The management of type 2 diabetes with fixed‐ratio combination insulin degludec/liraglutide (IDegLira) versus basal‐bolus therapy (insulin glargine U100 plus insulin aspart): a short‐term cost‐effectiveness analysis in the UK setting

Aim: To evaluate the cost‐effectiveness of IDegLira versus basal‐bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK. Methods: A Microsoft Excel model was used to evaluate the cost‐utility of IDegLira versus BBT over a 1‐year time horizon. Clinical input data were taken from the treat‐to‐target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c <7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event‐related disutilities were taken from published sources. Extensive sensitivity analyses were performed. Results: IDegLira was associated with an improvement of 0.05 quality‐adjusted life years (QALYs) versus BBT, due to reductions in non‐severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost‐effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses. Conclusions: IDegLira is a cost‐effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK

TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243]

Agitated or violent patients constitute 10% of all emergency psychiatric treatment. Management guidelines, the preferred treatment of clinicians and clinical practice all differ. Systematic reviews show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments. Worldwide, current treatment is not based on evidence from randomised trials. In Brazil, the combination haloperidol-promethazine is frequently used, but no studies involving this mix exist. TREC-Rio (Tranquilização Rápida-Ensaio Clínico [Translation: Rapid Tranquillisation-Clinical Trial]) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro, Brazil. TREC-Rio is a randomised, controlled, pragmatic and open study. Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed. TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible. Because the design of this trial does not substantially complicate clinical management, and in several aspects simplifies it, the study can be large, and treatments used in everyday practice can be evaluated

The Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE): study protocol for a cluster randomised controlled trial

Introduction People with type 1 diabetes (T1DM) require insulin therapy to sustain life, and need optimal glycaemic control to prevent diabetic ketoacidosis and serious long-term complications. Insulin is generally administered using multiple daily injections but can also be delivered using an infusion pump (continuous subcutaneous insulin infusion), a more costly option with benefits for some patients. The UK National Institute for Health and Care Excellence (NICE) recommend the use of pumps for patients with the greatest need, citing insufficient evidence to approve extension to a wider population. Far fewer UK adults use pumps than in comparable countries. Previous trials of pump therapy have been small and of short duration and failed to control for training in insulin adjustment. This paper describes the protocol for a large randomised controlled trial comparing pump therapy with multiple daily injections, where both groups are provided with high-quality structured education. Methods and analysis A multicentre, parallel group, cluster randomised controlled trial among 280 adults with T1DM. All participants attended the week-long dose adjustment for normal eating (DAFNE) structured education course, and receive either multiple daily injections or pump therapy for 2 years. The trial incorporates a detailed mixed-methods psychosocial evaluation and cost-effectiveness analysis. The primary outcome will be the change in glycosylated haemoglobin (HbA1c) at 24 months in those participants whose baseline HbA1c is at or above 7.5% (58 mmol/mol). The key secondary outcome will be the proportion of participants reaching the NICE target of an HbA1c of 7.5% (58 mmol/mol) or less at 24 months. Ethics and dissemination The protocol was approved by the Research Ethics Committee North West, Liverpool East and received Medicines and Healthcare products Regulatory Agency (MHRA) clinical trials authorisation. Each participating centre gave National Health Service R&D approval. We shall disseminate study findings to study participants and through peer reviewed publications and conference presentations, including lay user groups. Trial registration number ISRCTN 61215213

A systematic review of biomarkers for disease progression in Parkinson's disease

Peer reviewedPublisher PD

Development of an international, multidisciplinary, patient-centered Standard Outcome Set for Multiple Sclerosis: The S.O.S.MS project

BACKGROUND: Currently, outcomes of Multiple Sclerosis (MS) are not standardized and it is unclear which outcomes matter most to people living with MS. A consensus between patients and healthcare professionals on which outcomes to measure and how, would facilitate a move towards value-based MS care. OBJECTIVE: to develop an internationally accepted, patient-relevant Standard Outcome Set for MS (S.O.S.MS). METHODS: A mixed-method design was used, including a systematic literature review, four patient focus groups (n=30) and a RAND-modified Delphi process with seventeen MS experts of five disciplines from seven countries (the Netherlands, United States of America, Portugal, Ireland, India, New Zealand, Switzerland and Turkey). RESULTS: A standard outcome set for MS was defined, consisting of fourteen outcomes divided in four domains: disease activity (n=3), symptoms (n=4), functional status (n=6), and quality of life (n=1). For each outcome, an outcome measure was selected and the measurement protocol was defined. In addition, seven case-mix variables were selected. CONCLUSION: This standard outcome set provides a guideline for measuring outcomes of MS in clinical practice and research. Using this set to monitor and (inter)nationally benchmark real-world outcomes of MS can support improvement of patient value and ultimately guide the transition towards value-based MS care

Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement

Background: Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. Design: A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved. Results: Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients. Conclusions: This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.info:eu-repo/semantics/publishedVersio

Present and future pharmacotherapeutic agents in heart failure: an evolving paradigm

Many conditions culminate in heart failure (HF), a multi-organ systemic syndrome with an intrinsically poor prognosis. Pharmacotherapeutic agents that correct neurohormonal dysregulation and haemodynamic instability have occupied the forefront of developments within the treatment of HF in the past. Indeed, multiple trials aimed to validate these agents in the 1980s and early 1990s, resulting in a large and robust evidence-base supporting their use clinically. An established treatment paradigm now exists for the treatment of HF with reduced ejection fraction (HFrEF), but there have been very few notable developments in recent years. HF remains a significant health concern with an increasing incidence as the population ages. We may indeed be entering the surgical era for HF treatment, but these therapies remain expensive and inaccessible to many. Newer pharmacotherapeutic agents are slowly emerging, many targeting alternative therapeutic pathways, but with mixed results. Metabolic modulation and manipulation of the nitrate/nitrite/nitric oxide pathway have shown promise and could provide the answers to fill the therapeutic gap between medical interventions and surgery, but further definitive trials are warranted. We review the significant evidence base behind the current medical treatments for HFrEF, the physiology of metabolic impairment in HF, and discuss two promising novel agents, perhexiline and nitrite

European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer

The current status and future of andrology: A consensus report from the Cairo workshop group

Background In attempting to formulate potential WHO guidelines for the diagnosis of male infertility, the Evidence Synthesis Group noted a paucity of high-quality data on which to base key recommendations. As a result, a number of authors suggested that key areas of research/evidence gaps should be identified, so that appropriate funding and policy actions could be undertaken to help address key questions. Objectives The overall objective of this Consensus workshop was to clarify current knowledge and deficits in clinical laboratory andrology, so that clear paths for future development could be navigated. Materials and Methods Following a detailed literature review, each author, prior to the face-to-face meeting, prepared a summary of their topic and submitted a PowerPoint presentation. The topics covered were (a) Diagnostic testing in male fertility and infertility, (b) Male fertility/infertility in the modern world, (c) Clinical management of male infertility, and (d) The overuse of ICSI. At the meeting in Cairo on February 18, 2019, the evidence was presented and discussed and a series of consensus points agreed. Results The paper presents a background and summary of the evidence relating to these four topics and addresses key points of significance. Following discussion of the evidence, a total of 36 consensus points were agreed. Discussion The Discussion section presents areas where there was further debate and key areas that were highlighted during the day. Conclusion The consensus points provide clear statements of evidence gaps and/or potential future research areas/topics. Appropriate funding streams addressing these can be prioritized and consequently, in the short and medium term, answers provided. By using this strategic approach, andrology can make the rapid progress necessary to address key scientific, clinical, and societal challenges that face our discipline now and in the near future