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Results for “Multivariate response regression”

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PubMed1992

Extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma.

BACKGROUND: Many regimens are used for cutaneous T-cell lymphoma (CTCL), but with advanced disease response rates and patient survival are not adequate with any current therapy. Recently extracorporeal photochemotherapy (ECP) was proposed as an alternative therapy. OBJECTIVE: Our purpose is to present the results of ECP in patients with CTCL refractory to other treatments. METHODS: Patients with CTCL received ECP at 3- to 5-week intervals for at least 6 months. All patients except one were in stage T2 (patch/plaque) or higher. Eight patients had extracutaneous disease involving lymph nodes (six patients), bone marrow (five), or Sézary cells (six). The interval between initial symptoms and diagnosis was 5.9 +/- 1.9 years (mean +/- standard error of the mean) and the interval between diagnosis and ECP was 2.2 +/- 0.4 years. RESULTS: A complete response (disappearance of all lesions) was obtained in five patients (25%) and a partial response (disappearance of at least 50% of lesions) in six patients (30%). Four patients (20%) showed stabilization of their disease and five progressed (25%). The only variable that predicted responders versus nonresponders was the number of ECP sessions (p < 0.05 by multivariate logistic regression). In contrast, no separate beneficial effect of adjunctive chemotherapy (p > 0.5) or electron beam therapy (p > 0.1) was found. CONCLUSION: Long-term ECP may be an effective alternative treatment for CTCL refractory to other therapies and is likely to be even more useful when combined with other modalities.

Adult↗

PubMed2026

Exploring precision risk in pediatric vesicoureteral reflux: Innate immune gene variations and reflux outcomes in the RIVUR cohort.

INTRODUCTION: Children with vesicoureteral reflux (VUR) are at increased risk for morbidity from recurrent urinary tract infections (UTIs), yet the factors influencing spontaneous VUR resolution remain poorly defined. This study evaluates whether genetic variations in key urinary innate immune effectors (DEFA1A3, DMBT1, and RNASE7) influences VUR resolution and interacts with prophylaxis to alter clinical response. METHODS: We conducted a secondary analysis of 303 RIVUR participants with available DEFA1A3 and DMBT1 copy number variation (CNV) data and RNASE7 rs1263872 genotype. Primary outcomes were (1) VUR improvement (decrease in grade) and (2) VUR resolution at study exit. Multivariable logistic regression models included genotype, treatment, and their interactions, adjusting for age, sex, baseline grade (high vs low), laterality, bowel/bladder dysfunction, and any UTI. Internal validation used 2000-sample bootstrap with bias-corrected and accelerated confidence intervals and influence diagnostics. RESULTS: Clinical covariates did not significantly predict VUR improvement. Children with DEFA1A3 CNV >5 had higher odds of improvement (OR 2.36, 95% CI 1.12-4.96, p = 0.023), an effect that remained significant in bootstrap analyses. High-grade VUR was associated with lower odds of resolution (OR 0.34, 95% CI 0.12-0.94, p = 0.038). A significant interaction was observed between prophylaxis and high DMBT1 copy number for VUR resolution (interaction OR 2.99, 95% CI 1.11-8.04, p = 0.031); no interaction was seen for improvement. RNASE7 rs1263872 was not associated with either outcome. CONCLUSION: Innate immune gene variation may contribute to heterogeneity in VUR outcomes. High DEFA1A3 copy number was associated with reflux improvement and a DMBT1-prophylaxis interaction was associated with reflux resolution. The results of this study is hypothesis-generating and prompt further evaluation to assess whether a subset of children may experience structural benefit from prophylaxis or have a more favorable natural history based on their innate immune genotype.

Humans↗

PubMed2005

Factors associated with academic achievement in children with recent-onset seizures.

Children with chronic epilepsy are more at risk for achievement problems than either children without seizures or children with other chronic disorders. Factors that lead to such problems in children with epilepsy, however, are not well understood. Exploring these factors is important because academic underachievement can lead to poor social outcomes and contribute to underemployment or unemployment in adulthood. This descriptive, cross-sectional study investigated a group of children who had been diagnosed with seizures approximately 12 months previously, providing the opportunity to describe relationships among family and child characteristics; parent, child, and teacher responses; and child academic achievement at the same point in time across the sample. Seventy-two children had standardized test total battery scores, 101 had a teacher's rating of performance, and 67 had scores for both. Data were analyzed using multivariable regression. Child adaptive competency and seizure severity were associated with higher teacher ratings of academic performance (beta=0.73, p<0.0001 and beta=2.38, p=0.0182, respectively). Child adaptive competency was associated with higher total battery scores (beta=0.73, p<0.0001). Contrary to findings in studies of children with chronic epilepsy, mean academic achievement in this sample of children with recent-onset seizures was in the average range; however, 25% of the children were at or below one standard deviation below the mean on the teacher's rating of performance and 10% on the total battery. It is therefore important for health professionals and educators to regularly assess the child's academic functioning and school performance to identify those at risk for problems. Health professionals and educators need to collaborate on assessment and interventions to help maximize child academic success.

Achievement↗

PubMed2003

Childbirth education classes: sociodemographic disparities in attendance and the association of attendance with breastfeeding initiation.

OBJECTIVES: To examine sociodemographic disparities in attendance at childbirth classes, and to evaluate the association of attendance with breastfeeding initiation. METHODS: Parents of a nationally representative, cross-sectional sample of 2068 children ages 4-35 months were surveyed by telephone. The responses of 1540 mothers were included in the analysis. They were asked whether they had attended a childbirth class before giving birth. Disparities in attendance at childbirth classes and the association between attendance and breastfeeding initiation were examined using bivariate and multivariate logistic regression analyses. RESULTS: Two thirds (66%) of the children's mothers had ever attended a childbirth class. White mothers were twice as likely (OR 2.15, CI 1.39, 3.31) as African American mothers to have ever attended. Attendance also varied by education, household income, and marital status. Attendance at childbirth classes was associated with a 75% increase in the odds that a child will be breastfed (OR 1.75, CI 1.18, 2.60). CONCLUSIONS: Significant sociodemographic disparities exist in attendance at childbirth classes. Further research is needed to determine whether improving utilization of childbirth education classes reduces sociodemographic disparities in breastfeeding initiation.

Adult↗

PubMed1994

Determinants of plasma cholesterol responsiveness to diet.

Plasma cholesterol change, or 'responsiveness', to dietary saturated fat modification has long been acknowledged. The present study sought to determine the specific, predicted response of each cholesterol subfraction to known dietary manipulations. Two metabolically controlled diets, one with a low polyunsaturated:saturated fat (low P:S) ratio, and one with a high P:S ratio were fed in a crossover design to sixty-seven normolipidaemic subjects pooled from six foregoing metabolic studies. A series of statistical analyses was performed to identify the lipids and subfractions independently affected by the diet crossover. Multivariate analysis of variance revealed that the changes in total cholesterol (delta TC), low-density-lipoprotein-cholesterol (delta LDL-C), and high-density-lipoprotein-cholesterol (delta HDL-C) were the only statistically significant diet-specific 'responsive' lipids. Multiple regression was performed to identify the independent predictors of delta TC, delta LDL-C and delta HDL-C. It was found that age (years), extent of change in dietary saturated fat, and baseline LDL-C (mg/l) levels determine LDL-C change, while extent of change in saturated and polyunsaturated fat, and baseline HDL-C (mg/l) levels can predict HDL-C change. A series of equations to predict lipoprotein responsiveness to diet are derived for potential use in clinical practice.

Adult↗

PubMed2005

Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer.

BACKGROUND: Gefitinib is a selective inhibitor of the epidermal growth factor (EGFR) tyrosine kinase, which is overexpressed in many cancers, including non-small-cell lung cancer (NSCLC). We carried out a clinical study to compare the relationship between EGFR gene copy number, EGFR protein expression, EGFR mutations, and Akt activation status as predictive markers for gefitinib therapy in advanced NSCLC. METHODS: Tumors from 102 NSCLC patients treated daily with 250 mg of gefitinib were evaluated for EGFR status by fluorescence in situ hybridization (FISH), DNA sequencing, and immunohistochemistry and for Akt activation status (phospho-Akt [P-Akt]) by immunohistochemistry. Time to progression, overall survival, and 95% confidence intervals (CIs) were calculated and evaluated by the Kaplan-Meier method; groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. All statistical tests were two-sided. RESULTS: Amplification or high polysomy of the EGFR gene (seen in 33 of 102 patients) and high protein expression (seen in 58 of 98 patients) were statistically significantly associated with better response (36% versus 3%, mean difference = 34%, 95% CI = 16.6 to 50.3; P<.001), disease control rate (67% versus 26%, mean difference = 40.6%, 95% CI = 21.5 to 59.7; P<.001), time to progression (9.0 versus 2.5 months, mean difference = 6.5 months, 95% CI = 2.8 to 10.3; P<.001), and survival (18.7 versus 7.0 months, mean difference = 11.7 months, 95% CI = 2.1 to 21.4; P = .03). EGFR mutations (seen in 15 of 89 patients) were also statistically significantly related to response and time to progression, but the association with survival was not statistically significant, and 40% of the patients with mutation had progressive disease. In multivariable analysis, only high EGFR gene copy number remained statistically significantly associated with better survival (hazard ratio = 0.44, 95% CI = 0.23 to 0.82). Independent of EGFR assessment method, EGFR+/P-Akt+ patients had a statistically significantly better outcome than EGFR-, P-Akt-, or EGFR+/P-Akt- patients. CONCLUSIONS: High EGFR gene copy number identified by FISH may be an effective molecular predictor for gefitinib efficacy in advanced NSCLC.

Adult↗

PubMed2004

Utilization of inpatient care and its determinants among persons with intellectual disabilities in day care centres in Taiwan.

BACKGROUND: In Taiwan, current understanding is limited concerning the manner in which health services are utilized by persons with intellectual disabilities (ID). The objective of this study is to describe the patterns of inpatient care sought by persons with ID, and factors affecting inpatient care utilization. METHOD: The primary method used in this study was a cross-sectional survey of 1390 persons with ID in day care centres. Data were obtained from responses to a questionnaire, copies of which were mailed to 30 day care centres catering for persons with ID. The questionnaire assessed demographic and health characteristics, disability status, and inpatient care utilization for the 12 months leading up to the survey. Multivariate logistic regression analysis identified factors independently associated with inpatient care. RESULTS: Findings indicated that the average age of the people with ID in the centres was 13.7 years. Fifty per cent of people were afflicted with multiple handicaps, with an average of 26 outpatient visits made per person during the 12 months, and 16% of persons having been hospitalized within the previous year. The average hospital stay was 6 days. Inpatient care was more likely to be used by those individuals with an ID who were younger, had multiple handicaps, required rehabilitation, and had other disabilities and existing illnesses. CONCLUSIONS: The study concluded that the parameters describing age of persons with ID, as having an existing illness, and requiring rehabilitative care were statistically significant in the logistic regression model of the inpatient care.

Adolescent↗

PubMed2005

Hepatitis B vaccination in human immunodeficiency virus-infected adults receiving hemodialysis.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends hepatitis B virus (HBV) immunization for all hemodialysis (HD) patients because they are at high risk of infection. Several studies have shown that the development of protective antibody titers after HBV vaccination is much lower in HD patients. We hypothesized that human immunodeficiency virus (HIV) infection in patients with end-stage renal disease (ESRD) would further impair the immune response to hepatitis B vaccination. METHODS: We performed a retrospective cohort study of patients undergoing long-term hemodialysis from 1990 to 2002 at the United States-based dialysis facilities of Gambro Corporation, North America. The response rate defined as an increase in anti-HBs levels >/=10 mIU/L after a month of the third dose of HBV vaccination was determined in HIV-infected and a randomly selected group of ESRD patients. The demographic information, laboratory data, and hepatitis B surface antibody (anti-HBs) titers were recorded from the Gambro Corporation database on these patients. RESULTS: Of the 347 adult HIV ESRD patients, 116 received three doses of recombinant hepatitis B vaccination. Seventy percent were male, and the majority (86%) were black. Of the 116 patients who received three doses of HBV vaccination, 62 (53.4%) developed protective antibody titers. This was comparable to the response rate of 50.4% in the randomly selected 220 non-HIV hemodialysis patients. Among HIV ESRD patients, the mean hemoglobin (Hgb) was higher in patients who developed protective antibody titers (Hgb 11.61 +/- 2 vs. 10.55 +/- 1.86, P value <0.01). On multivariate logistic regression analysis, higher Hgb was associated with protective antibody titers (odds ratio: 1.34, 95% CI 0.99-1.72). Seventy percent of the HIV-infected responders maintained protective antibody titers 6 months after vaccination. CONCLUSION: Hepatitis B vaccination should be offered to all HIV-infected ESRD patients because over half of the patients with HIV and ESRD can develop protective antibodies.

Adult↗

PubMed1997

The impact of kyphosis on daily functioning.

OBJECTIVES: To determine whether moderate or severe kyphosis is associated with decrements in physical function, especially mobility. DESIGN: Cross-sectional analysis of a cohort study. SETTING: The Johns Hopkins Functional Status Laboratory, a multidisciplinary, standardized, quantitative assessment center. PARTICIPANTS: A total of 231 community-dwelling volunteers aged 59 and older who participated in a 1-day evaluation. MEASUREMENTS: Age, gender, self report of physical function, standardized measurement of: kyphosis (both qualitatively clinical criteria and quantitative assessment), time to walk 5 meters (0.1 seconds), and time to climb a flight of stairs (0.1 seconds) at usual pace. RESULTS: Using multivariate step-wise regression analysis, the presence and severity of kyphosis, measured qualitatively, was independently associated with time to walk 5 meters and to climb a flight of stairs (P = .015, P < .001, respectively), adjusting for moderate-severe scoliosis, heart rate response to exercise, arthritis, vertigo, age, and gender. Similarly, quantitative kyphosis was associated independently with stair climb time (P = .005). Qualitative kyphosis was also associated with difficulty reaching (OR = 2.21 (95% CI: 1.14 to 4.29)) and difficulty performing heavy housework (OR = 1.64 (95% CI: 1.03 to 2.61)), adjusting for prior diagnosis of moderate-severe scoliosis, prior diagnosis of arthritis, age, and gender. CONCLUSION: Kyphosis, by both clinical and quantitative assessment, is associated with diminished function, especially performance of mobility tasks. This association should be verified prospectively. If predictive, the impact of kyphosis on physical function should be considered in osteoporosis prevention and treatment counseling.

Activities of Daily Living↗

PubMed1984

Combination therapy with methotrexate and 5-fluorouracil: a prospective randomized clinical trial of order of administration.

Because of biochemical and tissue culture evidence casting doubt on the physiologic relevance of reported synergy afforded by sequential administration of methotrexate (MTX) followed by 5-fluorouracil (5-FU), a randomized controlled clinical trial was conducted in 108 patients with advanced cancer, including 70 with squamous cell carcinoma (SCC) of the head and neck, nine with SCC of other primary sites, 24 with colorectal, and five with gastric adenocarcinomas. Patients were randomized to receive weekly therapy consisting of MTX followed one hour later by 5-FU, or 5-FU followed one hour later by MTX. There was a trend to higher tumor response rates in patients treated with MTX before 5-FU (45% v 33% overall; 65% v 39% in patients with previously untreated head and neck cancer), but these differences were not significant, either by chi-square test or by multivariate stepwise logistic regression. The trend in survival favoring the reverse sequence of 5-FU before MTX was not significant in univariate analyses. Stepwise multivariate Cox model analysis showed that Eastern Cooperative Oncology Group performance status at study entry was the major prognostic factor for survival (P less than 0.001), but among the 70 patients with head and neck cancer, the sequence of drug administration was the only other significant prognostic factor for survival, and favored the sequence of 5-FU followed by MTX (P less than 0.025).

Adenocarcinoma↗

PubMed1992

Patterns of treatment failure and prognostic factors associated with the treatment of esophageal carcinoma with chemotherapy and radiotherapy either as sole treatment or followed by surgery .

PURPOSE: The records of patients with esophageal cancer who were treated with a combined modality therapy were reviewed to determine the effects of simultaneously administered chemotherapy and radiotherapy (RT) at sites of recurrence and the relationship between treatment outcome and clinicopathologic variables. PATIENTS AND METHODS: One hundred seventeen patients were treated with fluorouracil (800 mg/m2) [corrected] and cisplatin (80 mg/m2) combined with either 36 Gy (36 patients) or 54 to 60 Gy (35 patients) of RT as sole therapy. Forty-six patients underwent surgery after they had received chemotherapy and 36 Gy of RT as initial treatment. Patients with either squamous cell cancer (SCC) or adenocarcinoma were included. RESULTS: Complete endoscopic regression after an initial 36 Gy of RT and chemotherapy occurred in more than 50% of patients and in both tumor types. Relief of dysphagia accompanied tumor regression. Forty-two tumors were resected, and 11 showed a complete histologic response. Significant associations were demonstrated between enhanced survival and a diagnosis of SCC, a complete endoscopic response to initial chemotherapy and RT, and a tumor length of less than 5 cm. Multivariate analyses suggested that tumor length and complete endoscopic response were independent prognostic variables. The survival rate of patients treated by resection or radical-dosage RT was not significantly different. CONCLUSIONS: The relief of dysphagia demonstrates the palliative value of chemotherapy and RT in both tumor types. The similar survival rates of patients with SCC or adenocarcinoma treated either surgically or with high-dose combined therapy (54 to 60 Gy) emphasize the need to evaluate the role of surgery and combined treatment in randomized studies.

Adenocarcinoma↗

PubMed2005

Respiratory symptoms and hamsters or other pets: a large-sized population survey in Saitama Prefecture.

BACKGROUND: Keeping hamsters as pets has been increasing markedly. Clinical reports have suggested that hamster or other pet ownership is associated with respiratory symptoms. However, this association has not been fully investigated by population-based studies in Japan. The aim of the present study was to investigate the relationship between hamster ownership and respiratory symptoms by using a questionnaire. METHODS: During the period of August 1 to 20, 2002, we conducted a cross-sectional survey in Saitama Prefecture, which has a total population of approximately 7 million. First, we selected, proportionally to the population size, 100 areas from 5 administration districts of Saitama Prefecture. From each area, 30 households were chosen: 15 living in detached houses and 15 living in other types of dwelling, such as apartment houses. In this way, 2 groups based on type of dwelling (detached house versus other types) could be studied. A lay away plan was carried out. For the survey, 2 questionnaires were developed. One was a questionnaire dealing with household conditions, including pet keeping. The other sought details regarding individual health and lifestyle conditions. The questionnaire dealing with respiratory symptoms asked "whether the respondents had experienced respiratory symptoms (wheezing and/or breathlessness and/or bad cough) in the last 12 months." RESULTS: The response rate was 78.9%. There were 7,395 respondents in 2,368 households. There was no association between either dog or cat ownership and respiratory symptoms. In contrast, hamsters kept in the home were positively associated with respiratory symptoms. In a multivariate logistic regression analysis, hamster ownership increased the odds ratio for respiratory symptoms (odds ratio: 1.57; 95% confidence interval: 1.18-2.10). CONCLUSION: This large size population-survey indicated that hamster ownership is associated with respiratory symptoms.

Adolescent↗

PubMed2000

Does reengineering really work? An examination of the context and outcomes of hospital reengineering initiatives.

OBJECTIVE: To examine the effect of reengineering on the competitive position of hospitals. Although many promises have been made regarding outcomes of process reengineering, little or no research has examined this issue. This article provides an initial exploration of the direct effects of reengineering on the competitive cost position of hospitals and the modifying effects of implementation factors. DATA SOURCES/STUDY SETTING: Obtained for primary data from a 1996/1997 national survey of hospital restructuring and reengineering sponsored by the American Hospital Association and the Leonard Davis Institute for Health Economics. Responses from approximately 30 percent of all U.S. acute care hospitals with 100 or more inpatient beds in metropolitan service areas were combined with American Hospital Association annual survey and InterStudy HMO data in this study. STUDY DESIGN: A first-difference multivariate regression was utilized to examine the effects of reengineering and other explanatory variables on the change in the cost position of a hospital's expenses per adjusted patient day relative to its market's costs per adjusted patient day. DATA COLLECTION/EXTRACTION METHODS: The survey of hospital restructuring and reengineering was mailed to hospital chief executive officers. The CEOs identified reengineering and restructuring hospital activities over the previous five years. The extensiveness and components of reengineering and internal restructuring were identified and used in the empirical analysis. PRINCIPAL FINDINGS: Results suggest that reengineering without integrative and coordinative efforts may damage an organization's cost position. The use of steering committees, project teams, codification of the change process, and executive involvement in core changes modifies the results of reengineering to improve an organization's competitive position. CONCLUSIONS: In a national sample of hospitals, reengineering alone was not found to improve the relative cost-competitive position. Organizations attempting to improve their cost competitiveness must consider the way in which change is implemented. This research suggests that the process of change may be as important as the change instrument. Additional research is needed to explore differences between early and late adopters.

Analysis of Variance↗

PubMed1991

Analysis of longitudinal data with unmeasured confounders.

Confounding in longitudinal or clustered data creates special problems and opportunities because the relationship between the confounder and covariate of interest may differ across and within individuals or clusters. A well-known example of such confounding in longitudinal data is the presence of cohort and period effects in models of aging in epidemiologic research. We first formulate a data-generating model with confounding and derive the distribution of the response variable unconditional on the confounder. We then examine the properties of the regression coefficient for some analytic approaches when the confounder is omitted from the fitted model. The expected value of the regression coefficient differs in across- and within-individual regression. In the multivariate case, within- and between-individual information is combined and weighted according to the assumed covariance structure. We assume compound symmetry in the fitted covariance matrix and derive the variance, bias, and mean squared error of the slope estimate as a function of the fitted within-individual correlation. We find that even in this simplest multivariate case, the trade-off between bias and variance depends on a large number of parameters. It is generally preferable to fit correlations somewhat above the true correlation to minimize the effect of between-individual confounders or cohort effects. Period effects can lead to situations where it is advantageous to fit correlations that are below the true correlation. The results highlight the trade-offs inherent in the choice of method for analysis of longitudinal data, and show that an appropriate choice can be made only after determining whether within- or between-individual confounding is the major concern.

Analysis of Variance↗

PubMed1990

Infectious episodes in runners before and after the Los Angeles Marathon.

An epidemiologic study of Los Angeles Marathon (LAM) applicants was conducted to investigate the relationship between self-reported infectious episodes (IE), training data, and LAM participation. Eight days before the LAM, 4926 of 12,200 applicants were randomly selected, and sent a pilot-tested four page questionnaire, which was received 7 days after the LAM. The 2311 respondents were found to be 2.0 yr older and 7.6 min faster than other LAM finishers (p less than .01). Univariate and multivariate analyses (logistic regression) were conducted to test the relationship between IE and km/wk of running (6 total categories). The final model tested controlled for age, marital status, reported sickness in other members of the runner's home, perceived feelings of stress in response to personal training regimens, and the suppressive effect of sickness on regular training. In runners training greater than or equal to 97 vs less than 32 km/wk, the odds ratio (OR) for IE during the 2 month period prior to the LAM was 2.0 (95% confidence interval (CI) 1.2-3.4). A test for trend showed an increase in OR with increase in km/wk category (p = .04) which was largely explained by the increased odds of reported sickness in the greater than or equal to 97 km/wk category. Of the 1828 LAM participants without IE before the LAM, 236 (12.9%) reported IE during the week following the LAM vs 3 of 134 (2.2%) similarly experienced runners who did not participate, OR = 5.9 (95% CI 1.9-18.8). These data suggest that runners may experience increased odds for IE during heavy training or following a marathon race.

Adult↗

PubMed1983

The use of multivariate analysis of variance in physiological research: the two-group case.

The advantages of performing simultaneous inferences on the means of several response variables using multivariate analysis of variance are discussed. They include control over the problem of declaring false significant differences and the ability to investigate the effects of treatment on a given response variable after eliminating variations due to other response variables. Computational equivalencies with multiple linear regression in the two-group case are also discussed.

Analysis of Variance↗

PubMed1998

Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression.

AIMS: To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non-Hodgkin's lymphomas (NHL). METHODS AND RESULTS: Apoptotic fractions were quantified by use of the TdT (terminal deoxynucleotidyl-transferase)-mediated in-situ end-labelling technique (TUNEL), the percentage of positive cells constituting the apoptotic index (AI). Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI). Tissues were also stained for p53 protein with the DO-1 antibody. Patients were followed up until death (n = 33) or for an average of 63 months (n = 56). AI increased with malignancy grade and proliferative activity but was not related to location, cell of origin, clinical stage, bone marrow involvement and p53 expression. In multivariate analysis, overall survival was independently influenced by grade, stage, p53 LI and chemotherapy. The independent predictors of disease-free survival were Ki67 LI location and chemotherapy. AI turned out to be the only independent (negative) predictor of post-relapse survival. On the other hand, a low Ki67 LI increased the risk of relapse (logistic regression analysis) whereas a low p53 LI increased the probability of complete response. CONCLUSIONS: Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological parameters in NHL.

Adolescent↗

PubMed2004

UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer.

SN-38 is the active metabolite of irinotecan and it is metabolised through conjugation by uridine diphosphate glucuronosyl transferase (UGT1A1). The major toxicity of irinotecan therapy is diarrhoea, which has been related to the enzymatic activity of UGT1A1. We examined the influence of the UGT1A1 gene promoter polymorphism in the toxicity profile, in the response rate and in the overall survival (OS) in 95 patients with metastatic colorectal cancer treated with an irinotecan-containing chemotherapy. Genotypes were determined by analysing the sequence of TATA box of UGT1A1 of genomic DNA from the patients. Clinical parameters and genotypes were compared by univariate and multivariate statistical methods. The more frequent adverse effects were asthenia (34 patients), diarrhoea (29 patients) and neutropenia (20 patients). Severe diarrhoea was observed in 7/10 homozygous (70%) and 15/45 heterozygous (33%) in comparison to 7/40 (17%) wild-type patients (P=0.005). These results maintained the statistical significance in logistic regression analysis (P=0.01) after adjustment for other clinical relevant variables. The presence of severe haematological toxicity increased from wild-type patients to UGT1A1(*)28 homozygotes, but without achieving statistical significance. No relationship was found between the UGT1A1(*)28 genotypes and infection, nausea or mucositis. In univariate studies, patients with the UGT1A1(*)28 polymorphism showed a trend to a poorer OS (P=0.09). In the multivariate analysis, the genotype was not related to clinical response or to OS. The role of the UGT1A1 genotype as a predictor of toxicity in cancer patients receiving irinotecan demands the performance of a randomized trial to ascertain whether genotype-adjusted dosages of the drug can help to establish safe and effective doses not only for patients with the UGT1A1(*)28 homozygous genotype but also for those with the most common UGT1A1 6/6 or 6/7 genotype.

Adult↗