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Biomedical subjects

J Hetherington

Publications and source records attributed to J Hetherington.

At least 19 recordsLinked to original sources
PubMed2006

Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up.

Trial 24, one of three ongoing trials in the Early Prostate Cancer programme, is evaluating the efficacy and tolerability of bicalutamide (Casodex) 150 mg following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with early, non-metastatic prostate cancer. At 7 years' median follow-up, addition of bicalutamide significantly improved objective progression-free survival (PFS) for patients with locally advanced disease, reducing the risk of progression by 34% versus standard care alone (hazard ratio 0.66; 95% confidence interval 0.55, 0.79; P<0.001). In localized disease, a significant difference in objective PFS was not found. There was no significant difference in overall survival.

Anilides↗
PubMed2005

Phase III trial of satraplatin, an oral platinum plus prednisone vs. prednisone alone in patients with hormone-refractory prostate cancer.

Satraplatin is a novel oral platinum (IV) complex that shows activity against hormone-refractory prostate cancer (HRPC) in cisplatin-resistant human tumor lines in phase I and phase II trials. A randomized multicenter phase III trial with a target sample size of 380 patients was initiated in men with HRPC. After 50 randomized patients, the trial was closed to further accrual by the sponsoring company. An ad hoc analysis of all available data is reported here. Eligibility criteria included pathological proof of prostate cancer, documented progression despite prior hormonal manipulation, WHO PS 0-2, and no daily intake of narcotic analgesics. Patients were randomized between satraplatin 100 mg/m(2) for 5 days plus prednisone 10 mg orally BID or prednisone alone. Compliance was excellent. 48/50 patients have progressed and 42 have died, mostly due to prostate cancer. Median overall survival was 14.9 months (95% CI: 13.7-28.4) on the satraplatin plus prednisone arm and 11.9 months (95% CI: 8.4-23.1) on prednisone alone (hazard ratio, HR = 0.84, 95% CI: 0.46-1.55). A >50% decrease in prostrate specific antigen (PSA) was seen in 9/27 (33.3%) in the satraplatin plus prednisone arm vs. 2/23 (8.7%) on the prednisone alone arm. Progression-free survival was 5.2 months (95% CI: 2.8-13.7) on the satraplatin plus prednisone arm as compared to 2.5 months (95% CI: 2.1- 4.7) on the prednisone alone arm (HR = 0.50, 95% CI: 0.28-0.92). This difference is statistically significant (p = 0.023). Toxicity was generally minimal in both arms. This randomized comparison of a combination of satraplatin and prednisone versus prednisone alone supports the antitumor activity of the combination. Its role in the treatment of HPRC remains to be elucidated in an appropriate phase III setting.

Adenocarcinoma↗
PubMed2005

The Cochrane Collaboration.

The Cochrane Collaboration is an international, not-for-profit organisation that aims to help people make well-informed decisions about health care by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of health-care interventions. Cochrane systematic reviews are prepared according to predefined, explicit methodology, and published in The Cochrane Library. The abstracts and plain English summaries of the reviews are freely available on the Internet. All reviews are prepared and maintained under the editorial control of 50 Cochrane Collaborative Review Groups that focus on (groups of) health problems. The work of Collaborative Review Groups is supported, among others, by people working in Cochrane Fields. Cochrane Fields focus on dimensions of health care other than health problems. To date, the issue of nutrition has not been addressed sufficiently in The Cochrane Collaboration. Nutrition issues are very important for day-to-day health care and the initiatives to establish a new Cochrane Diet and Nutrition (Sub)Field will help to promote the preparation of systematic reviews of nutritional interventions by the variety of Collaborative Review Groups to whom such interventions are relevant. Many issues regarding nutritional interventions, however, are complex, and methodological challenges will have to be overcome. A Cochrane Diet and Nutrition (Sub)Field with experts on nutritional research can help fill this gap and make those reviews more possible.

Clinical Trials as Topic↗
PubMed2005

Bicalutamide ('Casodex') 150 mg in addition to standard care in patients with nonmetastatic prostate cancer: updated results from a randomised double-blind phase III study (median follow-up 5.1 y) in the early prostate cancer programme.

Trial 24 is one of three placebo-controlled trials within the ongoing bicalutamide ('Casodex') Early Prostate Cancer (EPC) programme evaluating bicalutamide 150 mg/day in addition to radical prostatectomy, radiotherapy or watchful waiting for T1b-4, any N, M0 prostate cancer. In Trial 24, at 5.1 y median follow-up, the addition of bicalutamide significantly (P < 0.0001) improved objective progression-free survival (PFS) and prostate-specific antigen PFS compared with standard care alone. There was no significant difference in overall survival (P = 0.746). In the context of the whole EPC programme, long-term bicalutamide is not appropriate for localised disease, yet provides advantages in delaying disease progression in patients with locally advanced prostate cancer.

Adult↗
PubMed2003

Tissue polypeptide-specific antigen (TPS) determinations before and during intermittent maximal androgen blockade in patients with metastatic prostatic carcinoma.

OBJECTIVE: To evaluate the prognostic significance of serially measured tissue polypeptide-specific antigen (TPS) levels in patients with metastatic prostatic carcinoma treated with intermittent maximal androgen blockade (MAB). To determine its value with respect to predicting response to treatment and time to clinical progression. Finally to compare TPS with prostate-specific antigen (PSA) measurements in terms of prognostic impact in patients with metastatic prostatic carcinoma. METHODS AND PATIENTS: TPS and PSA measurements were performed before start of and monthly during intermittent MAB in 68 patients participating in EORTC protocol 30954. Both TPS and PSA were measured in serum. Fifty-six patients from eight centers were included in the final analysis because at least three TPS values were available. TPS and PSA values were correlated with clinical course of the disease. Median follow-up was 21.3 months. Three patient groups were defined on clinical grounds: (a) clinically progressive disease (n=18); (b) clinically stable disease (n=33); and (c) patients who did not reach a predefined nadir PSA value following 9 months of treatment (n=5). RESULTS: Pretreatment TPS was significantly higher in the clinically progressive patients than in the other patient groups (p=0.0041). When grouping patients according to their pretreatment TPS values (cut-off value of 100 U/l) the pretreatment TPS value (>100 U/l) proved to be a statistically significant prognostic factor with respect to time to progression: elevated TPS was associated with a 3.8 increased risk for progressive disease (p=0.0055). Pretreatment PSA (>100 ng/ml) was of no prognostic value for time to progression. In five patients increase of TPS coincided with or preceded clinical progression during treatment, whereas PSA remained normal. CONCLUSION: Additional value of pretreatment TPS measurements in metastatic prostate cancer patients is found in defining the patients with rapid clinical progression. Following MAB an increase in TPS signifies clinical progression even if PSA is found to remain normal.

Androgen Antagonists↗
PubMed2001

Bicalutamide (Casodex) 150 mg as immediate therapy in patients with localized or locally advanced prostate cancer significantly reduces the risk of disease progression.

OBJECTIVES: To investigate the efficacy and tolerability of bicalutamide (Casodex) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with localized or locally advanced (T1b-T4, any nodal status, M0) prostate cancer. METHODS: This was a multicenter, prospective, randomized, double-blind, placebo-controlled trial in Europe, South Africa, Australia, and Mexico and is part of the Casodex Early Prostate Cancer program. RESULTS: A total of 3603 men were randomized to receive bicalutamide (n = 1798) or placebo (n = 1805). The patient demographics were well balanced between the two groups. Prior therapy of curative intent had been given to 64% of the patients (prostatectomy [44%], radiotherapy [18%], and prostatectomy and radiotherapy [2%]) and 36% had been monitored with watchful waiting. After a median follow-up of 2.6 years and a median exposure to the study drug of 2.2 years, a significant 43% reduction in the risk of objective progression was observed for the bicalutamide group compared with the placebo group (hazard ratio 0.57, 95% confidence interval 0.48 to 0.69, P << 0.0001). The time to prostate-specific antigen doubling was significantly delayed for the bicalutamide group compared with the placebo group (hazard ratio 0.37, 95% confidence interval 0.32 to 0.43, P << 0.001). The survival data were immature, with 7.2% overall mortality. The most frequently reported adverse events with bicalutamide were gynecomastia alone (17.4%), breast pain alone (17.6%), and gynecomastia with breast pain (47.5%). CONCLUSIONS: Bicalutamide 150 mg daily as immediate therapy, alone or as adjuvant to treatment of curative intent, significantly reduced the risk of disease progression in patients with localized or locally advanced prostate cancer. Longer follow-up is underway to assess any benefit in overall survival.

Adult↗
PubMed2001

The use of valrubicin for the chemoresection of superficial bladder cancer -- a marker lesion study.

OBJECTIVES: To assess the effect and tolerance of a 6-week course of intravesical valrubicin on a tumour intentionally left in the bladder (marker lesion) following incomplete transurethral resection of the bladder (TURBT). PATIENTS AND METHODS: In a prospective phase II study, 40 patients with refractory superficial transitional cell carcinoma (TCC), with or without carcinoma in situ, underwent TURBT at which a tumour <1 cm in diameter was deliberately left in the bladder. They were then treated with six instillations of 800 mg valrubicin at weekly intervals. Patients were assessed three months after the initial TURBT by cystoscopy and biopsy. Patients remaining clear of disease underwent repeat cystoscopies at 3-monthly intervals until recurrence or for up 2 years. RESULTS: 21/39 (54%) of patients were found to be clinically clear of disease upon cystoscopic examination at 3 months. 18/39 (46%) of patients were considered histologically clear of bladder disease. The current estimate of the mean time to recurrence is 248 days. CONCLUSIONS: A 6-week course of intravesical valrubicin has proved effective in ablating a marker tumour left in the bladder after incomplete TURBT and in preventing or delaying recurrence of further tumours in a group of patients with previously treated superficial TCC.

Administration, Intravesical↗
PubMed2001

Stabilization of HIV infection rates in urban Burkina Faso, 1995-1999.

The objectives of this study were to monitor the trends of the HIV epidemic between 1995 and 1999 among pregnant women in Bobo-Dioulasso, the second largest town of Burkina Faso, and to discuss the possible effect of preventive interventions (condom availability) on sexual transmission of HIV in this context. Age-specific trends in HIV prevalence obtained from sentinel surveillance programme were analysed. Among antenatal clinic attendees, HIV prevalence was 7.5% (n=401) in 1995, 10% (n=200) in 1996, 7.6% (n=448) in 1997, 8.4% (n=642) in 1998 and 5.3% (n=716) in 1999 without demonstrated temporal trend (P=0.12). The average number of condoms available per person (aged 15-49 years) per year increased from 0.6 in 1992 to 5.7 in 1995 and 6.0 in 1999. Anonymous surveys are less subject to selection bias and suggest a stabilization of the HIV prevalence around 7.3% in Bobo-Dioulasso. Distribution of condoms could explain at least, partly, this stabilization of the HIV epidemic.

Adolescent↗
PubMed2000

Quality of life of patients with newly diagnosed poor prognosis M1 prostate cancer undergoing orchiectomy without or with mitomycin C. Results from the EORTC Phase-III trial 30893.

OBJECTIVES: To compare the quality of life (QL) of patients with poor prognosis M1 prostate cancer treated with orchiectomy alone (ORCH) or orchiectomy combined with adjuvant mitomycin C (MMC; 15 mg/m(2) i.v. q 6 weeks: ORCH+MMC; EORTC trial 30893). METHODS: Patients with newly diagnosed M1 poor prognosis prostate cancer completed a truncated version of the EORTC QLQ-C30 (V 1.0) at randomization (baseline) and every 6-12 weeks thereafter until going off the protocol. Five ad hoc questions assessing lower urinary tract symptoms were included in the QL questionnaire. RESULTS: At least one QL form was completed by 177 of the 189 patients included in the trial, with baseline questionnaires available for 113 patients (ORCH n = 52; ORCH+MMC n = 61). In both arms, pain and urinary dysfunction improved during treatment. Compared with patients from the ORCH arm, the use of adjuvant MMC was associated with a significant reduction in global health status/QL and with impairment in 7 of 11 QL dimensions covered by the questionnaire. Some improvement in QL was observed after discontinuation of MMC. A survival benefit was not observed in the ORCH+MMC arm. CONCLUSIONS: Intravenous MMC (15 mg/m(2) q 6 weeks) cannot be recommended as adjuvant treatment in M1 poor prognosis prostate cancer due to its negative impact on QL and lack of efficacy. In general, QL assessments should be mandatory when adjuvant chemotherapy is evaluated in patients with metastatic prostate cancer.

Aged↗
PubMed1997

Clinical experience of trabeculotomy for the surgical treatment of aniridic glaucoma.

OBJECTIVE: The purpose of this study is to determine the efficacy of initial trabeculotomy in the patient with aniridic glaucoma. DESIGN: Clinical charts were reviewed. PARTICIPANTS: Twenty-nine eyes of 16 patients with aniridia were studied. INTERVENTION: Glaucoma surgery was performed. As an initial procedure, trabeculotomy was performed in 12 eyes, other surgery was performed in 17 eyes (trabeculectomy, 5; goniotomy, 5; other, 7). MAIN OUTCOME MEASURES: Success was defined as an intraocular pressure (IOP) of 21 mmHg or lower, and no further surgery was performed. RESULTS: Ten (83%) of 12 eyes obtained IOP control after first (6 eyes) or second (4 eyes) trabeculotomy with a mean follow-up period of 9.5 years. Five eyes maintained visual acuity of 20/40 to 20/200. No serious complications were found after trabeculotomy. Three (18%) of 17 eyes were controlled with the first glaucoma surgery other than trabeculotomy (goniotomy, trabeculectomy, trabeculectomy combined with trabeculotomy, and Molteno implant). Good IOP control was obtained in 8 (47%) of 17 eyes after several surgeries with a mean follow-up period of 10.4 years. Four of 17 eyes became phthisical. CONCLUSION: This study suggests that trabeculotomy is the preferred initial operation for uncontrolled glaucoma with aniridia.

Adolescent↗
PubMed1997

Influence of urological morbidity on quality of life in patients with prostate cancer.

OBJECTIVE: To evaluate the prevalence of urological morbidity in patients with prostate cancer and its influence on global quality of life (QL). METHODS: 379 patients with prostate cancer completed several questionnaires (EORTC QLQ-C33, I-PSS, PAIS [sexuality]) and were grouped according to the type of treatment they had undergone: observation only (n = 57), androgen deprivation (n = 112), radiotherapy (n = 114) and radical prostatectomy (n = 96). A group of 86 urologists also completed the questionnaires, imagining that they had stable prostate cancer and had been undergoing androgen deprivation for at least 1 year. Their responses were compared with those from patients who had undergone androgen deprivation. RESULTS: In all patient groups urinary symptoms were mostly mild to moderate but 12% of patients who had undergone radiotherapy and 11% of hormonally treated patients described severe symptoms. Severe urinary leakage occurred in 16% of patients who had undergone radical prostatectomy. 22% of all patients were impotent before treatment; after treatment sexual life was considerably disturbed in all patients except those who had undergone observation only. Fatigue was a general problem in all patients. In the logistic regression analysis fatigue and lower urinary tract symptoms (LUTS), but not disturbance of sexual life or urinary leakage, were correlated with global QL. In the doctor-patient comparison, doctors underestimated the disturbance of sexual life in patients who had undergone androgen deprivation therapy but overestimated the impairment of QL and psychological distress experienced by these patients. CONCLUSIONS: LUTS and fatigue are independent predictive factors for global QL after initial treatment in patients with prostate cancer. Radiotherapy of the prostate leads to more significant morbidity than was generally anticipated by doctors. The disagreement between doctors' and patients' assessments of QL following treatment indicates the necessity for further systematic QL evaluation in these patients.

Aged↗
PubMed1996

The quality of life of patients with newly diagnosed M1 prostate cancer: experience with EORTC clinical trial 30853.

This study was undertaken to evaluate the quality of life (QoL) of previously untreated patients with M1 prostate cancer before and during androgen-suppressive treatment. Assessment of QoL was included as an optimal component of EORTC protocol 30853, a phase III trial comparing LH-RH (luteinising hormone-releasing hormone) analogue combined with a non-steroidal anti-androgen versus orchiectomy in patients with M1 prostate cancer. At pretreatment and during the follow-up period, patients were asked to complete a questionnaire assessing their physical and psychosocial functioning, and their symptom levels. Physicians rated the patients' performance status, pain, urological symptoms and erectile function. Due to its optional nature, only a minority of the patients in the trial were recruited for the QoL investigation. 63 patients completed a pretreatment questionnaire, of whom 49 completed a second questionnaire at least once during the initial 15 month follow-up period. While statistically significant correlations were observed between patients' and physicians' ratings of physical functioning and pain, these were of only a moderate magnitude (r = 0.43 and 0.30, respectively). No significant association was observed between physicians' and patients' ratings of micturation problems or of erectile function. Before treatment, fatigue, pain and decreased social role and sexual functioning were the problems most frequently reported by patients. With an average of approximately 1 year follow-up, statistically significant improvements were observed in patients' self-reported urological symptoms and metastatic pain. No significant changes were noted for the other QoL domains assessed. The results of this study confirm earlier findings that physicians' ratings may not reflect accurately the functional health and symptom experience of their patients. Patient-based QoL questionnaires offer the most direct means of evaluating the subjective morbidity associated with prostate cancer and its treatment. To increase participation and compliance rates in future studies, it is recommended that QoL assessment be made mandatory in those clinical trials in which QoL is considered to be an important study endpoint.

Aged↗
PubMed1996

Trabeculectomy with intraoperative sponge 5-fluorouracil.

PURPOSE: To retrospectively assess the outcome of trabeculectomy surgery performed using intraoperative sponge 5-fluorouracil (5-FU) (50 mg/ml). METHODS: Trabeculectomy with intraoperative sponge 5-FU was performed on 140 eyes of 119 patients. The reduction in intraocular pressure (IOP), the number of supplementary postoperative injections, and any treatment complications were noted. RESULTS: The mean preoperative IOP was 25.7 +/- 8.6 mmHg. The mean postoperative IOP was 12.5 +/- 5.7 mmHg with a mean IOP reduction of 52 percent (P < 0.0001). One hundred twenty-one (86.4 percent) eyes required no postoperative glaucoma medications, with the mean number of glaucoma medications dropping from 2.5 +/- 1.1 before operation to 0.3 +/- 0.8 after operation (P < 0.001). One hundred five eyes received a mean of 5.3 +/- 2.7 postoperative 5-FU injections. There was no significant difference in final IOP or success rate between low- and high-risk eyes, but high-risk eyes seemed to require supplementary postoperative 5-FU. Corneal epithelial damage arose in 52 (37 percent) eyes and correlated strongly with postoperative 5-FU supplementation. CONCLUSION: Intraoperative sponge 5-FU is a reasonably safe and effective adjunct to trabeculectomy surgery.

Adolescent↗
PubMed1996

Collecting the evidence systematically. Ensuring that it is complete and up-to-date.

A complete and comprehensive search of the relevant evidence is an essential step in the preparation of a scientific systematic review. The Cochrane Pregnancy and Childbirth Database consists of some 600 systematic reviews, based on almost 6,000 randomized or quasi-randomized trials of care during pregnancy and childbirth. As ascertainment from electronic search of the National Library of Medicine MEDLINE database was not complete, the mainstay of our search strategy was a systematic hand search of some 60 journals, beginning with volumes published in 1950. Additional references were obtained from the list of references in primary research reports and conference reports. A major effort was made to identify unpublished trials and to obtain unpublished data from published trials.

Data Collection↗
PubMed1993

Detection of fundamental principles and a level of order for large-scale gene clustering on the Escherichia coli chromosome.

The Escherichia coli K-12 genetic map was divided into intervals of equal length to count the number of genes per interval. Plots of genes per interval at four sets of interval lengths revealed large-scale clustering of genes with the major clusters occurring at regularly spaced distances apart. Major gene cluster properties were analyzed at a scale of 100 intervals wherein each interval corresponded to a genetic map unit length of 1 min. In any major gene cluster, the highest gene concentration was observed at or near the midpoint interval, and the number of genes per interval was found to decline exponentially as a function of the linear distance from the midpoint or interval of peak gene concentration of that cluster. An autocorrelation analysis of gene content in first-neighbor intervals throughout the chromosome revealed an ordered first-neighbor relationship in comparison to 2,000 randomized interval versions of the chromosome. Attempts to simulate gene placement by a Gaussian model did not produce large-scale gene clustering in any way comparable to that observed on the chromosome. We propose that major gene clusters formed from smaller gene clusters, and the contemporary chromosome formed from fusion of homologous or heterologous major gene clusters.

Chromosome Mapping↗
PubMed1990

A cohort study of summary reports of controlled trials.

Substantial numbers of clinical trials continue to be reported only in summary reports that present insufficient methodological details to permit informed judgments about the likely validity of the conclusions. Using a cohort of 176 controlled trials reported in summary form, we tested the hypotheses that they would be more likely to be followed by full reports if, on the basis of the information provided in the summary report, (1) the trial was judged to be methodologically sound, (2) the results favored the test treatment, and (3) the sample size was relatively large. The results of univariate and multivariate analyses provided support for only the third of these hypotheses. Investigators, as well as those who fund and sanction the conduct of clinical research, should make greater efforts to ensure that clinical trials are reported properly.

Clinical Trials as Topic↗