bluuebunny/crossref_metadata_2025_split huggingface dataset:
PAPER: ACCUMULATION OF IRREVERSIBLE DISABILITY IN MULTIPLE SCLEROSIS - LESSONS FROM NATURAL HISTORY STUDIES AND THERAPEUTIC TRIALS
Authors: Confavreux C , Vukusic S 
Published: January 2025

There is good evidence that relapses in multiple sclerosis (MS) are the clinical counterpart of acute focal inflammation of the central nervous system (CNS), whereas progression is that of chronic diffuse neurodegeneration. The classical view is to consider MS solely as an organ-specific auto-immune disease, i.e. inflammation is the cause of neurodegeneration. Recurring relapses eventually lead to accumulation of disability, and clinical progression could also result from subclinical relapses. Recent observations suggest that this classical concept should be challenged. In particular, striking results have come from the study of the natural history of MS in the Lyons MS Natural History Cohort.1 Progression of irreversible disability from the assignment of a score of 4 on Kurtzke's disability status scale (DSS) to the assignment of a score of 6 or 7 is unaffected by the presence or the absence of a relapsing-remitting phase before the chronic progressive phase of MS. The same observation is true regarding the presence or absence of superimposed relapses during the progressive phase, either primary or secondary. Beta interferons lead to a 30% reduction in the relapse rate and to a more than 50% reduction in conventional magnetic resonance imaging (MRI) activity. Despite this effect on inflammation, the effect of interferons on disability is only marginal and this small effect may be relapse-reduction-driven. Administration of Campath-1H to MS patients with very active disease, results in a profound and prolonged lymphopenia, and the suppression of clinical and MRI activity. In spite of this, progression of clinical disability and cerebral atrophy still occurs. These observations support the view that in MS, relapses and focal inflammation do not influence the rate of progression of irreversible disability and diffuse neurodegeneration. They are consistent with what was shown in individual patients in the 1970s by performing serial quantitative neurological examinations over several years, and with what is emerging currently from early and serial structural brain MRI studies.
Pneumothorax following non-invasive ventilation for acute asthma
Authors: Medford AR , Pepperell JCT 
Published: January 2025

We describe a case of pneumothorax occurring in an asthmatic following NIV in a high dependency setting. He had been persistently hypoxaemic related to bilateral lower lobe collapse from extensive mucus plugging with no other secondary cause for his hypoxaemia or mucus plugging found. There was no obvious evidence of initial pneumothorax and we presume that barotrauma related to NIV was responsible. We review the limited evidence for NIV in acute asthma and the recommendations from national guidelines. We conclude that NIV should only be considered in acute asthma in the context of a randomised controlled trial and applied only in a high dependency or intensive therapy unit. Pneumothorax must be excluded in asthmatics that deteriorate suddenly on NIV.
The Solanaceae: foods and poisons
Authors: Lee MR 
Published: January 2025

The plant family Solanaceae contains important foodstuffs such as the potato, tomato and aubergine, together with powerful poisons including mandrake, henbane and deadly nightshade. In the first article in this short series on the family, the history and importance of the potato are described. It was first cultivated by the Inca people in the altiplano of the Andes in prehistoric times. Then it was translocated to Europe by the Spanish invaders. Originally reviled as ‘peasant food’, it was regarded with great suspicion as an evil plant and a potential cause of leprosy. Over several centuries it gradually became established throughout Britain, France and the continent, and in particular in Ireland, where its growth allowed the population to expand very rapidly between 1750 and 1850. In the late 1840s, nemesis arrived in the form of the potato blight and the Irish famine. The ‘tatties’ went black, a great hunger ensued and thousands died. Later, the causative fungus was isolated and steps were taken to avoid further similar disasters. It is not generally appreciated that potatoes can be poisonous if they are turning green or sprouting (chitting). The tuber is then producing toxic quantities of the alkaloid a-solanine. The clinical syndrome of potato poisoning is described briefly.
Septic deep venous thrombophlebitis and distant emboli in injecting drug users – treatment experience and outcome
Authors: Hakeem MJML , Bhattacharyya DN 
Published: January 2025

Injecting drug use is a world-wide problem responsible for numerous minor and major complications which are well recognised. After years of injecting drug use, superficial and peripheral veins may become obliterated and the committed drug user attempts to inject drugs into proximal and more central veins. Besides the potential for mechanical and toxic complications such as vascular injury, intra-arterial drug injection, pneumothoraces, mycotic aneurysms and deep abscess formation, use of large proximal veins may result in life threatening septic deep vein thrombophlebitis.1, 2, 5 Aseptic and septic thrombophlebitis of peripheral veins is a well recognised complication of intravenous catheters and usually responds to removal of the intravascular device. Catheter related septic thrombophlebitis of proximal large veins and great central veins are also widely reported. However septic or suppurative thrombophlebitis of deep veins in IDUs characterised by micro abscess formation within the thrombotic veins and repeated bacterial embolisation into the circulation, is a severe systemic disease which has received little attention in the literature.1, 3 We recently observed ten IDUs (11 episodes) with septic DVT admitted to the infectious diseases unit in Fife, Scotland within a period of 28 months. This report summarises our experience in the diagnosis,treatment and follow-up of these patients.
Vex not his ghost: King Lear and end-of-life care
Authors: Jeffrey E , Jeffrey D 
Published: January 2025

King Lear is not limited to a single ethical dilemma but is a play about the suffering of mankind. This paper investigates how elements of Shakespeare’s play might enrich our understanding of the challenges and opportunities of modern end-of-life care. The paper addresses the following key questions: How can King Lear inform our understanding of suffering and pain in a clinical context? What can King Lear teach the professional in terms of communication with a terminally ill patient and their family? How does Shakespeare illuminate sensitive areas of the discourse on suicide in the elderly?
ALLOPURINOL AND STEVENS-JOHNSON RISK
Authors: Perry Martin E 
Published: January 2025

Dr Foong helpfully highlights the well-established rare link between allopurinol and Stevens-Johnson syndrome, by reviewing the results of the EuroSCAR study (HBB Foong. Allopurinol and the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis. J R Coll Physicians Edinb 2009; 39:144–5). At rates of two per million population, it remains an extremely unusual phenomenon. His conclusions that ‘more often than not the drug is prescribed for asymptomatic hyperuricaemia’ are erroneous and lack evidence. The retrospective report of eight patients from 23 years ago and literature review which he quotes clearly do not provide a clear enough sample size to form a judgement. Hypersensitivity of a more benign nature is frequently mentioned as a reason for discontinuing allopurinol. However, it is estimated that 95% of patients are able to tolerate allopurinol.1 Side effects can include rash, diarrhoea, leukopenia, pruritis and fever. If the manifestations are only cutaneous, then desensitisation can be attempted commencing at doses as low as 50 μg and increasing to 100 mg over a four-week period. More than 70% of such patients are able to continue to take allopurinol, although sometimes late adjustment of the dose may be required. Education for practitioners regarding desensitisation regimens should allow more patients to tolerate the drug. Gout is undertreated at present, and patients should be on doses of allopurinol that allow a serum urate of <0.36 mmol/l.2,3 Dose titration can escalate to 900 mg if required. Undertreatment leads to flare and tophaceous disease, with radiographic damage and disability.4 Adverse reactions with allopurinol are unfortunate but extremely rare and should not be used as a reason for lowering the appropriate dosage of allopurinol as agreed in both national and international guidelines.2,3
Author’s reply
Authors: Foong HBB 
Published: January 2025

I thank Dr Perry for his interest in my article. I agree with him that if the manifestations of the side effects of allopurinol are mild, then desensitisation can be attempted at a lower dose. However, isolated asymptomatic hyperuricaemia does not warrant the use of allopurinol. One must distinguish the difference between gout and hyperuricaemia. Dr Perry’s references on the rheumatology guidelines for the management of gout apply to cases of gout and not to hyperuricaemia.1 In fact, the indications for allopurinol therapy are tophaceous gout, major uric acid overproduction (proven by urinary excretion >53 mmol/24 hours) frequent gouty attacks, recurrent uric acid renal calculi and prevention of acute urate nephropathy in patient receiving cytotoxic therapy for malignancies.2 In a study by Khoo3 a total of 13 patients were admitted for severe cutaneous adverse reactions to allopurinol during a three-year period. Almost 92% of them suffered from allopurinol hypersensitivity reactions, which included four patients with Stevens-Johnson syndrome. Allopurinol hypersensitivity syndrome, in contrast to other purely cutaneous drug eruptions, deserves special attention because of its multi-organ involvement, the liver and kidneys being most commonly affected. It was interesting to note that none of the 13 patients had clear clinical indications for allopurinol therapy. Asymptomatic hyperuricaemia is not uncommon, affecting an estimate of 5–8% of the population. As the risks, morbidity and mortality outweigh the benefits, it should only be prescribed when it is truly indicated.
INSULIN PEN DEVICES
Authors: Reith Sheila 
Published: January 2025

In their recent article (Insulin delivery devices. J R Coll Physicians Edinb 2009; 39:l46-50) Dr Graveling and Dr McIntyre state that insulin pen devices were developed by Dr John Ireland in l98l. The first pen device was actually designed jointly by John Paton of the Department of Clinical Physics and Bioengineering (DCP&B) in Glasgow, the late Dr John Ireland and myself.1 After the initial trials with the prototype pen, further devices were made by the DCP&B, and then Hypoguard was licensed to produce the first commercial insulin pen with the royalties being paid to the Greater Glasgow Health Board (GGHB), which held the patent on our behalf. Following this agreement, Michael Forsyth and other MPs tabled an Early Day Motion in the Commons congratulating John Paton, John Ireland and myself on our invention and on this example of co-operation between the NHS and private industry.2 Later, the patent was sold to Novo by GGHB. None of the three inventors received any financial reward. This letter is not in any way intended to minimise the contribution made by Dr John Ireland to this device, which is widely used today, but simply to set the record straight. I hope that this information will be of interest to readers of The Journal.
PAIN PALLIATION FOR BONE METASTASES
Authors: Syed GMS 
Published: January 2025

This refers to the symposium report ‘Palliative care in your hospital’ (Buchanan D.J R Coll Physicians Edin 2009; 39:252-6). In his discussion of new interventions Dr Edwards makes no reference to an important strategy for pain palliation due to skeletal metastases. I am referring to systemic radiotracer therapy. It may not be considered a ‘new’ way as the first therapy was performed in l941.1 There has been significant progress in systemic radiotracer therapy since then with the focus on developing specific and less toxic compounds. While phosphorus-32 has been in use for many decades and revisited,2 newer compounds such as Sr89,3 Sm153 EDTMP,4 Rel86 HEDP and Sn117m pentetate5 have been successfully employed for pain palliation. Targeted radiotracer therapies can ameliorate pain in 40-80% patients. Therapy is done on an outpatient basis. Onset of relief may take five days. The patient can be pain-free for about three months. Repeat therapies are indicated in patients who benefit from the first dose. Improved performance and quality of life has been reported in several studies. Patients with osteoblastic lesions show good response. Bone marrow suppression is a known toxicity but is usually mild and reversible in the majority. The cost of newer compounds limits frequent use. However, it is worthwhile when one takes into consideration the cost of alternate intervention and the potential benefit to the patient.
Do low-risk patients really need follow-up after a pulmonary embolism?
Authors: Alexander Lesley , Burnie Susan , Rossiter Catherine , Isles Chris 
Published: January 2025

Background: The British Thoracic Society recommend that pulmonary embolism (PE) patients with low-risk Pulmonary Embolism Severity Index (PESI) scores are considered for outpatient (OP) management, in settings where robust pathways for follow-up and monitoring exist. Methods: Retrospective cohort study. We reviewed the electronic records of 109 consecutive PE patients considered appropriate for OP management. Primary outcomes were the incidence of recurrent venous thromboembolism, major bleeding, mortality at 1 year and evidence of chronic thromboembolic pulmonary hypertension (CTEPH). Results: Low-risk PESI scores (I–II) were recorded in 78 (72%) patients, with higher scores a consequence of age and comorbidity rather than haemodynamic instability. There was a low rate of adverse outcomes despite a lack of formal follow up for most patients. There was no evidence of CTEPH in 34 patients who underwent echocardiography. Conclusion: Our analysis challenges the need for robust follow-up pathways for all patients with pulmonary embolism.
The Reconfiguration of Human Education in an Uncertain World
Authors: Fan (范国睿) Guorui 
Published: January 2025

Purpose In response to contemporary global challenges in politics, economics, and technology, coupled with escalating uncertainties, there arises an imperative to reconstruct an innovative and dynamic education system centered around the advancement of human well-being and sustainable development. Design/Approach/Methods Drawing upon empirical data from reputable international organizations, such as the United Nations, United Nations Educational, Scientific and Cultural Organization (UNESCO), the World Bank, and the Organisation for Economic Co-operation and Development (OECD), this study analyzes the uncertainties confronting world development. Furthermore, it elucidates the challenges and opportunities embedded in educational reform, delving into the complexities of contemporary uncertainties. Findings First, the enduring repercussions of the pandemic, including the persistent effects of “long COVID-19,” heightened geopolitical insecurities, repercussions of sluggish global economic growth, and challenges and opportunities posed by smart technology to economic and social development collectively contribute to an increasingly uncertain global landscape. Second, the inherent conservatism of the prevailing educational systems poses challenges in adapting to the evolving needs of social development. The uncertainty in economic and social development weakens societal support for educational reform, and a deteriorating labor market compels the re-evaluation of the education system rooted in industrialism, facing transformative challenges from generative artificial intelligence. Finally, recognizing the urgent need for revolutionary changes in human education, this study advocates for the expeditious reshaping of a new humanistic education paradigm. Originality/Value This study envisions a novel educational model capable of addressing the challenges posed by intelligent technology and emphasizes the creation of an open and dynamic education system by proposing a reconstruction of the education system oriented toward promoting human health and sustainable development. This study systematically examines the diverse uncertainties confronting human development, critically reflects on the inadequacies of the modern education system rooted in industrialism, and issues a cautionary call for the transition toward an intelligent education system.
Subacute Latissimus Dorsi Tendon Repair via a Single Posterior Incision
Authors: Spears Thomas , Luchini Patrick , Nayfa Robert , Chang Peter , LeClere Lance 
Published: January 2025

Background: This is a rare case of the surgical treatment of a subacute presentation of a latissimus dorsi tendon rupture via a posterior single-incision approach. Indications: The patient had extensive conservative, nonoperative treatment that failed, and ultimately a surgical intervention was required to return to his activities of daily living. Technique Description: The patient is positioned in a lateral decubitus position. A 10-cm incision is created along the posterior axillary fold. Sharp and blunt dissection is utilized to carefully mobilize the chronic tendon rupture. The tendon is captured with 2 suture tapes utilizing a locking Krackow whipstitch. The tendon footprint is identified between the pectoralis major and teres major. The insertion point is prepared with a Cobb to debride the soft tissue and decorticate the bone bed to optimize healing. Two endobuttons are loaded with the suture tapes and then passed through unicortical holes drilled in the tendon bed. Care is taken to ensure the 90° external rotation of the tendon is achieved. A tendon-slide technique is used to reduce the tendon to the humerus. Afterward, a free needle is used to pass 1 limb of the suture through the tendon before tying an additional knot for added fixation. Results: The patient was able to resume his activities of daily living without pain at the 4-month mark. Conclusions: After the failure of extensive nonoperative management, surgical treatment of a subacute complete rupture of the latissimus dorsi tendon via a single, posterior incision is an effective method of returning a patient to their painless activities of daily living. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Influenza vaccine outcomes: a meta-analysis revealing morbidity benefits amid low infection prevention
Authors: Presa Jesus , Arranz-Herrero Javier , Alvarez-Losa Laura , Rius-Rocabert Sergio , Pozuelo Maria Jose , Lalueza Antonio , Ochando Jordi , Eiros Jose María , Sanz-Muñoz Ivan , Nistal-Villan Estanislao 
Published: January 2025

BackgroundThe morbidity and mortality associated with influenza viruses are a significant public health challenge. Annual vaccination against circulating influenza strains reduces hospitalisations and increases survival rates but requires a yearly redesign of vaccines against prevalent subtypes. The complex genetics of influenza viruses with high antigenic drift create an ongoing challenge in vaccine development to address dynamic influenza epidemiology. Understanding the evolution of influenza viruses and the vaccine's effectiveness against different types and subtypes is pivotal to designing public health measures against influenza.MethodsWe conducted a systematic review and meta-analysis of 192 705 patients, collecting information on the incidence and severity of the disease. The results of this meta-analysis were further validated using data from 6 594 765 patients from TriNetX. We analysed the prevalence of the most common influenza A virus (IAV) subtypes (H1N1 and H3N2) and influenza B virus (IBV), as well as vaccination effectiveness against them in three age groups, given that age is associated with influenza disease severity.ResultsOur analysis reflects that overall vaccination against H1N1 IAV and IBV is effective in reducing infection and influenza-related complications in children aged <5 years old, individuals between 5 and 65 years old and older adults aged >65 years old. By contrast, while vaccination against H3N2 IAV is effective in protecting against infection in infants <5 years old, it provides reduced protection against infection in older individuals.ConclusionsDespite higher infection rates, vaccination against H3N2 remains as highly effective as vaccination against H1N1 and IBV in reducing influenza-related morbidity and mortality in all age groups. Detailing vaccine effectiveness in terms of infection protection and disease burden across different age groups is necessary for understanding vaccine impacts in terms of other outcomes,e.g.hospitalisations, mortality and disease severity; for improving vaccine formulations and public awareness; and for enhancing vaccination campaigns to improve coverage and public acceptance.
Machine learning-derived asthma and allergy trajectories in children: a systematic review and meta-analysis
Authors: Lisik Daniil , Özuygur Ermis Saliha Selin , Milani Gregorio Paolo , Spolidoro Giulia Carla Immacolata , Ercan Selin , Salisu Michael , Odetola Faozyat , Ghiglioni Daniele Giovanni , Pylov Danylo , Goksör Emma , Basna Rani , Wennergren Göran , Kankaanranta Hannu , Nwaru Bright I. 
Published: January 2025

IntroductionNumerous studies have characterised trajectories of asthma and allergy in children using machine learning, but with different techniques and mixed findings. The present work aimed to summarise the evidence and critically appraise the methodology.Methods10 databases were searched. Screening, data extraction and quality assessment were performed in pairs. Trajectory characteristics were tabulated and visualised. Associated risk factor and outcome estimates were pooled using a random-effects meta-analysis.Results89 studies were included. Early-onset (infancy) persistent, mid-onset (∼2–5 years) persistent, early-onset early-resolving (within ∼2 years) and early-onset mid-resolving (by ∼3–6 years) wheezing and eczema, respectively, were the most commonly identified disease trajectories. Intermediate/transient trajectories were rare. Male sex was associated with a higher risk of most wheezing trajectories and possibly with early-resolving eczema, while being slightly protective against mid-onset persistent eczema. Parental disease/genetic markers were associated with persistent trajectories of wheezing and eczema, respectively. Prenatal (and less so postnatal) tobacco smoke exposure was associated with most wheezing trajectories, as were lower respiratory tract infections in infancy (particularly with the early-onset resolving patterns). Most studies (69%) were of low methodological quality (particularly in modelling approaches and reporting). Few studies investigated allergic multimorbidity, allergic rhinitis and food allergy.ConclusionsChildhood asthma/wheezing and eczema can be characterised by a few relatively consistent trajectories, with some actionable risk factors such as pre-/postnatal smoke exposure. Improved computational methodology is warranted to better assess generalisability and elucidate the validity of intermediate/transient trajectories. Likewise, allergic multimorbidity and trajectories of allergic rhinitis and food allergy need to be further elucidated.