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Outcome predictors in substance use disorders.

Given the heterogeneous nature of substance abuse, it is notable that several predictors of response are independent of the primary drug of abuse or the treatment setting [208]. Although the strength of the relationship of predictor to outcome varies, the following factors have been identified consistently: severity of dependence or withdrawal; psychiatric comorbidity; substance-related problems; motivation (abstinence commitment); length of treatment; negative affective states; cognitive factors; personality traits and disorders; coping skills; multiple substance abuse; contingency contracting or coercion; genetic factors; sleep architecture; urges and craving; self-efficacy; and economic and social factors. Although it is well known that severity of dependence (including polysubstance abuse), serious psychiatric comorbidity, and social problems are associated with poor treatment response, only recently has research examined the efficacy of intervention strategies that specifically address these problems. Adequate treatment of psychiatric comorbidity and improvement in social, economic, and family functioning lead to better treatment outcomes. The development of specific techniques to enhance self-efficacy, motivation, coping skills, and functioning in the community are concrete examples of how the identification of factors associated with positive outcomes has led to the development of new treatments. Despite significant accomplishments, the field is left with many unanswered questions. Although several biologic markers, such as neuroendocrine response and sleep architecture, show promise as outcome predictors, it is not known whether these are critical factors in the initiation of substance use or its progression to dependence. Determining whether biologic markers are epiphenomena reflecting the amount and duration of substance abuse or are fundamental to the pathophysiology of dependence is a matter of urgent concern. With some exceptions, identification of biologic predictors has not led to innovative therapies. One of these exceptions is the development of naltrexone for the treatment of alcoholism, which was based in a solid theoretical rationale and followed by hypothesis-driven experiments. Similar opportunities should emerge from current basic science and clinical research. The application of pharmacogenetic techniques to the field of addiction also holds great promise. As future studies are undertaken, researchers and clinicians must be mindful that differences in outcome predictors across drugs of abuse and treatments may emerge as subgroups of individuals with addictive disorders and new therapies are identified. There is already evidence that early onset alcoholism is associated with poor response under some circumstances, yet may be a predictor of response to targeted pharmacotherapy with ondansetron [64, 112]. As the ability to subtype disorders based on meaningful biologic differences grows, it is anticipated that several relevant outcome predictors that are specific for pharmacotherapy will emerge.

Biomarkers↗

Preteenage drug use in Australia: the key predictors and school-based drug education.

PURPOSE: The promise that early intervention school-based drug education is it will have public health benefits. This argument was explored through identifying the key predictors of early adolescent social drug use. METHODS: A cross-sectional survey involving 3,019 6th year students, aged 11-12 years (participation rate: 99%), enrolled in 86 Melbourne primary schools was carried out to determine students' social drug use. In addition data were collected on known key social, personal, and education predictors. Logistic regression was used to identify significant predictors of drug experimentation and use. RESULTS: The key predictors of girls' tobacco use were friends' smoking (OR: 6.7), low literacy (OR: 4.4), and alcohol use (OR: 3.9). For boys they were friends' smoking (OR: 8.6), low literacy (OR: 4.2), and alcohol use (OR: 3.1). For alcohol use, the key predictors for girls were smoking (OR: 4.2), parents' drinking (OR: 3.9), and friends' drinking (OR: 3.8). For boys they were friends' drinking (OR: 3.3), smoking (O: 2.8), and poor literacy (OR: 2.6). Regarding analgesic use, for girls the key predictors were alcohol use (OR: 3.3), analgesic self-administration (OR: 2.4), and parents' drinking or working as tradespersons/laborers (OR: 1.7, respectively). For boys they were analgesic self-administration (OR: 2.5), drinking (OR: 1.9), smoking (OR: 1.7). CONCLUSIONS: The key predictors of social drug use--which suggests multiple recruitment pathways--were all outside the ambit of drug education programs. The impact of education on recruitment to drug use or experimentation among the young is therefore likely to be slight.

Australia↗

Clinical response predictors in a double-blind, placebo-controlled trial of fluoxetine for geriatric major depression. Fluoxetine Collaborative Study Group.

BACKGROUND: We attempted to determine baseline characteristics predicting response in a 6-week, double-blind, geriatric depression trial, which showed a significantly higher remission rate for fluoxetine (20 mg daily) than for placebo (31.6% vs. 18.6%, p < .001). METHODS: Outpatients (N = 671) were 60 years or older (mean +/- SD = 67.7 +/- 5.7), met Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev., American Psychiatric Association, 1987) criteria for unipolar major depression, had baseline scores on the 17-item Hamilton Depression Rating Scale (HAMD17) of 16 or more, and were randomized after a 1-week placebo lead-in. Potential baseline predictors of percentage change in last-visit-carried-forward HAMD21 total scores were entered into a stepwise regression model. The sample was randomly divided into two groups (development and validation data sets) so that potential predictors could be confirmed in a second analysis. RESULTS: Of the 266 variables considered for their prognostic ability, 13 were found to be significant predictors using the development data set, including (a) presence of somatic complaints, absence of agitation, and presence of previous accidental injury for fluoxetine response; and (b) reported feelings of emptiness, absence of somatic complaints, and absence of early insomnia for placebo response. The second analysis using the validation data set failed to confirm statistical significance of predictors identified in the development data set. CONCLUSIONS: Although potentially useful baseline characteristics were initially identified as response predictors, conservative statistical methods failed to confirm any significant predictors of differential responses between fluoxetine and placebo in this double-blind, placebo-controlled trial. These results suggest that response predictor analyses require confirmation before conclusions can be generalized.

Aged↗

Predictors of non-alcoholic fatty liver disease in obese children.

OBJECTIVE: To evaluate predictors of non-alcoholic fatty liver disease (NAFLD) in obese children. DESIGN: Cross-sectional study. SUBJECTS: Two hundred and sixty-eight obese children not consuming alcohol and without hepatitis B or C were consecutively studied at an auxology clinic. MEASUREMENTS: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, uric acid, glucose, glucose during oral glucose tolerance testing (OGTT), insulin, insulin during OGTT, insulin resistance as estimated by homeostasis model assessment (HOMA), C-reactive protein (CRP), and systolic and diastolic blood pressure were measured. Fatty liver was diagnosed by ultrasonography using standard criteria. Univariable and multivariable logistic regression was used to evaluate predictors of NAFLD. All predictors except gender and pubertal status were modeled as continuous variables. RESULTS: NAFLD was detected in 44% of obese children. At univariable analysis, male gender, Z-score of body mass index (BMI) (Z-BMI), ALT, AST, GGT, triglycerides, uric acid, glucose, glucose during OGTT, insulin, insulin during OGTT, HOMA, CRP and systolic blood pressure were predictors of NAFLD, whereas HDL-cholesterol and late-pubertal status were predictors of the normal liver. At multivariable analysis, however, only Z-BMI, ALT, uric acid, glucose during OGTT and insulin during OGTT were independent predictors of NAFLD. CONCLUSION: Z-BMI, ALT, uric acid, glucose during OGTT and insulin during OGTT are independent predictors of NAFLD in Italian obese children, with most of the prediction explained by ALT and Z-BMI.

Adolescent↗

Predictors of antihypertensive response to a standard dose of hydrochlorothiazide for essential hypertension.

BACKGROUND: Determinants of inter-individual variation in blood pressure (BP) response to antihypertensive therapy remain largely unknown. Although differences in race, age and measures of the renin-angiotensin-aldosterone system (RAAS) have been associated with variation in blood pressure response to hydrochlorothiazide, whether these characteristics make additive contributions to predicting response has not been established. We conducted a comprehensive search for predictors of BP response to a standard dose of hydrochlorothiazide in a biracial sample to estimate how much inter-individual variation in BP response could be explained by all of the identified predictors. METHODS: After withdrawal of antihypertensive medications for at least four weeks (baseline) and stabilization on a diet approximating 150 mmol sodium per day, 225 African American and 280 Caucasian subjects with diagnosed essential hypertension were treated for four weeks with hydrochlorothiazide 25 mg per day. At baseline and the end of treatment, subjects were admitted to the General Clinical Research Center for measurement of activity of the RAAS and other regulators of BP. Characteristics measured at study enrollment, at baseline, and in response to drug treatment were incorporated stepwise into linear regression models in order to quantify their additive contributions to predicting BP responses to hydrochlorothiazide. RESULTS: Black race and female gender were both associated with significantly greater systolic (SBP) and diastolic (DBP) blood pressure responses to hydrochlorothiazide. Together the combined effects of race and gender accounted for 11% inter-individual variation in SBP response (P < 0.0001) and 4% of inter-individual variation in DBP response (P < 0.0001). Additional statistically significant predictors of greater systolic and diastolic responses to hydrochlorothiazide included, shorter duration of diagnosed or treated hypertension (P < 0.001), higher baseline BP level (P < 0.0001), lower baseline plasma renin activity (P < 0.05), lower baseline urinary aldosterone excretion (P < 0.002), and greater decrease in urinary sodium excretion (P < or = 0.004). Greater decrease in weight was an additional statistically significant predictor of SBP but not DBP response, and older age was a predictor of diastolic but not SBP response. The combined effects of all identified predictors accounted for 38% of inter-individual variation in SBP response (P < 0.0001) and 20% of inter-individual variation in DBP response (P < 0.0001). CONCLUSIONS: A systematic search reveals numerous predictors of BP response to a standard antihypertensive dose of hydrochlorothiazide. However, because the majority of inter-individual variation in SBP and DBP responses remains unexplained, there is considerable opportunity for future investigations to improve the ability to predict individual BP responses to antihypertensive drug therapy.

Adult↗

Predictors of pregnancy and postpartum haemoglobin concentrations in low-income women.

OBJECTIVE: Pregnancy and postpartum iron status is of great public health importance, yet few studies have examined predictors of haemoglobin (Hb) concentration during this time. We identified predictors of Hb from 24 weeks' gestation until delivery and from 4 to 25 weeks postpartum. DESIGN: Blood was drawn as many as four times during care: at the initial visit, at 24-29 weeks' gestation, at delivery and postpartum. A longitudinal, multivariable linear regression model was used to predict Hb concentration. SETTING: A public health clinic in Raleigh, North Carolina. SUBJECTS: n=520 women who participated in the Iron Supplementation Study. RESULTS: Hb concentration at the previous blood draw, short stature, non-Hispanic white ethnicity/race, >12 years of education and smoking were positive predictors of pregnancy and postpartum Hb concentrations. Iron supplement use was a positive predictor, while inadequate weight gain and severe nausea/vomiting were negative predictors of gestational Hb. A high infant birth weight and postpartum haemorrhage were negative predictors of postpartum Hb. Pre-pregnancy body mass index had a slight positive relationship with gestational Hb, but had a strong negative relationship with postpartum Hb. The longitudinal model also confirmed the typical pattern of gestational Hb concentration. As the number of weeks between the initial visit and the 24- to 29-week visit increased, Hb at 24-29 weeks' gestation decreased. As gestational age increased from 24 weeks until delivery, Hb concentration increased as well. CONCLUSIONS: The predictors identified here could be used in clinical settings to target high-risk women for intervention.

Adult↗

Adjustment for strong predictors of outcome in traumatic brain injury trials: 25% reduction in sample size requirements in the IMPACT study.

The aim of this study was to quantify the potential reduction in sample size that can be achieved by adjustment for predictors of outcome in traumatic brain injury (TBI) trials. We used individual patient data from seven therapeutic phase III randomized clinical trials (RCTs; n = 6166) in moderate or severe TBI, and three TBI surveys (n = 2238). The primary outcome was the dichotomized Glasgow Outcome Scale at 6 months (favorable/unfavorable). Baseline predictors of outcome considered were age, motor score, pupillary reactivity, computed tomography (CT) classification, traumatic subarachnoid hemorrhage, hypoxia, hypotension, glycemia, and hemoglobin. We calculated the potential sample size reduction obtained by adjustment of a hypothetical treatment effect for one to seven predictors with logistic regression models. The distribution of predictors was more heterogeneous in surveys than in trials. Adjustment of the treatment effect for the strongest predictors (age, motor score, and pupillary reactivity) yielded a reduction in sample size of 16-23% in RCTs and 28-35% in surveys. Adjustment for seven predictors yielded a reduction of about 25% in most studies: 20-28% in RCTs and 32-39% in surveys. A major reduction in sample size can be obtained with covariate adjustment in TBI trials. Covariate adjustment for strong predictors should be incorporated in the analysis of future TBI trials.

Age Factors↗

Predictors of hospitalization and death among pre-dialysis patients: a retrospective cohort study.

BACKGROUND: Although there is abundant research describing predictors of patient morbidity and mortality among dialysis patients, predictors of adverse clinical outcomes among pre-dialysis patients are less well defined. The purpose of this study was to identify baseline predictors of first non-elective hospitalization among a retrospective cohort of 362 pre-dialysis patients. METHODS: Univariate and multivariate Cox proportional hazard models were used to identify predictors of hospitalization prior to dialysis initiation, adjusted for baseline creatinine level. Dialysis initiation, loss to follow-up, and study conclusion were censored events. Secondary outcomes included cause-specific hospitalization and death. RESULTS: Univariate analysis indicated that advanced age (RR 1.026, CI 1.016-1.037), number of prescribed anti-hypertensive medications (RR 1.149, CI 1.019-1.296), history of myocardial infarction (RR 1.979, CI 1.339-2.926), congestive heart failure (RR 2.299, CI 1.616-3.270), angina (RR 2.289, CI 1.695-3.091), peripheral vascular disease (RR 1.841, CI 1.282-2.644), renal failure secondary to nephrosclerosis (RR 1.413, CI 1.033-1.933) or renal artery stenosis (RR 1.587, CI 1.036-2.430), lower baseline haemoglobin level (RR 0.986, CI 0.979-0.992), and baseline creatinine greater than 300 micromol/l (RR 1.636, CI 1.233-2.171) were predictors of hospitalization. Gender, diabetes, diastolic blood pressure, mean arterial pressure, history of stroke, and hypoalbuminaemia did not predict outcome. Multivariate analysis, adjusted for baseline creatinine level, selected advanced age (RR 1. 017, CI 1.006-1.027), angina (RR 1.893, CI 1.371-2.613), peripheral vascular disease (RR 1.545, CI 1.054-2.266), and haemoglobin level (RR 0.987, CI 0.944-0.979) as independent predictors of hospitalization. CONCLUSION: Advanced age, co-morbid cardiovascular illness and anaemia are independent predictors of non-elective hospitalization prior to dialysis initiation. Further study is needed to determine the extent to which aggressive pre-dialysis management of anaemia and cardiovascular disease can improve patient outcomes.

Aged↗

Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy in HIV infected patients: natural history and clinical predictors.

PURPOSE: To characterize the natural course and clinical predictors of cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected patients after initiation of highly active antiretroviral therapy (HAART). METHODS: Retrospective analysis of 53 HIV-positive patients (73 eyes with CMV retinitis) treated with and without HAART. All participants continued to take anti-CMV therapy. Survival analysis was used to characterize the natural course of CMV retinitis. Proportional hazards analysis was performed to assess the correlation of the nine potential clinical predictors (baseline CD4 count, post-HAART CD4 count, post-HAART rise in CD4 count, baseline weight, post-HAART rise in weight, post-HAART percentage rise in weight, log of baseline HIV viral load, log of minimum post-HAART HIV viral load, and post-HAART log unit reduction in HIV viral load) with the duration of CMV retinitis remission. RESULTS: Patients receiving HAART had a median CMV retinitis remission duration of 574 days (95% confidence interval, 336-NA) whereas those not receiving HAART had a median remission duration of 80.5 days (95% confidence interval, 28-NA; P < 0.001). Within the HAART-treated population, the minimal viral load reached after HAART was the only clinical predictor to demonstrate significance (P = 0.0075). Several other clinical predictors demonstrated borderline significance; however, this was most likely due to the high correlation of these variables with the minimum post-HAART viral load. A potential secondary clinical predictor identified was the post-HAART rise in CD4 count (P = 0.085). CONCLUSION: With the introduction of HAART, HIV-infected patients have much longer remission durations from recurrent CMV retinitis. The minimum HIV viral load level reached after the initiation of HAART treatment appears to be more important than other clinical variables in the prediction of favorable CMV retinitis remission status. Furthermore, a rise in CD4 T-lymphocyte count by itself appears to be a less significant clinical predictor but may be useful in combination with the HIV viral load data. Selective discontinuation of anti-CMV therapy may be considered in patients with a favorable set of clinical predictors.

AIDS-Related Opportunistic Infections↗

Predictors of women's exercise maintenance after cardiac rehabilitation.

PURPOSE: Less than 50% of persons who participate in cardiac rehabilitation (CR) programs maintain an exercise regimen for as long as 6 months after completion. This study was conducted to identify factors that predict women's exercise following completion of a CR program. METHODS: In this prospective, descriptive study, a convenience sample of 60 women were recruited at completion of a phase II CR program. Exercise was measured using a heart rate wristwatch monitor over 3 months. Predictor variables collected at the time of the subjects' enrollment were age, body mass index, cardiac functional status, comorbidity, muscle or joint pain, motivation, mood state, social support, self-efficacy, perceived benefits or barriers, and prior exercise. RESULTS: Of women, 25% did not exercise at all following completion of a CR program and only 48% of the subjects were exercising at 3 months. Different predictors were found of the various dimensions of exercise maintenance. Predictors of exercise frequency were comorbidity and instrumental social support. Instrumental social support was the only predictor of exercise persistence. Comorbidity was the only predictor of exercise intensity. The only predictor of the total amount of exercise was benefits or barriers. CONCLUSIONS: Interventions aimed at increasing women's exercise should focus on increasing their problem-solving abilities to reduce barriers to exercise and increase social support by family and friends. Because comorbidity was a significant predictor of exercise, women should be encouraged to use exercise techniques that reduce impact on muscles and joints (eg, swimming) or exercising for short periods several times a day.

Adult↗

A systematic review of sociodemographic, physical, and psychological predictors of multidisciplinary rehabilitation-or, back school treatment outcome in patients with chronic low back pain.

STUDY DESIGN: A systematic review. OBJECTIVE: To determine predictors of outcome of multidisciplinary rehabilitation-or back school treatment for patients with chronic low back pain. SUMMARY OF BACKGROUND DATA: Numerous reviews have been performed to gain insight into which patients benefit from which treatment. However, no review has systematically focused on predictors from multiple domains (i.e., sociodemographic, physical, and psychological), or on treatment outcome measured as activity limitation or participation restriction. METHODS: Studies were found by searching medical and psychological databases, and screening references. Two reviewers independently assessed the methodological quality using standard criteria. Studies were only included if they met a predefined level of internal validity. A qualitative analysis was performed. RESULTS: Heterogeneity among studies in patient characteristics, predictors, treatment, and outcomes limited evidence. All reviewed studies were descriptive or exploratory in nature. Consistent evidence was found for the predictive value of pain intensity (more pain--> worse outcome), several work-related parameters (e.g., high satisfaction--> better outcome), and coping style (less active coping--> better outcome). Other sociodemographic and physical variables consistently lacked predictive value. No consistent evidence was found for other psychological variables. CONCLUSIONS: It is impossible to define a generic set of predictors of outcome of multidisciplinary rehabilitation and back schools for patients with chronic low back pain because the reviewed studies were descriptive or exploratory in nature, and most predictors were only studied once. Nevertheless, for several predictors, consistent evidence was found. Large confirmatory studies are needed to test the value of these predictors.

Chronic Disease↗

A randomized, controlled trial of the role of weaning predictors in clinical decision making.

OBJECTIVE: Weaning predictors are often incorporated in protocols to predict weaning outcome for patients on mechanical ventilation. The predictors are used as a decision point in protocols to determine whether a patient may advance to a spontaneous breathing trial. The impact of including predictors in a weaning protocol has not been previously studied. We designed a study to determine the effect of including a weaning predictor (frequency-tidal volume ratio, or f/Vt) in a weaning protocol. DESIGN: Randomized, blinded controlled trial. SETTING: Academic teaching hospitals. PATIENTS: Three hundred and four patients admitted to intensive care units at three academic teaching hospitals. INTERVENTIONS: Patients were screened daily for measures of oxygenation, cough and secretions, adequate mental status, and hemodynamic stability. Patients were randomized to two groups; in one group the f/Vt was measured but not used in the decision to wean (n = 151), but in the other group, f/Vt was measured and used, using a threshold of 105 breaths/min/L (n = 153). Patients passing the screen received a 2-hr spontaneous breathing trial. Patients passing the spontaneous breathing trial were eligible for an extubation attempt. MEASUREMENTS AND MAIN RESULTS: Groups were similar with regard to gender, age, and Acute Physiology and Chronic Health Evaluation II score. The median duration for weaning time was significantly shorter in the group where the weaning predictor was not used (2.0 vs. 3.0 days, p = .04). There was no difference with regard to the extubation failure, in-hospital mortality rate, tracheostomy, or unplanned extubation. CONCLUSIONS: Including a weaning predictor (f/Vt) in a protocol prolonged weaning time. In addition, the predictor did not confer survival benefit or reduce the incidence of extubation failure or tracheostomy. The results of this study indicate that f/Vt should not be used routinely in weaning decision making.

Adult↗

Further development of the Postpartum Depression Predictors Inventory-Revised.

OBJECTIVES: To describe the newly developed item coding and computation of the total score for the Postpartum Depression Predictors Inventory-Revised along with recommended cutoff points. DESIGN: Methodologic research. SETTING: Obstetrician and gynecologist offices in the Pacific Northwest. PARTICIPANTS: This longitudinal study included 139 women; the study began in the participant's third trimester of pregnancy and ended at 8 months after childbirth. METHODS: The participants completed the Postpartum Depression Predictors Inventory-Revised in their third trimester of pregnancy and again at 2 and 6 months after childbirth. Postpartum depression symptoms were measured by the Edinburgh Postnatal Depression Scale and psychiatric nurse practitioner interview at 2 and 6 months after childbirth. MAIN OUTCOME MEASURES: Sensitivity and specificity of the Postpartum Depression Predictors Inventory-Revised at three points: prenatal and 2 and 6 months after childbirth. RESULTS: The receiver operating characteristic curve analysis indicated that the Prenatal Postpartum Depression Predictors Inventory-Revised performed well and explained 67% of the variance of postpartum depressive symptomatology as measured by Edinburgh Postnatal Depression Scale scores. The Prenatal Postpartum Depression Predictors Inventory-Revised yielded a sensitivity of .76 and a specificity of .54 at a cutoff score of 10.5. CONCLUSIONS: A cutoff score of 10.5 is recommended when using the Postpartum Depression Predictors Inventory-Revised during pregnancy. Further research needs to be conducted on recommended cutoff scores for use of the Postpartum Depression Predictors Inventory-Revised during the postpartum period.

Analysis of Variance↗

Predictors of early recurrence of benign esophageal strictures.

OBJECTIVE: In the era of liberal proton pump inhibitor (PPI) use, benign esophageal strictures remain a significant management problem, with 30-40% of patients experiencing symptomatic recurrence within 1 yr of successful dilation. We therefore sought to examine predictors of early recurrence of benign esophageal strictures after endoscopic dilation. METHODS: Predictors for stricture recurrence were examined in 87 consecutive outpatients undergoing initial dilation over a 1-yr period. Patients with symptomatic recurrence of dysphagia requiring repeat dilation within 1 yr of initial successful dilation (cases) were compared to patients who did not require redilation (controls). Predictors were assessed by univariate and multivariate analysis. Kaplan-Meier analysis of significant predictors using time to first redilation was also performed. RESULTS: Of the patients, 36 required repeat dilation within 1 yr, whereas 51 did not (median follow-up, 33 months). Of all strictures, 67 (77%) were peptic, with the remainder caused by radiation, drug-related injury, or congenital stenosis, among other causes. In multivariate analysis, nonpeptic strictures were significant predictors for early recurrence, as was a narrower stricture diameter. For peptic strictures, the persistence of heartburn after dilation and the presence of a hiatal hernia were significant predictors. Of all peptic strictures, 84% of patients were on PPIs after dilation, with no difference between cases and controls. Of all patients with persistent heartburn after dilation, 90% were on PPIs. CONCLUSIONS: The persistence of heartburn after dilation is a strong predictor for early symptomatic recurrence of benign esophageal peptic strictures, despite a high rate of PPI use. This may suggest persistent acid reflux requiring optimization of acid reduction therapy. Alternatively, combined acid and alkaline reflux may account for progressive injury despite PPI therapy. Esophageal pH studies may be invaluable in making the distinction between acid and non-acidic (alkaline) reflux. Nonpeptic strictures are also more likely to have early recurrences and are therefore more difficult to manage.

Adult↗

Predictors of change during long-term analytic group psychotherapy.

BACKGROUND: All studies on patient variables as predictors of outcome are on short-term groups. Therefore, we wanted to study predictors of outcome in an observational study of 69 out-patients treated in long-term, analytic group therapy (mean = 32.5 months). METHODS: Based on results from research on short-term groups, we selected 6 predictor variables representing central domains (demographics, diagnosis, initial severity of disturbance, chronicity, expectancy, and treatment duration) and explored their relationship with 5 outcome variables (Global Assessment of Functioning, Global Severity Index, Inventory of Interpersonal Problems-Circumplex, global improvement, and chief complaints) by multiple regression analyses. RESULTS: Treatment duration up to 2.5 years was a strong positive predictor. Contrary to findings from many short-term studies, the presence of personality disorder, chronicity, and high initial severity of symptoms were not associated with less favourable outcome. Furthermore, marital status was not a positive predictor, and expectancy of a better outcome was only positively related to 1 of the outcome variables. Highly tentative results from exploratory stepwise regression analyses indicated that interpersonal problems on the subscale of 'coldness' might also be a negative predictor in long-term therapy. CONCLUSIONS: The study indicates that predictors of outcome in long-term group therapy may be different from those found in short-term therapy.

Adult↗

Pharmacogenomic predictor of sensitivity to preoperative chemotherapy with paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide in breast cancer.

PURPOSE: We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases. PATIENTS AND METHODS: One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases. RESULTS: Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes + prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant. CONCLUSION: A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).

Adult↗

Abdominal visceral fat and fasting insulin are important predictors of 24-hour GH release independent of age, gender, and other physiological factors.

Numerous physiological factors modulate GH secretion, but these variables are not independent of one another. We studied 40 younger (20-29 yr.; 21 men and 19 women) and 62 older (57-80 yr.; 35 men and 27 women) adults to determine the contributions of several demographic and physiological factors to the variability in integrated 24-h GH concentrations. Serum GH was measured every 10 min for 24 h in an enhanced sensitivity chemiluminescence assay. The predictor variables included: age group (young or old), gender, abdominal visceral fat (by computed tomography), total body fat mass and percentage body fat by dual-energy x-ray absorptiometry, serum IGF-I, fasting serum insulin, 24-h mean estradiol and testosterone, and peak oxygen uptake by graded exercise (treadmill) testing. Multiple ordinary least squares regression analysis was used to quantitatively assess the individual contribution that each predictive measure made to explain the variability among values of integrated 24-h GH concentrations while in the presence of the remaining predictors. The model explained 65% of the variance in integrated 24-h GH concentrations. Abdominal visceral fat (P < 0.002) and fasting insulin (P < 0.008) were consistently important predictors of integrated 24-h GH concentrations independent of age group, gender, and all other predictor variables. Although serum IGF-I was an important overall predictor of integrated 24-h GH concentrations (P = 0.002), this relationship was present only in the young subjects and was modulated by gender. The remaining variables failed to contribute significantly to the model. We conclude that abdominal visceral fat and fasting insulin are important predictors of integrated 24-h GH concentrations in healthy adults, independent of age and gender. Serum IGF-I is an important predictor of integrated 24-h GH concentrations in young but not older subjects. Bidirectional feedback between each of these three factors and GH secretion may account for the strong relationships observed.

Abdomen↗

Criticality of predictors in multiple regression.

A new method is proposed for comparing all predictors in a multiple regression model. This method generates a measure of predictor criticality, which is distinct from and has several advantages over traditional indices of predictor importance. Using the bootstrapping (resampling with replacement) procedure, a large number of samples are obtained from a given data set which contains one response variable and p predictors. For each sample, all 2p-1 subset regression models are fitted and the best subset model is selected. Thus, the (multinomial) distribution of the probability that each of the 2p-1 subsets is 'the best' model for the data set is obtained. A predictor's criticality is defined as a function of the probabilities associated with the models that include the predictor. That is, a predictor which is included in a large number of probable models is critical to the identification of the best-fitting regression model and, therefore, to the prediction of the response variable. The procedure can be applied to fixed and random regression models and can use any measure of goodness of fit (e.g., adjusted R2, Cp, AIC) for identifying the best model. Several criticality measures can be defined by using different combinations of the probabilities of the best-fitting models, and asymptotic confidence intervals for each variable's criticality can be derived. The procedure is illustrated with several examples.

Humans↗