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Long-term prognosis of primary biliary cirrhosis (PBC) in Japan and analysis of the factors of stage progression in asymptomatic PBC (a-PBC).

Objective: Based on data from a national survey of primary biliary cirrhosis (PBC), the pathology and prognosis of PBC in Japan were clarified. In particular, we tried to perform multivariate analysis of factors useful in determining prognosis of asymptomatic PBC (a-PBC). Methods: The survey was performed 10 times. Responses from 3778 of 4361 registered patients (416 institutions) were investigated (survey period: January 1968-December 1998). At the time of diagnosis, patients were classified as a-PBC or symptomatic PBC (s1-PBC; pruritus only, s2-PBC; jaundice and serum bilirubin level above 2 mg/dl). The survival rate was obtained by the Kaplan-Meier method. Logistic regression analysis was used in multivariate analysis of prognostic factors of a-PBC. Results: There were no significant differences in clinical findings from those in previous reports. The 5-year survival rates of patients with a-PBC, s1-PBC, and s2-PBC at the time of diagnosis were 97, 88, and 53%, respectively. Patients with a-PBC at the time of diagnosis were divided into groups: those in whom the disease progressed to s2-PBC (8%) and did not progress to s2-PBC (92%) at the final examination, and the prognosis was compared between groups. The prognosis was significantly poorer in the s2-PBC progression group. As a result of multivariate analysis for prediction of prognosis, levels at diagnosis of total serum bilirubin (T-Bil), albumin (Alb), total cholesterol (T-Cho), histological stage, and presence or absence of ursodeoxycholic acid (UDCA) administration were selected as significant factors (P<0.00001). Conclusion: Serum T-Bil, Alb, T-Cho, and histological stage at the time of diagnosis and presence or absence of UDCA administration were considered useful early prognostic indicators in patients diagnosed as having a-PBC whose prognosis may deteriorate with progression to s2-PBC.

Journal Article↗

Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.

PURPOSE: To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF(2)) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. METHODS AND MATERIALS: Measurements of SF(2) and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp(alpha,rho)). Regression analysis was performed to assess the prognostic power of tcp(alpha,rho) vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF(2) and CFE measurements alone. RESULTS: In a univariate regression analysis of 44 patients, tcp(alpha,rho) was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF(2) alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp(alpha,rho) emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp(alpha,rho), CFE was still a significant independent prognostic factor for local control, whereas SF(2) was not. The sensitivities of tcp(alpha,rho) and SF(2) as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. CONCLUSIONS: A Poisson tcp model incorporating individual SF(2), CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

Carcinoma, Squamous Cell↗

Clinical model to predict survival in chemonaive patients with advanced non-small-cell lung cancer treated with third-generation chemotherapy regimens based on eastern cooperative oncology group data.

PURPOSE: (1) Identify clinical factors that can be used to predict survival in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) treated with third-generation chemotherapy regimens, and (2) build a clinical model to predict survival in this patient population. PATIENTS AND METHODS: Using data from two randomized, phase III Eastern Cooperative Oncology Group (ECOG) trials (E5592/E1594), we performed univariate and multivariate stepwise Cox regression analyses to identify survival prognostic factors. We used 75% of randomly sampled data to build a prediction model for survival, and the remaining 25% of data to validate the model. RESULTS: From 1993 to 1999, 1,436 patients with stage IV or IIIB NSCLC with effusion were treated with platinum-based doublets (involving either paclitaxel, docetaxel, or gemcitabine). The response rate and median survival time were 20% and 8.2 months, respectively. One- and 2-year survivals were 33% and 11%, respectively. In multivariate analysis, six independent poor prognostic factors were identified: skin metastasis (hazard ratio [HR], 1.88), lower performance status (ECOG 1 or 2; HR, 1.46), loss of appetite (HR, 1.62), liver metastasis (HR, 1.32), >/= four metastatic sites (HR, 1.20), and no prior surgery (HR, 1.16). A nomogram using six pretreatment prognostic factors was built to predict 1- and 2-year survival. CONCLUSION: Six pretreatment factors can be used to predict survival in chemotherapy-naive NSCLC patients treated with standard chemotherapy. Using our prognostic nomogram, 1- and 2-year survival probability of NSCLC patients can be estimated before treatment. This prognostic model may help clinicians and patients in clinical decision making, as well as investigators in research planning.

Aged↗

The effects of atorvastatin on coronary endothelial function in patients with recent myocardial infarction.

BACKGROUND: Endothelial dysfunction is a key early event in atherosclerosis that occurs in acute coronary syndrome. It was reported that atorvastatin improves the endothelial function of skeletal muscle vessels, but the effect on the coronary artery is unknown. HYPOTHESIS: The purpose of this study is to determine the effects of atorvastatin on coronary endothelial function in humans. METHODS: Non-infarct-related coronary arteries of 48 patients with acute myocardial infarction who had undergone successful percutaneous transluminal coronary angioplasty were examined. Three groups were studied: hyperlipidemia with use of atorvastatin (Group 1, n=17), hyperlipidemia without statin use (Group 2, n=18), and normal cholesterol level controls (Group 3, n=13). Statin treatment was started at discharge. Acetylcholine (Ach) was infused into the coronary artery and the diameter was assessed by quantitative angiography at baseline and after 6 months. RESULTS: Acetylcholine given in doses of 1, 3, 10, and 30 mg/min increased the coronary artery diameter change in a dose-dependent manner. In the initial study, patients in the three groups had similar responses to Ach. The mean diameter change after 6 months was significantly improved in Group 1 compared with Groups 2 and 3 (-11 +/- 3% vs. -20 +/- 7% and -21 +/- 6%, respectively; p < 0.01 in each case). Multivariate regression analysis showed that atorvastatin (p < 0.01) was the significant determinant for improvement of endothelial function. CONCLUSIONS: These findings suggest that atorvastatin improves endothelial function of the coronary artery in patients with myocardial infarction.

Acetylcholine↗

Reversible color vision loss in occupational exposure to metallic mercury.

Color vision was evaluated in twenty-one mercury exposed workers and referents matched for sex, age, tobacco smoking, and alcohol habits. The Lanthony 15 Hue desaturated panel (D-15 d) was applied. In the workers, mean urinary Hg (HgU) was 115+/-61.5 microg/g creatinine; in all but one the values exceeded the biological limit (BEI) proposed by the American Conference of Governmental Industrial Hygienists. A dose-related subclinical color vision impairment was observed in Hg-exposed workers compared to the referents. Just after the survey, working conditions were improved. Twelve months later the workers were reexamined. Mean HgU was 10.0 microg/g creatinine and in no subjects was the BEI exceeded. Color perception was significantly improved compared to the first examination and, furthermore, no differences were observed between exposed workers and referents. The results add evidence that the color vision loss observed during the first part of the study was related to Hg exposure and, moreover, show that this effect is reversible. These data indicate that metallic Hg can induce a reversible impairment in color perception. This suggests that color vision testing should be included in studies on the early effects of Hg. The possibility of applying the D-15 d as an early effect index in the biological monitoring of Hg exposed workers should also be entertained.

Adult↗

Evaluating ecological condition using soil biogeochemical parameters and near infrared reflectance spectra.

Rapid, repeatable assessment of ecological condition is critical for quantitative ecosystem monitoring. Soils provide a sensitive, integrative indicator for which sampling and analysis techniques are well defined. We evaluated soil properties as indicators of ecological condition (subjectively classified into minimally/moderately/severely degraded based on vegetative, hydrologic and edaphic cues) at 526 sites within Ft. Benning military installation (Georgia, USA). For each sample, we measured 17 biogeochemical parameters, and collected high-resolution diffuse reflectance spectra using visible/near infrared reflectance spectroscopy (VNIRS). VNIR spectra have been related to numerous soil attributes - we examine them here for diagnosing integrated response (i.e., ecological condition). We used ordinal logistic regression (OLR) and classification trees (CT) to discriminate between condition categories using both sets of predictors (biogeochemistry and spectra). Sixteen biogeochemical parameters were significantly different across condition categories; however, multivariate models greatly improved discrimination ([calibration, validation] accuracy of [69%, 66%] and [96%, 73%] for OLT and CT models, respectively). Important predictors included total C, total P, and Mehlich K/Ca/Mg. VNIR spectra further improved discrimination ([calibration, validation] accuracy of [74%, 70%] and [96%, 75%] for OLR and CT models, respectively). While spectra were comparably effective at discriminating minimally degraded sites, they were significantly more effective at discriminating severely degraded sites. Error rates across confounding factors suggest that watershed of origin and landscape position were the only important confounders, likely due to imbalanced sampling. We conclude that multivariate diagnosis improves accuracy, and that VNIR spectroscopy, which yields substantial cost and logistical improvements over conventional analyses, provides an effective tool for rapid condition diagnosis.

Ecosystem↗

Maternal use of physical punishment in response to child misbehavior: implications for child abuse prevention.

OBJECTIVE: The objective was to examine the roles of cognition and affect in maternal use of physical punishment. METHOD: Through a review of the literature, distal and proximal predictors (cognitive and affective) of physical punishment use were identified. One hundred and ten mothers of 3-year-old children were interviewed regarding two disciplinary situations that occurred during the previous 2-week period that elicited their strongest reactions: one which resulted in the use of physical punishment (if this occurred) and one which did not. The individual and combined contributions of the predictors of physical punishment use were analyzed through logistic regression. RESULTS: The predictors of physical punishment following individual analyses were: maternal attitude toward physical punishment, maternal perception of the seriousness and intent of the child misbehavior, and maternal anger in response to the child misbehavior. Through multivariate analysis 54% of the variance in physical punishment use was explained. CONCLUSIONS: Both cognitive and affective factors affect the decision to use physical punishment with children. These findings can be useful in establishing parenting educational programming that is directed at decreasing the rates of physical punishment and subsequently child physical abuse.

Adoption↗

Temporal arteritis. A clinicopathologic study.

Clinical and laboratory findings of 237 consecutive patients who had 250 temporal artery biopsies performed at the Wilmer Institute during a 15-year period were reviewed. Biopsies were reviewed independently on three separate occasions by four observers who, unaware of the clinical history, made one of the following histopathologic diagnoses: active arteritis, healed arteritis, arteriosclerosis, atherosclerosis, normal, or other. Biopsies were reviewed a fourth time by the observers together to establish a consensus diagnosis. The frequency of intraobserver disagreement in biopsy interpretation ranged from 4.4 to 25.6% of cases. The frequency with which observers disagreed with the consensus diagnosis (interobserver variation) ranged from 4.3 to 13.5% of cases. Pre-biopsy steroid therapy for seven to eight weeks or longer was associated with loss of the histopathologic features of active arteritis. We recommend biopsies for all patients with known contraindications to steroid therapy. In addition, multivariant regression analysis suggests that certain patients can be selected who are likely to have positive biopsies. For some patients, the clinical diagnosis of temporal arteritis can be based on the clinical signs and symptoms and their response to a therapeutic trial of steroids.

Aged↗

Application of artificial neural networks in HPLC method development.

The use of artificial neural networks (ANNs) for response surface modelling in HPLC method development for amiloride and methychlothiazide separation is reported. The independent input variables were pH and methanol percentage in mobile phase. The outputs were capacity factors. The results were compared with a statistical method (multiple nonlinear regression analysis). Networks were able to predict the experimental responses more accurately than the regression analysis.

Amiloride↗

Behavioral effects of low-level exposure to Hg0 among dental professionals: a cross-study evaluation of psychomotor effects.

A Across-study design was used to evaluate the sensitivities of five psychomotor tasks previously used to assess preclinical effects of low-level Hg0 (urinary < or =55 microg/l). Pooling dental professional subject populations from six studies conducted over the last 6 years, a larger study population was obtained with a high degree of uniformity (N = 230). The five psychomotor tests were: Intentional Hand Steadiness Test (IHST); Finger Tapping: The One-Hole Test: NES Simple Reaction Time (SRT); and Hand Tremor. Multivariate analyses were conducted following the hierarchical analysis of multiple responses (HAMR) approach. First, multiple scores of each test were combined into a single-factor (or related summary) variable and its reliability was estimated. Second. multiple regression analyses were conducted including log-transformed [Hg0]U levels, age, gender, and alcohol consumption in each model. Computed were both B and bu, the magnitudes of the log-Hg0 standardized coefficient. respectively uncorrected and corrected for dependent variable attenuation due to unreliability. Results indicated remarkable differences in the effects of relative level of Hg0 on psychomotor performance. Significant associations were found for the IHST factor (B = 0.415, p < 10(-6)), followed by finger tapping, which was relatively meager and insignificant (B 0.141, p = 0.17). The IHST results hold the greatest occupational relevance for dental professionals who rely on manual dexterity in restorative dentistry. Further, this statistical approach is recommended in future studies for condensation of multiple scores into summary scores with enhanced reliabilities useful in correcting for attenuation relationships (B(u)s) with exposure levels.

Adult↗

Thermal enhancement of both tumour necrosis factor alpha-induced systemic toxicity and tumour cure in rats.

In vitro and in vivo studies have suggested synergistic anti-tumour activity of combined hyperthermia and tumour necrosis factor alpha (TNF-alpha). However, some studies indicated an increased systemic toxicity of TNF by additional hyperthermia. The aim of this study was to obtain starting dosages for a clinical phase I study on the application of deep local hyperthermia and systemic TNF. We investigated the effect of local hyperthermia on the toxicity and efficacy of systemic TNF. Rats (Wag/Rij) carrying a subcutaneously transplanted osteosarcoma in the hind leg received a single intravenous dose of recombinant human (rh) TNF-alpha, either at normothermia or at hyperthermia, by positioning the tumour bearing hind leg in a water bath of 43 degrees C. Dose-effect curves for lethality and tumour cure were established and LD50 and TCD50 values were calculated. Systemic toxicity was increased by local hyperthermia. The LD50 values (+/- s.e.) were 1088 (+/- 61) micrograms kg-1 at normothermia and 205 (+/- 23) micrograms kg-1 at hyperthermia, resulting in a thermal enhancement ratio (TER) of 5.3. Following normothermia, tumour cures were observed at TNF concentrations of 1000-1300 micrograms kg-1, while this was observed at doses of 50-300 micrograms kg-1 when combined with hyperthermia (TCD50 values of 1211 and 188 micrograms kg-1 respectively), resulting in a TER of 6.4. Systemic toxicity and anti-tumour activity of TNF are both increased by local hyperthermia. A safe starting dose for the combined clinical treatment would be 10% of the dose of TNF-alpha that has been recommended for phase II studies on intravenous bolus administration of TNF-alpha at normothermia. In view of the large variability in tumour sensitivity for TNF-alpha, the clinical usefulness of this combined treatment modality has to be determined.

Animals↗

Robustness testing of a tablet formulation using multivariate design.

A total of 45 experiments were carried out to evaluate the robustness of two similar tablet formulations--a product of two strengths--with respect to normal batch-to-batch variation of the excipients and the active pharmaceutical ingredient. The formulations consist of 10 ingredients. Because of the differing amounts of active pharmaceutical ingredients, the two formulations also differ in the amounts of two of the diluents and one of the binders. The excipients and active pharmaceutical ingredient were characterized in terms of multiple variables, and principal properties were calculated with principal component analysis. A Plackett and Burman design was applied to the principal properties. The relationships between the design factors and two responses, mean disintegration time and mean crushing strength, were evaluated by using regression methods. Both formulations were found to be robust under controlled conditions.

Chemistry, Pharmaceutical↗

Reduction by fentanyl of the Cp50 values of propofol and hemodynamic responses to various noxious stimuli.

BACKGROUND: Propofol and fentanyl infusion rates should be varied according to the patient's responsiveness to stimulation to maintain satisfactory anesthetic and operative conditions. However, somatic and autonomic responses to various noxious stimuli have not been investigated systematically for intravenous propofol and fentanyl anesthesia. METHODS: Propofol and fentanyl were administered via computer-assisted continuous infusion to provide stable concentrations and to allow equilibration between plasma-blood and effect-site concentrations. The propofol concentrations needed to suppress eye opening to verbal command and motor responses after 50-Hz electric tetanic stimulation, laryngoscopy, tracheal intubation, and skin incision in 50% or 95% of patients (Cp50 and Cp95) were determined at fentanyl concentrations of 0.0, 1.0, 2.0, 3.0, and 4.0 ng/ml in 133 patients undergoing lower abdominal surgery. The ability of propofol with fentanyl to suppress hemodynamic reactions in response to various noxious stimuli also was evaluated by measuring arterial blood pressure and heart rate before and after stimulation. RESULTS: The various Cp50 values for propofol alone (no fentanyl) for the various stimuli increased in the following order: Cp50loss of consciousness, 4.4 microg/ml (range, 3.8-5.0); Cp50tetanus, 9.3 microg/ml (range, 8.3-10.4); Cp50laryngoscopy, 9.8 microg/ml (range, 8.9-10.8); Cp50skin incision, 10.0 microg/ml (range, 8.1-12.2); and Cp50intubation, 17.4 microg/ml (range, 15.1-20.1; 95% confidence interval). The reduction of Cp50loss of consciousness, with fentanyl was minimal; 11% at 1 ng/ml of fentanyl and 17% at 3 ng/ml of fentanyl. A plasma fentanyl concentration of 1 ng/ml (3 ng/ml) resulted in a 31-34% (50-55%) reduction of the propofol Cp50s for tetanus, laryngoscopy, intubation, and skin incision. Propofol alone depresses prestimulation blood pressure but had no influence on the magnitude blood pressure or heart rate increase to stimulation. Propofol used with fentanyl attenuated the systolic blood pressure increases to various noxious stimuli in a dose-dependent fashion. CONCLUSIONS: The authors successfully defined the propofol concentration required for various stimuli. Tracheal intubation was the strongest stimulus. The absence of somatic reactions for propofol does not guarantee hemodynamic stability without fentanyl. Propofol with fentanyl was able to suppress motor and hemodynamic reactions to various noxious stimuli.

Adult↗

An approach to the analysis of trauma data having a response variable of death or survival.

OBJECTIVE: To present an analysis for identifying important factors related to the mortality of trauma patients. METHODS: Practical aspects of univariate and multivariate techniques are discussed, particularly with the nonstatistician in mind. The derivation and application of the linear logistic regression model are considered, and a checklist of information is suggested for reporting results from such an analysis. A brief comparison of the logistic model is made with other relevant types of statistical models.

Humans↗

Interest among gay/bisexual men in greater Boston in participating in clinical trials of preventive HIV vaccines.

To estimate interest in HIV preventive vaccine trials, we administered questionnaires to two otherwise demographically similar cohorts of older (mean 40 years) and younger (mean 23 years) gay men in Boston. Questionnaire responses were linked to concurrent behavioral and demographic data. Univariate analyses, performed separately for older and younger cohorts, identified factors that distinguished participants who were "very interested" from those who were "not at all interested". Multivariate logistic regression analyses were used to adjust for confounding. Among all 630 participants, 215 (34%) were "not at all" interested in participating, 306 (49%) were "somewhat" interested, and 102 (16%) were "very" interested. Older men were significantly more likely than younger men to be "very" interested and less likely to be "not at all interested." Among both older and younger men, perceived peer willingness to enroll in vaccine trials predicted interest after adjusting for confounding. Among older men, optimism about success in vaccine development also predicted interest. In the younger cohort, men recruited in community settings (e.g., bars, nightclubs) were more interested in vaccine trial participation than were those recruited by outreach workers and word of mouth on college campuses. Vaccine-induced seroconversion evoked significant concern.

AIDS Vaccines↗

Therapy-resistant periodontitis (II). Compliance and general and dental health experiences.

In this exploratory case-control study, somatic and psychological factors are used for exploring whether the anamnestic information gives support to the hypothesis of a relationship between therapy-resistant periodontitis and stress factors. From retrospective comparisons of pocket probing depth charts, we classified 22 patients as either non-responding or responding to periodontal treatment. The non-responding patient group, in comparison with the responding patient group, showed a profile over time of less pocket probing depth (PPD) reduction in response to periodontal treatment. Information registered in each patient's file regarding periodontal registrations and dental status was gathered, and an interview was conducted aiming at collecting information on dental experiences and attitudes. Bivariate and logistic multivariate regression analyses were performed. The NR-group patients experienced significantly more unpleasant feelings towards dental procedures and a higher tendency to experience pain in connection with dental procedures. This group was found to start smoking at an older age than the R-group. One reason for this may be that smoking debut at an older age is more related to stress conditions than debut at a younger age. The report highlights the possible contribution of stress factors in periodontal disease.

Adolescent↗

Lessons from in vitro perifusion of pancreatic islets isolated from 80 human pancreases.

We report the average insulin response to acute glucose measured by in vitro perifusion of pancreatic islets isolated from 80 consecutive human organs. Different perifusion parameters were considered [basal release, stimulation index (SI), time to peak, incremental area under the curve delta-AUC alpha)], and the correlation among them was determined. SI positively correlated with delta-AUC alpha (p < 0.001, r = 0.80) while negatively with time to peak (p < 0.05, r = -0.23). We also evaluated several variables of the isolation procedure that might affect responsiveness to glucose by human islets. Sex and age of pancreas donors, cold ischemia time, duration of the digestion, collagenase concentration, and lot characteristics (collagenase, trypsin, clostripain, and proteases activity), and final islet yield were considered. Multivariate regression analysis showed only an independent association between SI and the concentration of collagenase (p = 0.01).

Adolescent↗

Dietary intake of fruits, vegetables, and fat in Olmsted County, Minnesota.

OBJECTIVE: To assess self-reported dietary intake in the adult population of Olmsted County, Minnesota. SUBJECTS AND METHODS: We conducted a random-digit-dial telephone survey between March 1 and April 21, 1999, of 1232 adults residing in Olmsted County, Minnesota. We then mailed a structured questionnaire to the survey respondents and achieved a response rate of 732 individuals. Percentages of individuals and predictors of those who meet recommendations for intake of fruits and vegetables and for dietary fats were determined by using chi2 tests of general association and multivariate logistic regression. RESULTS: Only 16% of the population of Olmsted County reported meeting standard dietary recommendations for consuming both 5 or more servings of fruits and/or vegetables per day and no more than 30% of calories from fat. Fifty-one percent of the population was meeting neither recommendation. Women were more likely than men to report meeting both goals (22% vs 8%, P<.001), but still more women were meeting neither goal than were meeting both goals (40% vs 22%, P<.001). Multivariate logistic regression revealed the following factors to predict adherence to both goals: female sex, lower body mass index, nonsmoker, history of high cholesterol, and daily physical activity. CONCLUSION: Few individuals in Olmsted County are meeting national recommendations for intake of fruits, vegetables, and dietary fat. More effective interventions are needed to improve dietary habits in all subgroups of this community.

Adult↗