Characterization of 25 monoclonal antibodies to factor VIII-von Willebrand factor: relationship between ristocetin-induced platelet aggregation and platelet adherence to subendothelium

We have studied the role of factor VIII-von Willebrand factor (FVIII- vWF) in both platelet adherence to subendothelium and ristocetin- induced platelet aggregation using monoclonal antibodies to human FVIII- vWF. Twenty-five monoclonal antibodies were obtained, two of which were directed to the factor VIII moiety of FVIII-vWF; one of these two completely inhibited the procoagulant activity (FVIII:C). The remaining 23 monoclonal antibodies were directed to the von Willebrand factor moiety of FVIII-vWF. The ability of the latter monoclonal antibodies to inhibit platelet adherence to arterial subendothelium was investigated with a perfusion model. According to the number of platelets adhering to the subendothelium, three groups of monoclonal antibodies could be discerned: (A) antibodies not affecting platelet adherence; (B) antibodies that inhibited platelet adherence to the level as observed when von Willebrand's disease plasma was tested; and (C) antibodies that completely inhibited both platelet adherence to subendothelium and ristocetin-induced platelet aggregation. The two antibodies present in group C competed for the same or closely related epitope(s) present on FVIII-vWF. These results demonstrate that a domain is present on the FVIII-vWF molecule that is associated both with ristocetin-induced aggregation and with the ability of FVIII-vWF to support platelet adherence to the subendothelium. Based on these observations, it is concluded that ristocetin-induced binding of FVIII-vWF to platelets reflects, at least in part, a physiologic mechanism regulating the function of FVIII-vWF in primary hemostasis.     

Trisomy 3 in low-grade B-cell lymphomas of mucosa-associated lymphoid tissue

Characteristic chromosomal aberrations have been associated with subtypes of non-Hodgkin's lymphoma with distinct clinicopathologic features. Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) form such a group and might be expected to be characterized by a specific cytogenetic abnormality. Metaphase analyses of MALT lymphoma are rare due to problems with fresh tissue collection and poor in vitro proliferation. However, the small number of published series suggests that chromosome trisomies, particularly trisomy 3, might be characteristic of these tumors. The application of interphase cytogenetic techniques to routinely processed material allows the examination of a large series of archival cases and is particularly useful for the demonstration of chromosome trisomies. We have used this technique to analyze 70 cases of low-grade MALT lymphoma from various sites and found trisomy 3 in 60%. This finding compares with 16% in low- grade nodal B-cell lymphoma and 27% in primary splenic lymphoma of marginal zone type (splenic lymphoma with villous lymphocytes). These results provide further evidence that low-grade MALT lymphomas from all sites form a single pathologic entity distinct from nodal B-cell lymphomas. Although MALT lymphoma and primary splenic lymphoma may arise from marginal zone B cells, they are genetically distinct.     

Effects of patient deaths by suicide on clinicians working in mental health: A survey

In the UK, at least a quarter of suicides occurs in patients whilst under the care of mental health services. This study investigated the effects of such deaths on non-medical mental health clinicians. An online survey was conducted within a single NHS mental health Trust to elicit both quantitative and qualitative responses from staff across a range of professions. The survey focused on personal and professional impacts and available support. Participants reported significant negative emotional and professional effects that were long-lasting for some. These included mental health difficulties, loss of confidence regarding clinical responsibilities, and actual or contemplated career change. However, there was also some evidence of positive effects and professional growth. Support from colleagues and line managers is clearly important following deaths of patients by suicide. Clinicians' experiences of the support they had received in the workplace were polarized, suggesting that there is no single nor ideal approach that will meet everyone's needs. Participants made recommendations for the types of support that may be helpful. Most commonly, clinicians desired opportunities for focused reflection and support and help with the formal processes following the death. Sensitivity around how clinicians are notified about the death was highlighted as being particularly important. Conclusions are drawn as to how training institutions and employers can help staff to be better prepared for the potential occurrence of patient suicides and the formal processes that follow, with a view to mitigating risks of more serious harm to staff and hence indirectly to patients, and potential loss of highly trained clinicians to the workforce.     

Patient public involvement (PPI) in health literacy research: Engagement of adults with literacy needs in the co-creation of a hospital-based health literacy plan

Background

People with literacy needs can experience many challenges in accessing, understanding and using health services and health information. Such challenges can adversely impact patient-provider interactions and ultimately, health outcomes. Healthcare providers need to be aware of health literacy (HL) to address the demands of healthcare systems, improve their interactions with communities and patients and promote patient engagement for improved health outcomes.

Methods

This paper reports on a process of patient and public involvement (PPI) with participants in an adult literacy programme acting as PPI contributors to identify priority areas for a local hospital HL action plan and to develop a protocol for a PPI process with other groups. A qualitative community-based participatory research study design informed by principles of PPI was undertaken, drawing on the tools of participatory and visual methods, open discussion and workshop format to facilitate a process of co-creation. Three workshops with six PPI contributors took place to identify issues to be included in the hospital action plan. PPI contributors identified issues and grouped these into priority areas using discussion and ranking procedures.

Results

Key areas prioritised for HL action by the PPI contributors were: verbal communication, emphasising the patient's right to understand, and improved understanding of medication use. These were incorporated into the action plan. The workshop format and process were deemed acceptable to the group and input on improvements will be incorporated into further work in this area.

Conclusion

PPI acts as a lever in the knowledge translation process. Genuine engagement with service users can meaningfully contribute to relevant and sustainable changes to services as well as foster the empowerment of service users.

Patient or Public Contribution

Members of the public with literacy needs actively participated in the co-creation of a HL action plan for a local hospital and in the development of a protocol for a patient and public process for HL research.     

A systematic review of the effect of early mobilisation on length of stay for adults in the intensive care unit

Background

EM has been hypothesized to help prevent the development of ICU acquired weakness and may therefore result in positive outcomes for ICU patients.

Aim

To establish the impact of Early mobilisation (EM) on adult Intensive Care Unit (ICU) patients in terms of ICU length of stay (LOS), as well as hospital LOS, duration of mechanical ventilation, mortality, and functional independence.

Study design

A Systematic Review. EMBASE, MEDLINE, CINAHL, and the Cochrane Library were searched on 24th November 2020. Included studies and other systematic reviews were hand-searched for further includable studies. The primary outcome was ICU LOS whilst secondary outcomes were duration of MV, mortality, hospital LOS and functional independence. The PRISMA guidelines were utilized to perform the review. Ten randomized controlled trials with a combined total of 1291 patients met inclusion criteria and were scrutinized using the Joanna Briggs Institute (JBI) Checklist for Systematic Reviews. Revman 5.4.1 was used to conduct meta-analysis were possible.

Results

Results were limited by the evidence available for inclusion, in particular small sample sizes. However, a trend towards a shorter duration of ICU LOS and duration of mechanical ventilation emerged. There was also a trend towards higher rates of functional independence for intervention groups. Mortality rates appeared unaffected and results of meta-analysis were statistically non-significant (p = 0.90).

Conclusion

By applying a stricter time limit than previous systematic reviews a trend emerged that the commencement of EM has a positive effect on patient outcomes, in particular ICU LOS.

Relevance to clinical practice

The evidence base surrounding EM remains poor; however on the balance of the available evidence the application of EM should not be delayed.     

Middle eastern refugee children and adolescents mental health: A systematic review

Psychological problems have become a substantial burden on refugee communities, with a considerable impact on refugee children's quality of life and well-being. The available studies reveal growing mental health disorders in refugee children and adolescents, particularly traumas, anxiety, and depression disorders. This review aims to examine empirical evidence relating to the mental health of refugee children and adolescents in the Middle East. Following the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, this systematic literature review (2010–2020) identified 54 studies about Middle Eastern refugee children and adolescents' mental health. Eighteen studies were excluded based on their lack of relevance to the focus of the review. Of the remaining records, ten reported common mental health disorders, ten reported on Post-traumatic Stress Disorder, three reported the importance of mental health promotion in schools, while the others discussed protective factors. The results highlight a need to understand the mental health support needs of this group, add knowledge to this area of inquiry and provide baseline data regarding Middle Eastern refugee children and adolescents mental health. Differences across research designs were recorded to contextualize the quality of the study results. There is a paucity of studies investigating the causality, prevalence, risk factors, and interventions of non-traumatic-psychiatric disorders as well as the role of teacher in strengthen refugee's mental health. Limited information is available about suicidality and self-harm, protective factors, adversity, adaptation, acculturation, and social demographics in refugee children.