6 research outputs found
Australian Health Research Alliance: national priorities in data-driven health care improvement
No full textAbstract not available.Helena J Teede, Alison Johnson, Jim Buttery, Cheryl A Jones, Douglas IR Boyle, Garry LR Jennings, Tim Sha
Adherence to insulin treatment, glycaemic control, and ketoacidosis in insulin-dependent diabetes mellitus
No full textBackground. Intensive insulin treatment effectively delays the onset and slows the progression of microvascular complications in insulin-dependent diabetes mellitus (IDDM). Variable adherence to insulin treatment is thought to contribute to poor glycaemic control, diabetic ketoacidosis, and brittle diabetes in adolescents and young adults with IDDM. We assessed the association between the prescribed insulin dose and the amount dispensed from all community pharmacies with the Diabetes Audit and Research in Tayside Scotland (DARTS) database. Methods. We studied 89 patients, mean age 16 (SD 7) years, diabetes duration 8 (4) years, and glycosylated haemoglobin (HbA(1c)) 8.4 (1.9)%, who attended a teaching hospital paediatric or young-adult diabetes clinic in 1993 and 1994. The medically recommended insulin dose and cumulative volume of insulin prescriptions supplied were used to calculate the days of maximum possible insulin coverage per annum, expressed as the adherence index. Associations between glycaemic control (HbA(1c)), episodes of diabetic ketoacidosis, and all hospital admissions for acute complications and the adherence index were modelled. Findings. Insulin was prescribed at 48 (19) IU/day and mean insulin collected from pharmacies was 58 (25) IU/day. 25 (28%) of the 89 patients obtained less insulin than their prescribed dose (mean deficit 115 [68; range 9-246] insulin days/annum). There was a significant association between HbA(1c) and the adherence index (R2 = 0.39; p < 0.001). In the top quartile (HbA(1c) > 10%), 14 (64%) of individuals had an adherence index suggestive of a missed dose of insulin (mean deficit 55 insulin days/annum). There were 36 admissions for complications related to diabetes. The adherence index was inversely related to hospital admissions for diabetic ketoacidosis (p < 0.001) and all hospital admissions related to acute diabetes complications (p = 0.008). The deterioration in glycaemic control observed in patients aged 10-20 years was associated with a significant reduction (p = 0.01) in the adherence index. Interpretation. We found direct evidence of poor compliance with insulin therapy in young patients with IDDM. We suggest that poor adherence to insulin treatment is the major factor that contributes to long-term poor glycaemic control and diabetic ketoacidosis in this age group
Conditions for safe and effective ADEPT treatment
No full textAntibody directed enzyme prodrug therapy (ADEPT) is a drug delivery system developed for the treatment of cancer. ADEPT uses a systemically administered antibody, tethered to an enzyme, to localize enzyme in tumour deposits. When the antibody-enzyme has cleared from the circulation, a low-toxicity prodrug is given. The prodrug is converted by the tumour-bound enzyme into an active cytotoxic drug. The system has potential to generate a highly potent cytotoxic agent at the tumour site.
A clinical ADEPT system using MFECP1, a recombinant fusion protein consisting of an anti-carcinoembryonic antigen single chain Fv antibody and the bacterial enzyme carboxypeptidase G2, in combination with a bis-iodo phenol mustard prodrug (BIP) has been developed. A previous phase I/II clinical trial established the maximum tolerated dose of a single treatment cycle of this ADEPT system.
In-vivo models with human tumour xenografts indicate that repeated ADEPT treatment with MFECP1/BIP led to greater efficacy without increased toxicity. This thesis aims to establish conditions required for safe and effective ADEPT when using MFECP1/BIP in man. This was achieved by conducting a phase I/II clinical trial of repeat-treatment ADEPT and comparing and combining the results with data from the single-treatment trial. The combined dataset provided mechanistic and clinical information on 43 patients.
Multiple parameters were investigated to examine the likely cause of toxicity and clinical risk factors for its occurrence. Efficacy was evaluated using CT, FDG-PET and serum tumour markers. The nature of the immune response to MFECP1 was investigated and possible strategies to reduce immunogenicity were developed.
Results showed that repeated therapy was feasible in man and did not increase the risk of MFECP1 infusion reactions. At the maximum tolerated total prodrug dose for 2 ADEPT treatments, one of three patients experienced tumour response on FDG-PET imaging. This MD (Res) thesis significantly increases understanding of the conditions required for safe and effective ADEPT
Results of the first recorded evaluation of a national gestational diabetes mellitus register: Challenges in screening, registration, and follow-up for diabetes risk.
No full textOBJECTIVE:Gestational Diabetes Mellitus (GDM) increases the risk of type 2 diabetes. A register can be used to follow-up high risk women for early intervention to prevent progression to type 2 diabetes. We evaluate the performance of the world's first national gestational diabetes register. RESEARCH DESIGN AND METHODS:Observational study that used data linkage to merge: (1) pathology data from the Australian states of Victoria (VIC) and South Australia (SA); (2) birth records from the Consultative Council on Obstetric and Paediatric Mortality and Morbidity (CCOPMM, VIC) and the South Australian Perinatal Statistics Collection (SAPSC, SA); (3) GDM and type 2 diabetes register data from the National Gestational Diabetes Register (NGDR). All pregnancies registered on CCOPMM and SAPSC for 2012 and 2013 were included-other data back to 2008 were used to support the analyses. Rates of screening for GDM, rates of registration on the NGDR, and rates of follow-up laboratory screening for type 2 diabetes are reported. RESULTS:Estimated GDM screening rates were 86% in SA and 97% in VIC. Rates of registration on the NGDR ranged from 73% in SA (2013) to 91% in VIC (2013). During the study period rates of screening at six weeks postpartum ranged from 43% in SA (2012) to 58% in VIC (2013). There was little evidence of recall letters resulting in screening 12 months follow-up. CONCLUSIONS:GDM Screening and NGDR registration was effective in Australia. Recall by mail-out to young mothers and their GP's for type 2 diabetes follow-up testing proved ineffective
Feasibility and utility of a sickle cell disease registry for research and patient management
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis aimed to evaluate the feasibility and utility of a sickle cell disease registry for
clinical patient management and research. Five hospitals out of nine in the North West
London health region participated in the registry, with 78 percent coverage of the sickle
cell disease population. There was 80% case ascertainment in participating hospitals.
Aggregated anonymised demographic and diagnostic data was collected for all
haemoglobinopathy patients. This provided the core dataset for quantifying prevalence of
sickle cell and thalassaemia and mapping local hospital workloads and service
requirements. Thirteen percent of HbSS adult patients were taking hydroxycarbamide.
The cohort of patients treated with hydroxycarbamide was evaluated. Sixty two of the 80
patients started on treatment were included. Follow-up was censored after 9 years, totalling
249 person-years of data with a median follow-up of three years (IQR, 1-6). Results
showed that haematological benefits were maintained in the long-term with treatment, but
evidence of long-term clinical effectiveness was less strong. This appeared to be due to the
patterns of clinical management in everyday practice. Patients tend to be treated with
modest doses of hydroxycarbamide due to intolerance or inability to attain or maintain
maximum tolerated dose. For example maximum tolerated dose was the aim of treatment
for 91% of patients but it was achieved for 65% of participants. Non- compliance with
treatment and monitoring schedule was the main reason for non- attainment.
Results suggest that it is sensible to strive for maximum tolerated dose to ensure therapy
remains effective, but with more realistic expectations of the dose patients can attain and
maintain. Doses in adult patients average 20mg/kg/day and 25mg/kg/day in children. Adult
patients may be able to achieve a higher dose, if there was more stringent monitoring and
improved management of non-compliance.
The North West London HU Sub-Registry proved useful for measuring long-term
effectiveness and tolerability of hydroxycarbamide. Routinely collected data was utilized
for both clinical management and research purposes. The novelty lay in examination of the
nuances of routine clinical practice. An electronic patient record was developed as a
clinical management tool. It is the first study reporting long-term outcomes for UK sickle
cell disease patients on hydroxycarbamide.
Findings should help clinicians devise effective treatment protocols and strategies for
managing patients commenced on this therapy. Interventions need to be targeted at
increasing utilisation, patient adherence and persistence with treatment. The electronic
patient record could be used to maximise treatment benefit and improve adherence. More
effective involvement of the multidisciplinary team and primary care colleagues in patient
education and management should improve usage. Patients and carers need up to date and
easy to assimilate information to make informed decisions about treatment options.
Maintaining a SCD registry is challenging. Models which operate as clinical information
systems provide an incentive for participation. These enable active involvement of local
care providers in registry management and the ability to keep and utilize their own data.
Clinicians require accurate and current data for patient management and to enable them to
benchmark their local outcomes against national outcomes and care standards
The role of a nurse-led vascular risk reduction clinic in diabetes care
No full textBackground and Aims
Type 2 diabetes is characterised by excess vascular morbidity and mortality. Intensive vascular risk reduction in type 2 diabetes patients with microalbuminuria has been shown to significantly reduce future vascular events by 50%. The aim of this research was to determine whether an intensive, nurse-led clinic could achieve recommended vascular risk reduction targets in patients with type 2 diabetes compared with standard diabetes management. In addition, the study aimed to test the hypothesis that diabetes patients attending the vascular intervention clinic would have a clearer understanding of the
relationship between diabetes and heart disease than those randomised to standard diabetic care.
Method
Part 1: Two hundred patients with type 2 diabetes were randomised to receive either intensive nurse-led or standard diabetes care in a one-year study.
Part 2: Following completion of the vascular risk intervention study, a questionnaire examining knowledge of vascular risk targets, was sent to patients who completed the study.
Results
94 patients in each group completed the study. The groups were matched for age and baseline HbA1c, blood pressure and lipid profiles. More patients in the intensive group achieved targets than in the standard group, systolic BP (<130 mmHg) (33.0% vs 12.1%, p 0.001), diastolic BP (<80 mmHg) (75.5% vs 40.2% (p 0.001), cholesterol (< 4.8 mmol/L) (84.8% vs 63.6% (p 0.003), LDL cholesterol (< 2.6 mmol/L) (73.4% vs 54.5% (p 0.007) and HbA1c (<6.5 %) (53.2% vs 32.9% (p 0.005). There was a 75% response rate to the questionnaire. A surprisingly high number of patients did not know what their ideal blood pressure (67.2%), cholesterol (65.1%) or HbA1c (68.1%) should be, with no significant difference between the groups. However,
a high percentage of patients were aware that heart disease (89.2%) and stroke disease (82.8%) were complications associated with diabetes, with no significant difference
between the groups.
Conclusion: An intensive, nurse-led clinic is more successful in achieving vascular risk reduction targets than standard diabetes care. However, education programmes for patients with type 2 diabetes need to include information regarding vascular risk factors and their relationship to diabetes
