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Biomedical subjects

C C Bailey

Publications and source records attributed to C C Bailey.

At least 19 recordsLinked to original sources

Co-morbidity in patients with sight-threatening diabetic retinopathy.

PURPOSE: To describe the level of co-morbidity in patients with sight-threatening diabetic retinopathy in the United Kingdom. METHODS: Questionnaires were completed by patients undergoing first photocoagulation treatment for diabetic maculopathy or proliferative retinopathy during a 2 month period throughout the UK. RESULTS: Overall 15% of patients described angina, 9% had suffered a myocardial infarction and 6% a stroke. Self-reported renal disease was present in 8.5%. Foot ulceration was described by 10% of patients, and 4% had undergone an amputation. 35.5% of patients were on treatment for hypertension. 17.5% of patients had been hospitalised in the previous 6 months, and 3% of patients had died within 9 months of the laser treatment. CONCLUSIONS: There was significant co-morbidity in these patients, which may affect the management of their retinopathy.

Adolescent↗

Progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI).

In the last 20 years, the survival rate for children with acute lymphoblastic leukaemia (ALL) has markedly improved, largely owing to a decrease in relapses. However, children still die from complications of treatment and these are potentially preventable. We have analysed data from three large consecutive national protocols for ALL from 1980 to 1997 [Medical Research Council United Kingdom ALL (MRC UKALL) trials VIII, X and XI] to compare the incidence and causes of treatment-related deaths (TRD). The percentage of TRD has fallen from 9% to 2% (UKALL VIII to XI), largely as a result of a decrease in fatal infections. Deaths during induction have fallen from 3% to 1%, the main causes of death being bacterial, followed by fungal infection, while other causes, chiefly haemorrhage, have not declined. Remission deaths also decreased from 6% to 1%, particularly those deaths due to measles and pneumocystis carinii. More guidelines for surveillance and treatment of infections have been included within progressively more intensive protocols. Risk factor analysis showed increased TRD in patients with Down's syndrome, high leucocyte count and older age in UKALL XI. In contrast, the introduction of blocks of intensification was not associated with an increased death rate. While improved supportive care has reduced the incidence of TRD, there is still scope for further reduction by prompt treatment of suspected infection. Maintenance of herd immunity remains of vital importance in avoiding deaths from measles.

Antineoplastic Agents↗

Visual symptomatology in patients with sight-threatening diabetic retinopathy.

AIMS: To assess the level of visual symptomatology in patients with sight-threatening diabetic retinopathy. METHODS: Questionnaires were completed by patients undergoing first photocoagulation treatment for diabetic maculopathy or proliferative retinopathy during a 2-month period throughout the UK, and at 9 months' follow-up. RESULTS: There were high levels of visual symptomatology prior to the first laser treatment and at follow-up for both patients with maculopathy or with proliferative retinopathy. Only 25.1% of patients with maculopathy and 17.2% of patients with proliferative retinopathy were asymptomatic in terms of reading, seeing the television screen, recognizing faces or with their night vision at baseline. For those with maculopathy 20.1% were aware of colour vision abnormality in the eye to be treated at baseline and 9.5% were aware of new central scotomata since the treatment. Of those with proliferative retinopathy, 13% said that they had given up driving due to poor eyesight and 19% were aware of new peripheral field defects since the treatment. CONCLUSIONS: There are high levels of visual symptomatology for patients with sight-threatening diabetic retinopathy in the UK despite that fact that screening should aim to detect retinopathy prior to visual loss occurring. Patients should be aware that there may not be any significant improvement in their vision with laser treatment, and that the main aim of treatment is to reduce the likelihood of further visual deterioration.

Adolescent↗

Down's syndrome and acute lymphoblastic leukaemia: clinical features and response to treatment.

AIMS: To examine the clinical and biological features of acute lymphoblastic leukaemia in children with Down's syndrome (DS), to compare their survival with other children, and to determine if entry to trials and survival has improved. METHODS: Examination of presenting features and response to treatment in patients treated in two consecutive national trials, MRC UKALL X and XI. RESULTS: The proportion of children with DS was significantly higher in UKALL XI (1.9%) than UKALL X (0.9%). Children with DS tended to be under 10 years and to have the common ALL subtype. Cytogenetic analysis showed that favourable features, such as high hyperdiploidy and t(12;21) were less frequent but also that there was a lack of translocations associated with a poor prognosis. Children with DS showed no increase in risk of relapse at any site but their survival and event free survival were inferior to other children. These results were caused by an increased number of infective deaths during remission (11% compared to 2%). At five years overall survival was 73% in DS children compared with 82% in other children; event free survival was 53% compared to 63% in non-DS children. CONCLUSIONS: Entry of children with DS to national trials has increased and survival has improved. However they remain at risk of relapse and also of treatment related mortality. These findings emphasise the need for both intensive chemotherapy and optimal supportive care.

Child↗

Bone marrow transplantation versus chemotherapy in the treatment of very high-risk childhood acute lymphoblastic leukemia in first remission: results from Medical Research Council UKALL X and XI.

The role of bone marrow transplantation (BMT) in first remission of children with high-risk acute lymphoblastic leukemia (ALL) remains unclear. There were 3676 patients (aged 1 to 15 years) entered into the United Kingdom (UK) Medical Research Council (MRC) trials UKALL X and XI from 1985 to 1997. Of these patients, 473 patients (13%) were classified as very high (VH) risk and were eligible for a transplantation from a matched histocompatible sibling donor (MSD). We tissue-typed 286 patients; 99 patients had a matched related donor, and 76 patients received transplantations. Additionally, 25 children received transplantations from a matched unrelated donor (MUD) despite trial guidelines for MSD transplantations only. The median time to transplantation was 5 months (range, 2 to 19 months), and the median follow-up was 8 years. The 10-year event-free survival (EFS) adjusted for the time to transplantation, diagnostic white blood cell (WBC) count, Ph chromosome status, and ploidy was 6. 0% higher (95% confidence interval (CI), -10.5% to 22.5%) for 101 patients who received a first-remission transplantation (MSD and MUD) than for the 351 patients treated with chemotherapy (transplantation, 45.3%, vs chemotherapy, 39.3%). The transplantation group had fewer relapses (31%) compared to relapses in the chemotherapy group (55%); however, the transplantation group had more remission deaths (18%) compared to remission deaths in the chemotherapy group (3%). In contrast the adjusted 10-year EFS was 10. 7% higher (95% CI, -2.6% to 24.0%) for patients without a human leukocyte antigen (HLA)-matched donor than for those patients with a donor (no donor, 50.4%, vs donor, 39.7%). In conclusion, for the majority of children with VH-risk ALL, the first-remission transplantation has not improved EFS.

Adolescent↗

Long-term follow-up of the United Kingdom Medical Research Council protocols for childhood acute lymphoblastic leukaemia, 1980-1997. Medical Research Council Childhood Leukaemia Working Party.

Results of three consecutive completed UK trials (1980-1997) for childhood lymphoblastic leukaemia are presented. National accrual has progressively increased so that over 90% of all the country's ALL cases were treated on the latest trial reported, UKALLXI. From 1980 to 1990, event-free and overall survival progressively improved, following adoption of an American therapy template and use of two post-remission intensification modules. Since 1990 despite demonstration of the benefit of a third intensification module overall event-free survival (EFS) has not improved further. Survival remains high due to a good retrieval rate especially for those relapsing off treatment after receipt of two intensification pulses. Possible reasons for the plateau in event-free survival (including type and dose of induction steroid, dropping of induction anthracycline, type and dose of asparaginase, gaps early in therapy following intensification, and overall lack of compliance in maintenance) are being explored in the latest protocol ALL '97. Cranial irradiation had been successfully replaced by a long course of intrathecal methotrexate injections for the majority of patients. Age (<1 year >10 years) sex (male) and white count >50 x 10(9)/l plus slow initial bone marrow clearance were consistently the most important independent prognostic indicators during this time period. Rome/NCI criteria accurately predict standard and high-risk groups for B cell lineage, but not consistently for T cell disease. This international collaborative venture might help us to define those truly at highest risk, and how we can optimise therapy for specific subgroups including T-ALL and those with unfavourable cytogenetics.

Antineoplastic Combined Chemotherapy Protocols↗

Survival from childhood cancer in Yorkshire, U.K.: effect of ethnicity and socio-economic status.

The effect of ethnicity and socio-economic status on the survival of a population-based cohort of 1979 children diagnosed with cancer between 1974 and 1995 was investigated. Ethnicity was assigned by computer algorithms and visual inspection as south Asian (or not) for each child, based on their full name. Socio-economic status was measured using the Carstairs index, based on census areas of case residence at diagnosis. 15 children (0.8%) were lost to follow-up. Log-rank tests showed survival from all cancers did not differ between south Asians and other children and no increased risk was observed for south Asians in any diagnostic category, although numbers were small. Increasing levels of deprivation were associated with significant trends of poorer survival from all cancers, leukaemias and brain tumours. Risk of death was typically higher for children from the most deprived areas although differences were not statistically significant after accounting for other factors including ethnicity. Taking all children with malignant disease together, neither ethnicity nor socio-economic status appear to influence survival after taking other factors into consideration.

Adolescent↗

The National Diabetic Retinopathy Laser Treatment Audit. III. Clinical outcomes.

PURPOSE: To describe the short-term clinical outcomes for a cohort of patients undergoing first photocoagulation treatment for proliferative retinopathy or maculopathy in the United Kingdom. METHOD: Nine-month follow-up of the Royal College of Ophthalmologists' national audit of laser treatment for diabetic retinopathy. RESULTS: For eyes with maculopathy, 9.2% had had a deterioration in visual acuity equivalent to a doubling of the visual angle and 3.3% of eyes had a visual acuity of less than 6/60 at follow-up. There had been an improvement in the macular oedema or exudate in 64.6% and 77.3% respectively. Prognostic factors for a poorer visual acuity at follow-up were worse visual acuity at baseline, the presence of diffuse (vs focal) oedema and grid (vs focal) treatment. For eyes with proliferative retinopathy, the retinal neovascularisation had regressed fully in 50.8% of cases, whilst there had been no change or a deterioration in 10.3%. A visual acuity of less than 6/60 at follow-up was present in 8.6% of eyes. There was a poor morphological outcome at follow-up (as defined by rubeosis, new tractional detachment or having had a vitrectomy) in 7.2%. Risk factors for poor morphological outcome were the presence of 'high-risk characteristics', female sex and the presence of concurrent maculopathy at baseline. Regression of neovascularisation was associated with greater areas of retinal ablation at the initial treatment session. Although some eyes with proliferative retinopathy appeared to be undertreated initially compared with DRS and ETDRS protocols, some of these eyes did respond to lower amounts of treatment. CONCLUSION: For maculopathy, poorer outcome was related to worse visual acuity at baseline, diffuse (vs focal) maculopathy, and grid treatment. For proliferative retinopathy, poorer outcome was related to 'high-risk characteristics' and coexistence of maculopathy at baseline, and improvement was related to larger areas of ablation. The relationship of poor outcome with worse initial disease argues for earlier detection of retinopathy.

Diabetic Retinopathy↗

Ifosfamide/etoposide alternating with high-dose methotrexate: evaluation of a chemotherapy regimen for poor-risk osteosarcoma.

Fifteen patients with relapsed osteosarcoma were treated with an intensive combination chemotherapy schedule. Ifosfamide 2.5 g m(-2) daily and etoposide 150 mg m(-2) daily coincidentally for 3 days and high-dose methotrexate 8 g m(-2) (with folinic acid rescue) on days 10-14 in a planned 21 -day cycle. Feasibility, toxicity and response to this alternative combination for the treatment of relapsed osteosarcoma was assessed. There were 98 evaluable cycles for toxicity and tolerability. The majority of cycles were well tolerated. Haematological toxicity of grade 3/4 (common toxicity criteria) was seen in all courses. Renal tubular loss of electrolytes, particularly magnesium, occurred in 71% of cycles. Thirteen per cent of cycles were repeated within 21 days and 61% within 28 days. In the thirteen patients evaluable for response, a partial response rate of 31% was seen after two cycles. However, patients with stable disease continued on therapy, and an overall consequent response rate of 62% was observed. Four patients were alive with no evidence of disease at 8-74 months. Three are alive with disease (at 8-19 months). There were six deaths, all disease related. This regimen exhibits an encouraging response rate in a group of children with poor prognosis disease, with a tolerable toxicity profile.

Adolescent↗

A Vibrio cholerae pathogenicity island associated with epidemic and pandemic strains.

The bacterial species Vibrio cholerae includes harmless aquatic strains as well as strains capable of causing epidemics and global pandemics of cholera. While investigating the relationship between pathogenic and nonpathogenic strains, we identified a chromosomal pathogenicity island (PAI) that is present in epidemic and pandemic strains but absent from nonpathogenic strains. Initially, two ToxR-regulated genes (aldA and tagA) were studied and were found to be associated with epidemic and pandemic strains but absent in nontoxigenic strains. The region containing aldA and tagA comprises 13 kb of previously unidentified DNA and is part of a PAI that contains a regulator of virulence genes (ToxT) and a gene cluster encoding an essential colonization factor and the cholera toxin phage receptor (toxin-coregulated pilus; TCP). The PAI is 39.5 kb in size, has low %G+C (35%), contains putative integrase and transposase genes, is flanked by att sites, and inserts near a 10Sa RNA gene (ssrA), suggesting it may be of bacteriophage origin. We found this PAI in two clinical non-O1/non-O139 cholera toxin-positive strains, suggesting that it can be transferred within V. cholerae. The sequence within this PAI includes an ORF with homology to a gene associated with the type IV pilus gene cluster of enteropathogenic Escherichia coli, a transposase from Vibrio anguillarum, and several ORFs with no known homology. As the PAI contains the CTXPhi receptor, it may represent the initial genetic factor required for the emergence of epidemic and pandemic cholera. We propose to call this island VPI (V. cholerae pathogenicity island).

Aldehyde Dehydrogenase↗

Epidemiology of childhood brain tumours in Yorkshire, UK, 1974-95: geographical distribution and changing patterns of occurrence.

From a high-quality population-based register of children with cancer, 455 cases diagnosed with central nervous system (CNS) tumours were analysed to examine patterns of occurrence and geographical distribution. There was a significant increase of 1.8% (95% CI 0.5-3.1, P < 0.01) in average annual incidence for all CNS tumours, mainly accounted for by a 3.1% rise (95% CI 0.1-6.1, P < 0.05) in primitive neuroectodermal tumours (PNETs) over the 22-year period 1974-95. These increases were not explained by an increase in the proportion of histologically verified tumours. In the most recent time period (1986-95), astrocytomas occurred more commonly than previously in 0 to 4-year olds. Geographical differences in incidence were evident at a large scale, between counties, for all tumours and astrocytomas, with lower rates in the most urbanized areas. At the level of census district and electoral wards, no association between incidence of CNS tumours and socioeconomic group, person-based population density or ethnicity was observed using Poisson regression modelling. Based on small-scale census geography, the patterns of distribution of CNS tumours do not suggest strong associations with geographical determinants of risk. This study finds a rising incidence of all CNS tumours and particularly primitive neuroectodermal tumours and shows that astrocytomas appear to be occurring at a younger age, most probably because of improved diagnosis with non-invasive technology.

Adolescent↗

The National Diabetic Retinopathy Laser Treatment Audit. I. Maculopathy.

The National Diabetic Retinopathy Laser Treatment Audit is a prospective survey of laser treatment for diabetic retinopathy throughout the United Kingdom. This paper describes the methodology of the study and presents data on 546 patients who were undergoing their first photocoagulation treatment for diabetic maculopathy (without proliferative retinopathy) during a 2 month period in 1995. Validation of the level of participation, patient demographic features, sources of referral, the level of systematic screening and waiting times are described. Maculopathy was detected as a result of systematic screening in 65.2%, whilst 12.3% of cases presented symptomatically. The percentage of cases treated within 8 weeks of listing was 83.1%, whilst 7% waited for more than 12 weeks for their laser treatment. The retinopathy features and the type of treatment given are also described. The maculopathy was said to be predominantly exudative in nature in 69.8% of cases, and 96.2% of these eyes were treated with focal macular laser. The maculopathy was said to be diffusely oedematous in nature in 8.6% of cases, and 78.7% of these eyes were treated with grid macular laser.

Adult↗

The National Diabetic Retinopathy Laser Treatment Audit. II. Proliferative retinopathy.

The National Diabetic Retinopathy Laser Treatment Audit is a prospective survey of laser treatment for diabetic retinopathy throughout the United Kingdom. This paper presents data on 284 patients who were undergoing their first panretinal photocoagulation for proliferative retinopathy during a 2 month period in 1995, describing the demographic features, the level of systematic screening, the sources of referral, and the waiting times. For those cases where proliferative retinopathy was present at the first ophthalmology outpatient visit, the retinopathy was detected as a result of systematic screening in 46.8%, whilst 28.7% presented symptomatically. Of these patients 28.4% waited for more than 12 weeks from referral to the time of laser treatment, but once the patient had been listed for laser treatment this was performed within 8 weeks in 95.3%. The retinopathy features and the type of treatment given are also described. Compared with the DRS and ETDRS recommendations, at least 32.5-40.2% of eyes may be undertreated initially, and for those with high-risk characteristics these figures were at least 30.8-38.5%.

Adolescent↗

The impact of age on outcome in lymphoblastic leukaemia; MRC UKALL X and XA compared: a report from the MRC Paediatric and Adult Working Parties.

The purpose of the study was to examine the influence of age on outcome in a large cohort of children and adults with lymphoblastic leukaemia who were treated on two similar trials. Factors influencing outcome were examined in 2204 patients aged over 1 year treated between 1985 and 1992 on the parallel Medical Research Council Trials UKALL X and XA, for children and adults, respectively. There was a progressive worsening in survival with increasing age from 85% (95% CI 83-87) at 5 years for children aged 1-9 to 24% (CI 17-31) for patients over 40. Induction failures, deaths in remission and bone marrow relapses increased significantly with age. Analysis of clinical and biological features showed dominance of early B-ALL in childhood and increasing incidence of the Ph' chromosome with age. Over 80% of eligible children, but a much lower proportion of adults especially those over 40, was entered. Compliance was stricter in the paediatric trial but most deviations in adults involved giving more treatment. Analysis of results in a proportional hazards model confirmed the overwhelming independent influence of age; with all other factors equal a 10 year old had half the risk of treatment failure of a 20 year old and a 44 year old double the risk. Selective entry to therapeutic trials and increased treatment-related toxicity are features of adult ALL but age itself remains a dominant prognostic factor. While improved supportive care and refinements of conventional therapy may have some effect on prognosis, new understandings and treatment approaches to adult ALL are needed.

Adolescent↗

Dental parameters in the long-term survivors of childhood cancer compared with siblings.

There have been a number of reports on the dental health of long-term survivors (LTS) of childhood malignancy as compared with normal controls. However, it is usually difficult to identify a meaningful control population as most of these patients are from widely differing geographical areas and socio-economic status. The aim of this investigation was, therefore, to study the dental health of LTS compared with siblings. 46 LTS who had siblings of a similar age were identified for the study. Both groups were examined for dental caries, gingivitis and enamel defects. There was no statistically significant difference in the mean DMFS of the test and control groups. However, the LTS had a significantly (P = 0.006) higher number of decayed surfaces (1.50 +/- 0.30) as compared with their siblings (0.50 +/- 0.20). The LTS also had a significantly higher prevalence of severe gingivitis (1.11 +/- 0.33) compared with controls (0.02 +/- 0.02). There was a significantly higher prevalence of all types of enamel defects in the LTS and fewer teeth with no enamel defect as compared with their siblings, with the mean values being 15.7 +/- 0.9 and 25.3 +/- 0.3, respectively. It was concluded that there was a higher prevalence of untreated dental disease and developmental defects in long-term survivors.

Adolescent↗

Continuing (maintenance) therapy in lymphoblastic leukaemia: lessons from MRC UKALL X. Medical Research Council Working Party in Childhood Leukaemia.

The relationship between the prescribed dose of drugs during continuing (maintenance) therapy, the degree of marrow suppression caused, and subsequent event-free survival was examined in a cohort of 740 children with lymphoblastic leukaemia treated on MRC UKALL X. Girls, younger children, and patients who had received intensification treatment, were prescribed lower doses of mercaptopurine, became neutropenic more readily, and had more interruptions of treatment. Children who had one or more episodes of neutropenia with a count of <0.5 x 10(9)/l had a better prognosis than those who never became neutropenic. We conclude that early intensification treatment influences the probability of neutropenia during continuing treatment and that patients exhibiting myelosuppression during this phase of treatment have a better chance of prolonged remission.

Adolescent↗