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Background Incontinence-associated dermatitis (IAD) is prevalent in long-term care (LTC) facilities and homecare settings amongst adults who are incontinent of urine and/or faeces. Strategies to protect skin integrity are needed. This study aimed to co-design and test the feasibility of a training manual and care guidance (IAD-Manual) to prevent and treat IAD in LTC facilities and homecare settings. Methods This was a three-phase study: (1) developing the intervention, (2) designing the empirical study (a cluster RCT with an embedded process evaluation) to assess its effectiveness (not reported here) and (3) a 3-month feasibility study. The feasibility study recruited three LTC facilities and two homecare providers, randomising them (each as a cluster) to intervention or control. Process evaluation interviews with two care recipients, 11 family carers and 13 care staff implementing the IAD-Manual and their managers were conducted. Observations of 22 episodes of care assessed fidelity to the intervention. Qualitative data were analysed using thematic analysis. Summary feasibility outcome measures using means or proportions together with 95% confidence intervals were reported. Results Five sites were recruited from 49 approached. All randomised sites were retained. Seventy-six (16% [95% CI: 13–20%]) of the 477 participants approached were randomised, of which 58 (76% [95% CI: 65–85%]) completed the study. Candidate IAD outcomes had complete or almost-complete 3-month outcome data in those participants remaining, whereas other outcome measures had contrastingly poor data completeness largely due to participant cognitive impairment. Process evaluation showed few potential participants had the capacity to consent, and gaining consultee approval was challenging. Care staff at study sites liked the IAD-Manual, describing it as ‘ helpful ’. Twenty-eight people accessed the IAD-Manual online, and 15 care staff downloaded a certificate of completion of training. Intervention fidelity was not always observed. Conclusions It was feasible to develop the IAD-Manual. The RCT as designed was not feasible in its original form, with specific challenges regarding site and participant recruitment, governance and intervention fidelity. Trial registration This trial was prospectively registered on 07/02/2020 (intervention development) ISRCTN26169429 and 28/02/2024 (feasibility study) ISRCTN70866724.

Background Incontinence-associated dermatitis (IAD) is prevalent in long-term care (LTC) facilities and homecare settings amongst adults who are incontinent of urine and/or faeces. Strategies to protect skin integrity are needed. This study aimed to co-design and test the feasibility of a training manual and care guidance (IAD-Manual) to prevent and treat IAD in LTC facilities and homecare settings. Methods This was a three-phase study: (1) developing the intervention, (2) designing the empirical study (a cluster RCT with an embedded process evaluation) to assess its effectiveness (not reported here) and (3) a 3-month feasibility study. The feasibility study recruited three LTC facilities and two homecare providers, randomising them (each as a cluster) to intervention or control. Process evaluation interviews with two care recipients, 11 family carers and 13 care staff implementing the IAD-Manual and their managers were conducted. Observations of 22 episodes of care assessed fidelity to the intervention. Qualitative data were analysed using thematic analysis. Summary feasibility outcome measures using means or proportions together with 95% confidence intervals were reported. Results Five sites were recruited from 49 approached. All randomised sites were retained. Seventy-six (16% [95% CI: 13-20%]) of the 477 participants approached were randomised, of which 58 (76% [95% CI: 65-85%]) completed the study. Candidate IAD outcomes had complete or almost-complete 3-month outcome data in those participants remaining, whereas other outcome measures had contrastingly poor data completeness largely due to participant cognitive impairment. Process evaluation showed few potential participants had the capacity to consent, and gaining consultee approval was challenging. Care staff at study sites liked the IAD-Manual, describing it as 'helpful'. Twenty-eight people accessed the IAD-Manual online, and 15 care staff downloaded a certificate of completion of training. Intervention fidelity was not always observed. Conclusions It was feasible to develop the IAD-Manual. The RCT as designed was not feasible in its original form, with specific challenges regarding site and participant recruitment, governance and intervention fidelity. Trial registration This trial was prospectively registered on 07/02/2020 (intervention development) ISRCTN26169429 and 28/02/2024 (feasibility study) ISRCTN70866724. Keywords: Incontinence-associated dermatitis, Social care, Intervention development, Co-design, Training manual, Feasibility cluster RCT, Prevention, Treatment, Long-term care (LTC)

The work presented here is a sociological and bioethical analysis of the medical condition known as Syndrome X/Metabolic Syndrome. The term is a recent name given to a group of cardiac/diabetic risk factors that include high cholesterol, insulin resistance, obesity, high blood pressure and high fat levels in the blood (Garber 2004). Interest in the topic was reawakened by Reaven (1988) who first coined the term ‘Syndrome X’ to describe a cluster of risk factors that he believed was linked to insulin resistance. In recent years the number of ‘new’ diseases that have been detected and identified by medicine has increased rapidly, with examples such as clinical obesity and infertility. Commentators have speculated as to why this may be happening and one suggestion is that our lives are becoming ever more medicalised (Moynihan and Smith 2002). The thesis consists of three main strands. The first strand is a sociological analysis of the Metabolic Syndrome concept and how it came to be constructed as a medical condition, with particular emphasis on whether the syndrome represents an example of the medicalisation of obesity. The second strand looks at the relationship between sociology and bioethics, and whether research from the former can help inform the ethical debate in the other. In this regard, I hope to show in this thesis that it is possible to conduct social and bioethical analyses side by side, and that these can be complementary and give you a richer understanding of a topic. The third strand is a discussion of the main ethical issues surrounding this ‘new’ diagnosis, with particular emphasis on the issue of blame and responsibility in relation to this condition.

Target-D, a new person-centred e-health platform matching depression care to symptom severity prognosis (minimal/mild, moderate or severe) has demonstrated greater improvement in depressive symptoms than usual care plus attention control. The aim of this study was to evaluate the cost-effectiveness of Target-D compared to usual care from a health sector and partial societal perspective across 3-month and 12-month follow-up. A cost-utility analysis was conducted alongside the Target-D randomised controlled trial; which involved 1,868 participants attending 14 general practices in metropolitan Melbourne, Australia. Data on costs were collected using a resource use questionnaire administered concurrently with all other outcome measures at baseline, 3-month and 12-month follow-up. Intervention costs were assessed using financial records compiled during the trial. All costs were expressed in Australian dollars (A$) for the 2018-19 financial year. QALY outcomes were derived using the Assessment of Quality of Life-8D (AQoL-8D) questionnaire. On a per person basis, the Target-D intervention cost between $14 (minimal/mild prognostic group) and $676 (severe group). Health sector and societal costs were not significantly different between trial arms at both 3 and 12 months. Relative to a A$50,000 per QALY willingness-to-pay threshold, the probability of Target-D being cost-effective under a health sector perspective was 81% at 3 months and 96% at 12 months. From a societal perspective, the probability of cost-effectiveness was 30% at 3 months and 80% at 12 months. Target-D is likely to represent good value for money for health care decision makers. Further evaluation of QALY outcomes should accompany any routine roll-out to assess comparability of results to those observed in the trial. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000537459).

To examine the health care costs associated with mental disorders and subthreshold mental disorders within a nationally representative sample of children and adolescents in Australia. Data were derived from the Young Minds Matter Survey (N = 6,310). Mental disorders were classified using the Diagnostic Interview Schedule for Children Version IV. Participant data were linked to administrative data on health care costs. Adjusted generalized linear regression models and two-part models were used to estimate mean differences in costs between those with a mental disorder or subthreshold disorder and those without. Costs associated with health care attendances and medications were higher for children and adolescents with mental disorders and subthreshold mental disorders compared to those without a mental disorder. The additional population health care costs due to mental disorders amounted to AUD$234 million annually in children and adolescents, of which approximately 16% was attributed to out-of-pocket costs. Findings showed that those with subthreshold mental disorders or comorbid mental disorders have substantial additional costs of Medicare-funded medical and pharmaceutical services. Mental disorders in children and adolescents are associated with significant health care costs. Further research is needed to ensure that this population is receiving effective and efficient care.

Background The Illumina HumanMethylation450 BeadChip (HM450K) measures the DNA methylation of 485,512 CpGs in the human genome. The technology relies on hybridization of genomic fragments to probes on the chip. However, certain genomic factors may compromise the ability to measure methylation using the array such as single nucleotide polymorphisms (SNPs), small insertions and deletions (INDELs), repetitive DNA, and regions with reduced genomic complexity. Currently, there is no clear method or pipeline for determining which of the probes on the HM450K bead array should be retained for subsequent analysis in light of these issues. Results We comprehensively assessed the effects of SNPs, INDELs, repeats and bisulfite induced reduced genomic complexity by comparing HM450K bead array results with whole genome bisulfite sequencing. We determined which CpG probes provided accurate or noisy signals. From this, we derived a set of high-quality probes that provide unadulterated measurements of DNA methylation. Conclusions Our method significantly reduces the risk of false discoveries when using the HM450K bead array, while maximising the power of the array to detect methylation status genome-wide. Additionally, we demonstrate the utility of our method through extraction of biologically relevant epigenetic changes in prostate cancer.

Background DNA methylation is a critical molecular mark involved in cellular differentiation and cell-specific processes. Single-cell whole genome DNA methylation profiling methods hold great potential to resolve the DNA methylation profiles of individual cell-types. Here we present a method that couples single-cell combinatorial indexing (sci) with enzymatic conversion (sciEM) of unmethylated cytosines. Results The sciEM method facilitates DNA methylation profiling of single-cells that is highly correlated with single-cell bisulfite-based workflows (r 2  > 0.99) whilst improving sequencing alignment rates, reducing adapter contamination and over-estimation of DNA methylation levels (CpG and non-CpG). As proof-of-concept we perform sciEM analysis of the temporal lobe, motor cortex, hippocampus and cerebellum of the human brain to resolve single-cell DNA methylation of all major cell-types. Conclusion To our knowledge sciEM represents the first non-bisulfite single-cell DNA methylation sequencing approach with single-base resolution.

ObjectiveA major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy.DesignWe conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325 mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3 months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints.ResultsAt 3 months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=−0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention.ConclusionsWe provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice.Trial NumberNCT00468910

A CT acute stroke protocol demonstrated an extensive left common carotid thrombus extending into the left internal carotid artery (ICA) with a large penumbra of the left middle cerebral artery territory. Functional VITT assays demonstrated mixed results with a positive serotonin release assay (SRA) but negative customised flow cytometry and Multiplate platelet aggregation tests. Significant platelet increment, rising fibrinogen and decreasing D-dimer levels were noted following IVIg (figure 3). Continued improvement ensued over several months, and at last follow-up 3 months after admission she was independently mobile but requiring some assistance from family members, exhibiting mild left-sided neglect and a hemianopia.

Cellulose acetate (CA) fibers loaded with the ester prodrugs of naproxen, including methyl ester, ethyl ester and isopropyl ester, were prepared through electrospinning using acetone/ N , N -dimethylacetamide(DMAc)/ethanol (4:1:1, v/v/v) as solvent. The chemical and morphological characterizations of the medicated fibers were investigated by means of SEM, DSC, XRD and FTIR, as well as the studies of the drug release properties. The results indicated that the morphology and diameter of the fibers were influenced by the concentration of spinning solution, applied voltage, electrospun solvent and the surfactants. The average diameters of the fibers ranged between 100 and 500 nm for three prodrugs. There was good compatibility between CA and three prodrugs in the blended fibers, respectively. In vitro release indicated that constant drug release from the fiber was observed over 6 days. The prodrugs were successfully encapsulated into the fibers, and this system was stable in terms of effectiveness in release.