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P Selby

Publications and source records attributed to P Selby.

At least 19 recordsLinked to original sources
PubMed2002

Comparison of the RNA-amplification based methods RT-PCR and NASBA for the detection of circulating tumour cells.

Increasingly, reverse transcriptase polymerase chain reaction (RT-PCR) is used to detect clinically significant tumour cells in blood or bone marrow. This may result in a redefinition of disease-free and clinical relapse. However, its clinical utility may be limited by lack of automation or reproducibility. Recent studies have suggested nucleic acid sequence-based amplification of target RNA may be more robust. In this study, nucleic acid sequence-based amplification was established to detect melanoma, colorectal and prostate cancer cells. Nucleic acid sequence-based amplification and RT-PCR both successfully amplified target RNA in peripheral blood samples from patients with melanoma and colorectal cancer, but only RT-PCR detected PSA in blood samples from patients with prostate cancer. There was relatively good agreement between sample replicates analyzed by RT-PCR (Kappa values of one for tyrosinase, 0.67 for CK-20 and one for PSA), but less agreement when analyzed by nucleic acid sequence-based amplification. This may limit the routine use of NASBA for the detection of clinically significant disease. In summary, RT-PCR appears at present to be the most reliable and reproducible method for the detection of low-level disease in cancer patients, although prospective studies are warranted to assess the clinical utility of different molecular diagnostic methods.

Colorectal Neoplasms↗
PubMed2002

Incidence and natural history of Paget's disease of bone in England and Wales.

This study used a large, primary care, record-linkage resource (the General Practice Research Database [GPRD]) to evaluate the incidence, clinical presentation, and natural history of Paget's disease of bone in England and Wales. Between 1988 and 1999, we identified 2465 patients with the recorded diagnosis of Paget's disease of bone, within the five million subjects > or = 18 years old who were registered in the GPRD. The validity of diagnostic recording was assessed by questionnaire to individual general practitioners (GPs) in 150 patients; the diagnosis was confirmed in 93.8% of responders. The mean age of patients with Paget's disease was 75 years and 51% were men. The prevalence of the disorder was 0.3% among men and women aged > or = 55 years; incidence rates for clinically diagnosed Paget's disease rose steeply with age (men, 5 per 10,000 person-years; women, 3 per 10,000 person-years at the age of 75 years). Over the 11-year period of the study, the age- and sex-adjusted incidence rate of clinically diagnosed Paget's disease declined from 1.1 per 10,000 person-years to 0.7 per 10,000 person-years. Each patient with Paget's disease was matched to three controls matched by age, gender, and general practice. Cases had a greater risk of back pain (relative risk [RR], 2.1; 95% CI, 1.9-2.3), osteoarthritis (OA; RR, 1.7; 95% CI, 1.5-1.9), hip arthroplasty (RR, 3.1; 95% CI, 2.4-4.1), knee arthroplasty (RR, 1.6; 95% CI, 1.0-2.6), fracture (RR, 1.2; 95% CI, 1.0-1.5), and hearing loss (RR, 1.6; 95% CI, 1.3-1.9). Seven patients with Paget's disease developed a malignant bone neoplasm (0.3%). Using life table methodology, the estimated number of people who died within 5 years of follow-up was 32.7% among the patients with Paget's disease and 28.0% among the control patients.

Adult↗
PubMed2001

Validating automated screening for psychological distress by means of computer touchscreens for use in routine oncology practice.

The aim of the study was to confirm the validity of using touchscreen computers for screening for clinically significant levels of distress among cancer patients in routine oncology practice. The Hospital Anxiety and Depression Scale (HADS), EORTC Quality of Life questionnaire (QLQ-C30), Mental Health Inventory-MHI5 and a Concerns Checklist were administered via touchscreen computer to 172 chemotherapy out-patients, twice, 2-4 weeks apart. A standard psychiatric interview (Present State Examination - PSE) was conducted within a week of the second assessment. On interview, 23% of patients were identified as 'cases'. Using the available data (questionnaires, sociodemographic details, self-reported past psychiatric history), the best screening strategy combined scores from MHI-5 and HADS from a single time-point with the following rules: if MHI-5 < 11 = non-case; if MHI-5 > or = 11 then use HADS; then, if HADS > or = 9 = 'case' (sensitivity 85%; specificity 71%; misclassification rate 26%; positive predictive value 47%). The computerized screening system enabled data to be collected, scored, collated and reported in real time to identify patients who warrant further clinical assessment. It offers the potential for improving 'case' detection in routine oncology practice while reducing the burden of questions put to 'non-cases'. Further work is needed to develop optimal choice of screening questions for this purpose.

Depression↗
PubMed2001

ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial.

The purpose of this randomized trial was to compare the efficacy of 6 cycles of prednisolone, Adriamycin (doxorubicin), bleomycin, vincristine (Oncovin) and etoposide (PABlOE) with 3 cycles of PABIOE that alternate with 3 cycles of chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) in patients with advanced Hodgkin's disease. Between October 1992 and April 1996, 679 patients were entered onto the study. 41 of these did not match the protocol requirements on review and were excluded from further analysis, most of these being reclassified as NHL on histological review. Of the remaining 638 patients, 319 were allocated to receive PABIOE and 319 were allocated to receive ChlVPP/PABlOE. The complete remission (CR) rates were 78% and 64%, for ChlVPP/PABlOE and PABIOE respectively after initial chemotherapy (P< 0.0001). 124 patients were re-evaluated subsequently following radiotherapy to residual masses. The CR rates changed from 78% to 88% for ChlVPP/PABlOE and from 64% to 77% for PABlOE when re-evaluated in this manner (treatment difference still significant, P = 0.0002). The treatment associated mortality in the PABlOE arm was 2.2% (7 deaths), while there were no such deaths in the ChlVPP/PABlOE arm (P = 0.015). The failure-free survival was significantly greater in the ChlVPP/PABlOE arm (P< 0.0001) as was the overall survival (P = 0.01). The failure-free and overall survival rates at 3 years were 77% and 91% in the ChlVPP/PABlOE arm, compared with 58% and 85% in the PABIOE arm, respectively. These results indicate that ChlVPP alternating with PABIOE is superior to PABIOE alone as initial treatment for advanced Hodgkin's disease.

Adolescent↗
PubMed2001

Self-reported quality of life of individual cancer patients: concordance of results with disease course and medical records.

PURPOSE: To investigate the applicability of a standard quality of life (QL) questionnaire to individual cancer patients and to explore the potential for impact of QL information on the process of care by comparing at group level the QL results with the medical records. PATIENTS AND METHODS: One hundred fourteen consecutive patients at the oncology clinics at St James's Hospital, Leeds, United Kingdom, completed the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 on a touch-screen computer over a 6-month period. The QL results were compared with the corresponding medical records at individual and group level. RESULTS: For individual patients, the serial measurement of QL allowed recognition of patterns over time corresponding to disease course. At group level, a higher proportion of patients reported problems on EORTC QLQ-C30 than were mentioned in the medical records (McNemar paired test, P <.01). Most often clinicians mentioned pain (22% to 39%), and at the initial visit role (66%), and social issues (77%). For the rest of the symptoms and functions, the problems were recorded in between 1% and 25% of the notes, but 20% to 76% of the patients reported QL impairment. Problems that were not recorded in the medical notes tended to be of low severity, with a significant trend observed for pain, fatigue, nausea/vomiting, dyspnea, loss of appetite, and physical function scale (chi(2) test, 11.55 to 34.42, df = 1, P <.001). CONCLUSION: The QL data on individual patients was consistent with the clinical records, thus providing evidence for the validity of these measures in assessment of the individual. The QL profiles had more information on symptoms and particularly on functional issues, such as emotional distress and physical performance.

Disease Progression↗
PubMed2001

Circulating neuroblastoma cells detected by reverse transcriptase polymerase chain reaction for tyrosine hydroxylase mRNA are an independent poor prognostic indicator in stage 4 neuroblastoma in children over 1 year.

PURPOSE: In this prospective, multicenter study, the independent prognostic power of neuroblastoma cells detected by reverse transcriptase polymerase chain reaction (RT-PCR) for tyrosine hydroxylase (TH) mRNA was evaluated. PATIENTS AND METHODS: The clinical significance of disease detected by RT-PCR in peripheral blood from children at diagnosis was compared with established prognostic markers [ie, age, lactate dehydrogenase (LDH), neuron-specific enolase, ferritin, and MYCN gene amplification] by multivariate analysis. The value of disease detection by RT-PCR during treatment and follow-up was also examined. RESULTS: TH mRNA was detected in peripheral blood from 33 of 49 (67%) children with stage 4 neuroblastoma > 1 year old at diagnosis and was a significant predictive factor for overall survival [hazard ratio (HR) = 2.40, 95% confidence interval (CI) 1.19 to 4.84, P =.014) and event-free survival (HR = 2.09, 95% CI 1.06 to 4.17, P =.034) in a multivariate analysis. Detection of disease in blood from clinically disease-free children was related to increased risk of death (HR 2.54, 95% CI 1.42 to 4.55, P =.0014). CONCLUSION: TH mRNA in peripheral blood of children with neuroblastoma is a poor prognostic indicator, reflecting the propensity for dissemination via the bloodstream. When combined with a serum LDH > 1500 IU/L, this is the most powerful poor prognostic model at diagnosis for children > 1 year old with stage 4 disease. The detection of TH mRNA in peripheral blood from clinically disease-free children is related to increased risk of relapse and death.

Age Factors↗
PubMed2001

Minimal residual disease at the time of peripheral blood stem cell harvest in patients with advanced neuroblastoma.

BACKGROUND: Despite treatment with high-dose myeloblative chemotherapy and peripheral blood stem cell (PBSC) rescue, a high proportion of children with neuroblastoma relapse and die. Re-infusion of PBSC contaminated with tumour at the time of autologous transplantation may play a significant role in this relapse. In this study the frequency of tumour contamination in PB from children with neuroblastoma has been investigated. PROCEDURE: Minimal residual disease was measured using RT-PCR for tyrosine hydroxylase (TH) mRNA in PBSCs from patients with advanced neuroblastoma. PBSCs from 18 patients in complete clinical remission were studied. RESULTS: Studies in other cancers have suggested minimal contamination of PBSCs with tumour cells; TH mRNA was detected by RT-PCR in 50% (9/18) of PBSC harvests. Seventy-seven percent (7/9) of patients with TH mRNA in PBSC died of disease compared to 44% (4/9) who were TH mRNA-negative. CONCLUSIONS: Therefore, the presence of TH mRNA in PBSCs appeared to be associated with an unfavourable outcome, although this was not statistically significant. In summary, RT-PCR for TH mRNA is a sensitive method for the identification of tumour cells in PBSC harvest. The presence of TH mRNA in PBSC harvest may reflect disease status and be associated with an unfavourable outcome, although long-term clinical outcome studies in a larger patient cohort are required.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis.

The aim of this study was to determine whether clodronate reduced the incidence of vertebral fractures in patients with osteoporosis. We report here the interim analysis after 1 year of a 3-year double-blind placebo-controlled study. The objectives of the interim analysis were to determine whether there was a trend in fracture frequency and to examine the effects of clodronate on bone mineral density (BMD). Patients with densitometrically proven osteoporosis (T-score <-2.5 and <-3 for women and men, respectively) or with at least one prevalent vertebral fracture were recruited to a 3-year double-blind, controlled study. Patients were randomized to three strata, namely women with postmenopausal osteoporosis (stratum I, n = 483), women with secondary osteoporosis (II, n = 110), and men with osteoporosis of any causation (III, n = 84). They received either clodronate 800 mg daily by mouth or an identical placebo, and all patients received a calcium supplement of 500 mg daily. BMD was measured at six monthly intervals, and lateral spine radiographs for vertebral morphometry were obtained at baseline and 1 year. Treatment with clodronate was associated with a significant increase in BMD at the spine of 3.2 +/- 0.3% (p < 0.0001 vs. baseline) compared with a nonsignificant change of 0.5 +/- 0.3% in the placebo group (p < 0.0001 between treatments). At the hip, clodronate was associated with a significant increase in total hip BMD of 1.3 +/- 0.3% (p = 0.018 vs. baseline) compared with a small decrease of 0.4 +/- 0.3% in the placebo group (p = 0.027 for the difference between treatment groups). The mean changes at the spine and hip were similar in all three strata. Incident vertebral fractures were observed in 27 patients at 1 year in the placebo group (9.0%) and in 14 patients receiving clodronate (4.9%) (relative risk 0.54; 95% CI 0.29-1.02; p = 0.07). A trend was observed in all treatment strata. Treatment was well tolerated, with no significant adverse events attributable to clodronate treatment. We conclude that clodronate 800 mg daily is effective in preventing bone loss, and at 1 year, there is a trend consistent with antifracture efficacy in patients with established osteoporosis regardless of causation.

Bone Density↗
PubMed2001

Heavily smoking women who cannot quit in pregnancy: evidence of pharmacokinetic predisposition.

SUMMARY: Smoking in pregnancy is associated with a well-characterized increase in perinatal risks. Despite their wish to discontinue smoking, some pregnant women cannot stop. To characterize nicotine and cotinine levels in women who could not quit smoking after the first trimester, the authors recruited 19 white women (age 17-41 years) between 14-23 weeks of gestation who could not quit smoking. They started smoking at ages 11-22 years (mean 14.5) and smoked for 17 +/- 6 years. They had their first cigarettes 5-60 minutes after waking up (mean 12). Nicotine levels were compared with those expected in white patients in the general population, and the cotinine levels per cigarette smoked were compared with the population-based values. Sixteen of the 19 women had nicotine levels substantially lower than those expected. The mean level of serum cotinine produced by one cigarette per day was 19.1 +/- 15.8 ng/mL (range 6.1-67). The expected levels in white patients in the general population are 13 +/- 7.7 ng/mL. The data suggest that pregnant women who cannot quit heavy smoking in the second trimester form a selective group with pharmacokinetic predisposition to a high rate of nicotine metabolism.

Adolescent↗
PubMed2001

Abrupt discontinuation of psychotropic drugs during pregnancy: fear of teratogenic risk and impact of counselling.

OBJECTIVE: To assess the consequences to mother and baby of abruptly discontinuing antidepressant or benzodiazepine medication during pregnancy and to assess the impact of our counselling. PARTICIPANTS: All women who consulted the Motherisk Program between November 1996 and December 1997 and who stopped taking antidepressant or benzodiazepine medication when pregnancy was confirmed agreed to participate in the study. DESIGN AND INTERVENTIONS: Subjects were interviewed, received counselling, and completed a questionnaire 1 month after their initial call and after the birth of their baby. RESULTS: Of 36 women who completed the study, 34 discontinued their medication abruptly for fear of harming the fetus, 28 on the advice of their physician; 26 (70.3%) women reported physical and psychological adverse effects, 11 reported psychological effects only, and 11 reported suicidal ideation (4 were admitted to hospital). After counselling, 22 of 36 (61.1%) women resumed taking their medication, and 4 found that they no longer required it. One woman had a therapeutic abortion and 2 experienced spontaneous abortions; there were therefore 35 healthy babies (including 2 sets of twins) born to 33 women; 14 of 21 mothers breast-fed their babies while taking their psychotropic medication, with no adverse effects reported. CONCLUSIONS: When assessing the risks and benefits of taking psychotropic medication during pregnancy, women and their physicians should be aware that the abrupt discontinuation of psychotropic drugs can lead to serious adverse effects. Counselling is effective in reassuring women to adhere to therapy.

Adult↗
PubMed2001

Discontinuing antidepressants and benzodiazepines upon becoming pregnant. Beware of the risks of abrupt discontinuation.

QUESTION: Two of my patients are planning to become pregnant. One is taking paroxetine and the other lorazepam. We have discussed what to do when they become pregnant and have decided they should stop taking these drugs as soon as pregnancy is confirmed. Is this the right decision? ANSWER: The decision to discontinue these drugs during pregnancy should be based on scientific evidence rather than "hearsay" that women should not take psychotropic medications during pregnancy. Recent epidemiologic studies have documented the relative safety of these drugs, so women should not feel compelled to stop taking them when they become pregnant. If, after receiving appropriate evidence-based information, a woman decides to stop taking the drugs, they should be gradually tapered off to avoid abrupt discontinuation syndrome.

Anti-Anxiety Agents↗
PubMed2000

Repeatability of tibia lead measurement by X-Ray fluorescence in a battery-making workforce.

The purpose of this study was to remeasure in vivo tibia lead levels in a lead-acid battery manufacturing workforce measured in a previous survey and believed to be unrealistically high. Tibia lead levels were measured by K-shell X-ray fluorescence (XRF) spectroscopy in a stratified random sample (n=40) of the original study group (n=381). The repeat survey showed much lower tibia lead levels (median=54.3 microg lead/g bone mineral, compared to 217.9 microg lead/g bone mineral, n=40). Tibia lead levels were significantly correlated with duration of occupational exposure, zinc protoporphyrin levels, and cumulative blood lead index, but not with current blood lead levels. Thirty-eight of the 40 subjects underwent two consecutive tibia lead measurements to assess the test-retest repeatability of the XRF tibia lead measurement technique. The intraclass correlation coefficient between repeated measurements was 0.926 (P=0.0001). Three measurement pairs differed by more than 20 microg/g. There was no fixed or proportional bias between the two sets of measurements. We conclude that the technique offers a highly repeatable measurement of tibia bone lead. However, care needs to be taken to avoid contamination when performing measurements on active lead workers.

Adult↗
PubMed2000

Preliminary evidence for impaired estrogen receptor-alpha protein expression in osteoblasts and osteocytes from men with idiopathic osteoporosis.

Although osteoporosis is usually associated with women, 1 in 12 men in the UK have the disease, and a third of these cases are idiopathic. Estrogen is now known to be associated with bone loss in older men, but we found, previously, that levels of this hormone were normal in younger cases of male idiopathic osteoporosis (MIO) in the age range 33-61 years. We therefore hypothesized that their estrogen responses in bone might be defective, through impaired estrogen receptor-alpha (ER)-alpha expression. Consequently, in the present study, we compared expression of ER-alpha by indirect immunofluorescence, semiquantitative image analysis, and in situ reverse transcription-polymerase chain reaction in bone sections from MIO patients (33-56 years) (N = 7); age-matched control men (N = 7); and, for reference, ovarian steroid (OS)-replete (N = 7) and OS-deficient women (N = 6). In the control men, 23 +/- 6% (mean +/- SEM) of osteoblasts and 14 +/- 2% of osteocytes expressed ER-alpha protein, similar to OS-replete women. Although receptor expression decreased in OS-deficient women, the loss of ER-alpha protein in MIO patients was more severe (1 +/- 0.5% osteocytes, 2 +/- 1% osteoblasts expressed receptor); however, ER-alpha messenger RNA (mRNA) was still expressed in controls and MIO patients. Bone loss in these patients may be due to deficient ER-alpha protein expression.

Adult↗
PubMed1999

Quality of life instruments in oncology.

The objective of this article is to aid clinicians in understanding the current state of the development and application of quality of life (QOL) instruments as outcome measures in cancer clinical research and practice. As a result of the achievements of the past two decades, the concept of QOL has been defined and many reliable and valid measurement tools have been developed. The two main approaches to QOL assessment, psychometric-based and utility-based, are discussed together with a brief description of the strategies for meaningful interpretation of QOL profiles. QOL measures in oncology have the potential to be used to study populations in randomised clinical trials, to aid patient-clinician interactions in routine practice and to support policy decision making and economic evaluation of healthcare provision.

Clinical Trials as Topic↗