The effect of strategies of personal resilience on depression recovery in an Australian cohort : a mixed methods study

Strategies of personal resilience enable successful adaptation in adversity. Among patients experiencing depression symptoms, we explored which personal resilience strategies they find most helpful, and tested the hypothesis that use of these strategies improves depression recovery. We used interview and survey data from the Diagnosis, Management and Outcomes of Depression in Primary Care 2005 cohort of patients experiencing depression symptoms in Victoria, Australia. 564 participants answered a computer assisted telephone interview question at 12 months follow-up, about what they found most helpful for their depression, stress or worries. Depressive disorder and severity were measured at annual follow-up using the Composite International Diagnostic Interview and the PHQ-9 self-rating questionnaire. Using interview responses we categorised participants as users or not of strategies of personal resilience, specifically, drawing primarily on expanding their own inner resources or pre-existing relationships: 316 (56%) were categorised as primarily users of personal resilience strategies. Of these, 193 (61%) reported expanding inner resources, 79 (25%) drawing on relationships, and 44 (14%) reported both. There was no association between drawing on relationships and depression outcome. There was evidence supporting an association between expanding inner resources and depression outcome: 25% of users having major depressive disorder one year later compared to 38% of non-users (adjusted OR 0.59, CI 0.36-0.97). This is the first study to show improved outcome for depression for those who identify as most helpful the use of personal resilience strategies. The difference in outcome is important as expanding inner resources includes a range of low intensity, yet commonly available strategies

Pollen-pistil interactions and self-incompatibility in the Asteraceae: new insights from studies of Senecio squalidus (Oxford ragwort)

Background Pollen-pistil interactions are an essential prelude to fertilization in angiosperms and determine compatibility/incompatibility. Pollen-pistil interactions have been studied at a molecular and cellular level in relatively few families. Self-incompatibility (SI) is the best understood pollen-pistil interaction at a molecular level where three different molecular mechanisms have been identified in just five families. Here we review studies of pollen-pistil interactions and SI in the Asteraceae, an important family that has been relatively understudied in these areas of reproductive biology. Scope We begin by describing the historical literature which first identified sporophytic SI (SSI) in species of Asteraceae, the SI system later identified and characterized at a molecular level in the Brassicaceae. Early structural and cytological studies in these two families suggested that pollen-pistil interactions and SSI were similar, if not the same. Recent cellular and molecular studies in Senecio squalidus (Oxford ragwort) have challenged this belief by revealing that despite sharing the same genetic system of SSI, the Brassicaceae and Asteraceae molecular mechanisms are different. Key cellular differences have also been highlighted in pollen-stigma interactions, which may arise as a consequence of the Asteraceae possessing a ‘semi-dry' stigma, rather than the ‘dry' stigma typical of the Brassicaceae. The review concludes with a summary of recent transcriptomic analyses aimed at identifying proteins regulating pollen-pistil interactions and SI in S. squalidus, and by implication the Asteraceae. The Senecio pistil transcriptome contains many novel pistil-specific genes, but also pistil-specific genes previously shown to play a role in pollen-pistil interactions in other species. Conclusions Studies in S. squalidus have shown that stigma structure and the molecular mechanism of SSI in the Asteraceae and Brassicaceae are different. The availability of a pool of pistil-specific genes for S. squalidus offers an opportunity to elucidate the molecular mechanisms of pollen-pistil interactions and SI in the Asteracea

Interaction of preimplantation factor with the global bovine endometrial transcriptome

Preimplantation factor (PIF) is an embryo derived peptide which exerts an immune modulatory effect on human endometrium, promoting immune tolerance to the embryo whilst maintaining the immune response to invading pathogens. While bovine embryos secrete PIF, the effect on the bovine endometrium is unknown. Maternal recognition of pregnancy is driven by an embryo-maternal cross talk, however the process differs between humans and cattle. As many embryos are lost during the early part of pregnancy in cattle, a greater knowledge of factors affecting the embryo-maternal crosstalk, such as PIF, is needed to improve fertility. Therefore, for the first time, we demonstrate the effect of synthetic PIF (sPIF) on the bovine transcriptome in an ex vivo bovine endometrial tissue culture model. Explants were cultured for 30h with sPIF (100nM) or in control media. Total RNA was analysed via RNA-sequencing. As a result of sPIF treatment, 102 genes were differentially expressed compared to the control (Padj<0.1), although none by more than 2-fold. The majority of genes (78) were downregulated. Pathway analysis revealed targeting of several immune based pathways. Genes for the TNF, NF-κB, IL-17, MAPK and TLR signalling pathways were down-regulated by sPIF. However, some immune genes were demonstrated to be upregulated following sPIF treatment, including C3. Steroid biosynthesis was the only over-represented pathway with all genes upregulated. We demonstrate that sPIF can modulate the bovine endometrial transcriptome in an immune modulatory manner, like that in the human endometrium, however, the regulation of genes was much weaker than in previous human work

Embedding effective depression care: using theory for primary care organisational and systems change

Background: depression and related disorders represent a significant part of general practitioners (GPs) daily work. Implementing the evidence about what works for depression care into routine practice presents a challenge for researchers and service designers. The emerging consensus is that the transfer of efficacious interventions into routine practice is strongly linked to how well the interventions are based upon theory and take into account the contextual factors of the setting into which they are to be transferred. We set out to develop a conceptual framework to guide change and the implementation of best practice depression care in the primary care setting.Methods: we used a mixed method, observational approach to gather data about routine depression care in a range of primary care settings via: audit of electronic health records; observation of routine clinical care; and structured, facilitated whole of organisation meetings. Audit data were summarised using simple descriptive statistics. Observational data were collected using field notes. Organisational meetings were audio taped and transcribed. All the data sets were grouped, by organisation, and considered as a whole case. Normalisation Process Theory (NPT) was identified as an analytical theory to guide the conceptual framework development.Results: five privately owned primary care organisations (general practices) and one community health centre took part over the course of 18 months. We successfully developed a conceptual framework for implementing an effective model of depression care based on the four constructs of NPT: coherence, which proposes that depression work requires the conceptualisation of boundaries of who is depressed and who is not depressed and techniques for dealing with diffuseness; cognitive participation, which proposes that depression work requires engagement with a shared set of techniques that deal with depression as a health problem; collective action, which proposes that agreement is reached about how care is organised; and reflexive monitoring, which proposes that depression work requires agreement about how depression work will be monitored at the patient and practice level. We describe how these constructs can be used to guide the design and implementation of effective depression care in a way that can take account of contextual differences.Conclusions: ideas about what is required for an effective model and system of depression care in primary care need to be accompanied by theoretically informed frameworks that consider how these can be implemented. The conceptual framework we have presented can be used to guide organisational and system change to develop common language around each construct between policy makers, service users, professionals, and researchers. This shared understanding across groups is fundamental to the effective implementation of change in primary care for depressio

Target-D: a stratified individually randomized controlled trial of the diamond clinical prediction tool to triage and target treatment for depressive symptoms in general practice: study protocol for a randomized controlled trial.

BackgroundDepression is a highly prevalent and costly disorder. Effective treatments are available but are not always delivered to the right person at the right time, with both under- and over-treatment a problem. Up to half the patients presenting to general practice report symptoms of depression, but general practitioners have no systematic way of efficiently identifying level of need and allocating treatment accordingly. Therefore, our team developed a new clinical prediction tool (CPT) to assist with this task. The CPT predicts depressive symptom severity in three months' time and based on these scores classifies individuals into three groups (minimal/mild, moderate, severe), then provides a matched treatment recommendation. This study aims to test whether using the CPT reduces depressive symptoms at three months compared with usual care.MethodsThe Target-D study is an individually randomized controlled trial. Participants will be 1320 general practice patients with depressive symptoms who will be approached in the practice waiting room by a research assistant and invited to complete eligibility screening on an iPad. Eligible patients will provide informed consent and complete the CPT on a purpose-built website. A computer-generated allocation sequence stratified by practice and depressive symptom severity group, will randomly assign participants to intervention (treatment recommendation matched to predicted depressive symptom severity group) or comparison (usual care plus Target-D attention control) arms. Follow-up assessments will be completed online at three and 12 months. The primary outcome is depressive symptom severity at three months. Secondary outcomes include anxiety, mental health self-efficacy, quality of life, and cost-effectiveness. Intention-to-treat analyses will test for differences in outcome means between study arms overall and by depressive symptom severity group.DiscussionTo our knowledge, this is the first depressive symptom stratification tool designed for primary care which takes a prognosis-based approach to provide a tailored treatment recommendation. If shown to be effective, this tool could be used to assist general practitioners to implement stepped mental-healthcare models and contribute to a more efficient and effective mental health system.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR 12616000537459 ). Retrospectively registered on 27 April 2016. See Additional file 1 for trial registration data

The scratch test for identifying the lower liver edge is at least as accurate as percussion and is significantly more effective for young trainees-a randomised comparative trial

BACKGROUND: Clinical examination of the liver requires experience to achieve accuracy. The scratch test is a simple technique to identify the lower liver edge and enhance liver palpation, and may be easier for trainees

Integration, Coordination and Multidisciplinary Care: What can These Approaches Offer to Australian Primary Health Care?

Australia's population is ageing and the consequential burden of chronic disease increasingly challenges the health system. This has raised interest in, and awareness of, approaches built on multidisciplinary teams and integrated and coordinated care in managing the complex care needs of patient groups such as the chronically ill or frail aged. A systematic investigation of the literature relating to these approaches provided the opportunity to explore the meaning of these terms and their potential application and relevance to the Australian primary health care setting. Five systematic reviews of a sentinel condition and an exemplar approach to coordinated and multidisciplinary care were completed. Common learnings from the individual reviews were identified. The literature suggests that approaches encouraging a coordinated and multidisciplinary plan of care for individual patients and/or particular populations may improve a variety of outcomes. There are many methodological considerations in conducting reviews of complex interventions and in assessing their applicability to the Australian health system

Real-world outcomes associated with new cancer medicines approved by the Food and Drug Administration and European Medicines Agency: A retrospective cohort study.

PURPOSE: Real-World Data (RWD) studies are increasingly used to support regulatory approvals, reimbursement decisions, and changes in clinical practice for novel cancer drugs. However, few studies have systematically appraised their quality or compared outcomes to pivotal trials. METHODS: All RWD studies (2010-2019) for drugs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) from 2010 to 2015 for solid organ tumours in the non-curative setting were identified. Quality assessment was undertaken using the Newcastle Ottawa Scale. Survival differences between each RWD study and the pivotal trial were determined using a related sample Wilcoxon signed-rank test. RESULTS: 293 RWD studies for 45 of the 57 drug indications approved by the FDA/EMA were identified. The most common tumour types were prostate cancer (29%, n = 86) and melanoma (15%, n = 43). A quarter of the studies had industry funding. No high-quality studies were identified, and 78% were low quality. Comparative survival analysis between RWD and pivotal trials was possible for 224 studies (37 drug indications). Differences in median survival between the RWD studies and their corresponding trial ranged from -32 months to 21 months (IQR -4·2 months to 1·6 months). Low-quality studies were more likely to report superior survival outcomes (23%) compared to higher quality studies (8%) (p = 0.02). CONCLUSION: RWD study quality for novel cancer drugs is low and of insufficient rigour to inform reimbursement decisions and clinical practice. RWD studies seeking publication should provide a completed quality assessment tool on submission. Greater investment in properly designed RWD studies is required