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Biomedical subjects

J Forbes

Publications and source records attributed to J Forbes.

At least 19 recordsLinked to original sources

Interpreting self reported limiting long term illness.

OBJECTIVE: To examine the association between self reported limiting long term illness and other dimensions of self reported health. DESIGN: Stratified random sample of general population. SETTING: Lothian region, Scotland, in 1993. SUBJECTS: 6212 men and women aged 16 and over. MAIN OUTCOME MEASURES: Limiting long term illness was assessed by the same question as used in the 1991 United Kingdom census. The short form 36 health survey was used to assess other dimensions of health. RESULTS: Rates of limiting long term illness were much higher than reported in the census. Scores on general and physical health scales had strong associations with limiting long term illness, but after adjustment for these associations psychosocial health measures had little influence on limiting long term illness. Being at the lower rather than the upper quartile on the physical functioning scale more than doubled the odds of having limiting long term illness. Reported prevalence of many common illnesses was between two and three times higher among those with limiting long term illness. CONCLUSIONS: A positive response to the question used by the census to define limiting long term illness was strongly associated with physical limitations on activity and less strongly influenced by scores on scales of mental and social wellbeing. Socioeconomic effects on limiting long term illness seem largely mediated through measures of general health and physical limitations on health.

Activities of Daily Living

The International (Ludwig) Breast Cancer Study Group Trials I-IV: 15 years follow-up.

BACKGROUND: Adjuvant systemic therapy prolongs disease-free and overall survival in both pre- and postmenopausal patients. Available data shown benefit from multi-agent chemotherapy, prolonged tamoxifen treatment, and ovarian ablation, and that the combination of chemo- and endocrine therapy might be advantageous. In 1978 the International (Ludwig) Breast Cancer Study Group (IBCSG) initiated four complementary randomized controlled clinical trials to evaluate the roles of chemo-endocrine combinations or endocrine therapy alone in specific populations defined by risk (for pre- and perimenopausal patients) or by age (for postmenopausal patients). The results at 10 and 13 years' median follow-up for these trials are summarized in this report and are compared to those of the Overview meta-analysis with regard to chemo-endocrine or endocrine therapy combinations. Furthermore, types of first relapses by sites and second malignant diseases are reported. PATIENTS AND METHODS: 1601 evaluable patients with node positive disease were included into the studies I-IV. In Trial I (491 premenopausal patients with 1-3 positive axillary nodes) we studied the addition of low-dose continuous prednisone (p) to a cyclophosphamide-methotrexate-fluorouracil (CMF) combination. In Trial II 327 premenopausal patients with four or more positive axillary nodes were randomized to one year CMFp or to a surgical oophorectomy followed by CMFp. In Trial III (463 postmenopausal patients 65 years old or younger), combined chemoendocrine therapy (one year of CMFp plus tamoxifen (T)) was compared to endocrine therapy (1 year of p + T) or to surgery alone. In Trial IV 320 postmenopausal patients 66 to 80 years old were treated either by surgery alone or by surgery followed by 1 year prednisone and tamoxifen. RESULTS: In Trial I the addition of prednisone allowed a higher dose of cytotoxics to be administered compared with CMF alone. Despite this increased dose intensity, 13-year disease-free survival (DFS) and overall survival (OS) were similar for the two treatment groups (49% vs. 52% DFS, 59% vs. 65% OS for CMFp vs. CMF). In Trial II the addition of surgical oophorectomy to CMFp yielded an improved outcome which approached statistical significance for the subset of 107 patients known to have estrogen receptor-positive tumors (DFS, 23% vs. 15%, p = 0.13; OS, 41% vs. 30%, p = 0.12). In Trial III combined chemoendocrine therapy improved DFS and OS compared with endocrine therapy alone (p + T) given for the same duration, or no adjuvant treatment (DFS, 35% vs. 25% vs. 14%, p < 0.0001; OS, 48% vs. 36% vs. 32%, p = 0.01). In Trial IV p + T improved DFS compared with no adjuvant therapy (27% vs. 15%, p = 0.004). Despite competing risks for this elderly population, OS was also improved but the result was not statistically significant (34% vs. 22%, p = 0.08). CONCLUSIONS: The overall results of these four trials indicate that the continuation of investigations on combined chemo-endocrine therapies is warranted. The prognosis of the patients, all node-positive, treated with the most effective adjuvant treatment is such that there is a large potential for improvement.

Aged

A pilot study of the economic cost and clinical outcome of day patient vs inpatient management of active rheumatoid arthritis.

The aims of this pilot study, which compares day patient with inpatient care for management of active RA were (i) to test the feasibility of a trial protocol design including the method of randomization and the practicality of data collection, and (ii) to obtain preliminary information on economic cost and clinical outcome of these two methods of management. Twenty consecutive patients requiring admission for management of active RA were randomized to receive either day patient or inpatient care. All hospital, transport, community and indirect costs incurred over a 6-month period from recruitment were collected for each patient. Disease activity and clinical outcome were assessed using the Ritchie articular index, ESR, Health Assessment Questionnaire, Functional Independence Measure and Hospital Anxiety and Depression Scale. The trial protocol was found to be feasible and no patient allocated to the day patient group requested or required to be transferred to inpatient care. Day care was significantly cheaper than inpatient care despite higher transport costs; the total cost of treating 10 day patients was UK 10,272 pounds compared with 14,528 pounds for 10 inpatients. Clinical outcome was comparable in both groups for all parameters studied and there was no obvious detrimental effect on patients receiving day care. This pilot study demonstrates that day care is feasible and acceptable to patients with active RA. The preliminary data suggest that day care is substantially cheaper than inpatient care and does not apparently compromise clinical outcome.

Ambulatory Care

Visual performance and objectively measured grades of cataract. A correlation of methods designed for use in longitudinal trials.

Objective quantification of cataract and subjective assessment of visual performance are essential features of anticataract or cataractogenic drug trials. The constrains of a longitudinal trial require a compromise in contrast sensitivity measurement between sensitivity and speed. Such a system has been developed for use in longitudinal anticataract trials. An objective cataract assessment system has also been developed for these trials. Visual performance parameters and objectively measured grades of cataract using these systems were correlated in a group of patients with early lens opacities. Overall the correlation was poor in all three morphological types of cataract. Possible reasons for this and implications for future anticataract trials are discussed.

Aged

The surgery of early breast cancer.

This review highlights important issues for surgeons treating early breast cancer. The optimal use of ovarian ablation, the value and timing of radiotherapy for breast preservation, and axillary dissection are considered. New information on the importance of local surgery, even for older women, and the biology of small (up to 10 mm), screen-detected cancers has been recently reported. The value of support services for women having breast cancer surgery is stressed.

Breast Neoplasms

An evaluation of community antenatal care.

A study to ascertain how the community based antenatal services in the East End of Glasgow related to the guidelines set by a Working Party on Ante-Natal and Intrapartum Care (Royal College of Obstetricians and Gynaecologists, 1982) is reported. All community based clinics were visited and described. The socio-economic status of the sample population was defined and users' views and preferences sought. The women sampled were often socially and economically disadvantaged. Unemployment was high. They received their community antenatal care from midwives, general practitioners and consultants in both health centres and general practitioner surgeries. Women were generally satisfied with the care they received. Answers to more specific questions indicated, however, that more information and individualised care would be appreciated.

Adult

High-resolution proton and carbon-13 NMR of membranes: why sonicate?

We have obtained high-field (11.7-T) proton and carbon-13 Fourier transform (FT) nuclear magnetic resonance (NMR) spectra of egg lecithin and egg lecithin-cholesterol (1:1) multibilayers, using "magic-angle" sample spinning (MASS) techniques, and sonicated egg lecithin and egg lecithin-cholesterol (1:1) vesicles, using conventional FT NMR methods. Resolution of the proton and carbon-13 MASS NMR spectra of the pure egg lecithin samples is essentially identical with that of sonicated samples, but spectra of the unsonicated lipid, using MASS, can be obtained very much faster than with the more dilute, sonicated systems. With the 1:1 lecithin-cholesterol systems, proton MASS NMR spectra are virtually identical with conventional FT spectra of sonicated samples, while with 13C NMR, we demonstrate that most 13C nuclei in the cholesterol moiety can be monitored, even though these same nuclei are essentially invisible, i.e., are severely broadened, in the corresponding sonicated systems. In addition, 13C MASS NMR, spectra can again be recorded much faster than with sonicated samples, due to concentration effects. Taken together, these results strongly suggest there will seldom be need in the future to resort to ultrasonic disruption of lipid bilayer membranes in order to obtain high-resolution proton or carbon-13 NMR spectra.

Carbon Isotopes

Monitoring distributional assumptions and early stopping for a prospective clinical trial using Monte Carlo simulation.

We have applied the technique of Monte Carlo simulation to the determination of sample size for a partially completed clinical trial of chemotherapy for breast cancer. Simulations based on results observed after the entry of 243 patients in 2 years indicated a power greater than that predicted by the calculations made before the protocol was activated, and allowed a recommendation for an eventual trial closure earlier than would have been permitted by traditional methods. Both estimative and predictive approaches to the simulation of expected survival times for censored patients are presented. The use of simulation is recommended as an aid in reassessing the exact nature of the underlying survival distributions (as these affect the sample size calculations) and in optimizing stopping rules relating to patient accrual to a clinical trial in progress.

Breast Neoplasms

Drug resistance in clinical practice: patterns of treatment failure in patients receiving systemic therapy for advanced breast cancer.

Strategies for overcoming the causes of drug resistance should take account of the patterns of treatment failure seen in clinical practice. We have analysed the patterns of disease progression in 267 patients with advanced breast cancer receiving systemic therapy. First disease progression on therapy most commonly occurred in tissues involved by tumour at the commencement of treatment. However in 40% of patients, first documentation of disease progression included a tissue not previously known to contain metastatic disease. In only 3% of patients was this new tissue the central nervous system. This pattern of disease progression was not influenced by treatment type (i.e. endocrine or cytotoxic), tumour response to treatment, oestrogen receptor status, prior adjuvant cytotoxic treatment, or disease free interval. These results question the wisdom of always ceasing existing therapy and substituting new treatment when progressive disease is first documented.

Antineoplastic Agents

The pharmacokinetics of sulphasalazine in young and elderly patients with rheumatoid arthritis.

The clinical pharmacokinetics of enteric-coated sulphasalazine (Salazopyrin-EN) were studied after acute and chronic dosing in 20 patients with 'active' rheumatoid arthritis. 12 elderly (mean age 74.4 +/- 1 yr; range 71-83) and 8 young (mean age 40.5 +/- 1.4 yr; range 35-46) patients were given a single 2 g oral dose of sulphasalazine after an overnight fast. Serum and urine samples were collected at regular intervals over a 96 hour period for estimation of concentrations of sulphasalazine, sulphapyridine and its metabolites. This procedure was repeated after 17 days of continuous treatment with salazopyrin-EN 2 g daily in order to compare the drug's kinetics at 'steady-state'. Whilst the interindividual variation in kinetic parameters was large, age and acetylator status had a significant influence on a number of factors. The elimination half-life of sulphasalazine was prolonged in the elderly whilst renal clearance was increased in slow acetylators at 'steady-state'. The tmax and apparent volume of distribution of sulphapyridine were increased in the elderly after a single drug dosage but these differences disappeared with regular dosing. The Cmax, elimination half-life, 'steady-state' serum concentration, apparent volume of distribution and total clearance of sulphapyridine were all affected by acetylator status. We conclude that old age has only a minor effect on the body's handling of sulphasalazine and sulphapyridine but that acetylator phenotype plays a significant role in determining the 'steady-state' serum concentrations of sulphapyridine. This is likely to have practical implications with regard to some of the drug's adverse effects.

Acetylation

The external transcribed spacer and preceding region of Xenopus borealis rDNA: comparison with the corresponding region of Xenopus laevis rDNA.

We report sequence data from a cloned rDNA unit from Xenopus borealis, extending leftwards from the 18S gene to overlap a region previously sequenced by R. Bach, B. Allet and M. Crippa (Nucleic Acids Research 9, 5311-5330). Comparison with data from other species of Xenopus leads to the inference that the transcription initiation site in X.borealis is in the newly sequenced region and not, as was previously thought, in the region sequenced earlier. The X.borealis external transcribed spacer thus defined is some 612 nucleotides long, about 100 nucleotides shorter than in X.laevis. The X.borealis and X.laevis external transcribed spacers show a pattern of extensive but interrupted sequence divergence, with a large conserved tract starting about 100 nucleotides downstream from the transcription initiation site and shorter conserved tracts elsewhere. The regions in between the conserved tracts differ in length between the respective external transcribed spacers indicating that insertions and deletions have contributed to their divergence, as previously inferred for the internal transcribed spacers. Much of the overall length difference is in the region flanking the 18S gene, where there are also length microheterogeneities in X.laevis rDNA. As in X.laevis, the transcribed spacer sequences flanking the 18S gene in X.borealis contain no major tracts of mutual complementarity. The accumulated data on transcribed spacers in Xenopus render it unlikely that processing of ribosomal precursor RNA involves interaction between the regions flanking 18S RNA.

Animals