39 research outputs found

    Developing a nature recovery network using systematic conservation planning

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    Conservation area networks in most countries are fragmented and inadequate. To tackle this in England, government policies are encouraging stakeholders to create local-level nature recovery networks. Here, we describe work led by a wildlife organization that used the systematic conservation planning approach to identify a nature recovery network for three English counties and select focal areas within it where they will focus their work. The network was based on identifying core zones to maintain current biodiversity and recovery zones for habitat restoration, meeting area-based targets for 50 priority habitat, landscape, landcover, and ecosystem service types. It included the existing designated sites for conservation, which cover 6.05% of the study site, and identified an additional 11.6% of land as core zones and 18% as recovery zones, reflecting the organization's call for 30% of England to be conserved and connected by 2030. We found that systematic conservation planning worked well in this context, identifying a connected, adequate, representative, and efficient network and producing transparent and repeatable results. The analysis also highlighted the pressing need for government agencies to provide national-level guidance and datasets for setting targets and including species data in spatial planning, creating a national framework to inform local action

    Blood eosinophil-guided oral prednisolone for COPD exacerbations in primary care in the UK (STARR2): A non-inferiority, multicentre, double-blind, placebo-controlled, randomised controlled trial

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    Background: Systemic glucocorticoids are recommended for use in chronic obstructive pulmonary disease (COPD) exacerbations; however, there is increased harm associated with their use. We hypothesised that the use of eosinophil biomarker-directed oral prednisolone therapy at the time of an exacerbation of COPD was effective at reducing prednisolone use without affecting adverse outcomes. Methods: The studying acute exacerbations and response (STARR2) study was a multicentre, randomised, double-blind, placebo-controlled trial conducted in 14 primary care practices in the UK. We included adults (aged ≥ 40 years), who were current or former smokers (with at least a 10 pack year smoking history) with a diagnosis of COPD, defined as a post-bronchodilator FEV1/forced vital capacity ratio of less than 0·7 previously recorded by the primary care physician, and a history of at least one exacerbation in the previous 12 months requiring systemic corticosteroids with or without antibiotics. All study staff and participants were masked to study group allocation and to treatment allocation. Participants were randomly assigned (1:1) to blood eosinophil-directed treatment (BET; to receive oral prednisolone 30 mg once daily if eosinophil count was high [ ≥ 2%] or placebo if eosinophil count was low [ \u3c 2%]) or to standard care treatment (ST; to receive prednisolone 30 mg once daily irrespective of the point-of-care eosinophil result). Treatment was prescribed for 14 days and all patients also received antibiotics. The primary outcome was the rate of treatment failure, defined as any need for re-treatment with antibiotics or steroids, hospitalisation for any cause, or death, assessed at 30 days after exacerbation in the modified intention-to-treat population. Participants were eligible for re-randomisation at further exacerbations (with a maximum of four exacerbations per participant). A safety analysis was conducted on all randomly assigned participants. Although designed as a superiority trial, after identification of an error in the randomisation code before data lock the study converted to show non-inferiority. An upper margin of 1·105 for the 95% CI was defined as the non-inferiority margin. This study was registered with EudraCT, 2017-001586-24, and is complete. Findings: Between Nov 6, 2017, and April 30, 2020, 308 participants were recruited from 14 general practices. 144 exacerbations (73 in the BET group and 71 in the ST group) from 93 participants (mean age 70 years [range 46–84] and mean percent predicted FEV1 60·9% [SD 19·4]; 52 [56%] male and 41 [44%] female; ethnicity data was not collected]) were included in the modified intention-to-treat analysis. There were 14 (19%) treatment failures at 30 days post-exacerbation in the BET group and 23 (32%) in the ST group; we found a large non-significant estimated effect between BET and ST (RR 0·60 [95% CI 0·33–1·04]; p=0·070) in reducing treatment failures after a COPD exacerbation. The non-inferiority analysis supported that BET was non-inferior to ST. Frequency of adverse events were similar between the study groups; glycosuria (2/102 [2%] in BET group and 1/101 [1%] in the ST group) and hospital admission for COPD exacerbation (2/102 [2%] in BET group and 1/101 [1%] in the ST group) were the two most common adverse events in both groups. No deaths occurred in the study. Interpretation: Blood eosinophil-directed prednisolone therapy at the time of an acute exacerbation of COPD is non-inferior to standard care and can be used to safely reduce systemic glucocorticoid use in clinical practice. Funding: National Institute for Health and Care Research

    Investigating the effect of providing monetary incentives to participants on completion rates of referred co-respondents: an embedded randomized controlled trial. Study within a trial (SWAT) protocol

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    Background Parent-report questionnaires are a common method of generating data on child outcomes in mental health studies. A second report from another person who knows the child (co-respondent) is implemented to reduce bias and increase objectivity. The success of this approach is dependent on the engagement of co-respondents, which can be difficult. Financial incentives are used to increase data return in clinical trials, and to promote referral rates in online marketing. This protocol describes the use of an embedded randomised controlled trial (RCT) to investigate the effect of financial incentives on rates of co-respondent data completion. In the host RCT (of an online intervention designed to reduce the impact of a parent's anxiety on their child) index participants (i.e. parents) are asked to invite a co-respondent to complete measures on the index child. This study will test the hypothesis that providing monetary incentives to index participants will increase the outcome measure completion rate of co-respondents. Methods Embedded RCT of two parallel groups. Participants in the intervention arm will be sent a £10 voucher if their chosen co-respondent completes online baseline measures. Participants in the control arm will not be offered payment regardless of their chosen co-respondent's behaviour. 1754 participants will take part. Analysis will compare co-respondent outcome measure completion rates between the two arms at baseline and follow-up. Conclusion Findings from this study will provide evidence on the impact of offering payment to index participants on return rates of co-respondent data. This will inform resource allocation within future clinical trials

    Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS) : introduction and methodology

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    Funding Information: The Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS) project was conducted by the Clinical Urology and Epidemiology (CLUE) Working Group and supported by the Academy of Finland (309387, 340957), Sigrid Jusélius Foundation and Competitive Research Funding of the Helsinki University Hospital (TYH2019321; TYH2020248). The sponsors had no role in the analysis and interpretation of the data or the manuscript preparation, review, or approval. Funding Information: KMA received a research grant from Astra Zeneca, and is consultant for Gedeon Richter, and received reimbursement for attending a scientific meeting from GSK (Tesaro Bio). RMT received reimbursement for attending a scientific meeting from Olympus. LIL, GHG, YL, RC, ALL, VJS, IEJK, PJK, RJC, RLA, KA, KMA, IB-L, MHB, JLC, SC, PJG, HAG-P, FZG, HAG, LH, MLI-K, KMJ, PKK, NK, TPK, AJK, TK, HL, AKM, BTN, TPN, CN, SMO, SP, NP, CBBR, ARR, TS, RMT, RWMV, YW, YX, LY, JH, and KAOT have no financial conflicts of interest. GHG and RC were panel members of the European Association of Urology (EAU) ad hoc Guideline on Thromboprophylaxis in Urological Surgery. KAOT was chair of the European Association of Urology (EAU) ad hoc Guideline on Thromboprophylaxis in Urological Surgery and panel member of the American Society of Hematology (ASH) Guideline Panel on Prevention of Venous Thromboembolism (VTE) in Surgical Hospitalized Patients. Publisher Copyright: © 2021, The Author(s).Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. Methods We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. Discussion This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. Systematic review registration PROSPERO CRD42021234119Peer reviewe

    Systematic Reviews and Meta-Analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery

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    Objective: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. Background: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. Methods: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. Results: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. Conclusions: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding

    A family of process-based models to simulate landscape use by multiple taxa

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    Context: Land-use change is a key driver of biodiversity loss. Models that accurately predict how biodiversity might be affected by land-use changes are urgently needed, to help avoid further negative impacts and inform landscape-scale restoration projects. To be effective, such models must balance model realism with computational tractability and must represent the different habitat and connectivity requirements of multiple species. Objectives: We explored the extent to which process-based modelling might fulfil this role, examining feasibility for different taxa and potential for informing real-world decision-making. Methods: We developed a family of process-based models (*4pop) that simulate landscape use by birds, bats, reptiles and amphibians, derived from the well-established poll4pop model (designed to simulate bee populations). Given landcover data, the models predict spatially-explicit relative abundance by simulating optimal home-range foraging, reproduction, dispersal of offspring and mortality. The models were co-developed by researchers, conservation NGOs and volunteer surveyors, parameterised using literature data and expert opinion, and validated against observational datasets collected across Great Britain. Results: The models were able to simulate habitat specialists, generalists, and species requiring access to multiple habitats for different types of resources (e.g. breeding vs foraging). We identified model refinements required for some taxa and considerations for modelling further species/groups. Conclusions: We suggest process-based models that integrate multiple forms of knowledge can assist biodiversity-inclusive decision-making by predicting habitat use throughout the year, expanding the range of species that can be modelled, and enabling decision-makers to better account for landscape context and habitat configuration effects on population persistence

    Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

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    Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

    Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology

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    Background: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries.Methods: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty.Discussion: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach.Systematic review registration: PROSPERO CRD42021234119</p
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