Understanding the factors that affect retention within the mental health nursing workforce: a systematic review and thematic synthesis.

There are over 41 000 vacant nursing posts across the United Kingdom's National Health Service (NHS), with more people leaving the profession that joining it. Despite mental health being acknowledged as a priority area, some of the most significant staff shortages are occurring within mental health services. Urgent action is needed to retain the mental health nurses (MHNs) currently in post to ensure the profession is fit for purpose and aid future recruitment efforts. This review set out to identify the individual factors that affect the retention of MHNs. A systematic search of six databases was conducted (CINAHL, PsychINFO, MEDLINE, Web of Science (Core collection), EMBASE and the British Nursing Index). Studies were systematically screened for inclusion based on predetermined eligibility criteria. The studies were quality assessed using the Mixed Methods Appraisal Tool (MMAT). Findings were synthesized using Thematic Synthesis. A total of 23 studies consisting of a range of study designs were included in the review. Four key themes emerged from the synthesis: Individual characteristics, Working within mental health services, Training and skills and Work environment. The findings from this review suggest that MHNs encounter some factors unique to working in mental health services, which suggests that retention strategies should be specific to each nursing speciality. Beyond nursing speciality, the factors identified vary between clinical settings in mental health due to the differences in work environments and services they provide. Future studies should now set out to explore what factors exist in which clinical settings to inform better tailored retention strategies to generate better outcomes.

Eye Movement Desensitization and Reprocessing (EMDR) for the treatment of psychosis: a systematic review.

Background: Psychosis is a public health concern. There is increasing evidence suggesting trauma can play a pivotal role in the development and maintenance of psychosis. Eye Movement Desensitization and Reprocessing (EMDR) is an effective treatment for trauma and could be a vital addition to the treatment of psychosis. Objective: To explore the evidence for EMDR as a treatment for psychosis, focussing on the safety, effectiveness and acceptability of this intervention for this population. Methods: Four databases (Cochrane, EMBASE, MEDLINE PsychINFO), and the Francine Shapiro Library were systematically searched, along with grey literature and reference lists of relevant papers. No date limits were applied as this is an area of emerging evidence. Studies were screened for eligibility based on inclusion and exclusion criteria. The included studies were quality assessed and data was extracted from the individual studies, and synthesized using a narrative synthesis approach. Results: Six studies met the inclusion criteria (1 RCT, 2 Pilot studies, 2 Case series and 1 Case report). Across the studies EMDR was associated with reductions in delusional and negative symptoms, mental health service and medication use. Evidence for reductions in auditory hallucinations and paranoid thinking was mixed. No adverse events were reported, although initial increases in psychotic symptoms were observed in two studies. Average dropout rates across the studies were comparable to other trauma-focused treatments for PTSD. The acceptability of EMDR was not adequately measured or reported. Conclusion: EMDR appears a safe and feasible intervention for people with psychosis. The evidence is currently insufficient to determine the effectiveness and acceptability of the intervention for this population. Larger confirmative trials are required to form more robust conclusions.

Antecedentes: La psicosis es un problema de salud pública. Cada vez hay más evidencia sugiriendo que el trauma puede desempeñar un papel fundamental en el desarrollo y mantenimiento de la psicosis. La desensibilización y reprocesamiento por movimiento ocular (EMDR en su sigla en inglés) es un tratamiento efectivo para el trauma y podría ser una adición vital al tratamiento de la psicosis.Objetivo: explorar el evidencia de EMDR como tratamiento para la psicosis, enfocándose en la seguridad, efectividad y aceptabilidad de esta intervención para esta población.Métodos: Se realizaron búsquedas sistemáticas en cuatro bases de datos (Cochrane, EMBASE, MEDLINE PsychINFO) y la Biblioteca Francine Shapiro, junto con literatura gris y listas de referencias de artículos relevantes. No se aplicaron límites de fecha ya que esta es un área con evidencia emergente. Los estudios se seleccionaron determinando su elegibilidad según los criterios de inclusión y exclusión. Los estudios incluidos fueron evaluados de acuerdo a su calidad y los datos se extrajeron de los estudios individuales y se sintetizaron utilizando un enfoque de síntesis narrativa.Resultados: Seis estudios cumplieron los criterios de inclusión (1 ensayo controlado aleatorio, 2 estudios piloto, 2 series de casos y 1 informe de caso). En todos los estudios, EMDR se asoció con reducciones en los síntomas delirantes y negativos, el servicio de salud mental y el uso de medicamentos. La evidencia de reducciones en las alucinaciones auditivas y el pensamiento paranoico fue mixta. No se informaron eventos adversos, aunque se observaron aumentos iniciales en los síntomas psicóticos en dos estudios. Las tasas promedio de abandono en los estudios fueron comparables a otros tratamientos centrados en el trauma para el TEPT. La aceptabilidad de EMDR no se midió ni informó adecuadamente.Conclusión: EMDR parece una intervención segura y factible para personas con psicosis. La evidencia es actualmente insuficiente para determinar la efectividad y la aceptabilidad de la intervención para esta población. Se requieren ensayos confirmatorios más grandes para formar conclusiones más sólidas.

Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin.

BACKGROUND: Epidemiological studies suggest that metformin may reduce the incidence of cancer in patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing this drug are underway. Transcriptomic profiling of tumour samples is an excellent tool to understand drug bioactivity, identify candidate biomarkers and assess for mechanisms of resistance to therapy. METHODS: Thirty-six patients with untreated primary breast cancer were recruited to a window study and transcriptomic profiling of tumour samples carried out before and after metformin treatment. RESULTS: Multiple genes that regulate fatty acid oxidation were upregulated at the transcriptomic level and there was a differential change in expression between two previously identified cohorts of patients with distinct metabolic responses. Increase in expression of a mitochondrial fatty oxidation gene composite signature correlated with change in a proliferation gene signature. In vitro assays showed that, in contrast to previous studies in models of normal cells, metformin reduces fatty acid oxidation with a subsequent accumulation of intracellular triglyceride, independent of AMPK activation. CONCLUSIONS: We propose that metformin at clinical doses targets fatty acid oxidation in cancer cells with implications for patient selection and drug combinations. CLINICAL TRIAL REGISTRATION: NCT01266486.

Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer.

Late-phase clinical trials investigating metformin as a cancer therapy are underway. However, there remains controversy as to the mode of action of metformin in tumors at clinical doses. We conducted a clinical study integrating measurement of markers of systemic metabolism, dynamic FDG-PET-CT, transcriptomics, and metabolomics at paired time points to profile the bioactivity of metformin in primary breast cancer. We show metformin reduces the levels of mitochondrial metabolites, activates multiple mitochondrial metabolic pathways, and increases 18-FDG flux in tumors. Two tumor groups are identified with distinct metabolic responses, an OXPHOS transcriptional response (OTR) group for which there is an increase in OXPHOS gene transcription and an FDG response group with increased 18-FDG uptake. Increase in proliferation, as measured by a validated proliferation signature, suggested that patients in the OTR group were resistant to metformin treatment. We conclude that mitochondrial response to metformin in primary breast cancer may define anti-tumor effect.

Radiogenomics Monitoring in Breast Cancer Identifies Metabolism and Immune Checkpoints as Early Actionable Mechanisms of Resistance to Anti-angiogenic Treatment.

Anti-VEGF antibody bevacizumab has prolonged progression-free survival in several cancer types, however acquired resistance is common. Adaption has been observed pre-clinically, but no human study has shown timing and genes involved, enabling formulation of new clinical paradigms. In a window-of-opportunity study in 35 ductal breast cancer patients for 2weeks prior to neoadjuvant chemotherapy, we monitored bevacizumab response by Dynamic Contrast-Enhanced Magnetic Resonance [DCE-MRI], transcriptomic and pathology. Initial treatment response showed significant overall decrease in DCE-MRI median K(trans), angiogenic factors such ESM1 and FLT1, and proliferation. However, it also revealed great heterogeneity, spanning from downregulation of blood vessel density and central necrosis to continued growth with new vasculature. Crucially, significantly upregulated pathways leading to resistance included glycolysis and pH adaptation, PI3K-Akt and immune checkpoint signaling, for which inhibitors exist, making a strong case to investigate such combinations. These findings support that anti-angiogenesis trials should incorporate initial enrichment of patients with high K(trans), and a range of targeted therapeutic options to meet potential early resistance pathways. Multi-arm adaptive trials are ongoing using molecular markers for targeted agents, but our results suggest this needs to be further modified by much earlier adaptation when using drugs affecting the tumor microenvironment.

Slip imaging: reducing ambiguity in breast lesion assessment.

Ultrasound elasticity imaging (elastography) is gaining popularity as an adjunct to B-mode ultrasound for breast cancer diagnosis. Cancerous masses are usually stiffer than normal tissue, hence, using elasticity imaging should lead to better differentiation between benign and malignant masses than using B-mode alone. Clinicians assess the mobility of masses on palpation; cancers usually being less mobile. We introduce a method to estimate mobility, called slip imaging and combine it with conventional B-mode and elasticity data. In the reported evaluation on 70 women recalled to a breast assessment clinic, images were scored by three breast radiologists independently. Diagnostic accuracy increased from 75.7% with B-mode alone, to 78.1% when including elasticity imaging, to 80.0% when further including slip imaging. Specificity increased (74.6%:75.4%:82.5% respectively), with an apparent trade-off in sensitivity (77.1%:81.3%:77.1%). We conclude that Slip imaging is potentially a useful adjunct to B-mode and elasticity imaging and should undergo further research and development.

Radiologic characteristics and management of screen-detected metastatic carcinoid tumor of the breast: a case report.

Carcinoid tumors are known to metastasize to the breast, but their appearance can mimic a primary breast carcinoma, making biopsy essential in order to give the correct preoperative diagnosis. It has been suggested that core biopsy might precipitate a carcinoid crisis and should be avoided. We describe a case of screen-detected carcinoid tumor metastasis in the breast safely diagnosed by core biopsy and present the imaging findings, including magnetic resonance imaging and elastography. This case illustrates the importance of preoperative histologic diagnosis in enabling the appropriate surgical or medical management of these patients. Review of the literature also supports the policy that biopsy of nonhormonally active tumors may be safely performed.