Acupuncture for the treatment of phantom limb syndrome in lower limb amputees: a randomised controlled feasibility study

Background: Post amputation, the complication phantom limb pain (PLP) is prevalent and difficult to manage. This study aimed to determine whether it was feasible and acceptable to undertake a definitive multi-centred randomised controlled trial assessing the effectiveness of acupuncture for treating lower limb amputees with PLP. Methods: A mixed methods embedded design including a randomised controlled trial and semi-structured interviews was undertaken. A total of 15 participants with PLP were randomly assigned to receive either 8 pragmatic Traditional Chinese Medicine acupuncture treatments and usual care or usual care alone over four weeks. Outcomes measures were completed at baseline, weekly throughout the study and at one month post completion of the study and included; a numerical pain rating scale, Short-Form McGill Pain Questionnaire 2, EQ-5D-5L, Hospital Anxiety and Depression Scale, Perceived Stress Scale 10 item, Insomnia Severity Index, Patient Global Impression of Change. Post completion of the trial, participants in the acupuncture group were interviewed about their experience. Feasibility specific data were also collected. Results: Of 24 amputees meeting the study inclusion criteria 15 agreed to participate (recruitment rate 62.50%). Qualitatively acupuncture was perceived to be beneficial and effective. Quantitatively acupuncture demonstrated clinically meaningful change in average pain intensity (raw change=2.69) and worst pain intensity (raw change = 4.00). Feasibility specific data identified that before undertaking a definitive trial, recruitment, practitioner adherence to the acupuncture protocol, completion of outcome measures at one month follow up and blinding should be addressed. Appropriate outcome measures were identified for use in a definitive trial. Data were generated for future sample size calculations (effect size 0.64). Allowing for a 20% dropout rate, a sample size of 85 participants per group would be needed in a future definitive trial. Conclusions: A future definitive trial may be possible if the areas identified in this study are addressed. As acupuncture may be effective at treating PLP and as this feasibility study suggests a definitive trial may be possible, a multi-centred trial with adequate sample size and blinding is now needed. Trial registration: ClinicalTrials.gov: NCT02126436. Registration date: 9.4.2014

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Training future generations to deliver evidence-based conservation and ecosystem management

Data availability statement: No data was used in this study.Peer review: The peer review history for this article is available at: https://publons.com/publon/10.1002/2688-8319.12032.Supporting Information: eso312032-sup-0001-SuppMat.docx (21.1 KB) available at: https://besjournals.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1002%2F2688-8319.12032&file=eso312032-sup-0001-SuppMat.docx. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.Copyright © 2021 The Authors. 1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. 2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. 3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. 4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas. Making informed conservation and ecosystem management choices is based upon a sound understanding of the relevant evidence. There is an increasing wealth of conservation science available, and access to this is becoming easier. But, are conservation practitioners being trained to utilize this information? In conservation, decision-making is often based upon past experience or expert knowledge, as opposed to the full body of scientific literature (e.g., Pullin, Knight, Stone, & Charman, 2004; Rafidimanantsoa, Poudyal, Ramamonjisoa, & Jones, 2018). The failure to include scientific evidence in decision-making has the potential to reduce the effectiveness of management, or even lead to detrimental actions being undertaken (Walsh, Dicks, & Sutherland, 2015). Evidence-based conservation (EBC) seeks to avoid this by providing tools to facilitate and inform decision-making. To do this, scientific evidence is collated and critically appraised for its quality and relevance, and integrated with other knowledge, experience, values and costs (Sutherland, Pullin, Dolman, & Knight, 2004). Wider adoption of EBC requires conservation professionals to be trained in its principles and taught how to use it to inform conservation decision-making.MAVA Foundation; Arcadia Fund

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Die Delphi-Methode - eine Einführung

Die Delphi-Methode hat sich von einem „Klassiker“ zu unterschiedlichen Delphi-Methoden oder „Typen“ entwickelt, die sehr unterschiedliche Funktionen haben können und in verschiedenen Themenfeldern Einsatz finden. Dabei setzen sich mehr und mehr die online-Varianten durch. Beliebt sind auch Delphi-Methoden mit Instant-Feedback wie das Realtime Delphi. Diese Einführung erläutert die unterschiedlichen Definitionen, Typen und Einsatzfelder und zeigt die wichtigsten zu beachtenden Punkte bei der Anwendung eines der Delphi-Verfahren auf. Besonderes Augenmerk ist hier auf die Teilnehmenden und ihre unterschiedlichen Hintergründe und Expertisen sowie die Gestaltung des „Fragebogens“ zu legen. So sind typische Fragen eines Delphis die nach der Wichtigkeit oder dem Zeithorizont der Verwirklichung einer Zukunftsthese, z. B. einer Problemlösung im Gesundheitssystem, einer Technologie oder Bildungsmaßnahme. Die Delphi-Methode wird auch in Zukunft einen Platz im Methoden-Kanon der Zukunftsforschung sowie der allgemeinen empirischen Forschung unterschiedlicher Disziplinen (z. B. Betriebswirtschaftslehre) haben. Sie wird mehr und mehr in Gesamtprozesse integriert und als ein Baustein im Methoden-Mix, z. B. mit Szenarien gekoppelt, angesehen

Development of a model on factors affecting instrumental activities of daily living in people with mild cognitive impairment - A Delphi study

Introduction: The level of function of instrumental activities of daily living (IADL) is crucial for a person's autonomy. A clear understanding of the nature of IADL and its limitations in people with mild cognitive impairment (MCI) is lacking. Literature suggests numerous possible influencing factors, e.g. cognitive function, but has not considered other domains of human functioning, such as environmental factors. Our aim was to develop a comprehensive model of IADL functioning that depicts the relevant influencing factors. Methods: We conducted a four-round online Delphi study with a sample of international IADL experts (N = 69). In the first round, panelists were asked to mention all possible relevant cognitive and physical function factors, as well as environmental and personal factors, that influence IADL functioning. In the subsequent rounds, panelists rated the relevance of these factors. Consensus was defined as: 1) ≥70% agreement between panelists on a factor, and 2) stability over two successive rounds. Results: Response rates from the four rounds were high (83 to 100%). In the first round, 229 influencing factors were mentioned, whereof 13 factors reached consensus in the subsequent rounds. These consensual factors were used to build a model of IADL functioning. The final model included: five cognitive function factors (i.e. memory, attention, executive function, and two executive function subdomains -problem solving / reasoning and organization / planning); five physical function factors (i.e. seeing functions, hearing functions, balance, gait / mobility functions and functional mobility functions); two environmental factors (i.e. social network / environment and support of social network / environment); and one personal factor (i.e. education). Conclusions: This study proposes a comprehensive model of IADL functioning in people with MCI. The results from this Delphi study suggest that IADL functioning is not merely affected by cognitive function factors, but also by physical function factors, environmental factors and personal factors. The multiplicity of factors mentioned in the first round also underlines the individuality of IADL functioning in people with MCI. This model may serve as a basis for future research in IADL functioning in people with MCI