Honorary contracts publications

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Research outputs from staff with honorary RD&E contracts.


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Now showing 1 - 5 of 597
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    Common maternal and fetal genetic variants show expected polygenic effects on risk of small- or large-for-gestational-age (SGA or LGA), except in the smallest 3% of babies
    (Public Library of Science, 2020-12-07) Beaumont, Robin N.; Wood, A. R.; Knight, Bridget A.; Hattersley, Andrew T.; Freathy, Rachel M.
    Babies born clinically Small- or Large-for-Gestational-Age (SGA or LGA; sex- and gestational age-adjusted birth weight (BW) <10th or >90th percentile, respectively), are at higher risks of complications. SGA and LGA include babies who have experienced environment-related growth-restriction or overgrowth, respectively, and babies who are heritably small or large. However, the relative proportions within each group are unclear. We assessed the extent to which common genetic variants underlying variation in birth weight influence the probability of being SGA or LGA. We calculated independent fetal and maternal genetic scores (GS) for BW in 11,951 babies and 5,182 mothers. These scores capture the direct fetal and indirect maternal (via intrauterine environment) genetic contributions to BW, respectively. We also calculated maternal fasting glucose (FG) and systolic blood pressure (SBP) GS. We tested associations between each GS and probability of SGA or LGA. For the BW GS, we used simulations to assess evidence of deviation from an expected polygenic model. Higher BW GS were strongly associated with lower odds of SGA and higher odds of LGA (ORfetal = 0.75 (0.71,0.80) and 1.32 (1.26,1.39); ORmaternal = 0.81 (0.75,0.88) and 1.17 (1.09,1.25), respectively per 1 decile higher GS). We found evidence that the smallest 3% of babies had a higher BW GS, on average, than expected from their observed birth weight (assuming an additive polygenic model: Pfetal = 0.014, Pmaternal = 0.062). Higher maternal SBP GS was associated with higher odds of SGA P = 0.005. We conclude that common genetic variants contribute to risk of SGA and LGA, but that additional factors become more important for risk of SGA in the smallest 3% of babies.
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    Online Education and Cognitive Behavior Therapy Improve Dementia Caregivers' Mental Health: A Randomized Trial
    (Elsevier Science, 2020-12-04) Ballard, Clive
    Objectives: To compare online cognitive-behavioral therapy (CBT) with and without telephone support respectively to online psychoeducation in a randomized controlled trial (RCT) in caregivers of people with dementia with mild anxiety or depression. Design: Three-arm parallel-group RCT comparing online CBT with and without telephone support respectively to online psychoeducation. Setting and participants: Online study with caregivers of people with dementia. Measures: The primary outcome measure was mental health measured by General Health Questionnaire-12 (GHQ-12) at 26 weeks. Secondary outcomes included the Hospital Anxiety and Depression Scale (HADS); the Relative Stress Scale (RSS) and the Short Sense of Competency Questionnaire. The primary analysis focused on people completing GHQ-12 at both baseline and 26 weeks, evaluated using analysis of covariance. Results: 638 people were randomized to the 3 treatment arms, of whom 208 were included in the analysis population. There were significant improvements in GHQ-12 in all treatment arms compared to baseline (P < .001 for all interventions), but neither CBT with nor without telephone support conferred any significant advantage compared to psychoeducation. For the secondary outcomes, there were no significant differences between CBT with telephone support and psychoeducation, but CBT without telephone support was less effective than psychoeducation with respect to HADS depression subscale [mean difference 1.86, 95% confidence interval (CI) 0.61, 3.11; P = .004] and caregiver stress (RSS mean difference 3.11, 95% CI 0.13, 6.09; P = .04). Good safety was achieved in all 3 treatment arms, with no deaths or serious adverse events. Conclusions and implications: Online CBT with telephone support and psychoeducation both achieved significant benefits over 26 weeks compared with baseline in mental health and mood, but there were no advantages for CBT compared with the psychoeducation intervention. CBT without telephone support was less effective with respect to mood outcomes than psychoeducation and should not be recommended based on current evidence.
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    Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study
    (HighWire, 2021-02) Jones, A. G.; Hattersley, Andrew T.; McDonald, Timothy J.
    Objective: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). Research design and methods: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. Results: Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R 2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. Conclusions: Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.
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    Ventilation bundle compliance in two Australian intensive care units: An observational study
    (Elsevier Science, 2021-07) Endacott, Ruth
    Background: The ventilation bundle has been used in adult intensive care units to decrease harm and improve quality of care for mechanically ventilated patients. The ventilation bundle focuses on prevention of specific complications of mechanical ventilation; ventilator-associated pneumonia, sepsis, barotrauma, pulmonary oedema, pulmonary embolism, and acute respiratory distress syndrome. The Institute for Healthcare Improvement ventilation bundle consists of five structured evidence-based interventions: head of the bed elevation at 30-45°; daily sedation interruptions and assessment of readiness to extubate; peptic ulcer prophylaxis; deep vein thrombosis prophylaxis; and daily oral care with chlorhexidine. Objectives: The objective of the study was to evaluate the use of the ventilation bundle in two intensive care units in Victoria, Australia. Methods: This is a 3-month prospective observational study in two intensive care units. Patient medical records were reviewed on days 3, 4, and 5 of mechanical ventilation using a prevalidated ventilation bundle checklist. Results: A total of 96 critically ill patients required mechanical ventilation for more than 2 d. Patients had a mean age of 64.50 y (standard deviation = 14.89), with an Acute Physiology, Age, Chronic Health Evaluation (APACHE) III mean score of 79.27 (standard deviation = 27.11). The mean ventilation bundle compliance rate was 88.3% on the three consecutive mechanical ventilation days (day 3 = 79.4%, day 4 = 91.1%, and day 5 = 96.7%). There was a statistically significant difference in the mean APACHE III score between patients who had head of bed elevation and those without head of bed elevation, on days 3 (p = <0.001) and 4 (p = 0.007). Conclusion: The ventilation bundle elements were used in Australian intensive care units. The likelihood of having all ventilation bundle elements on day 3 was low if the patient's APACHE III score was high. However, the ventilation bundle compliance rate increased with mechanical ventilation days.
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    Patient involvement in regulation: an unvalued imperative
    (Elsevier Science, 2021-06-05) Campbell, Bruce