A survey of UK General Practitioners about depression, antidepressants and withdrawal: Implementing the 2019 Public Health England Report

Background: In 2019 a literature review indicated that more than half of people who try to come off antidepressants experience withdrawal effects. Both NICE guidelines and the Royal College of Psychiatrists updated their positions in line with that review, and Public Health England published a 152-page report called Dependence and withdrawal associated with some prescribed medicines: an evidence review. The report made several recommendations relevant to GP practice. Method: In order to facilitate implementation of these recommendations an online survey was designed to explore UK GPs’ experiences, opinions, knowledge and needs in relation to depression, antidepressants, and withdrawal. 66 GPs had completed the survey when COVID-19 occurred. Results: In keeping with previous findings, this small sample of GPs had a predominantly psycho-social perspective on the causes of, and treatments for, depression. They broadly considered antidepressants effective for moderate/severe depression and ineffective for minimal/mild depression, for which they preferred psychological therapies and social prescribing. There was a marked lack of consistency in GPs’ knowledge about the incidence and duration of withdrawal effects. Only a minority (29%) felt their knowledge about withdrawal was ‘adequate’ and fewer (17%) believed this about their ‘Ability to distinguish between withdrawal effects and return of the original problem (eg depression)’. Two thirds (68%) would like more training on these matters. Conclusion: It is hoped that even this small sample will be helpful when designing, and seeking funding for, GP training programmes, and when implementing the PHE recommendations for support services, based in the primary care system, for the millions of people contemplating or initiating withdrawal from antidepressants every year in the UK

A second independent audit of electroconvulsive therapy in England, 2019: Usage, demographics, consent, and adherence to guidelines and legislation

Objectives. To assess progress towards improving the administering of Electroconvulsive therapy (ECT) in England since an audit covering 2011, 2013 and 2015. The same information was gathered, for 2019, on usage, demographics, consent, and adherence to national guidelines and the Mental Health Act. Design and Methods. Freedom of Information Act requests were sent to 56 National Health Service Trusts. Results. Thirty-seven trusts (66%) provided data. The gradual decline in the use of ECT in England has levelled off at about 2,500 people per year. There was a 47-fold difference between the Trusts with the highest and lowest rates per capita. Most recipients are still women (67%), and over 60 (58%). Only one Trust could report how many people received psychological therapy prior to ECT, as required by government (N.I.C.E.) guidelines. More than a third of ECT (37%) is still given without consent, with 18% of Trusts non-compliant with legislation concerning second opinions. There were slight declines, compared to a previous audit, in the use of standardised depression scales, down to 30%, and standardised measures of cognitive dysfunction, down to 24%. Only six Trusts provided any data for positive outcomes; seven for adverse effects. None provided data on efficacy or adverse effects beyond end of treatment. Twelve used identical sentences to each other, verbatim, in response to one or more questions. Conclusions. Given the apparent failure of current monitoring and accrediting ECT clinics in England, by the Royal College of Psychiatrists’ ECT Accreditation Service (ECTAS), an independent government sponsored review is urgently needed

Accretion stream mapping with genetically modified "fire-flies"

We apply an eclipse mapping technique using `genetically modified fire-flies' to the eclipse light curves of HU Aqr and EP Dra. The technique makes as few assumptions as possible about the location of accretion stream material, allowing the emission to be located anywhere within the Roche lobe of the white dwarf. We model two consecutive eclipses in the UBVR_c band for HU Aqr, and four consecutive `white'-light eclipses for EP Dra, to determine the changing brightness distribution of stream material. We find fire-fly distributions which are consistent with accretion through a curtain of material in both HU Aqr and EP Dra, and show that the previously assumed two part ballistic and magnetic trajectory is a good approximation for polars. Model fits to the colour band data of HU Aqr indicate that the material confined to the magnetic field lines is brightest, and most of the emission originates from close to the white dwarf. There is evidence for emission from close to a calculated ballistic stream in both HU Aqr and EP Dra.We propose that a change in the stream density causes a change in the location of the bright material in the accretion stream in EP Dra.Comment: accepted for publication in MNRA

Why do patients decline surgical trials? Findings from a qualitative interview study embedded in the Cancer Research UK BOLERO trial (Bladder cancer: Open versus Lapararoscopic or RObotic cystectomy)

Background Surgical trials have typically experienced recruitment difficulties when compared with other types of oncology trials. Qualitative studies have an important role to play in exploring reasons for low recruitment, although to date few such studies have been carried out that are embedded in surgical trials. The BOLERO trial (Bladder cancer: Open versus Lapararoscopic or RObotic cystectomy) is a study to determine the feasibility of randomisation to open versus laparoscopic access/robotic cystectomy in patients with bladder cancer. We describe the results of a qualitative study embedded within the clinical trial that explored why patients decline randomisation. Methods Ten semi-structured interviews with patients who declined randomisation to the clinical trial, and two interviews with recruiting research nurses were conducted. Data were analysed for key themes. Results The majority of patients declined the trial because they had preferences for a particular treatment arm, and in usual practice could choose which surgical method they would be given. In most cases the robotic option was preferred. Patients described an intuitive ‘sense’ that favoured the new technology and had carried out their own inquiries, including Internet research and talking with previous patients and friends and family with medical backgrounds. Medical histories and lifestyle considerations also shaped these personalised choices. Of importance too, however, were the messages patients perceived from their clinical encounters. Whilst some patients felt their surgeon favoured the robotic option, others interpreted ‘indirect’ cues such as the ‘established’ reputation of the surgeon and surgical method and comments made during clinical assessments. Many patients expressed a wish for greater direction from their surgeon when making these decisions. Conclusion For trials where the ‘new technology’ is available to patients, there will likely be difficulties with recruitment. Greater attention could be paid to how messages about treatment options and the trial are conveyed across the whole clinical setting. However, if it is too difficult to challenge such messages, then questions should be asked about whether genuine and convincing equipoise can be presented and perceived in such trials. This calls for consideration of whether alternative methods of generating evidence could be used when evaluating surgical techniques which are established and routinely available

Return to Play after Cervical Spine Injuries: A Consensus of Opinion

Study Design: Survey. Objective: Sports-related spinal cord injury (SCI) represents a growing proportion of total SCIs but lacks evidence or guidelines to guide clinical decision-making on return to play (RTP). Our objective is to offer the treating physician a consensus analysis of expert opinion regarding RTP that can be incorporated with the unique factors of a case for clinical decision-making. Methods: Ten common clinical scenarios involving neurapraxia and stenosis, atlantoaxial injury, subaxial injury, and general cervical spine injury were presented to 25 spine surgeons from level 1 trauma centers for whom spine trauma is a significant component of their practice. We evaluated responses to questions about patient RTP, level of contact, imaging required for a clinical decision, and time to return for each scenario. The chi-square test was used for statistical analysis, with p \u3c 0.05 considered significant. Results: Evaluation of the surgeons’ responses to these cases showed significant consensus regarding return to high-contact sports in cases of cervical cord neurapraxia without symptoms or stenosis, surgically repaired herniated disks, and nonoperatively healed C1 ring or C2 hangman’s fractures. Greater variability was found in recommendations for patients showing persistent clinical symptomatology. Conclusion: This survey suggests a consensus among surgeons for allowing patients with relatively normal imaging and resolution of symptoms to return to high-contact activities; however, patients with cervical stenosis or clinical symptoms continue to be a challenge for management. This survey may serve as a basis for future clinical trials and consensus guidelines

Efficacy, Safety, and Timing of Anticoagulant Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients With Acute Spinal Cord Injury: A Systematic Review

Study Design: Systematic review. Objectives: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to initiate and/or discontinue anticoagulant, mechanical, and/or prophylactic inferior vena cava filter following acute SCI? (3) What is the cost-effectiveness of these treatment options? Methods: A systematic literature search was conducted to identify studies published through February 28, 2015. We sought randomized controlled trials evaluating efficacy and safety of antithrombotic strategies. Strength of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Nine studies satisfied inclusion criteria. We found a trend toward lower risk of DVT in patients treated with enoxaparin. There were no significant differences in rates of DVT, PE, bleeding, and mortality between patients treated with different types of low-molecular-weight heparin or between low-molecular-weight heparin and unfractionated heparin. Combined anticoagulant and mechanical prophylaxis initiated within 72 hours of SCI resulted in lower risk of DVT than treatment commenced after 72 hours of injury. Conclusion: Prophylactic treatments can be used to lower the risk of venous thromboembolic events in patients with acute SCI, without significant increase in risk of bleeding and mortality and should be initiated within 72 hours. © 2017, © The Author(s) 2017

A thermally stable {FeNO}(8) complex: properties and biological reactivity of reduced MNO systems

Reduced nitrogen oxide ligands such as NO−/HNO or nitroxyl participate in chemistry distinct from nitric oxide (NO). Nitroxyl has been proposed to form at heme centers to generate the Enemark–Feltham designated {FeNO}8 system. The synthesis of a thermally stable {FeNO}8 species namely, [Co(Cp*)2][Fe(LN4)(NO)] (3), housed in a heme-like ligand platform has been achieved by reduction of the corresponding {FeNO}7 complex, [Fe(LN4)(NO)] (1), with decamethylcobaltocene [Co(Cp*)2] in toluene. This complex readily reacts with metMb, resulting in formation of MbNO via reductive nitrosylation by the coordinated HNO/NO−, which can be inhibited with GSH. These results suggest that 3 could serve as a potential HNO therapeutic. Spectroscopic, theoretical, and structural comparisons are made to 1 and the {CoNO}8 complex, [Co(LN4)(NO)] (2), an isoelectronic analogue of 3

Palliative Medicines for Children – A New Frontier in Paediatric Research

Objectives: This paper seeks to highlight from a UK perspective the current lack of a research evidence base in paediatric palliative care that has resulted in a paucity of available medicines with appropriate formulations (strength and dosage form) to provide symptom management for children with life-limiting illnesses and to raise awareness of this group of “therapeutic orphans”. Currently, clinicians have limited, often unsuitable medication choices for their paediatric palliative care patients, with little hope of moving away from the status quo. / Key findings: Most medicines used in children receiving palliative care are old and off-patent drugs, developed for and tested in an adult population. Many are not available in suitable formulations (dosage form and strength) for administration to children and there are often no age-related profiles of adverse drug reactions or for safe dosing. / Summary: Existing regional paediatric palliative care networks and support organisations should lobby funding bodies and the academic community to support appropriate research for this group of therapeutic orphans. Support must also be provided to pharmaceutical companies in the development of suitable products with appropriate formulations

A Metastatic Middle Cerebral Artery Aneurysm Caused by an Intraluminal Bronchogenic Tumor Embolus

Objective and Importance: To describe the clinical presentation and neuropathological findings of metastatic cerebral aneurysms of bronchogenic origin. Metastatic bronchogenic cerebral aneurysms are exceptionally rare and have only been reported in association with high grade hemorrhage. Clinical Presentation: One patient presenting with a history of headache, speech difficulty, left-sided “numbness”, left seventh nerve palsy and left hemiparesis was found to have intraparenchymal and subarachnoid hemorrhage with an aneurysm of the right distal Sylvian middle cerebral artery. Intervention: Pterional craniotomy with excision of mycotic segment. Surgical specimen sent to pathology for routine histology and immunohistochemistry. Conclusion: Patients with metastatic cerebral aneuryms of bronchogenic origin usually present with subarachnoid hemorrhage, contrary to prior observations that “hemorrhage from neoplasia-induced aneurysms is paradoxically rare.” A tumor embolus should be considered in the differential diagnosis of a mycotic aneurysm