Toward Shared Decision-Making in Degenerative Cervical Myelopathy: Protocol for a Mixed Methods Study

BACKGROUND Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this. OBJECTIVE The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes. METHODS Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders. RESULTS Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway. CONCLUSIONS This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/46809

Time is a terrible thing to waste!:Optimising Intraoperative Monitoring Practitioner time to maximise in-house IOM service provision and reduce spend on external IOM service provision

Intraoperative neurophysiological monitoring (IOM) during orthopaedic and neurosurgical operations informs surgeons about the integrity of patients’ central and peripheral nervous systems. It is provided by IOM practitioners (IOMPs), who are usually Neurophysiology healthcare scientists. Increasing awareness of the benefits for patient safety and surgical outcomes, along with post-COVID-19 service recovery, has resulted in a material increase in demand for IOM provision nationally, and particularly at Salford Royal Hospital (SRH), which is a regional specialist neurosciences centre.There is a shortage of IOMPs in the UK NHS. At SRH this is exacerbated by staff capacity shortage, requiring £202,800 of supplementary private provision in 2022. At SRH, IOMPs work in pairs. Our productive time is wasted by delays to surgical starts beyond our control and by paired-working for much of a surgery session. This Quality Improvement (QI) project set out to release productive time by: calling the second IOMP to theatre only shortly before start time, the other IOMP returning to the office during significant delays, releasing an IOMP from theatre when appropriate, and providing a laptop in theatre for other work. We tested and refined these change ideas over two plan-do-study-act improvement cycles. Compared with complete paired-working, we increased the time available for additional productive work and breaks from an average of 102 to 314 minutes per operating day, not quite achieving our project target of 360 minutes.The new ways of working we developed are a step towards ability (when staff capacity increases) to test supporting two (simultaneous) operations with three IOMPs (rather than two pairs of IOMPs). Having significantly improved use of staff time, we then also used our QI project data to make a successful business case for investment in two further IOMP posts with a predicted net saving of £20,000 per year along with other associated benefits

Study of Whole blood in Frontline Trauma (SWiFT): implementation study protocol

Introduction Uncontrolled bleeding is a major cause of death for patients with major trauma. Current transfusion practices vary, and there is uncertainty about the optimal strategy. Whole blood (WB) transfusion, which contains all components in one bag, is considered potentially advantageous, particularly for resuscitating patients with major bleeding in the prehospital setting. It could potentially improve survival, reduce donor risk and simplify the processes of delivering blood transfusions outside hospitals. However, the evidence supporting the effectiveness and safety of WB compared with the standard separate blood component therapy is limited. A multicentre randomised controlled trial will be conducted, alongside an implementation study, to assess the efficacy, cost-effectiveness and implementation of prehospital WB transfusion in the prehospital environment. The implementation study will focus on evaluating the acceptability and integration of the intervention into clinical settings and on addressing broader contextual factors that may influence its success or failure.Methods and analysis A type 1 effectiveness–implementation hybrid design will be employed. The implementation study will use qualitative methods, encompassing comprehensive interviews and focus groups with operational staff, patients and blood donor representatives. Staff will be purposefully selected to ensure a wide range of perspectives based on their professional background and involvement in the WB pathway. The study design includes: (1) initial assessment of current practice and processes in the WB pathway; (2) qualitative interviews with up to 40 operational staff and (3) five focus groups with staff and donor representatives. Data analysis will be guided by the theoretical lenses of the Normalisation Process Theory and the Theoretical Framework of Acceptability.Ethics and dissemination The study was prospectively registered and approved by the South Central—Oxford C Research Ethics Committee and the Health Research Authority and Health and Care Research Wales. The results will be published in peer-reviewed journals and provided to all relevant stakeholders.Trial registration number ISRCTN23657907; EudraCT: 2021-006876-18; IRAS Number: 300414; REC: 22/SC/0072

What Are the Effects of Different Abutment Morphologies on Peri-implant Hard and Soft Tissue Behavior? A Systematic Review and Meta-Analysis

To evaluate the effect of different abutment morphologies on peri-implant hard and soft tissue behavior

Supplemental material for The use of process mapping in healthcare quality improvement projects

<p>Supplemental material for The use of process mapping in healthcare quality improvement projects by Grazia Antonacci, Julie E Reed, Laura Lennox and James Barlow in Health Services Management Research</p

The Tyrosine Kinases Inhibitors (TKI) Staurosporine/Midostaurin Act as Cation Channel Inhibitors with Antiproliferative Effects in DIPG36 and DIPG50 cells

Ion channels and transporters are up-regulated in 33% and down-regulated in 48% of cases in paediatric tumour brain. No data are available on ion channels in Diffuse Intrinsic Pontine Glioma (DIPG) which is a rare, paediatric high-grade glioma of pons. Tyrosine kinases have been proposed as molecular targets. Staurosporine (STS) is a multitarget TKI with ion channel modulatory actions. Investigations are carried out on DIPG patient-derived H3.1K27M (DIPG36) and H3.3K27M (DIPG50) cells using staurosporine (STS) and its structural analogue midostaurin (MIDO). We investigated their antiproliferative effects using crystal violet staining and the 96 multi-well CCK-8 assay. On DIPG36, staurosporine 2.14 μM reduced cell survival by -68.94±0.82% and -100±0.40% after 48h and 72h of incubation time, respectively, while midostaurin 2.14 μM was more potent reducing cell survival by -100±18% at all incubation time. On DIPG50 cells, staurosporine 2.14 μM reduced cell survivals by -47±15.14% after 48h and -94±12.6% after 72h of incubation time, and midostaurin 2.14 μM reduced it by -63.85±14.56% after 48h and -97±12.9% after 72h of incubation time. These data were confirmed using clonogenic assay on DIPG36 cells, in which midostaurin 2.14 μM reduced the number of colonies from N=345 to N=0 after 72h of incubation time. We failed to collect data on clonogenic assay on the DIPG50 cells because they were not adherent. On concentration-response relationship investigations, both staurosporine and midostaurin (0.1μM-100μM), reduced cell proliferation in the sub-micromolar concentrations. The IC50 of STS in 96-wells CCK-8 assay after 48h of incubation time were: 5x10-10 M in DIPG50 and 8.9x10-8 in DIPG36 cells. Midostaurin showed an IC50 of 10-7 M and 4.739x10-7M respectively, after 48h and 72h of incubation times. The KATP channel blocker repaglinide(0.1μM-200μM) reduced cell proliferation with an IC50 of 80x10-6M on DIPG36 and 20x10-4 M on DIPG50 cells, respectively, after 48h of incubation time. It also caused a partial reduction of the colonies formation while MIDO fully reduced it. Patch-clamp investigations of the whole-cell inward and outwardcation currents showed that, the currents of DIPG36 cells (N cells=20) were acutely inhibited by -74%±56(+20mV Vm), -50%±43 (+40mV Vm) and -46%±30 (+60mV Vm) by STS 2.14μM vs controls. The STSresponsive currents were fully inhibited by the not selective K+ ion channel blockers TEA-BaCl2 (5 mM) and were sensitive to the KATP channel blocker glibenclamide (100 M). STS reduced the capsazepine-sensitive current recorded at +80mV Vm in the same cells. No data were collected with MIDO in this cell type because of seal instability. On DIPG50 cells (N cells=3), midostaurin 2.14 M at t=0 failed to inhibit the control currents at negative potentials while after 20 min of incubation time reduced currents by -22% (-60mV Vm) and -28% (-80mV Vm) vs control. At positive potentials, at t=0, MIDO reduced the control currents by -64% (+60mV Vm) with an increasing inhibitory effect of -97% after 20 min (+60mV Vm). These findings suggest that the unselective TKI STS and MIDO showed antiproliferative effects in either DIPG36 and DIPG50 cells and their action can be mediated by inhibition of cation channels

The deduced structure of the T cell receptor gamma locus in Canis lupus familiaris

Analyzing the recent high-quality genome sequence of the domestic dog (Canis lupus familiaris), we deduced for the first time in a mammalian species belonging to Carnivora order, the genomic structure and the putative origin of the TRG locus. New variable (TRGV), joining (TRGJ) and constant (TRGC) genes for a total of 40 are organized into eight cassettes aligned in tandem in the same transcriptional orientation, each containing the basic recombinational unit V-J-J-C, except for a J-J-C cassette, that lacks the V gene and occupies the 3' end of the locus. Amphiphysin (AMPH) and related to steroidogenic acute regulatory protein D3-N-terminal like (STARD3NL) genes flank, respectively, the 5' and 3' ends of the canine TRG locus that spans about 460kb. Moreover LINE1 elements, evenly distributed along the entire sequence, significantly (20.59%) contribute to the architecture of the dog TRG locus. Eight of the 16 TRGV genes are functional and belong to 4 different subgroups. Canine TRGJ genes are two for each cassette and only seven out of 16 are functional. The germline configuration and the exon-intron organization of the 8 TRGC genes was determined, six of them resulting functional. The dot plot similarity genomic comparison of human, mouse and dog TRG loci highlighted the occurrence of reiterated duplications of the cassettes during the dog TRG locus evolution. On the other hand the low ratio of functional genes to the total number of canine TRG genes (21/40), suggest that there is no correlation between the extensive duplications of the cassettes and a need for new functional genes. Furthermore the comparison revealed that the TRGC6, C7 and C8 genes are highly related across species suggesting these existed before the primate-rodent-canidae lineages diverged

Soft tissue dimensional changes after alveolar ridge preservation using different sealing materials: a systematic review and network meta-analysis.

BACKGROUND Alveolar ridge preservation (ARP) is a proactive treatment option aiming at attenuating post-extraction hard and soft tissue dimensional changes. A high number of different types of biomaterials have been utilized during ARP to seal the socket, but their effectiveness in terms of soft tissue outcomes has rarely been investigated and compared in the literature. OBJECTIVE To evaluate the efficacy of different types of membranes and graft materials in terms of soft tissue outcomes (keratinized tissue width changes, vertical buccal height, and horizontal changes) after ARP, and to assign relative rankings based on their performance. MATERIALS AND METHODS The manuscript represents the proceedings of a consensus conference of the Italian Society of Osseointegration (IAO). PUBMED (Medline), SCOPUS, Embase, and Cochrane Oral Health's Information Specialist were utilized to conduct the search up to 06 April 2021. English language restrictions were placed and no limitations were set on publication date. Randomized controlled trials that report ARP procedures using different sealing materials, assessing soft tissue as a primary or secondary outcome, with at least 6-week follow-up were included. Network meta-analysis (NMA) was performed using mean, standard deviation, sample size, bias, and follow-up duration for all included studies. Network geometry, contribution plots, inconsistency plots, predictive and confidence interval plots, SUCRA (surface under the cumulative ranking curve) rankings, and multidimensional (MDS) ranking plots were constructed. RESULTS A total of 11 studies were included for NMA. Overall, the level of bias for included studies was moderate. Crosslinked collagen membranes (SUCRA rank 81.8%) performed best in vertical buccal height (VBH), autogenous soft tissue grafts (SUCRA rank 89.1%) in horizontal width change (HWch), and control (SUCRA rank 85.8%) in keratinized mucosa thickness (KMT). CONCLUSIONS NMA confirmed that the use of crosslinked collagen membranes and autogenous soft tissue grafts represented the best choices for sealing sockets during ARP in terms of minimizing post-extraction soft tissue dimensional shrinkage. CLINICAL RELEVANCE Grafting materials demonstrated statistically significantly better performances in terms of soft tissue thickness and vertical buccal height changes, when covered with crosslinked collagen membranes. Instead, soft tissue grafts performed better in horizontal width changes. Non-crosslinked membranes and other materials or combinations presented slightly inferior outcomes