Evidence-based clinical practice guidelines on the management of pain in older people - a summary report.

OBJECTIVE: The objective of this study is to develop an update of the evidence-based guidelines for the management of pain in older people. DESIGN: Review of evidence since 2010 using a systematic and consensus approach is performed. RESULTS: Recognition of the type of pain and routine assessment of pain should inform the use of specific environmental, behavioural and pharmacological interventions. Individualised care plans and analgesic protocols for specific clinical situations, patients and health care settings can be developed from these guidelines. CONCLUSION: Management of pain must be considered as an important component of the health care provided to all people, regardless of their chronological age or severity of illness. By clearly outlining areas where evidence is not available, these guidelines may also stimulate further research. To use the recommended therapeutic approaches, clinicians must be familiar with adverse effects of treatment and the potential for drug interactions

Opioid prescription at postoperative discharge: a retrospective observational cohort study

Opioid misuse is now considered a major public health epidemic in North America, with substantial social and financial consequences. As well as socio-economic and commercial drivers, modifiable risk-factors that have resulted in this crisis have been identified. The purpose of this study was to identify whether, within England, modifiable drivers for persistent postoperative opioid use were present. This was a retrospective cohort study of practice at 14 National Health Service hospitals across England. Data were collected retrospectively and validated for adult patients undergoing elective intermediate and major or complex major general surgical procedures between 1 and 31 March 2019. Of the 509 patients enrolled from 14 centres, 499 were included in the data analysis. In total, 31.5% (157/499) patients were in the intermediate surgery cohort and 68.5% (342/499) were in the major or complex major surgery cohort, with 21.0% (33/157) and 21.6% (74/342) discharged with opioid medicines to be taken at regular intervals, respectively. There were similar median oral morphine equivalent doses prescribed at discharge. Of patients prescribed regular opioid medicines, 76.6% (82/107) had a specified duration at discharge. However, 72.9% (78/107) had no written deprescribing advice on discharge. Similarly, of patients prescribed ‘when required’ opioids, 59.6% (93/156) had a specified duration of their prescription and 33.3% (52/156) were given written deprescribing advice. This study has identified a pattern of poor prescribing practices, a lack of guidance and formal training at individual institutions and highlights opportunities for improvement in opioid-prescribing practices within England

Characterising the evidence base for advanced clinical practice in the UK: a scoping review protocol

Copyright © Author(s) (or their employer(s)) 2020. Introduction A global health workforce crisis, coupled with ageing populations, wars and the rise of non-communicable diseases is prompting all countries to consider the optimal skill mix within their health workforce. The development of advanced clinical practice (ACP) roles for existing non-medical cadres is one potential strategy that is being pursued. In the UK, National Health Service (NHS) workforce transformation programmes are actively promoting the development of ACP roles across a wide range of non-medical professions. These efforts are currently hampered by a high level of variation in ACP role development, deployment, nomenclature, definition, governance and educational preparation across the professions and across different settings. This scoping review aims to support a more consistent approach to workforce development in the UK, by identifying and mapping the current evidence base underpinning multiprofessional advanced level practice in the UK from a workforce, clinical, service and patient perspective. Methods and analysis This scoping review is registered with the Open Science Framework (https://osf.io/tzpe5). The review will follow Joanna Briggs Institute guidance and involves a multidisciplinary and multiprofessional team, including a public representative. A wide range of electronic databases and grey literature sources will be searched from 2005 to the present. The review will include primary data from any relevant research, audit or evaluation studies. All review steps will involve two or more reviewers. Data extraction, charting and summary will be guided by a template derived from an established framework used internationally to evaluate ACP (the Participatory Evidence-Informed Patient-Centred Process-Plus framework). Dissemination The review will produce important new information on existing activity, outcomes, implementation challenges and key areas for future research around ACP in the UK, which, in the context of global workforce transformations, will be of international, as well as local, significance. The findings will be disseminated through professional and NHS bodies, employer organisations, conferences and research papers.Health Education England (DN384826— Evaluation for HEE ACP Programme—Current Evidence Based for Advanced Level Practice within Health and Related Environments)

Characterising the outcomes, impacts and implementation challenges of advanced clinical practice roles in the UK: A scoping review

Copyright © Author(s) (or their employer(s)) 2021. Objectives In response to demographic and health system pressures, the development of non-medical advanced clinical practice (ACP) roles is a key component of National Health Service workforce transformation policy in the UK. This review was undertaken to establish a baseline of evidence on ACP roles and their outcomes, impacts and implementation challenges across the UK. Design A scoping review was undertaken following JBI methodological guidance. Methods 13 online databases (Medline, CINAHL, ASSIA, Embase, HMIC, AMED, Amber, OT seeker, PsycINFO, PEDro, SportDiscus, Osteopathic Research and PenNutrition) and grey literature sources were searched from 2005 to 2020. Data extraction, charting and summary was guided by the PEPPA-Plus framework. The review was undertaken by a multi-professional team that included an expert lay representative. Results 191 papers met the inclusion criteria (any type of UK evidence, any sector/setting and any profession meeting the Health Education England definition of ACP). Most papers were small-scale descriptive studies, service evaluations or audits. The papers reported mainly on clinical aspects of the ACP role. Most papers related to nursing, pharmacy, physiotherapy and radiography roles and these were referred to by a plethora of different titles. ACP roles were reported to be achieving beneficial impacts across a range of clinical and health system outcomes. They were highly acceptable to patients and staff. No significant adverse events were reported. There was a lack of cost-effectiveness evidence. Implementation challenges included a lack of role clarity and an ambivalent role identity, lack of mentorship, lack of continuing professional development and an unclear career pathway. Conclusion This review suggests a need for educational and role standardisation and a supported career pathway for advanced clinical practitioners (ACPs) in the UK. Future research should: (i) adopt more robust study designs, (ii) investigate the full scope of the ACP role and (iii) include a wider range of professions and sectors.Health Education England (DN384826— Evaluation for HEE ACP Programme—Current Evidence Based for Advanced Level Practice within Health and Related Environments)

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Corrigendum to Evidence-based clinical practice guidelines on the management of pain in older people – a summary report

[This corrects the article DOI: 10.1177/2049463720976155.]

Rare missense variants in Tropomyosin-4 (TPM4) are associated with platelet dysfunction, cytoskeletal defects, and excessive bleeding

Background: A significant challenge is faced for the genetic diagnosis of inherited platelet disorders in which candidate genetic variants can be found in more than 100 bleeding, thrombotic, and platelet disorder genes, especially within families in which there are both normal and low platelet counts. Genetic variants of unknown clinical significance (VUS) are found in a significant proportion of such patients in which functional studies are required to prove pathogenicity. Objective: To identify the genetic cause in patients with a suspected platelet disorder and subsequently perform a detailed functional analysis of the candidate genetic variants found. Methods: Genetic and functional studies were undertaken in three patients in two unrelated families with a suspected platelet disorder and excessive bleeding. A targeted gene panel of previously known bleeding and platelet genes was used to identify plausible genetic variants. Deep platelet phenotyping was performed using platelet spreading analysis, transmission electron microscopy, immunofluorescence, and platelet function testing using lumiaggregometry and flow cytometry. Results: We report rare conserved missense variants (p.R182C and p.A183V) in TPM4 encoding tromomyosin-4 in 3 patients. Deep platelet phenotyping studies revealed similar platelet function defects across the 3 patients including reduced platelet secretion, and aggregation and spreading defects suggesting that TPM4 missense variants impact platelet function and show a disordered pattern of tropomyosin staining. Conclusions: Genetic and functional TPM4 defects are reported making TPM4 a diagnostic grade tier 1 gene and highlights the importance of including TPM4 in diagnostic genetic screening for patients with significant bleeding and undiagnosed platelet disorders, particularly for those with a normal platelet count

Correlated Mutations: A Hallmark of Phenotypic Amino Acid Substitutions

Point mutations resulting in the substitution of a single amino acid can cause severe functional consequences, but can also be completely harmless. Understanding what determines the phenotypical impact is important both for planning targeted mutation experiments in the laboratory and for analyzing naturally occurring mutations found in patients. Common wisdom suggests using the extent of evolutionary conservation of a residue or a sequence motif as an indicator of its functional importance and thus vulnerability in case of mutation. In this work, we put forward the hypothesis that in addition to conservation, co-evolution of residues in a protein influences the likelihood of a residue to be functionally important and thus associated with disease. While the basic idea of a relation between co-evolution and functional sites has been explored before, we have conducted the first systematic and comprehensive analysis of point mutations causing disease in humans with respect to correlated mutations. We included 14,211 distinct positions with known disease-causing point mutations in 1,153 human proteins in our analysis. Our data show that (1) correlated positions are significantly more likely to be disease-associated than expected by chance, and that (2) this signal cannot be explained by conservation patterns of individual sequence positions. Although correlated residues have primarily been used to predict contact sites, our data are in agreement with previous observations that (3) many such correlations do not relate to physical contacts between amino acid residues. Access to our analysis results are provided at http://webclu.bio.wzw.tum.de/~pagel/supplements/correlated-positions/

Silencing of Vlaro2 for chorismate synthase revealed that the phytopathogen Verticillium longisporum induces the cross-pathway control in the xylem

The first leaky auxotrophic mutant for aromatic amino acids of the near-diploid fungal plant pathogen Verticillium longisporum (VL) has been generated. VL enters its host Brassica napus through the roots and colonizes the xylem vessels. The xylem contains little nutrients including low concentrations of amino acids. We isolated the gene Vlaro2 encoding chorismate synthase by complementation of the corresponding yeast mutant strain. Chorismate synthase produces the first branch point intermediate of aromatic amino acid biosynthesis. A novel RNA-mediated gene silencing method reduced gene expression of both isogenes by 80% and resulted in a bradytrophic mutant, which is a leaky auxotroph due to impaired expression of chorismate synthase. In contrast to the wild type, silencing resulted in increased expression of the cross-pathway regulatory gene VlcpcA (similar to cpcA/GCN4) during saprotrophic life. The mutant fungus is still able to infect the host plant B. napus and the model Arabidopsis thaliana with reduced efficiency. VlcpcA expression is increased in planta in the mutant and the wild-type fungus. We assume that xylem colonization requires induction of the cross-pathway control, presumably because the fungus has to overcome imbalanced amino acid supply in the xylem