Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

What matters to users of services? An explorative study to promote shared decision making in health care

Background Involving service users and carers in decisions about their health care is a key feature of health‐care practice. Professional health and social care students need to develop skills and attributes to best enable this to happen. Aims The aims were to explore service user and carer perceptions of behaviours, attributes and context required to enable shared decision making; to compare these perceptions to those of students and academic staff with a view to utilizing the findings to inform the development of student assessment tools. Methods A mixed methods approach was used including action learning groups (ALG) and an iterative process alongside a modified Delphi survey. Participants The ALGs were from an existing service user and carer network. The survey was sent to sixty students, sixty academics and 30 service users from 16 different professional disciplines, spanning four Universities in England. Results The collaborative enquiry process and survey identified general agreement that being open and honest, listening, showing respect, giving time and being up to date were important. The qualitative findings identified that individual interpretation was a key factor. An unexpected result was an insight into possible insecurities of students. Conclusions The findings indicate that distilling rich qualitative information into a format for student assessment tools could be problematic as the individual context could be lost, it is therefore proposed that the information could be better used as a learning rather than assessment tool. Several of those involved identified how they valued the process and found it beneficial.     

The contribution of primary care practitioners to interventions reducing loneliness and social isolation in older people—An integrative review

Background

Social connection is a fundamental human need. Its absence can lead to loneliness and social isolation, adversely impacting health and well-being. Given their regular contact and trusted relationships with older people, practitioners delivering community-based primary care are well-positioned to address this issue. However, their contribution to addressing loneliness and social isolation is unclear.

Aim

This integrative review explores the contribution of the primary care workforce to interventions aimed at reducing loneliness and social isolation in community-dwelling older people.

Method

Using an integrative review method, Scopus, Web of Science, CINAHL and PubMed were searched for original research published between 2000 and 2022. Fourteen papers reporting 13 primary studies were appraised for methodological quality and included in the review. Data were extracted into a summary table and analysed using thematic analysis.

Results

Included studies came from over six countries. Internationally, primary care services have diverse structures, funding and workforces influencing their response to loneliness and social isolation. All but one intervention was multi-component, with ten studies including a group-based activity and three providing primarily individual-level activities. Only six studies reported reductions in loneliness following the intervention. Three themes were identified: characteristics of interventions; implementation context, barriers and facilitators; and differing contributions of primary care practitioners in addressing loneliness and social isolation of older people.

Conclusion

There is increasing demand and scope for primary care practitioners to assist lonely and socially isolated older people. It is important to understand how to equip and incentivise these practitioners to routinely identify, assess and respond to lonely and socially isolated older people despite varying implementation contexts. There is a need for further research that explores how the primary care team can be better utilised to deliver effective interventions that reduce the health impacts of loneliness and social isolation.     

Global Health and Emergency Care: A Resuscitation Research Agenda—Part 2

At the 2013 Academic Emergency Medicine global health consensus conference, a breakout session to develop a research agenda for resuscitation was held. Two articles are the result of that discussion. This second article addresses data collection, management, and analysis and regionalization of postresuscitation care, resuscitation programs, and research examples around the world and proposes a strategy to strengthen resuscitation research globally. There is a need for reliable global statistics on resuscitation, international standardization of data, and development of an electronic standard for reporting data. Regionalization of postresuscitation care is a priority area for future research. Large resuscitation clinical research networks are feasible and can give valuable data for improvement of service and outcomes. Low‐cost models of population‐based research, and emphasis on interventional and implementation studies that assess the clinical effects of programs and interventions, are needed to determine the most cost‐effective strategies to improve outcomes. The global challenge is how to adapt research findings to a developing world situation to have an effect internationally.