Older adult experience of care and staffing on hospital and community wards: a cross-sectional study.

BACKGROUND: Recent major concerns about the quality of healthcare delivered to older adults have been linked to inadequate staffing and a lack of patient-centred care. Patient experience is a key component of quality care - yet there has been little research on whether and how staffing levels and staffing types affect satisfaction amongst older adult hospital inpatients. This study aimed to evaluate the association between registered nurse and healthcare assistant staffing levels and satisfaction with care amongst older adult hospital inpatients, and to test whether any positive effect of higher staffing levels is mediated by staff feeling they have more time to care for patients. METHODS: Survey data from 4928 inpatients aged 65 years and older and 2237 medical and nursing staff from 123 acute and community medical wards in England, United Kingdom (UK) was collected through the Royal College of Psychiatrist's Elder Care Quality Mark. The cross-sectional association between staffing ratios and older adult patient satisfaction, and mediation by staff perceived time to care, was evaluated using multi-level modelling, adjusted for ward type and with a random effect for ward identity. RESULTS: Higher numbers of patients per healthcare assistant were associated with poorer patient satisfaction (adjusted ß = - 0.32, 95% CI - 0.55 to 0.10, p < 0.01), and this was found to be partially mediated by all ward staff reporting less time to care for patients (adjusted ß = - 0.10, bias-corrected 95% CI - 1.16 to - 0.02). By contrast, in both unadjusted and adjusted models, the number of patients per registered nurse was not associated with patient satisfaction. CONCLUSIONS: Older adult hospital patients may particularly value the type of care provided by healthcare assistants, such as basic personal care and supportive communication. Additionally, higher availability of healthcare assistants may contribute to all ward staff feeling more able to spend time with patients. However, high availability of registered nurses has been shown in other research to be vital for ensuring quality and safety of patient care. Future research should seek to identify the ideal balance of registered nurses and healthcare assistants for optimising a range of outcomes amongst older adult patients.

Management of Antipsychotic-Related Sexual Dysfunction: Systematic Review.

INTRODUCTION: Sexual dysfunction is one of the most frequently occurring side-effects of antipsychotic medication, impacting both quality of life and adherence to treatment. Despite this, limited evidence-based guidance on treatment options is available. AIM: To synthesize and analyze the evidence on management of antipsychotic-related sexual dysfunction, specifically taking note of the more recently developed antipsychotics that have been incorporated in studies over the past decade. METHODS: EMBASE, Medline, and PsychINFO databases were searched using search terms related to sexual or erectile dysfunction, treatments, and antipsychotics. 2 reviewers independently assessed papers for the inclusion criteria for randomized controlled trials (RCTs) of treatments for antipsychotic-related sexual dysfunction, including adjunctive medications and a switch of antipsychotic. Studies were excluded if participants did not have recorded sexual dysfunction at baseline. MAIN OUTCOME MEASURE: The primary outcome measure was any change in sexual function. RESULTS: 6 RCTs were identified, all of which investigated different interventions; hence, it was not possible to synthesize the data quantitatively. Results were overall limited by small sample size, brief treatment duration, and the potential for bias. 2 studies, one assessing adjunctive sildenafil and the other adjunctive aripiprazole, reported a reduction in antipsychotic-related sexual dysfunction. CLINICAL IMPLICATIONS: Due to the lack of high-quality data, no clinical recommendations can be made. STRENGTHS & LIMITATIONS: A comprehensive search strategy was used with an extensive number of relevant search terms including "erectile dysfunction" and newer antipsychotics such as aripiprazole. In light of evidence that prolactin is not a reliable marker for sexual dysfunction, this review focused its inclusion criteria on participants presenting with sexual dysfunction rather than with hyperprolactinemia, which should give its recommendations more validity. However, only 6 RCTs were identified, and results were overall limited by small sample size, brief treatment duration, and the potential for bias. CONCLUSION: Our findings highlight the paucity of high-quality research in this area, and conjecture that it may be difficult to recruit participants with antipsychotic-related sexual dysfunction. Future research may be necessary to unlock and address these difficulties. Furthermore, fully powered future studies should focus on the management of sexual dysfunction rather than the surrogate marker of hyperprolactinemia. Allen K, Baban A, Munjiza J, et al. Management of Antipsychotic-Related Sexual Dysfunction: Systematic Review. J Sex Med 2019;16:1978-1987.

An evaluation of the role of the Assistant Practitioner in critical care.

AIMS: To determine whether the Assistant Practitioner role has fulfilled the expectations of the original implementation plan which was to introduce this new role into the Critical Care Department of a large NHS Trust. This service evaluation will examine the introduction of Assistant Practitioners by establishing the perceptions of this new role and the impact of this change from key groups of staff, within the Critical Care Department. BACKGROUND: The Department of Health (DoH) recognized the potential of assistant practitioners in a range of care settings. As a participant in this DoH initiative the Trust introduced the role into a number of areas. This service evaluation was undertaken following the training of small cohorts of Assistant Practitioners within the Critical Care Department. METHODS: A literature review was conducted initially searching the key words assistant practitioner, role development and critical care. A service evaluation was undertaken using questionnaires and semi-structured interviews for data collection. The data was analysed using a thematic approach. RESULTS: The responses from the various staff groups revealed a number of key themes including patient care skills, role, preparation and training, drug administration and patient allocation. CONCLUSIONS: Overall, the data suggests that the Assistant Practitioner role has fulfilled the expectations of the original implementation plan as they deliver care to patients in the clinical environment as required. However, the data also reveals that there are still issues to be resolved. RELEVANCE TO CLINICAL PRACTICE: The study has shown the Assistant Practitioners to be excellent in delivering patient care; however, there are limitations due to the complexity of the patient group in critical care areas.

Syntheses of novel azasugar-containing mimics of heparan sulfate fragments as potential heparanase inhibitors.

A series of eight novel, highly modified mono-, di- and trisaccharide derivatives, each containing an iminoalditol moiety, has been synthesized in the quest for potential heparanase inhibitors.

Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells.

Immunodeficient mice are increasingly used to assay human hematopoietic repopulating cells as well as leukemia-initiating cells. One method commonly used to isolate these rare cells is to sort cells stained with fluorochrome-conjugated antibodies into fractions, then transplant the different fractions into immunodeficient mice to test their repopulating ability. The antibodies are generally treated as being neutral in terms of their effects on the experiment. Human repopulating cells are thought to express CD34 and lack CD38. Here we present evidence that anti-CD38 antibodies have a profound inhibitory effect on engraftment of cord blood and leukemia cells. We show that this effect is Fc-mediated and can be overcome by treating mice with immunosuppressive antibodies. When this inhibitory effect is prevented, we demonstrate that the CD34(+)CD38(+) fraction of certain acute myeloid leukemia samples contains all, or at least most, leukemia-initiating cell capacity. This study highlights the potential pitfall of antibody-mediated clearance of repopulating cells and is important for any groups working with this model. More importantly, the work suggests that there is greater variation in the phenotypes of leukemia-initiating cells than previously suggested.

Stem/progenitor cell-like properties of desmoglein 3dim cells in primary and immortalized keratinocyte lines.

We showed previously that primary keratinocytes selected for low desmoglein 3 (Dsg3) expression levels exhibited increased colony-forming efficiency and heightened proliferative potential relative to cells with higher Dsg3 expression levels, characteristics consistent with a more "stem/progenitor cell-like" phenotype. Here, we have confirmed that Dsg3(dim) cells derived from cultured primary human adult keratinocytes have comparability with alpha(6)(bri)/CD71(dim) stem cells in terms of colony-forming efficiency. Moreover, these Dsg3(dim) cells exhibit increased reconstituting ability in in vitro organotypic culture on de-epidermalized dermis (DED); they are small, actively cycling cells, and they express elevated levels of various p63 isoforms. In parallel, using the two immortalized keratinocyte cell lines HaCaT and NTERT, we obtained essentially similar though occasionally different findings. Thus, reduced colony-forming efficiency by Dsg3(bri) cells consistently was observed in both cell lines even though the cell cycle profile and levels of p63 isoforms in the bri and dim populations differed between these two cell lines. Dsg3(dim) cells from both immortalized lines produced thicker and better ordered hierarchical structural organization of reconstituted epidermis relative to Dsg3(bri) and sorted control cells. Dsg3(dim) HaCaT cells also show sebocyte-like differentiation in the basal compartment of skin reconstituted after a 4-week organotypic culture. No differences in percentages of side population cells (also a putative marker of stem cells) were detected between Dsg3(dim) and Dsg3(bri) populations. Taken together our data indicate that Dsg3(dim) populations from primary human adult keratinocytes and long-term established keratinocyte lines possess certain stem/progenitor cell-like properties, although the side population characteristic is not one of these features. Disclosure of potential conflicts of interest is found at the end of this article.

Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples.

Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme that is responsible for the oxidation of intracellular aldehydes. Elevated levels of ALDH have been demonstrated in murine and human progenitor cells compared with other hematopoietic cells, and this is thought to be important in chemoresistance. A method for the assessment of ALDH activity in viable cells recently has been developed and made commercially available in a kit format. In this study, we confirmed the use of the ALDH substrate kit to identify cord blood stem/progenitor cells. Via multicolor flow cytometry of cord blood ALDH+ cells, we have expanded on their phenotypic analysis. We then assessed the incidence, morphology, phenotype, and nonobese diabetic/ severe combined immunodeficiency engraftment ability of ALDH+ cells from acute myeloid leukemia (AML) samples. AML samples had no ALDH+ cells at all, an extremely rare nonmalignant stem/progenitor cell population, or a less rare, leukemic stem cell population. Hence, in addition to identifying nonmalignant stem cells within some AML samples, a high ALDH activity also identifies some patients' CD34+/ CD38- leukemic stem cells. The incidence of normal or leukemic stem cells with an extremely high ALDH activity may have important implications for resistance to chemotherapy. Identification and isolation of leukemic cells on the basis of ALDH activity provides a tool for their isolation and further analysis.

Down-regulation of human topoisomerase IIalpha correlates with altered expression of transcriptional regulators NF-YA and Sp1.

Topoisomerase IIalpha (Topo IIalpha) is an essential nuclear enzyme with a role in the maintenance of DNA topology. Topo IIalpha is a target for several anticancer drugs and the levels of activity of this enzyme have been implicated in the development of drug resistance. Our objective was to identify regulatory transcription factors involved in drug-induced down-regulation of Topo IIalpha. A breast cancer cell line was subjected to a pulsed exposure of doxorubicin and resistant clones propagated. Whole-cell extracts were studied by immunoblotting and RT-PCR for drug-induced changes in the amounts Topo IIalpha, Sp1, Sp3, NF-Y and MDR1. Topo IIalpha levels were reduced in six out of eight cell lines. Of these, three showed concomitant changes in the expression of Sp1 and NF-YA. Thus, we provide the first evidence for roles of Sp1 and NF-Y in bringing about the drug-induced down-regulation of Topo IIalpha gene expression.

Synthetic ceramides induce growth arrest or apoptosis by altering cellular redox status.

Reactive oxygen species (ROS) and ceramide are each partly responsible for the signal transduction of a variety of extracellular agents. Furthermore, the application of synthetic, short-chain ceramides mimics the cellular responses to these extracellular agents. However, the significance of ROS involvement in ceramide signaling pathways is poorly understood. Here we describe that the cellular responses to C2-/C6-ceramide of growth arrest in U937 monocytes and apoptosis in Jurkat T-cells are preceded by a rise in mitochondrial peroxide production. In Jurkat T-cells, this is associated with a large time- and dose-dependent loss of cellular glutathione. However, in U937 monocytes, glutathione loss is transient. Differences in the magnitude and kinetics of this alteration in cellular redox state associate with discrete outcomes, namely growth arrest or apoptosis.