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Background: General practitioners (GPs) need robust, up-to-date evidence to deliver high-quality patient care. There is limited literature regarding the role of international GP professional organizations in developing and publishing clinical guidelines to support GPs clinical decision making., Objective: To identify evidence-based guidance and clinical guidelines produced by GP professional organizations and summarize their content, structure, and methods of development and dissemination., Methods: Scoping review of GP professional organizations following Joanna Briggs Institute guidance. Four databases were searched and a grey literature search was conducted. Studies were included if they were: (i) evidence-based guidance documents or clinical guidelines produced de novo by a national GP professional organization, (ii) developed to support GPs clinical care, and (iii) published in the last 10 years. GP professional organizations were contacted to provide supplementary information. A narrative synthesis was performed., Results: Six GP professional organizations and 60 guidelines were included. The most common de novo guideline topics were mental health, cardiovascular disease, neurology, pregnancy and women's health and preventive care. All guidelines were developed using a standard evidence-synthesis method. All included documents were disseminated through downloadable pdfs and peer review publications. GP professional organizations indicated that they generally collaborate with or endorse guidelines developed by national or international guideline producing bodies., Conclusion: The findings of this scoping review provide an overview of de novo guideline development by GP professional organizations and can support collaboration between GP organizations worldwide thus reducing duplication of effort, facilitating reproducibility, and identifying areas of standardization., Protocol Registration: Open Science Framework: https://doi.org/10.17605/OSF.IO/JXQ26., (© The Author(s) 2023. Published by Oxford University Press.)

Background: GPs aim to provide patient-centred care combining clinical evidence, clinical judgement, and patient priorities. Despite a recognition of the need to translate evidence to support patient care, barriers exist to the use of evidence in practice., Aim: To ascertain the needs and preferences of GPs regarding evidence-based guidance to support patient care. The study also aimed to prioritise content and optimise structure and dissemination of future evidence-based guidance., Design & Setting: This was a convergent parallel mixed-methods study in collaboration with the national GP professional body in the Republic of Ireland (Irish College of General Practitioners [ICGP]). Quantitative and qualitative findings were integrated at the interpretive level., Method: A national GP survey was administered via the ICGP (December 2020) and seven GP focus groups were undertaken (April-May 2021)., Results: Of 3496 GPs, a total of 509 responders (14.6%) completed the survey and 40 GP participants took part in focus groups. Prescribing updates, interpretation of test results, chronic disease management, and older person care were the preferred topics for future evidence-based guidance. GPs reported that they required rapid access to up-to-date and relevant evidence summaries online for use in clinical practice. Access to more comprehensive reviews for the purposes of continuing education and teaching was also a priority. Multimodal forms of dissemination were preferred to increase uptake of evidence in practice., Conclusion: GPs indicated that rapid access to up-to-date, summarised evidence-based resources, available from their professional organisation, is preferred. Evidence should reflect the disease burden of the population and involve multifaceted dissemination approaches., (Copyright © 2023, The Authors.)

Introduction: General practitioners (GPs) strive to use a patient centered approach to achieve shared decision making by integrating clinical evidence, clinical judgement, and patient priorities. In order to achieve this standard of care, GPs require relevant, up to date and high quality evidence. Currently there is a gap in the literature regarding the role of GP professional organisations internationally in producing and publishing evidence based guidance and clinical guidelines for GPs. This protocol outlines a scoping review to identify what evidence-based guidance is produced by general practitioner professional organisations internationally in terms of topic content, the structure and methods used to develop guidance and ways of disseminating this guidance, to support general practice clinical decision making. Methods: This scoping review will be conducted using the framework proposed by the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping reviews (PRISMA-ScR), will be used to guide the reporting. Two researchers will search electronic databases (Medline, Embase, Cochrane Library and Scopus), grey literature sources and contact international GP professional organisations directly to identify appropriate studies for inclusion. Key information will be categorised and classified to generate a summary of the methods used internationally to develop and implement evidence-based guides for general practitioners and a narrative synthesis will be conducted. Conclusions: This scoping review will examine current practice internationally regarding the role of General Practice professional organisations in producing and publishing clinical guidelines and evidence based guidance to support general practitioner's clinical decision making to benefit patient care., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 O'Brien E et al.)

Aims: To estimate the uptake of diabetic retinopathy screening among adults with type 2 diabetes and to identify and compare factors associated with attendance at the national diabetic retinal screening programme, and other screening services provided by ophthalmic surgeons, community ophthalmologists and optometrists., Methods: An observational retrospective cohort study was carried out using data from the 2016 audit of care delivered by general practices (n = 30) enrolled in a structured diabetes care initiative. Attendance at any screening in the previous 12 months, and attendance across different types of service (national programme and other screening services) was calculated. Logistic regression was performed to examine predictors associated with (1) attendance at any screening and (2) attendance at the national programme (RetinaScreen). Sociodemographic, clinical, and lifestyle factors were examined as predictors., Results: Data were available for 1106 people with type 2 diabetes aged ≥18 years. Overall, 863 (78%) of patients had a record of screening attendance in the previous 12 months. Of those screened, 494 (57.2%) attended RetinaScreen only, 258 (28.7%) attended other screening services only, and 111 (12.9%) attended both services. Statistically significant predictors of attendance at any screening were tablet/injectable controlled diabetes, attendance at a diabetes nurse specialist (DNS) in the past 12 months and a blood glucose level which was not on target (HbA1c >7.0% or >53 mmol/mol). In addition to these factors, when examining predictors of attendance at the national screening programme specifically, females were less likely to attend., Conclusions: Most patients managed in a structured diabetes care programme in primary care attended screening. Those with on target blood glucose control, those who were on oral or injectable medication or had been seen by a DNS were more likely to attend for annual screening. Of those who attended screening, almost one-third attended other screening services and so were not availing of the national programme, which is free, quality assured and has an integrated treatment arm., (Copyright © 2021 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Introduction: General practitioners (GPs) strive to use a patient centered approach to achieve shared decision making by integrating clinical evidence, clinical judgement, and patient priorities. In order to achieve this standard of care, GPs require relevant, up to date and high quality evidence. Currently there is a gap in the literature regarding the role of GP professional organisations internationally in producing and publishing evidence based guidance and clinical guidelines for GPs. This protocol outlines a scoping review to identify what evidence-based guidance is produced by general practitioner professional organisations internationally in terms of topic content, the structure and methods used to develop guidance and ways of disseminating this guidance, to support general practice clinical decision making. Methods: This scoping review will be conducted using the framework proposed by the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping reviews (PRISMA-ScR), will be used to guide the reporting. Two researchers will search electronic databases (Medline, Embase, Cochrane Library and Scopus), grey literature sources and contact international GP professional organisations directly to identify appropriate studies for inclusion. Key information will be categorised and classified to generate a summary of the methods used internationally to develop and implement evidence-based guides for general practitioners and a narrative synthesis will be conducted. Conclusions: This scoping review will examine current practice internationally regarding the role of General Practice professional organisations in producing and publishing clinical guidelines and evidence based guidance to support general practitioner's clinical decision making to benefit patient care., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 O'Brien E et al.)

Introduction: General practitioners (GPs) strive to use a patient centred approach to achieve shared decision making by integrating clinical evidence, clinical judgement, and patient priorities. This protocol outlines a scoping review to identify what evidence-based guidance is produced by general practitioner professional organisations internationally to support general practice clinical decision making. Methods: This scoping review will be conducted using the framework proposed by the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for scoping reviews (PRISMA-ScR), will be used to guide the reporting. Two researchers will search electronic databases (Medline, Embase, Cochrane Library and Scopus), grey literature sources and contact international GP professional organisations directly to identify appropriate studies for inclusion. Key information will be categorised and classified to generate a summary of the methods used internationally to develop and implement evidence-based guides for general practitioners and a narrative synthesis will be conducted. Conclusions: This scoping review will identify the role of GP professional organisations in generating, endorsing and/or disseminating evidence-based guidance for supporting general practitioner's clinical decision making to benefit patient care., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 O'Brien E et al.)

Aim: To examine the quality of care delivered by a structured primary care-led programme for people with Type 2 diabetes mellitus in 1999-2016., Methods: The Midland Diabetes Structured Care Programme provides structured primary care-led management. Trends over time in care processes were examined (using a chi-squared trend test and age- and gender-adjusted logistic regression). Screening and annual review attendance were reviewed. A composite of eight National Institute for Health and Care Excellence-recommended processes was used as a quality indicator. Participants who were referred to diabetes nurse specialists were compared with those not referred (Student's t-test, Pearson's chi-squared test, Wilcoxon-Mann-Whitney test). Proportions achieving outcome targets [HbA 1c ≤58 mmol/mol (7.5%), blood pressure ≤140/80 mmHg, cholesterol <5.0 mmol/l] were calculated., Results: Data were available for people with diabetes aged ≥18 years: 1998/1999 (n=336); 2003 (n=843); 2008 (n=988); and 2016 (n=1029). Recording of some processes improved significantly over time (HbA 1c , cholesterol, blood pressure, creatinine), and in 2016 exceeded 97%. Foot assessment and annual review attendance declined. In 2016, only 29% of participants had all eight National Institute for Health and Care Excellence processes recorded. A higher proportion of people with diabetes who were referred to a diabetes nurse specialist had poor glycaemic control compared with those not referred. The proportions meeting blood pressure and lipid targets increased over time., Conclusions: Structured primary care led to improvements in the quality of care over time. Poorer recording of some processes, a decline in annual review attendance, and participants remaining at high risk suggest limits to what structured care alone can achieve. Engagement in continuous quality improvement to target other factors, including attendance and self-management, may deliver further improvements., (© 2018 Diabetes UK.)

Background: High intrapatient tacrolimus variability has been associated with worse clinical outcomes postrenal transplantation. Theoretically, tacrolimus levels consistently outside the target therapeutic window may result in allograft dysfunction as subtherapeutic tacrolimus levels predispose to episodes of acute rejection, whereas supratherapeutic levels may cause nephrotoxicity., Methods: We investigated the effect of tacrolimus variability in a "Symphony" style low-dose tacrolimus based regime, by collecting data from 432 patients over a 4-year period.Three hundred seventy-six patients were included, with a mean follow-up of 1495 days. Tacrolimus variability 6 to 12 months after renal transplantation was calculated, and outcomes were compared in low (n = 186) and high variability (n = 190) groups., Results: High variability patients were found to be at increased risk of rejection during the first posttransplant year (P = 0.0054) and to have reduced rejection-free survival (hazard ratio, 1.953; 95% confidence interval, 1.234-3.093; P = 0.0054). High variability patients had significantly worse (P < 0.0001) glomerular filtration rates at 1, 2, 3, and 4 years posttransplant. High variability patients were at increased risk of allograft loss (hazard ratio, 4.928; 95% confidence interval, 2.050-11.85; P = 0.0004)., Conclusions: This suggests that highly variable tacrolimus levels predict worse outcomes postrenal transplantation, although the causal nature of this relationship remains unclear. High tacrolimus variability may identify a subset of patients who warrant increased surveillance and patient education regarding dietary and medication compliance.

Background: The aim of the present study was to assess the performance of three primary care-led initiatives providing structured care to patients with Type 2 diabetes in Ireland, a country with minimal incentives to promote the quality of care., Methods: Data, from three primary care initiatives, were available for 3010 adult patients with Type 2 diabetes. Results were benchmarked against the national guidelines for the management of Type 2 diabetes in the community and results from the National Diabetes Audit (NDA) for England (2008/2009) and the Scottish Diabetes Survey (2009)., Results: The recording of clinical processes of care was similar to results in the UK however the recording of lifestyle factors was markedly lower. Recording of HbA1c, blood pressure and lipids exceeded 85%. Recording of retinopathy screening (71%) was also comparable to England (77%) and Scotland (90%). Only 63% of patients had smoking status recorded compared to 99% in Scotland while 70% had BMI recorded compared to 89% in England. A similar proportion of patients in this initiative and the UK achieved clinical targets. Thirty-five percent of patients achieved a target HbA1c of < 6.5% (< 48 mmol/mol) compared to 25% in England. Applying the NICE target for blood pressure (≤ 140/80 mmHg), 54% of patients reached this target comparable to 60% in England. Slightly less patients were categorised as obese (> 30 kg/m²) in Ireland (50%, n = 1060) compared to Scotland (54%)., Conclusions: This study has demonstrated what can be achieved by proactive and interested health professionals in the absence of national infrastructure to support high quality diabetes care. The quality of primary care-led diabetes management in the three initiatives studied appears broadly consistent with results from the UK with the exception of recording lifestyle factors. The challenge facing health systems is to establish quality assurance a responsibility for all health care professionals rather than the subject of special interest for a few.

Background: Succinate is produced petrochemically from maleic anhydride to satisfy a small specialty chemical market. If succinate could be produced fermentatively at a price competitive with that of maleic anhydride, though, it could replace maleic anhydride as the precursor of many bulk chemicals, transforming a multi-billion dollar petrochemical market into one based on renewable resources. Actinobacillus succinogenes naturally converts sugars and CO2 into high concentrations of succinic acid as part of a mixed-acid fermentation. Efforts are ongoing to maximize carbon flux to succinate to achieve an industrial process., Results: Described here is the 2.3 Mb A. succinogenes genome sequence with emphasis on A. succinogenes's potential for genetic engineering, its metabolic attributes and capabilities, and its lack of pathogenicity. The genome sequence contains 1,690 DNA uptake signal sequence repeats and a nearly complete set of natural competence proteins, suggesting that A. succinogenes is capable of natural transformation. A. succinogenes lacks a complete tricarboxylic acid cycle as well as a glyoxylate pathway, and it appears to be able to transport and degrade about twenty different carbohydrates. The genomes of A. succinogenes and its closest known relative, Mannheimia succiniciproducens, were compared for the presence of known Pasteurellaceae virulence factors. Both species appear to lack the virulence traits of toxin production, sialic acid and choline incorporation into lipopolysaccharide, and utilization of hemoglobin and transferrin as iron sources. Perspectives are also given on the conservation of A. succinogenes genomic features in other sequenced Pasteurellaceae., Conclusions: Both A. succinogenes and M. succiniciproducens genome sequences lack many of the virulence genes used by their pathogenic Pasteurellaceae relatives. The lack of pathogenicity of these two succinogens is an exciting prospect, because comparisons with pathogenic Pasteurellaceae could lead to a better understanding of Pasteurellaceae virulence. The fact that the A. succinogenes genome encodes uptake and degradation pathways for a variety of carbohydrates reflects the variety of carbohydrate substrates available in the rumen, A. succinogenes's natural habitat. It also suggests that many different carbon sources can be used as feedstock for succinate production by A. succinogenes.

Cdc7-Dbf4 is a two-subunit kinase required for initiating DNA replication. The Dbf4 regulatory subunit is required for Cdc7 kinase activity. Previous studies have shown that the C termini of Dbf4 orthologs encode a single (putative) C(2)H(2) zinc (Zn) finger, referred to as "motif C." By mutational analysis we show that the Zn finger is not required for the essential function of Dbf4. However, deletion and point mutants altering conserved Zn-finger residues exhibit a substantially slowed S-phase, DNA damage sensitivity, and a hypo-mutagenic phenotype following UV irradiation. Using two-hybrid and biochemical assays, we show that the Dbf4 Zn finger interacts with Cdc7 and stimulates its kinase activity. However, a separable Dbf4 region also mediates an interaction with Cdc7 such that only the loss of both Cdc7-interacting regions results in lethality. In contrast, an N-terminal BRCT-like domain is not required for induced mutagenesis nor does it interact with Cdc7. By making chimeric Dbf4 proteins that contain known BRCT domains in Saccharomyces cerevisiae, we show that the BRCT domain from Rev1, a translesion DNA polymerase, can uniquely substitute for the Dbf4 BRCT domain. Thus, we have mapped regions on budding yeast Dbf4 required for binding and activating Cdc7 kinase. Our data also suggest that the Dbf4 and Rev1 BRCT domains interact with a common protein or structure, although the precise function of both domains and their binding partners remains elusive.

Objective: To study variation in quality of life and quality of care in patients with diabetes experiencing three different models of care: traditional hospital care, hospital/general practitioner (GP) shared care, and structured GP care., Research Design and Methods: A cross-sectional study involving 1,456 patients with diabetes (71% response rate) was conducted. Quality of life was assessed with the Audit of Diabetes-Dependent Quality of Life (ADDQoL) instrument and quality of care with a 10-point process-of-care report card., Results: The adjusted odds ratio (OR) for a high (upper quartile) ADDQoL score was significantly increased in the structured care relative to the traditional hospital care group (OR 1.7 [95% CI 1.2-2.5]). A significantly higher proportion of structured GP care patients reported compliance with seven or more key process-of-care measures compared with the other models of care., Conclusions: Diabetes quality of life may be enhanced when care is provided in a primary care setting without compromising quality of care.

Background: In the Irish Midland Health Service Executive (HSE) Diabetes Structured Care Project, additional resources were targeted at general practice in the absence of a local hospital-based specialized diabetes unit., Objective: We assessed the performance of the Midland HSE Diabetes Structured Care programme in 2003, bench-marked against Primary Care Trust (PCT) data from the 2003/2004 National Diabetes Audit for England., Methods: Data on 947 patients (72% of eligible patients) from all 20 general practices participating in the structured-care programme were collected retrospectively over a 12-month period. The data included demographic and clinical variables as well as key process-of-care and intermediate outcome indicators used in the National Diabetes Audit for England., Results: The level of recording of process-of-care measures was near or above the upper quartile for PCTs in England. The proportion of patients with HbA(1c) concentrations at target levels (<6.5%) in the Midlands HSE project (26.8%) was virtually identical to the upper quartile level for PCTs in England (27.4%). The proportion of patients reaching target total cholesterol levels (<5.0 mmol/l) (54.6%) was close to the mean for PCTs in England (56.6%), and performance with regard to target blood pressure levels was equally poor in both the Midlands HSE (18.0%) and in PCTs in England (20.8%)., Conclusion: Primary-care-led structured care, with relatively limited but well-focused investment, can achieve quality of care for patients with diabetes, comparable to international best practice.