Centredness in health care: A systematic overview of reviews

IntroductionThe introduction of effective, evidence‐based approaches to centredness in health care is hindered by the fact that research results are not easily accessible. This is partly due to the large volume of publications available and because the field is closely linked to and in some ways encompasses adjoining fields of research, for example, shared decision making and narrative medicine. In an attempt to survey the field of centredness in health care, a systematic overview of reviews was conducted with the purpose of illuminating how centredness in health care is presented in current reviews.MethodsSearches for relevant reviews were conducted in the databases PubMed, Scopus, Cinahl, PsychINFO, Web of Science and EMBASE using terms connected to centredness in health care. Filters specific to review studies of all types and for inclusion of only English language results as well as a time frame of January 2017–December 2018, were applied.ResultsThe search strategy identified 3697 unique reviews, of which 31 were included in the study. The synthesis of the results from the 31 reviews identified three interrelated main themes: Attributes of centredness (what centredness is), Translation from theory into practice (how centredness is done) and Evaluation of effects (possible ways of measuring effects of centredness). Three main attributes of centeredness found were: being unique, being heard and shared responsibility. Aspects involved in translating theory into practice were sufficient prerequisites, strategies for action and tools used in safeguarding practice. Further, a variety and breadth of measures of effects were found in the included reviews.ConclusionsOur synthesis demonstrates that current synthesized research literature on centredness in health care is broad, as it focuses both on explorations of the conceptual basis and the practice, as well as measures of effects. This study provides an understanding of the commonalities identified in the reviews on centredness in healthcare overall, ranging from theory to practice and from practice to evaluation.Patient or Public ContributionPatient representatives were involved during the initiation of the project and in decisions about its focus, although no patient or public representatives made direct contributions to the review process.     

Outbreak of Salmonella Newport linked to imported frozen cooked crayfish in dill brine,Sweden, July to November 2019

In autumn 2019, the Public Health Agency of Sweden identified a cluster of Salmonella Newport cases by whole genome sequencing (WGS). Cases’ distribution in place and time indicated a nation-wide ongoing outbreak. An investigation was initiated to identify the source and prevent further cases. We conducted a case–case study based on notified salmonellosis cases and a Salmonella trawling questionnaire, comparing 20 outbreak cases and 139 control cases. Food exposures were compared by adjusted odds ratios (aOR) with 95% confidence interval (CI) using logistic regression. Implicated foods were sampled. Outbreak cases were more likely to have consumed crayfish (aOR = 26; 95% CI: 6.3–105). One specific brand of imported frozen, pre-cooked whole crayfish in dill brine was identified as the source. Salmonella Newport was later detected in different batches from retail and in one sample from border control. Isolates from food samples clustered with the human outbreak strain by WGS. Although the retailer made a complete recall, two more cases were identified long afterwards. This investigation demonstrated the successful use of a case–case study and targeted microbiological testing to identify the source. The immediate action taken by the retailer was important to confirm the source and stop the outbreak.     

Mechanical coupling of supracellular stress amplification and tissue fluidization during exit from quiescence

Cellular quiescence is a state of reversible cell cycle arrest that is associated with tissue dormancy. Timely regulated entry into and exit from quiescence is important for processes such as tissue homeostasis, tissue repair, stem cell maintenance, developmental processes, and immunity. However, little is known about processes that control the mechanical adaption to cell behavior changes during the transition from quiescence to proliferation. Here, we show that quiescent human keratinocyte monolayers sustain an actinomyosin-based system that facilitates global cell sheet displacements upon serum-stimulated exit from quiescence. Mechanistically, exposure of quiescent cells to serum-borne mitogens leads to rapid amplification of preexisting contractile sites, leading to a burst in monolayer tension that subsequently drives large-scale displacements of otherwise motility-restricted monolayers. The stress level after quiescence exit correlates with the level of quiescence depth at the time of activation, and a critical stress magnitude must be reached to overcome the cell sheet displacement barrier. The study shows that static quiescent cell monolayers are mechanically poised for motility, and it identifies global stress amplification as a mechanism for overcoming motility restrictions in confined confluent cell monolayers.

Quiescence refers to a state of cell cycle arrest in which cells are retained in a standby mode, ready to re-enter the cell cycle upon activation by a given physiological stimuli. The pool of quiescent cells in the human body is typically represented by tissue-specific stem and progenitor cells, naive immune cells, fibroblasts, and epithelial cells (1, 2). In addition, certain cancer cells have the ability to evade cancer therapy by entering a dormant quiescence-like state (1, 2). Accordingly, careful regulation of entry into and exit out of quiescence is important for several physiological processes such as tissue homeostasis and repair, stem cell maintenance, immunity, reproduction, and development (1, 2).During homeostasis, the balance between quiescent and proliferating cells is controlled by constituents of the microenvironment such as soluble factors, extracellular matrix components, blood vessels, and neighboring cells. On the other hand, during episodes that require extensive tissue renewal and remodeling, for example after injury, coordinated stimulation of quiescent cells into proliferation is facilitated by increased exposure to blood-borne and cell-secreted mitogens through local inflammatory responses such as increased blood flow, increased vascular permeability (vasodilation), and immune cell recruitment (3, 4). Accordingly, a commonly used methodology for studies of quiescence in cultured mammalian cells involves consecutive treatments with serum-free and serum-containing growth medium (1).Quiescent cells are required to maintain a high level of preparedness in order to facilitate rapid activation of specialized cell functions once cell division is stimulated. In agreement with this, quiescent stem cells and naive immune cells have been shown to possess multiple epigenetic and posttranslation mechanisms that facilitate the rapid expression of linage-specific genes following stimulation of quiescence exit (2, 5–14). However, little is known about mechanical forces that facilitate adaptation to cell cycle–activated behaviors.Quiescence exit is frequently associated with activation of cell motility. For example, quiescent stem and naive immune cells migrate out of their niches in response to cell cycle activation in order to support tissue homeostasis, repopulate injured tissue, or to perform immune surveillance at distal locations (15–18). In addition, reawakening of dormant quiescent cancer cells can cause tumor relapse and formation of metastases years after remission (19). In multilayered epithelial tissue, like the skin, exit from quiescence during homeostasis is associated with lateral migration to suprabasal regions, while skin injury evokes massive reawakening of basally localized keratinocytes concomitant with activation of cell sheet displacement by collective migration to restore damaged epidermal surfaces (20–23). The strong correlation between quiescence exit and cell migration in multiple physiological settings suggests the existence of mechanisms that link quiescence exit to activation of cell motility.The dynamics of epithelial collectives is largely regulated by mechanical forces generated through cell–cell interactions as well as interactions between cells and the extracellular environment (24). Key components involved in controlling these forces are cytoskeletal components such as actinomyosin and adhesion complexes such as adherent junctions and focal adhesion complexes (25). Additional factors that have been reported to influence the dynamic behavior of epithelial monolayers include the presence of epithelial edges (24, 26), mechanical stretching or compression (27, 28), expression of the endosomal Rab5 protein (29), exposure of cells to growth factors (30–32), local changes in cell shape (33), and the ability of cells to undergo neighbor exchange (34, 35). In addition, recent studies have also identified a functional link between cell cycle progression and force fluctuation leading to dynamic behavior of cultured epithelial monolayers (36, 37).In this study, we have investigated a mechanical link between quiescence exit and activation of large-scale cell sheet displacements. Using traction force microscopy (TFM), we found that confluent cell monolayers install an actinomyosin-based system during quiescence that produces a coordinated burst of contractile forces and intercellular tension across the epithelial monolayer immediately following exposure to serum-borne mitogens. By combining experiments and theoretical modeling, we show that the amplified forces are essential for driving coordinated cell sheet displacements within otherwise motility-restricted cell monolayers. Furthermore, the magnitude of mechanical forces created during quiescence exit and the extent of cell sheet displacement correlate with quiescence depth. Our study provides evidence that quiescent keratinocyte monolayers possess mechanical preparedness for motility and establish monolayer stress amplification as a strategy for overcoming the motility barrier in confined cell sheets.     

A “leap in the dark?” Lessons for the United Kingdom from past extensions of bar opening hours

The Licensing Act of 2003 for England and Wales paves the way for 24-hour opening of licensed premises. Senior members of the United Kingdom Government have claimed that the pressure of rigid closing times contributes to the rising problem of binge-drinking and associated harm in the UK. Removing set opening times it is hoped will reduce these problems. These plans have been widely criticised. Moreover, international evidence suggests this may not be the case. Studies from Europe, Iceland, Australia and North America have indicated that extending trading hours may not only fail to reduce alcohol-related problems but might increase them. Evidence exists of licensing liberalisation being followed by rises in alcohol consumption, violent crime, traffic accidents, illicit drug use as well as extra public health and tourism costs.     

Design and Evaluation of Orally Dispersible Tablets Containing Amlodipine Inclusion Complexes in Hydroxypropyl-β-cyclodextrin and Methyl-β-cyclodextrin

The development of new orally dispersible tablets containing amlodipine (AML) inclusion complexes in hydroxypropyl-β-cyclodextrin (HP-β-CD) and in methyl-β-cyclodextrin (Me-β-CD) was studied. The methods of obtaining amlodipine and the physical and chemical properties of the inclusion complexes using the two cyclodextrins was investigated separately. Solid inclusion complexes were obtained by three methods: kneading, coprecipitation, and lyophilization, at a molar ratio of 1:1. For comparison, a physical mixture in the same molar ratio was prepared. The aim of the complexation process was to improve the drug solubility. As the lyophilization method leads to a complete inclusion of the drug in the guest molecule cavity, for both used cyclodextrins, these types of compounds were selected as active ingredients for the design of orally dispersible tablets. Subsequently, the formulation of the orodispersible tablets containing AML-HP-β-CD and AML-Me-β-CD inclusion complexes and quality parameters of the final formulation were evaluated. The results prove that F1 and F4 formulations, based on silicified microcrystalline cellulose, which contains insignificant proportions of very small or very large particles, had the lowest moisture degree (3.52% for F1 and 4.03% for F4). All of these demonstrate their porous structure, which led to good flowability and compressibility performances. F1 and F4 formulations were found to be better to manufacture orally dispersible tablets.     

Antiviral flavans from the leaves of Pithecellobium clypearia

Two new antiviral flavan derivatives were isolated from a methanol extract of leaves of Pithecellobium clypearia as guided by antiviral assays. The structures were characterized, by spectroscopic analyses, as 7-O-galloyltricetifavan (1) and 7,4'-di-O-galloyltricetifavan (2). Cytopathic effect (CPE) reduction assay showed that both compounds 1 and 2 possess antiviral activity against respiratory syncytial virus (RSV), with 50% inhibition concentration (IC(50)) values of 5 and 10 microg/mL, respectively; influenza A (H1N1) virus, with IC(50) values of 15.7 and 30 microg/mL; Coxsackie B3 (Cox B3) virus, with IC(50) values of 12.5 and 25 microg/mL, respectively; and Herpes simplex virus type 1 (HSV-1) with IC(50) values of 30 and 20 microg/mL, respectively. Cytotoxicity evaluation using the MTT assay showed that both compounds 1 and 2 were also moderately toxic to several cultured cell lines.