General practice palliative care: Patient and carer expectations, advance care plans and place of death-a systematic review

Background: With an increasing ageing population in most countries, the role of general practitioners (GPs) and general practice nurses (GPNs) in providing optimal end of life (EoL) care is increasingly important. Objective: To explore: (1) patient and carer expectations of the role of GPs and GPNs at EoL; (2) GPs’ and GPNs’ contribution to advance care planning (ACP) and (3) if primary care involvement allows people to die in the place of preference. Method: Systematic literature review. Data sources: Papers from 2000 to 2017 were sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases. Results: From 6209 journal articles, 51 papers were relevant. Patients and carers expect their GPs to be competent in all aspects of palliative care. They valued easy access to their GP, a multidisciplinary approach to care and well-coordinated and informed care. They also wanted their care team to communicate openly, honestly and empathically, particularly as the patient deteriorated. ACP and the involvement of GPs were important factors which contributed to patients being cared for and dying in their preferred place. There was no reference to GPNs in any paper identified. Conclusions: Patients and carers prefer a holistic approach to care. This review shows that GPs have an important role in ACP and that their involvement facilitates dying in the place of preference. Proactive identification of people approaching EoL is likely to improve all aspects of care, including planning and communicating about EoL. More work outlining the role of GPNs in end of life care is required

General practice physicians\u27 and nurses\u27 self- reported multidisciplinary end-of-life care: A systematic review

Background: General practitioners (GPs) and general practice nurses (GPNs) face increasing demands to provide end-of-life care (EoLC) as the population ages. To enhance primary palliative care (PC), the care they provide needs to be understood to inform best practice models of care. Objective: To provide a comprehensive description of the self-reported role and performance of GPs and GPNs in (1) specific medical/nursing roles, (2) communication, (3) care co-ordination, (4) access and out-of-hours care, and (5) multidisciplinary care. Method: Systematic literature review. Data included papers (2000 to 2017) sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases. Results: From 6209 journal articles, 29 reviewed papers reported the GPs’ and GPNs’ role in EoLC or PC practice. GPs report a central role in symptom management, treatment withdrawal, non-malignant disease management and terminal sedation. Information provision included breaking bad news, prognosis and place of death. Psychosocial concerns were often addressed. Quality of communication depended on GP–patient relationships and GP skills. Challenges were unrealistic patient and family expectations, family conflict and lack of advance care planning. GPs often delayed endof-life discussions until 3 months before death. Home visits were common, but less so for urban, female and part-time GPs. GPs co-ordinated care with secondary care, but in some cases parallel care occurred. Trust in, and availability of, the GP was critical for shared care. There was minimal reference to GPNs’ roles. Conclusions: GPs play a critical role in palliative care. More work is required on the role of GPNs, case finding and models to promote shared care, home visits and out-of-hours services

Customized interface biofunctionalization of decellularized extracellular matrix: towards enhanced endothelialization

Interface biofunctionalization strategies try to enhance and control the interaction between implants and host organism. Decellularized extracellular matrix (dECM) is widely used as a platform for bioengineering of medical implants, having shown its suitability in a variety of preclinical as well as clinical models. In this study, specifically designed, custom-made synthetic peptides were used to functionalize dECM with different cell adhesive sequences (RGD, REDV, and YIGSR). Effects on in vitro endothelial cell adhesion and in vivo endothelialization were evaluated in standardized models using decellularized ovine pulmonary heart valve cusps (dPVCs) and decellularized aortic grafts (dAoGs), respectively. Contact angle measurements and fluorescent labeling of custom-made peptides showed successful functionalization of dPVCs and dAoGs. The functionalization of dPVCs with a combination of bioactive sequences significantly increased in vitro human umbilical vein endothelial cell adhesion compared to nonfunctionalized controls. In a functional rodent aortic transplantation model, fluorescent-labeled peptides on dAoGs were persistent up to 10 days in vivo under exposure to systemic circulation. Although there was a trend toward enhanced in vivo endothelialization of functionalized grafts compared to nonfunctionalized controls, there was no statistical significance and a large biological variability in both groups. Despite failing to show a clear biological effect in the used in vivo model system, our initial findings do suggest that endothelialization onto dECM may be modulated by customized interface biofunctionalization using the presented method. Since bioactive sequences within the dECM–synthetic peptide platform are easily interchangeable and combinable, further control of host cell proliferation, function, and differentiation seems to be feasible, possibly paving the way to a new generation of multifunctional dECM scaffolds for regenerative medicinePeer ReviewedPostprint (published version

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Systematic review of general practice end-of-life symptom control

Background End of life care (EoLC) is a fundamental role of general practice, which will become more important as the population ages. It is essential that general practice’s role and performance of at the end of life is understood in order to maximise the skills of the entire workforce. Objective To provide a comprehensive description of the role and performance of general practitioners (GPs) and general practice nurses (GPNs) in EoLC symptom control. Method Systematic literature review of papers from 2000 to 2017 were sought from Medline, PsycINFO, Embase, Joanna Briggs Institute and Cochrane databases. Results From 6209 journal articles, 46 papers reported GP performance in symptom management. There was no reference to the performance of GPNs in any paper identified. Most GPs expressed confidence in identifying EoLC symptoms. However, they reported lack of confidence in providing EoLC at the beginning of their careers, and improvements with time in practice. They perceived emotional support as being the most important aspect of EoLC that they provide, but there were barriers to its provision. GPs felt most comfortable treating pain, and least confident with dyspnoea and depression. Observed pain management was sometimes not optimal. More formal training, particularly in the use of opioids was considered important to improve management of both pain and dyspnoea. Conclusions It is essential that GPs receive regular education and training, and exposure to EoLC from an early stage in their careers to ensure skill and confidence. Research into the role of GPNs in symptom control needs to occur

General practice physicians’ and nurses’ self-reported multidisciplinary end-of-life care: a systematic review

General practitioners (GPs) and general practice nurses (GPNs) face increasing demands to provide end-of-life care (EoLC) as the population ages. To enhance primary palliative care (PC), the care they provide needs to be understood to inform best practice models of care.To provide a comprehensive description of the self-reported role and performance of GPs and GPNs in (1) specific medical/nursing roles, (2) communication, (3) care co-ordination, (4) access and out-of-hours care, and (5) multidisciplinary care.Systematic literature review. Data included papers (2000 to 2017) sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases.From 6209 journal articles, 29 reviewed papers reported the GPs' and GPNs' role in EoLC or PC practice. GPs report a central role in symptom management, treatment withdrawal, non-malignant disease management and terminal sedation. Information provision included breaking bad news, prognosis and place of death. Psychosocial concerns were often addressed. Quality of communication depended on GP-patient relationships and GP skills. Challenges were unrealistic patient and family expectations, family conflict and lack of advance care planning. GPs often delayed end-of-life discussions until 3 months before death. Home visits were common, but less so for urban, female and part-time GPs. GPs co-ordinated care with secondary care, but in some cases parallel care occurred. Trust in, and availability of, the GP was critical for shared care. There was minimal reference to GPNs' roles.GPs play a critical role in palliative care. More work is required on the role of GPNs, case finding and models to promote shared care, home visits and out-of-hours services

General practice nurses and physicians and end of life: A systematic review of models of care

BACKGROUND: General practitioners (GPs) and general practice nurses (GPNs) face increasing demands to provide palliative care (PC) or end-of-life care (EoLC) as the population ages. In order to maximise the impact of GPs and GPNs, the impact of different models of care that have been developed to support their practice of EoLC needs to be understood.OBJECTIVE: To examine published models of EoLC that incorporate or support GP and GPN practice, and their impact on patients, families and the health system.METHOD: Systematic literature review. Data included papers (2000 to 2017) sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases.RESULTS: From 6209 journal articles, 13 papers reported models of care supporting the GP and GPN's role in EoLC or PC practice. Services and guidelines for clinical issues have mixed impact on improving symptoms, but improved adherence to clinical guidelines. National Frameworks facilitated patients being able to die in their preferred place. A single specialist PC-GP case conference reduced hospitalisations, better maintained functional capacity and improved quality of life parameters in both patients with cancer and without cancer. No studies examined models of care aimed at supporting GPNs.CONCLUSIONS: Primary care practitioners have a natural role to play in EoLC, and most patient and health system outcomes are substantially improved with their involvement. Successful integrative models need to be tested, particularly in non-malignant diseases. Such models need to be explored further. More work is required on the role of GPNs and how to support them in this role.</p

Customized interface biofunctionalization of decellularized extracellular matrix: towards enhanced endothelialization

Interface biofunctionalization strategies try to enhance and control the interaction between implants and host organism. Decellularized extracellular matrix (dECM) is widely used as a platform for bioengineering of medical implants, having shown its suitability in a variety of preclinical as well as clinical models. In this study, specifically designed, custom-made synthetic peptides were used to functionalize dECM with different cell adhesive sequences (RGD, REDV, and YIGSR). Effects on in vitro endothelial cell adhesion and in vivo endothelialization were evaluated in standardized models using decellularized ovine pulmonary heart valve cusps (dPVCs) and decellularized aortic grafts (dAoGs), respectively. Contact angle measurements and fluorescent labeling of custom-made peptides showed successful functionalization of dPVCs and dAoGs. The functionalization of dPVCs with a combination of bioactive sequences significantly increased in vitro human umbilical vein endothelial cell adhesion compared to nonfunctionalized controls. In a functional rodent aortic transplantation model, fluorescent-labeled peptides on dAoGs were persistent up to 10 days in vivo under exposure to systemic circulation. Although there was a trend toward enhanced in vivo endothelialization of functionalized grafts compared to nonfunctionalized controls, there was no statistical significance and a large biological variability in both groups. Despite failing to show a clear biological effect in the used in vivo model system, our initial findings do suggest that endothelialization onto dECM may be modulated by customized interface biofunctionalization using the presented method. Since bioactive sequences within the dECM–synthetic peptide platform are easily interchangeable and combinable, further control of host cell proliferation, function, and differentiation seems to be feasible, possibly paving the way to a new generation of multifunctional dECM scaffolds for regenerative medicinePeer Reviewe

General practice nurses and physicians and end of life: A systematic review of models of care

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Background: General practitioners (GPs) and general practice nurses (GPNs) face increasing demands to provide palliative care (PC) or end-of-life care (EoLC) as the population ages. In order to maximise the impact of GPs and GPNs, the impact of different models of care that have been developed to support their practice of EoLC needs to be understood. Objective: To examine published models of EoLC that incorporate or support GP and GPN practice, and their impact on patients, families and the health system. Method: Systematic literature review. Data included papers (2000 to 2017) sought from Medline, Psychinfo, Embase, Joanna Briggs Institute and Cochrane databases. Results: From 6209 journal articles, 13 papers reported models of care supporting the GP and GPN\u27s role in EoLC or PC practice. Services and guidelines for clinical issues have mixed impact on improving symptoms, but improved adherence to clinical guidelines. National Frameworks facilitated patients being able to die in their preferred place. A single specialist PC-GP case conference reduced hospitalisations, better maintained functional capacity and improved quality of life parameters in both patients with cancer and without cancer. No studies examined models of care aimed at supporting GPNs. Conclusions: Primary care practitioners have a natural role to play in EoLC, and most patient and health system outcomes are substantially improved with their involvement. Successful integrative models need to be tested, particularly in non-malignant diseases. Such models need to be explored further. More work is required on the role of GPNs and how to support them in this role