial infarction patients and other ACS patients admitted concurrently (n=1365 episodes). Patient data was analyzed in terms of those with prior ACS/revascularization, and those without. RESULTS: Men with prior established ACS/revascularization were twice as likely to have received revascularization procedures (coronary artery bypass graft or percutaneous coronary intervention) prior to admission when controlling for age, total cholesterol and insurance status [odds ratio (OR) 1.97, 95% confidence interval (CI) 1.18-3.29, P=0.011]. No gender differences were seen in acute-phase reperfusion (OR 0.96, 95% CI 0.76-1.24, P>0.05) or antiplatelet therapy (OR 0.99, 95% CI 0.69-1.41, P>0.05). For patients with prior ACS/revascularization, men were twice as likely to receive statins on discharge after adjustment for age and total cholesterol (OR 1.94, 95% CI 1.02-3.71, P=0.045). CONCLUSIONS: Women were treated differently to men. Fewer women with a positive history of ACS received revascularization prior to current admission and fewer women were prescribed lipid-lowering medications on discharge. Acute phase hospital treatment was not gender determined. These findings have implications for secondary prevention in Ireland.

Acute Disease↗

Modelling dairy intake on the development of acute coronary syndromes: the CARDIO2000 study.

BACKGROUND: Dairy consumption may be associated with a small but worthwhile reduction in cardiovascular disease risk, but results from epidemiological studies are inconsistent. The aim of the present study was to evaluate the association between dairy consumption and the prevalence of a first, non-fatal event of an acute coronary syndrome, in a Greek sample. DESIGN: Seven hundred male and 148 female patients with first event of an acute coronary syndrome and 1078 population-based controls, age and sex matched, were randomly selected. METHODS: Detailed information regarding their medical records, alcohol intake, physical activity and smoking habits was recorded. Nutritional habits were evaluated with a semi-quantitative food-frequency questionnaire. Multiple logistic regression analysis estimated the odds ratio of having acute coronary syndrome by level of dairy intake, after taking into account the effect of several confounders. RESULTS: An inverse relationship was observed between dairy products consumption and odds of having acute coronary syndrome. One portion increase in weekly dairy products intake was associated with 12% lower likelihood of having acute coronary syndrome, after controlling for various potential confounders (P<0.001). Cut-off analysis showed that 7.4 portions per week are the optimal consumption that benefits people from having acute coronary syndrome. CONCLUSIONS: Dairy consumption seems to offer significant protection against coronary heart disease, irrespective of various clinical, lifestyle and other characteristics of the participants.

Case-Control Studies↗

Continuity of medical care, health insurance, and nonmedical advice in the first 3 years of life.

OBJECTIVES: The study seeks to evaluate whether continuity in medical care provides a mechanism that contributes to increased parental awareness of the importance of dental services, nutrition, and child development and whether health insurance encourages such continuity. METHODS: Data pertaining to medical utilization and dental, child nutrition, and child development counseling were extracted from the National Maternal and Infant Health Survey, 1988 and the 1991 Longitudinal Follow-up. These data permit the investigation of whether having continuity in medical care for a child increases the likelihood that the child's parent receives advice about dental health, nutrition, and child development. Restricting the analyses to Caucasian and African American women and excluding respondents with missing information on the child's health care utilization yielded 7056 participants. We created a set of binomial logit models, with correction for clustering (due to sample design). These models jointly estimate the likelihood that a child was classified as having continuity of care and the likelihood that the child's mother received advice about the 3 areas of interest. RESULTS: Private fee-for-service health insurance was found to increase the likelihood that a child receives continuity of care. When primary care was provided with high continuity of care, the probability that physicians provide mothers with dental, nutritional, and developmental advice was increased. CONCLUSIONS: These results suggest that continuity of care may have important spillover effects beyond direct medical care by improving maternal information about child dental care, nutrition, and developmental issues.

Child Health Services↗

Increasing response rates in a survey of Medicaid enrollees: the effect of a prepaid monetary incentive and mixed modes (mail and telephone).

OBJECTIVES: We sought to evaluate the effect of pairing a mixed-mode mail and telephone methodology with a prepaid US 2.00 dollars cash incentive on response rates in a survey of Medicaid enrollees stratified by race and ethnicity. RESEARCH DESIGN: Sampling was conducted in 2 stages. The first stage consisted of a simple random sample (SRS) of Medicaid enrollees. In the second stage, American Indian, African American, Latino, Hmong, and Somali enrollees were randomly sampled. A total of 8412 enrollees were assigned randomly to receive a mail survey with no incentive or a US 2.00 dollars bill. RESULTS: The response rate within the SRS after the mail portion was 54% in the incentive group and 45% in the nonincentive group. Response rates increased considerably with telephone follow-ups. The incentive SRS response rate increased to 69%, and the nonincentive response rate increased to 64%. Differences between incentive conditions are more pronounced after the first mailing (P < 0.01); almost all differences remained significant (P < 0.05) after the completion of the mail mode. The inclusion of the US 2.00 dollars incentive had similar effects on response rates and cost across the different racial and ethnic strata, except for Latino enrollees. CONCLUSIONS: A mixed-mode mail and telephone methodology is effective for increasing response rates in a Medicaid population overall and within different racial and ethnic groupings. The effectiveness of this strategy can be enhanced, in terms of response rate and cost, by including a US 2.00 dollars prepaid incentive.

Ethnicity↗

Barriers to care among American Indians in public health care programs.

OBJECTIVE: We sought to examine the extent to which reported barriers to health care services differ between American Indians (AIs) and non-Hispanic Whites (Whites). METHODS: A statewide stratified random sample of Minnesota health care program enrollees was surveyed. Responses from AI and White adult enrollees (n=1281) and parents of child enrollees (n=572) were analyzed using logistic regression models that account for the complex sample design. Barriers examined include: financial, access, and cultural barriers, confidence/trust in providers, and discrimination. RESULTS: Both AIs and Whites report barriers to health care access. However, a greater proportion of AIs report barriers in most categories. Among adults, AIs are more likely to report racial discrimination, cultural misunderstandings, family/work responsibilities, and transportation difficulties, whereas Whites are more likely to report being unable to see their preferred doctor. A higher proportion of adult enrollees compared with parents of child enrollees report barriers in most categories; however, differences between parents of AIs and White children are more substantial. In addition to racial discrimination and cultural misunderstandings, parents of AI children are more likely than parents of White enrollees to report limited clinic hours, lack of respect for religious beliefs, and mistrust of their child's provider as barriers. CONCLUSIONS: Although individuals have enrolled in health care programs and have access to care, barriers to using these services remain. Significant differences between AIs and Whites involve issues of trust, respect, and discrimination. Providers must address barriers experienced by AIs to improve accessibility, acceptability, and quality of care for AI health care consumers.

Adult↗

Conducting multiple-site clinical trials in medical rehabilitation research.

This article examines the distinctive opportunities and challenges of multiple-site clinical trials, as distinguished from trials conducted by a single program. Among the topics discussed are: the role of clinical trials generally in medical rehabilitation research; definitions of "clinical trials" and "multiple site"; the distinction between exploratory and capstone trials; the potential advantages and disadvantages of multiple-site trials; planning issues in terms of sampling designs, the choice of outcome measures, approaches to dealing with intervention fidelity, organizational structures, authorship, and the conduct of collateral studies; and implementation issues in terms of pilot-testing procedures, handling emerging issues, and optimizing communication.

Evidence-Based Medicine↗

Ventriculostomy-Related Infections by Country-Income Level: A Systematic Review and Bayesian Hierarchical Meta-analysis.

Our objective was to perform a systematic review and meta-analysis of published literature on ventriculostomy-related infection (VRI) and evaluate temporal and global trends. We conducted a systematic review and Bayesian hierarchical random-effects meta-analysis of VRI rates in adults, stratified by country-income level (high-income countries [HIC]; low- or middle-income countries [LMIC]), study design, sample size, enrollment period, VRI intervention, and VRI definition. We identified 159 articles published between 1989 and 2025 that included 523,704 patients with 7293 VRIs. The pooled VRI rate was 8.64% [95% CI: 7.44-9.97], with moderate heterogeneity and good model fit. The leave-one-out sensitivity analysis showed a mean absolute change of 0.06% and a maximum change of 0.2%, indicating robust analysis. Five of the 33 represented countries had VRI rates below the global pooled rate of 8.64%. Four were HICs: Singapore (VRI rate 3.3% [0.8-7]), the United States (VRI rate 4.6% [3.4-5.9]), Germany (VRI rate 6.1% [1.1-18.9]), Norway (8.3% [0.3-68.4]), with 1 LMIC: China (8.5% [5.4-12.4]). VRI was significantly higher in studies using definitions beyond CSF culture alone for VRI (+3.16% [0.11- 6.52]) and in those from Europe (+7.29% [4.62-10.10]) and the Western Pacific (+4.09% [1.55-6.98]). No other subgroup demonstrated significant differences. This Bayesian meta-analysis provides global estimates and factors associated with VRI. Standardization of VRI definitions is critical for future benchmarking of VRI rates.

Humans↗

Integrative genomic and transcriptomic analysis of hypertension in a Taiwanese population.

OBJECTIVES: Hypertension is highly prevalent in Asian populations and represents a major cardiovascular risk factor. However, most genome-wide association studies (GWASs) and transcriptome-wide association studies (TWASs) have focused primarily on Caucasian cohorts. This study aimed to identify genetic loci and gene expression signatures associated with hypertension in an Asian population. METHODS: We analyzed 10 739 hypertensive patients and 49 668 controls from the Taiwan Biobank, testing 4 512 191 genome-wide single nucleotide polymorphisms (SNPs). Integrated GWAS, TWAS, and expression quantitative trait locus (eQTL) analyses were conducted to characterize genetic risk. Additionally, a polygenic risk score (PRS) was constructed using a split-sample design to evaluate genetic risk stratification. RESULTS: We identified 14 loci significantly associated with hypertension, including a novel locus at 5p13.1. eQTL analysis linked this locus to DAB2 expression in whole blood. TWAS detected 55 hypertension-associated genes, with 20 (36%) overlapping GWAS loci. Several novel genes outside GWAS loci, including FBXL15, KCNIP2, and CRIP3, were highly significant and implicated in vascular biology and hypertension mechanisms. PRS analysis effectively differentiated hypertension risk, with individuals in the top 10% showing a > 3.5-fold increased risk compared to the bottom 10%. CONCLUSIONS: Our findings provide new insights into the genetic and transcriptomic landscape of hypertension in Asians. The identification of novel loci and genes advances understanding of disease biology and may guide precision medicine approaches for risk prediction and therapeutic development.

Female↗

A classification-based machine learning approach for the analysis of genome-wide expression data.

Three important areas of data analysis for global gene expression analysis are class discovery, class prediction, and finding dysregulated genes (biomarkers). The clinical application of microarray data will require marker genes whose expression patterns are sufficiently well understood to allow accurate predictions on disease subclass membership. Commonly used methods of analysis include hierarchical clustering algorithms, t-, F-, and Z-tests, and machine learning approaches. We describe an approach called the maximum difference subset (MDSS) algorithm that combines classification algorithms, classical statistics, and elements of machine learning and provides a coherent framework. By integrating prediction accuracy, the MDSS algorithm learns the critical threshold of statistical significance (the alpha or P-value), eliminating the arbitrariness of setting a threshold of statistical significance and minimizing the effect of the normality assumptions. To reduce the false positive rate and to increase external validity of the predictive gene set, a jackknife step is used. This step identifies and removes genes in the initial MDSS with low combined predictive utility. The overall MDSS provides a prediction that is less dependent on an arbitrary study design (sample inclusion or exclusion) and should thus have high external validity. We demonstrate that this approach, unlike other published methods, identifies biomarkers capable of predicting the outcome of anthracycline-cytarabine chemotherapy in cases of acute myeloid leukemia. By incorporating two criteria-statistical significance and predictive utility-the approach learns the significance level relevant for a given data set. The MDSS approach can be used with any test and classifier operator pair.

Acute Disease↗