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Cell-cycle regulators and the Ki-67 labeling index can predict the response to chemoradiotherapy and the survival of patients with locally advanced squamous cell carcinoma of the esophagus.

BACKGROUND: We investigated whether aberrant p53 and p16 expression, the Ki-67 labeling index (LI), and int-2/cyclin D1 gene amplification predict the response to chemoradiotherapy (CRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: p53 and p16 expression status, the Ki-67 LI, and int-2/cyclin D1 amplification were assessed by immunohistochemical staining and slot blot analysis in pretreatment endoscopic biopsy specimens of 41 patients with T4 or M1 Lym (distant lymph node metastasis) ESCC. All patients received a course of chemotherapy (5-fluorouracil and cisplatin) with radiotherapy. RESULTS: The CRT therapeutic response rate was 71%, and resection after CRT was successful in 15 of the cases in which the CRT effect was significant. The cumulative survival rate after CRT in the p53-negative patients was significantly higher than in the p53-positive patients (P =.037). The mean Ki-67 LI in the CRT response cases was significantly higher than in the CRT no-response cases (P =.023). Multivariate regression analysis revealed high Ki-67 LI to be an independent variable linked to a pathologic complete response to CRT (P =.033). The cumulative survival rate after CRT in the group that was p53-negative and int-2/cyclin D1 amplification-positive was significantly higher than in the other groups (P =.008). CONCLUSIONS: Evaluating predictive factors in pretreatment endoscopic biopsy specimens may allow selection of more suitable multimodal treatment for ESCC patients and improve their quality of life.

Adenocarcinoma↗

Simultaneous inference for generalized linear models with unmeasured confounders.

Tens of thousands of simultaneous hypothesis tests are routinely performed in genomic studies to identify differentially expressed genes. However, due to unmeasured confounders, many standard statistical approaches may be substantially biased. This paper investigates the large-scale hypothesis testing problem for multivariate generalized linear models in the presence of confounding effects. Under arbitrary confounding mechanisms, we propose a unified statistical estimation and inference framework that harnesses orthogonal structures and integrates linear projections into three key stages. It begins by disentangling marginal and uncorrelated confounding effects to recover the latent coefficients. Subsequently, latent factors and primary effects are jointly estimated through lasso-type optimization. Finally, we incorporate projected and weighted bias-correction steps for hypothesis testing. Theoretically, we establish the identification conditions of various effects and non-asymptotic error bounds. We show effective Type-I error control of asymptotic-tests as sample and response sizes approach infinity. Numerical experiments demonstrate that the proposed method controls the false discovery rate by the Benjamini-Hochberg procedure and is more powerful than alternative methods. By comparing single-cell RNA-seq counts from two groups of samples, we demonstrate the suitability of adjusting confounding effects when significant covariates are absent from the model.

Hidden variables↗

Clinical significance of changes in serum hepatitis B virus DNA titer in patients with chronic hepatitis B treated with interferon.

BACKGROUND: Interferon (IFN) has been used in the treatment of patients with chronic hepatitis B virus (HBV) infection. Nonetheless, the changes in serum HBV DNA titer during IFN treatment and the effect of these changes on the therapeutic results have not been well studied. METHODS: Twenty patients with chronic hepatitis B who were positive for serum hepatitis B e antigen (HBeAg) and HBV DNA received IFN-alpha 2a 4.5 million units by subcutaneous injection three times a week for 24 weeks. Twenty age- and sex-matched patients with chronic hepatitis B were selected as a control group. Treatment response was defined as the normalization of serum alanine aminotransferase (ALT) and the seroconversion of serum HBeAg 24 weeks after discontinuation of the IFN treatment. Serum HBV DNA was measured using the branched DNA (bDNA) signal amplification assay. RESULTS: There was no significant difference in pretreatment mean serum ALT and HBV DNA titer in either the IFN-treated or the control group. Treatment response was found in six (30%) of 20 IFN-treated patients and in four (20%) of 20 control patients (p > 0.05). Serum HBV DNA titer fell after IFN treatment and remained undetectable only in patients with final treatment response. Serum HBV DNA was negative at week 12 of the IFN treatment in four (67%) of six patients with treatment responses, significantly higher than in none (0%) of 14 patients without a treatment response (p = 0.001). Multivariate logistic regression revealed that the negativity of serum HBV DNA at week 12 of the IFN treatment successfully predicted treatment response. CONCLUSIONS: Thirty percent of the patients with chronic hepatitis B responded to IFN-alpha 2a 4.5 million units subcutaneously injected three times a week for 24 weeks. Negativity of serum HBV DNA measured by bDNA assay at week 12 of the IFN treatment may suggest a beneficial treatment outcome.

Adult↗

Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems.

Acute GVHD remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). In a retrospective analysis, the response of 443 HSCT patients who received prednisone, 60 mg/m2, for 14 days followed by an 8-week taper, as initial therapy for acute GVHD from 1990 through 1999 at a single institution was examined. Median patient age was 29.0 years (range, 0.3-60.3 years), with 40% of patients <20 years old. Patients received HSCT from 201 related (189 matched sibling/12 partially matched) and 242 unrelated (130 HLA-A, B, DRB1 matched/112 partially matched) donors. GVHD score was measured and outcomes compared using the Minnesota, Consensus, and International Bone Marrow Transplant Registry (IBMTR) grading systems. Prior to initiation of steroid therapy, severe (grades III-IV) acute GVHD was observed in 57 (13%) patients (Minnesota or Consensus grading) and in 192 (43%) patients (IBMTR grading). At day 28 of treatment, overall improvement was observed in 55% of patients, with durable (> or = 28 days) complete response observed in 35% and partial response observed in 20% of patients. Patients with acute lower gastrointestinal GVHD (+/- other organ involvement) had lower response rates. In multivariate logistic regression analysis, recipients of related donor grafts and recipients of GVHD prophylaxis other than methotrexate alone had the highest likelihood of overall response. Initial Minnesota GVHD grade or Consensus GVHD grade was not associated with significant differences in overall response, whereas patients with an initial IBMTR grade of B or C had a higher likelihood of response. Chronic GVHD developed in 42% of patients by 1 year after HSCT. The probability of survival at 1 year after initiation of steroid therapy was 53% (95% confidence interval, 48%-58%). In Cox regression analysis, factors associated with better survival included patients' youth, receipt of related or HLA-matched unrelated grafts, and administration of GVHD prophylaxis other than T-cell depletion in all 3 grading systems. Lower initial GVHD grade (I-II or A-B) led to better survival. These data suggest that steroids provide an active but inadequate therapy for acute GVHD, especially with higher grade GVHD. More effective prophylaxis and therapy for acute GVHD is needed for mismatched unrelated donor recipients and for those with severe GVHD.

Acute Disease↗

Exposure to organic solvents and personality.

OBJECTIVES: Although cognitive and neuropsychological changes have been found after high cumulative exposures to solvents, it is not clear whether such exposures are associated with personality characteristics. To study this two groups of British and Chinese dockyard painters who had been heavily exposed to paint solvents have been investigated. METHODS: 260 Male dockyard painters in the United Kingdom, 539 local community controls, 109 Chinese dockyard painters, and 255 dockyard controls completed the Eysenck personality questionnaire, neuroticism (N) and social conformity or dissimulation (L) scales. The non-parametric Kruskal-Wallis test was used to evaluate differences in scores of personality traits between painters and controls. Adjusted relative risks for painters having high N and L scores were calculated in a Breslow-Cox regression analysis, and exposure-response relations were examined in multivariate logistic regression analysis. Non-parametric Spearman's correlation was used to examine relations between previously determined neuropsychological symptoms and personality. RESULTS: Both British and Chinese data showed that mean neuroticism scores of painters were significantly higher than controls, whereas scores of social conformity did not differ. Relative risk of being a painter increased significantly with increasing N scores, but L scores showed no such trend. In a case-control analysis, there were significant exposure-response relations for the N score. In the United Kingdom the odds ratios (ORs) (95% confidence interval (95% CI), were 2.03 (0.79 to 5.22) for 1-4 years of exposure, 2.38 (0.82 to 6.91) for 5-9 years, 7.05 (1.27 to 39.25) for 10-14 years, and 1.76 (0.63 to 4.89) for 15-41 years. In the Chinese painters, ORs were 4.66 (1.38 to 15.75) for 2-14 years, 10.03 (2.96 to 34.04) for 15-18 years, and 13.56 (3.78 to 48.59) for 19-43 years. Neuroticism was significantly positively related to neuropsychological symptoms in all subjects. Social conformity showed no association with neuropsychological symptoms in British painters and a negative relation among the Chinese painters. CONCLUSION: Increasing symptoms suggesting neuroticism seemed to relate to the duration of painting whereas scores for social conformity and dissimulation did not. The relation between exposure time and response suggests that increased neuroticism may be caused by long term occupational exposure to organic solvents.

Adolescent↗

Cue-signal-response analysis of TNF-induced apoptosis by partial least squares regression of dynamic multivariate data.

Biological signaling networks process extracellular cues to control important cell decisions such as death-survival, growth-quiescence, and proliferation-differentiation. After receptor activation, intracellular signaling proteins change in abundance, modification state, and enzymatic activity. Many of the proteins in signaling networks have been identified, but it is not known how signaling molecules work together to control cell decisions. To begin to address this issue, we report the use of partial least squares regression as an analytical method to glean signal-response relationships from heterogeneous multivariate signaling data collected from HT-29 human colon carcinoma cells stimulated to undergo programmed cell death. By partial least squares modeling, we relate dynamic and quantitative measurements of 20-30 intracellular signals to cell survival after treatment with tumor necrosis factor alpha (a death factor) and insulin (a survival factor). We find that partial least squares models can distinguish highly informative signals from redundant uninformative signals to generate a reduced model that retains key signaling features and signal-response relationships. In these models, measurements of biochemical characteristics, based on very different techniques (Western blots, kinase assays, etc.), are grouped together as covariates, showing that heterogenous data have been effectively fused. Importantly, informative protein predictors of cell responses are always multivariate, demonstrating the multicomponent nature of the decision process.

Apoptosis↗

Kinetics of the hepatitis C virus during interferon therapy as a marker of therapeutic response.

BACKGROUND: The viral load and subtype of hepatitis C virus (HCV) are predictors of the efficacy of interferon (IFN) therapy. The kinetics of HCV during IFN therapy have been described recently, suggesting that HCV infection is highly dynamic. These observations have raised the issue as to whether early monitoring of the viral load can help guide IFN therapy. METHODS: We measured HCV-RNA levels at 0, 24 and 48 h after the start of IFN-alpha treatment (10 MU daily for 2 weeks and then three times weekly for 22 weeks) or IFN-beta treatment (6 MU daily for 6 weeks). Then we analyzed the relationship between HCV kinetics and therapeutic response using stepwise multivariate logistic regression analysis. RESULTS: The exponential decay slope of the viral load during the first 24 h, not the first 48 h or the next 24 h, was a predictor of viral eradication at 6 months after completion of the treatment (sustained response; P = 0.0023). This decay slope was not affected by the HCV serotype or the type of IFN used. Initial viral load and HCV serotype were also predictors, as reported previously (P < 0.0001 and P = 0.0347, respectively). We also proposed a model using a prognostic index that predicted a sustained response with more than 80% sensitivity, specificity and efficacy in an independent and external group of patients. CONCLUSION: This study demonstrated that the exponential decay slope of the viral load during the first 24 h was an important predictor of the response to IFN therapy as well as the initial viral load and HCV serotype. The model may also be useful for the clinical management of IFN therapy.

Antiviral Agents↗

Polymorphisms in the interferon-gamma gene at position +874 in patients with chronic hepatitis C treated with high-dose interferon-alpha and ribavirin.

To investigate the influence of the T-to-A polymorphic sequence at position +874 in the interferon (IFN)-gamma gene (+874 IFN-gamma) on the response to combination therapy with high-dose interferon and ribavirin, the single nucleotide polymorphisms were determined by using a polymerase chain reaction sequence-specific primers approach in 150 histologically proved chronic hepatitis C (CHC) patients. The distribution of genotypes for +874 IFN-gamma were T/T: 6 (4.0%), T/A: 31 (20.7%) and A/A: 113 (75.3%) and 24.7% (37/150) of patients were inherited T allele. After undergoing combination therapy with high-dose IFN-alpha and ribavirin, 70.7% (106/150) of patients achieved sustained viral response (SVR). Based on multivariate regression analyses, the independent factors predicting HCV SVR after combination therapy were HCV genotype non-1b (P<0.001) and low pretreatment HCV RNA levels (P=0.041) (odds ratios/95% C.I.: 10.150/4.023-25.609 and 0.581/0.345-0.979, respectively). No association between genotypes, A or T alleles of +874 IFN-gamma and response to combination therapy with high-dose IFN-alpha and ribavirin. In conclusion, we found that with high SVR rates after combination therapy with high-dose IFN-alpha and ribavirin, HCV genotypes and pretreatment serum HCV RNA levels, but not inheritance of the IFN-gamma polymorphism at the position +847, were predictors for SVR.

Adult↗

A caveat concerning independence estimating equations with multivariate binary data.

Clustered binary data occur commonly in both the biomedical and health sciences. In this paper, we consider logistic regression models for multivariate binary responses, where the association between the responses is largely regarded as a nuisance characteristic of the data. In particular, we consider the estimator based on independence estimating equations (IEE), which assumes that the responses are independent. This estimator has been shown to be nearly efficient when compared with maximum likelihood (ML) and generalized estimating equations (GEE) in a variety of settings. The purpose of this paper is to highlight a circumstance where assuming independence can lead to quite substantial losses of efficiency. In particular, when the covariate design includes within-cluster covariates, assuming independence can lead to a considerable loss of efficiency in estimating the regression parameters associated with those covariates.

Biometry↗

Brief report: the burden of diabetes therapy: implications for the design of effective patient-centered treatment regimens.

BACKGROUND: Management of diabetes, and in particular blood glucose, can be complex and burdensome. OBJECTIVE: To evaluate patient views of the burdens of therapy and its impact on self-management. PATIENTS: Veteran patients with type 2 diabetes. DESIGN: Mailed survey. MEASUREMENTS: Patients described their views of the burden of diabetes treatments, adherence, and clinical and demographic status. Factors associated with ratings of burden and adherence to therapy were examined using multivariate regression methods. RESULTS: The response rate was 67% (n=1,653). Patients viewed pills as the least burdensome treatment and insulin as the most burdensome. Ratings of the burden of insulin were lower if a patient had prior experience with therapy. Adherence to prescribed therapy varied substantially; for example, patients followed medication recommendations more closely than other areas of self-management. Multivariate analyses showed that the main predictor of adherence was patients' ratings of the burden of therapy. CONCLUSIONS: Injected insulin regimens are viewed as highly burdensome by patients, although this burden is attenuated by experience. Adherence to self-management is strongly and independently correlated with views of treatment burden. The burden of diabetes-related treatments may be a source of suboptimal glucose control seen in many care settings. Providers should consider the burden of treatment for a particular patient and its impact on adherence as part of a decision-making process to design effective treatment regimens.

Aged↗

Laparoscopic myotomy for achalasia: predictors of successful outcome after 200 cases.

OBJECTIVE: Laparoscopic myotomy is the preferred treatment of achalasia. Our objectives were to assess the long-term outcome of esophageal myotomy and to identify preoperative factors influencing the outcome. METHODS: Preoperative and long-term outcome data were collected from patients undergoing laparoscopic myotomy for achalasia at our institution. The primary endpoint of the study was the postoperative change (delta) in dysphagia score. This score was calculated by combining the frequency and the severity of dysphagia. Persistent postoperative dysphagia was defined as 1 standard deviation less than the mean delta score of all patients. Logistic regression was used to identify independent preoperative factors associated with successful myotomy. RESULTS: A total of 200 consecutive patients were included in the study. At a mean follow-up of 42.1 months, the mean delta dysphagia score was 7.1 +/- 2.6; therefore, the myotomy was considered successful when the delta score was >4.5. According to this definition, 170 (85%) patients achieved excellent dysphagia relief (responders). Responders had higher preoperative low esophageal sphincter (LES) pressure than nonresponders: 42.6 +/- 13.1 versus 23.8 +/- 7.0 mm Hg (P = 0.001). High preoperative LES pressure remained an independent predictor of excellent response in the multivariate logistic regression model. Patients with LES pressure >35 mm Hg had an odds ratio of 21.3, making more likely to achieve excellent dysphagia relief after myotomy compared with those with LES pressure < or =35 mm Hg (odds ratio, 21.3; 95% confidence interval, 6.1-73.5, P = 0.0001). CONCLUSION: Laparoscopic myotomy can durably relieve symptoms of dysphagia. Elevated preoperative LES pressure represents the strongest positive outcome predictor.

Adolescent↗

Clinical evaluation of subjective and objective changes in motor activity and attention in children with attention-deficit/hyperactivity disorder in a double-blind methylphenidate trial.

The aim of this study was to determine drug-dependent effects on attention and motor activity in children with attention-deficit/hyperactivity disorder (ADHD) in a double-blind methylphenidate (MPH) trial using both subjective behavior ratings and objective measures of function. In particular, we were interested in the relationship between changes of those subjective and objective measures. A total of 44 ADHD children with the combined subtype completed a randomized, double-blind, placebo-controlled, crossover trial with 2 doses of MPH (0.25; 0.5 mg/kg body weight) and placebo. In each condition, computerized attention tasks were performed, teacher-behavior ratings were obtained, and actigraph data were collected in both clinical and naturalistic settings. Trend tests revealed linear effects of MPH dose on actigraph data in the test session (p = 0.02) and at school (p = 0.001), as well as on sustained attention (p < 0.001), while inhibitory control showed a quadratic dose-response curve (p < 0.001). Multivariate regression analyses revealed that changes of both, hyperactive-impulsive symptoms (28%) and inattentive symptoms (23%) could be explained by objective changes of motor activity. Thus, for clinical practice, it should be taken into account that behavior ratings of ADHD symptoms seemed to be predominantly influenced by changes of motor activity.

Analysis of Variance↗

Retreatment tuberculosis cases. Factors associated with drug resistance and adverse outcomes.

STUDY OBJECTIVE: Risk factors associated with treatment failure and multidrug-resistant tuberculosis (MDR-TB) were examined among HIV-seronegative patients who were previously treated for tuberculosis (TB). DESIGN: Prospective, cohort study of patients referred to the study hospital for retreatment of TB between March 1986 and March 1990. PATIENTS: The patients belonged to three groups, according to outcomes following their previous treatment: 37 patients who abandoned treatment or suffered relapse after completion of therapy (group A), 91 patients who failed to respond to the first-line drug regimen (group B), and 78 patients who failed to respond to the second-line drug regimen (group C). RESULTS: Patients with Mycobacterium tuberculosis strains resistant to rifampin and isoniazid were found in 2 (6%) in group A, 29 (33%) in group B, and 49 (65%) in group C. Cure was achieved in 77% in group A, 54% in group B, and 36% in group C. Death occurred in none of the patients in group A, 8% in group B, and 24% in group C. In a multivariate logistic regression analysis, unfavorable response (failure to sterilize sputum culture, death, and abandonment) was significantly associated with infection with a multidrug-resistant M tuberculosis strain (p = 0.0002), cavitary disease (p = 0.0029), or irregular use of medications (p < 0.0001). CONCLUSIONS: These observations show that a previous treatment outcome and current clinical and epidemiologic histories can be used to predict the development of MDR-TB and adverse outcomes in patients undergoing retreatment for TB. Such information may be useful for identifying appropriate patient candidates for programs such as directly observed therapy.

Adult↗

[How to increase the optimal rate of secondary cytoreductive surgery in recurrent epithelial ovarian cancer].

BACKGROUND & OBJECTIVE: Optimal secondary cytoreduction is of prognostic importance for recurrent epithelial ovarian cancer. To increase the optimal rate of secondary cytoreductive surgery in these patients is helpful for improving the prognosis of recurrent epithelial ovarian cancer patients. In this retrospective study, we investigated how to increase the optimal rate of secondary cytoreductive surgery in recurrent epithelial ovarian cancer patients. METHODS: The clinical data of 54 patients with recurrent epithelial ovarian cancer were analyzed retrospectively, who received secondary cytoreductive surgery during March 1 1997 to March 31 2003 in Cancer Center, Sun Yat-sen University. Nineteen patients had tumors only in pelvis, and 35 patients both in pelvis and abdomen. Single tumor was found in 16 patients and multiple tumors in 38 patients. Thirty-eight patients had ascites and 16 patients no ascites. Preoperative chemotherapy was given to 20 cases, and responses were observed in 12 patients and no response in 8. Multivariate logistic regression was carried out to investigate the relationship of residual diseases of secondary cytoreduction with age, time to recurrence, recurrent sites, ascites, and preoperative salvage chemotherapy. RESULTS: Optimal surgical cytoreduction was obtained in 81.5% (44/54) of the patients, with no macroscopic residual diseases in 53.7% (29/54) and residual diseases <or=2 cm in 27.8% (15/54). Logistic regression showed that recurrent sites and ascites were the significant factors for residual diseases after secondary cytoreductive surrey (both P <or= 0.05). Optimal cytoreduction was obtained in 100% (12/12) of the patients whose salvage chemotherapy before secondary cytoreduction was effective and in 37.5% (3/8) cases whose chemotherapy before secondary cytoreduction was ineffective (P<or=0.05, Chi(2) test). Complicated surgical procedures involving gastrointestinal tract, urinary tract, liver or spleen were carried out in 40.7% (22/54) of the patients. Post-operation complications occurred in 16.6% (9/54) and post-operation death rate was 1.9% (1/54). CONCLUSION: It could be helpful for obtaining optimal secondary cytoreduction and avoiding helpless laparotomy to select patients properly according to the border of recurrent tumor, recurrent site, with or without ascites and the response of salvage chemotherapy before secondary cytoreduction and to do careful preoperative preparations.

Adult↗

Determinants of modern health care use by families after a childhood burn in Ghana.

OBJECTIVES: This study examined determinants of modern health care use by families after their child aged 0-5 years sustained a burn injury in the Ashanti Region of Ghana. METHODS: A community based survey of children aged 0-5 years was conducted in 50 enumeration areas in the region. Mothers of all children with scars as evidence of a burn were selected for a follow up interview using a standard questionnaire two to three months later. Determinants of health care use were investigated through a multivariate logistic regression using interview responses from mothers of 617 children for whom report on some treatment was given. RESULTS: Overall, 48% of the burned children were taken to a modern health facility for treatment. Of those taken to a modern health facility, 68% were sent within 24 hours of the burn event. Factors with large adjusted odds ratios for modern health care use included wound infection, burns covering 6% or more of the body surface, and third degree burns. Compared with scalds, children with contact and flame burns were less likely to be taken to a health facility, as were burns to rural children, and those given first aid treatment at home. CONCLUSIONS: It is concluded that families, particularly rural residents, should be educated about appropriate health care seeking practices after a burn.

Adult↗

Cephalometric analysis in patients with obstructive sleep apnea. Part II: Prognostic value in treatment with a mandibular advancement device.

BACKGROUND: The mandibular advancement device (MAD) is accepted as an additional treatment option for snoring and mild obstructive sleep disorders. Its therapeutic efficacy can only be verified through nocturnal polysomnography with the appliance in situ. The relevance of the craniofacial skeletal and soft-tissue structures as an etiological cofactor is controversial. While the lateral cephalogram of the facial skeleton is of no direct diagnostic relevance, it remains unclear to what extent cephalometric assessment can provide prognostic information to better ensure treatment success with an MAD. METHODS AND RESULTS: This study is based on the evaluation of 57 patients diagnosed polysomnographically with obstructive sleep apnea (OSA). The patients were treated primarily with a modified activator; after 6-12 weeks, control polysomnography was carried out in the sleep laboratory. The cephalometric variables were analyzed using a multivariate regression procedure with the response variable of treatment outcome. In addition to a horizontal craniofacial morphology, the downward and forward posture of the hyoid is a prognostic variable for effective therapy with an MAD.

Adult↗

Patient satisfaction and quality of care at four diagnostic imaging procedures: mammography, double-contrast barium enema, abdominal ultrasonography and vaginal ultrasonography.

The objective of this study was to measure patient satisfaction and to investigate the practical implications of monitoring the quality of care at four radiology procedures. A survey was conducted immediately after the examinations in eight radiology departments: 550 patients attending for mammography, 110 for double-contrast barium enema (DCBE), 97 for abdominal ultrasonography and 90 for vaginal ultrasonography. Outcome measures were seven questionnaire scales: pain, emotional distress, information received, staff's punctuality and technical ability, facilities, and general satisfaction. Response rate was 87 %. Multivariate regression analysis showed significant differences between procedures on all scales (p < 0.001). Differences considered to be of practical importance, i. e. >/= 7 scale points, were detected on five of the scales. Mammography and DCBE caused the most pain, and vaginal US and DCBE caused the most distress. The US procedures entailed dissatisfaction with information about the procedures. The DCBE patients recorded dissatisfaction with the staff's lack of punctuality, and these and the mammography patients recorded dissatisfaction with the facilities. The findings indicate a potential for improving patients' experiences. Several aspects of care, i. e. pain management, attention to the patient's emotional concerns, explanation of procedures, punctuality and quality of the facilities, can be improved.

Abdomen↗

The role of intensive therapy and autologous blood and marrow transplantation for chemotherapy-sensitive relapsed and primary refractory non-Hodgkin's lymphoma: identification of major prognostic groups.

Patients with intermediate grade non-Hodgkin's lymphoma (NHL) who relapse or fail to achieve a complete remission after anthracycline-containing induction regimens have a poor outcome with conventional-dose salvage treatment. This outcome may be improved with intensive therapy and autologous transplantation (ABMT) but even in patients with proven chemotherapy-sensitive disease, relapse rates of up to 60% are observed. Reliable and powerful prognostic indicators are needed to identify appropriate patients for this expensive procedure and those subjects to whom alternative or additional treatment should be offered. We were interested in testing the hypothesis that tumour burden, and hence remission status immediately prior to transplant, is an important prognostic indicator of survival. We aggressively treated patients with conventional-dose salvage chemotherapy to maximum tumour response, and tested, by multivariate regression analysis, predictors of outcome post-transplant. We studied 81 consecutive patients with intermediate grade and immunoblastic NHL who achieved either a partial (PR) or complete remission (CR) following repetitive cycles of conventional-dose salvage therapy. Intensive therapy consisted of etoposide (60 mg/kg) and intravenous melphalan (160-180 mg/m2) with or without total body irradiation (TBI) followed by infusion of autologous unpurged bone marrow and/or blood cells. The predicted 4-year survival and progression-free survival (PFS) with a median follow-up of 37 months was 58% and 48% (95% confidence interval (CI) 37-55%), respectively. The only factor predictive of outcome was remission status at transplant (P=0.0001). The PFS at 4 years for the CR group was 61% (95% CI 53-75%). In contrast, only 25% (95% CI 11-40%) of patients undergoing autotransplant in PR were progression free at 4 years. We conclude that remission status at transplant after maximum tumour reduction is a powerful prognostic indicator.

Adult↗