Exploration of knowledge and understanding in patients with primary adrenal insufficiency: a mixed methods study.

BACKGROUND: Primary adrenal insufficiency (PAI) is a rare and severe condition requiring lifelong steroid replacement. During acute illness or stressful events, it is important to appropriately adjust glucocorticoid dose; failure to do so may lead to an adrenal crisis. The aim of the study was to explore patients PAI knowledge and understanding of the condition, steroid replacement adjustment during acute illness or stress and provided education. METHODS: Ten adult patients with PAI were purposefully recruited from two hospitals in a tertiary NHS Trust in England, UK. Data was collected using a mixed method approach utilising semi-structured audio-recorded interviews and hospital case note review. Interviews were transcribed verbatim and analysed using Burnard's content analysis framework. Information from the hospital case note review was captured using a matrix table based on pre-defined criteria. RESULTS: Four key themes emerged: 'Addison's disease and hydrocortisone replacement'; 'stress and corticosteroids'; 'patient compliance/adherence' and 'transition'. Patients reported feelings of 'going through a transition from uncertainty to adaption' following diagnosis. All participants had a good level of knowledge and understanding of required medication however application in times of need was poor. Medication adherence and prevention of a crisis relied not only on patient knowledge and application but also the support of family and health professionals. Health care professional knowledge required improvement to aid diagnosis and management of PAI. CONCLUSION: Patients with PAI did not apply existing knowledge to adjust steroid dose during acute illness or stress. Although a sample of limited size, our study identified there is a need to further explore why patients with Addison's disease do not apply existing knowledge during times of increased need. Future research should consider appropriate behaviour change interventions to promote medication adherence to reduce risk of an adrenal crisis.

Ability of an ELISA-Based Seed Health Test to Detect Erwinia stewartii in Maize Seed Treated with Fungicides and Insecticides.

Two sets of experiments were done to examine whether seed-treatment chemicals affected the ability of an enzyme-linked immunosorbent assay (ELISA)-based seed health test to detect Erwinia stewartii. The chemicals evaluated included Actellic, Apron, Captan, Cruiser, Gaucho, Maxim, Poncho, Thiram, and Vitavax in 11 seed-treatment combinations. In one experiment, seed-treatment chemicals were evaluated quantitatively in a critical region of ELISA absorbance values near 0.5 using maize seed that were spiked with uniform quantities of a liquid suspension of E. stewartii. The number of bacteria in each sample was estimated from ELISA absorbance values using standard curves. Log CFU of E. stewartii per sample were not significantly different among the untreated control and the 11 seed treatments compared with Tukey's Studentized Range Test (P = 0.05). Means of log CFU/ml for all treatments were tightly clustered around 5.70 which corresponded to an absorbance value of 0.440 and a bacterial population of about 500,000 CFU/ml. In a second set of experiments, seed treatment chemicals were evaluated based on qualitative decisions that resulted from the ELISA-based seed health test of seed lots of Jubilee and A632 infected with E. stewartii. The number of negative samples was not substantially greater than expected based on binomial probabilities except for samples of Captan/Vitavax-treated A632, which we considered to be a type I error. The mean absorbance values of positive samples ranged from 1.42 to 1.72 for A632 and from 1.51 to 1.91 for Jubilee and did not differ significantly among the seed treatments. There was no consistent evidence from these experiments that fungicide or insecticide seed treatments interfered with the sensitivity of the ELISA or altered low (e.g., 0.5) or high (e.g. 1.4 to 1.9) absorbance values. The ability of the ELISA-based seed health test to detect E. stewartii in maize seed was not affected by these seed treatments.

Do doctors know best? Comments on a failed trial.

A randomised controlled trial was planned to compare two different treatment strategies--structured problem solving and selective serotonin reuptake inhibitor (SSRI) medication--for patients with mild to moderate major depression. The trial was to be conducted in the primary care setting with all treatment given by general practitioners. When no patients had been recruited into the study after six months, we performed an audit of all patients with depressive symptoms attending the doctors' practices over three weeks. Exclusion criteria were changed to ease entry into the trial, but still no patients were recruited over the following six months. What went wrong?

Functional consequences of mutations in the MODY4 gene (IPF1) and coexistence with MODY3 mutations.

AIMS/HYPOTHESIS: The aim of this study was to examine the putative role of mutations in the insulin promoter 1 (IPF1) gene in early-onset diabetes. METHODS: We carried out mutation screening of the IPF1 gene in 115 Scandinavian families with at least two members with onset of diabetes younger than 40 years. The allele frequencies were also tested in 183 unrelated patients with late-onset Type II (non-insulin-dependent) diabetes mellitus and in 92 non-diabetic control subjects. RESULTS: Two novel IPF1 variants (G212R and P239Q) and one previously reported (D76N) IPF1 variant were identified in the 115 families (3.5%). The D76N variant was found in one MODY3 family (S315fsinsA of HNF1alpha) and also in two families with late-onset Type II diabetes. The P239Q variant was identified in two families with early-onset diabetes including one with MODY3 (R272C of HNF1alpha) and in three families with late-onset Type II diabetes. Despite the fact that the variants did not segregate completely with diabetes, the non-diabetic carriers of the IPF1 variants had increased blood glucose concentrations (p < 0.05) and reduced insulin:glucose ratios (p < 0.05) during an oral glucose tolerance test compared with non-diabetic family members without these variants. In addition, when the G212R and P239Q variants were expressed in cells without IPF1 i.e.. Nes2y cells, both variants showed about a 50% reduction in their ability to activate insulin gene transcription compared to wild-type IPF1, as measured by reporter gene assay. CONCLUSION/INTERPRETATION: Although mutations in the IPF-1 gene are rare in early- (3.5 %) and late-onset (2.7 % ) Type II diabetes, they are functionally important and occur also in families with other MODY mutations.