Global Adversities, the Media, and Mental Health

Global communities are currently confronted with a number of complex problems and threats, the reality of which is amplified by the media. These environmental and socio-political stressors have been accompanied by the spread of problematic psychological and behavioural tendencies, such as the growing polarisation of opinions and values, online radicalisation and extremism, deepening xenophobia and nationalism, the proliferation of irrational beliefs and conspiracy theories, and resistance to rational public policy measures. Here we argue that although they fall outside the scope of psychopathology, they nevertheless currently constitute a major challenge for psychiatry as a research domain and a clinical practise. To substantiate this claim, we outline the mechanisms by which media-transmitted stressors impact mental well-being and possibly psychopathology. The common denominator of these global problems and the media's construction of reality is the increase in uncertainty, unpredictability, and uncontrollability, which prompts defensive responding and, in predisposed individuals, functions as a potent source of chronic stress. These contribute to cognitive inflexibility, a strong predisposing factor for the development of rigid beliefs and attitudes, which to varying degrees underlie the adverse psychological and behavioural tendencies mentioned above. We suggest that the tightening of beliefs and ideas that is the result of cognitive rigidity may correspond to the clinical characteristics of induced delusional disorder. This can be seen as a (ultimately maladaptive) defensive strategy for coping with a high degree of uncertainty and unpredictability. We conclude by briefly outlining the possible ways in which psychiatry can face this challenge.

L-asparaginase mediated therapy in L-asparagine auxotrophic cancers: A review

Microbial L-asparaginase is the most effective first-line therapeutic used in the treatment protocols of paediatric and adult leukemia. Leukemic cell’s auxotrophy for L-asparagine is exploited as a therapeutic strategy to mediate cell death through metabolic blockade of L-asparagine using L-asparaginase. Escherichia coli and Erwinia chrysanthemi serve as the major enzyme deriving sources accepted in clinical practise and the enzyme has bestowed improvements in patient outcomes over the last 40 years. However, an array of side effects generated by the native enzymes due to glutamine co-catalysis and short serum stays augmenting frequent dosages, intended a therapeutic switch towards the development of biobetter alternatives for the enzyme including the formulations resulting in sustained local depletion of L-asparagine. In addition, the treatment with L-asparaginase in few cancer types has proven to elicit drug-induced cytoprotective autophagy mechanisms and therefore warrants concern. Although the off-target glutamine hydrolysis has been viewed in contributing the drug-induced secondary responses in cells deficient with asparagine synthetase machinery, the beneficial role of glutaminase-asparaginase in proliferative regulation of asparagine prototrophic cells has been looked forward. The current review provides an overview on the enzyme’s clinical applications in leukemia and possible therapeutic implications in other solid tumours, recent advancements in drug formulations, and discusses the aspects of two-sided roles of glutaminase-asparaginases and drug-induced cytoprotective autophagy mechanisms.

Decision-Making Process for the Management of Acute Stroke in Patients on Oral Anticoagulant: From Guidelines to Clinical Routine

Background: The occurrence of both ischaemic (IS) and haemorrhagic stroke in patients on anticoagulation is a major issue due to the frequency of their prescriptions in westernised countries and the expected impact of anticoagulant activity on recanalization during an IS or on the outcomes associated with intracerebral haemorrhage (ICH). Several guidelines are available but sometimes differ in their conclusions or regarding specific issues, and their application in routine emergency settings may be limited by particular individual issues or heterogeneous local specificities.Methods: Based on the current guidelines and additional published data, the algorithms proposed in this paper aim to help the decision-making process regarding stroke management in the setting of concurrent anticoagulants by addressing specific clinical situations based on clinical variables commonly encountered in real-world practise.Results: For patients on non–vitamin K oral anticoagulants, reversion can be achieved with specific antidotes, but only idarucizumab, the specific dabigatran antidote, is indicated in both IS and ICH. Due to the low risk of a prothrombotic effect, idarucizumab can be immediately used in IS patients eligible for thrombolysis before the dabigatran concentration is known. To optimise ICH management, the time since symptom onset, with thresholds proposed at 6 and 9 hours based on the expected timing of haematoma expansion, could also to be taken into account.Conclusions: Anticoagulant reversal in patients presenting with a stroke remains a major issue, and algorithms based on a step-by-step approach may be useful for clinical practise. Real-life studies strongly support the benefits of idarucizumab availability in stroke units and emergency departments.

Clinical review of retinotopy

Two observations made 29 years apart are the cornerstones of this review on the contributions of Dr Gordon T. Plant to understanding pathology affecting the optic nerve. The first observation laid the anatomical basis in 1990 for the interpretation of optical coherence tomography (OCT) findings in 2009. Retinal OCT offers clinicians detailed in vivo structural imaging of individual retinal layers. This has led to novel observations which were impossible to make using ophthalmoscopy. The technique also helps to re-introduce the anatomically grounded concept of retinotopy to clinical practise. This review employs illustrations of the anatomical basis for retinotopy through detailed translational histological studies and multimodal brain-eye imaging studies. The paths of the prelaminar and postlaminar axons forming the optic nerve and their postsynaptic path from the dorsal lateral geniculate nucleus to the primary visual cortex in humans are described. With the mapped neuroanatomy in mind we use OCT-MRI pairings to discuss the patterns of neurodegeneration in eye and brain that are a consequence of the hard wired retinotopy: anterograde and retrograde axonal degeneration which can, within the visual system, propagate trans-synaptically. The technical advances of OCT and MRI for the first time enable us to trace axonal degeneration through the entire visual system at spectacular resolution. In conclusion, the neuroanatomical insights provided by the combination of OCT and MRI allows us to separate incidental findings from sinister pathology and provides new opportunities to tailor and monitor novel neuroprotective strategies.

The Role of Exosomes in Viral Hepatitis and Its Associated Liver Diseases

Exosomes, the important carriers between cells, can carry proteins, micro ribonucleic acids (miRNAs), long non-coding RNAs (lncRNAs) and other molecules to mediate cellular information transduction. They also play an important role in the pathogenesis, prognosis and treatment of viral hepatitis and its associated liver diseases. Several studies have reported that viral hepatitis and its associated liver diseases, including hepatitis A, B, C and E; hepatic fibrosis and hepatocellular carcinoma, were closely associated with exosomes. Exploring the role of exosomes in viral hepatitis and associated liver diseases will enhance our understanding of these diseases. Therefore, this review mainly summarised the role of exosomes in viral hepatitis and its associated liver diseases to identify new strategies for liver diseases in clinical practise.

Associations Between Relapses and Psychosocial Outcomes in Patients With Schizophrenia in Real-World Settings in the United States

Aim: To assess associations between relapses and psychosocial outcomes in adult patients with schizophrenia treated in United States (US) healthcare settings.Methods: Data were derived from a point-in-time survey of psychiatrists and their patients with schizophrenia conducted across the US, France, Spain, China, and Japan between July and October 2019. For the purposes of this analysis, only data from US practitioners and patients were included. Disease-specific programmes (DSPs) are large surveys with a validated methodology conducted in clinical practise; they describe current disease management, disease burden, and associated treatment effects (clinical and physician-perceived). Participating psychiatrists completed patient record forms for their next 10 consecutive adult consulting patients with schizophrenia, with the same patients invited to voluntarily complete a patient self-completion (PSC) questionnaire. Surveys contained questions on the patients' disease background, treatment history, prior hospitalisation due to schizophrenia relapse and a series of psychosocial outcomes. Associations between relapses in the last 12 months and psychosocial outcomes were examined using multiple regression.Results: A total of 124 psychiatrists provided data on 1,204 patients. Of these, 469 patients (mean age, 39.6 years; 56.5% male) had known hospitalisation history for the last 12 months and completed a PSC; 116 (24.7%) patients had ≥1 relapse. Compared to patients without relapses, patients who relapsed were more likely to be homeless, unemployed, previously incarcerated, and currently have difficulties living independently (all p < 0.05). Patients who experience a relapse also had greater working impairment and poorer quality of life compared with those who did not relapse. In general, psychosocial outcomes became poorer with an increasing number of relapses.Conclusions: In this population of patients with schizophrenia from the US, relapse was significantly associated with poor psychosocial outcomes, with a greater number of relapses predicting worse outcomes. Early intervention to reduce the risk of relapse may improve psychosocial outcomes in patients with schizophrenia.

448 Foundation Doctor Local Peer-Led and Organised Basic Surgical Skills in General Surgery and Plastic Surgery

Aim Foundation doctors are under pressure early in their careers to attend highly subscribed and expensive surgical courses. We assessed the feasibility of a foundation doctor led and locally organised basic surgical skills introduction. Method The lead foundation doctor organised a basic surgical skills introduction for foundation year doctors at Salisbury District Hospital liaising with the postgraduate centre and local surgical consultants. This training was supervised by local consultants and registrars. This teaching delivered theory and practise in suturing, knot tying and laparoscopy by local and familiar trainers. Feedback was collected using the Likert scale. Results 12 foundation doctors attended. 100% either agreed or strongly agreed the introduction was helpful and well organised. 25% either agreed or strongly agreed feeling confident with suturing and knot tying before the teaching which increased to 92% after teaching. Only 8.3% either agreed or strongly agreed feeling confident with the principles of basic laparoscopy before teaching which increased to 83% after teaching. 100% either agreed or strongly agreed the teaching will improve their clinical practise and enhance their interest in surgery. 92% strongly agreed or agreed that the teaching improved their knowledge in basic surgical skills, and the peer led and organised structure was an effective teaching method. Conclusions Foundation doctor locally peer led teaching organised with supervision by local consultants is an effective method of delivering basic surgical skills with improvement especially marked in basic laparoscopy and help enhance interest in surgical training.

The RAI-6 Questionnaire: A New Screening Questionnaire to Monitor Complications of Radioiodine Treatment

Objective: The aim of this study is to develop a simple and efficient screening questionnaire to be able to routinely monitor potential radioiodine therapy-induced complications.Materials and Methods: A new radioiodine 6 (RAI-6) questionnaire containing six questions adressing salivary, ocular, and nasal symptoms as well as quality of life was developed. Validation of the RAI-6 questionnaire was assessed with a group of fifty-four patients diagnosed with differentiated thyroid carcinoma treated post-operatively with radioiodine therapy, and in a group of fifty healthy volunteers. The patient's group was subdivided into subgroups according to the radioiodine dose received: 23 patients received less or 30 mCi, 28 patients received 100 mCi, and three patients received between 200 and 300 mCi. We asked the patients to complete the RAI-6 questionnaire in a retrospective manner, regarding their situation before radioiodine therapy and regarding their actual symptoms after radioiodine therapy. The time needed to complete the RAI-6 was also assessed both in patients and in healthy volunteers.Results: The mean post radioiodine treatment RAI-6 score were significantly higher than the mean pre radioiodine RAI-6 scores (p < 0.001) and the scores of healthy participants (p < 0.001). The mean total RAI-6 scores increased significantly with increasing radioiodine dose. A total mean RAI-6 score of each question was also analysed and revealed that ocular and nasal discomfort as well as quality of life were the items which affected the patients most after radioiodine treatment. The mean time to fill the RAI-6 questionnaire was 2 min for patients and 49 s for healthy volunteers.Conclusion: The RAI-6 represents a new questionnaire which is easy and quick to complete. This simple screening tool can be recommended for general clinical practise and further epidemiological research.

Defining Satisfactory Methods of Treatment in Rare Diseases When Evaluating Significant Benefit–The EU Regulator's Perspective

Since the implementation of the EU Orphan Regulation in 2000, the Committee for Orphan Medicinal Products at the European Medicines Agency has been evaluating the benefits of proposed orphan medicines vs. satisfactory treatment methods. This type of evaluation is foreseen in the Orphan Regulation as the orphan designation criterion called the “significant benefit.” In this article, based on 20 years of experience, we provide a commentary explaining what is considered a satisfactory method of treatment in the context of the EU Orphan Regulation and for the purpose of the assessment of significant benefit. We discuss the challenges posed by continuously changing clinical practise, which is associated with the increasing number of treatment options, evolving nature of medicinal therapeutic indications and our understanding of them.

A Critical Review of Herbo-Mineral Formulations in Jwara Chikitsa

Fever is a generalized body reaction to a variety of infectious and non-infectious causes. Fever was referred to as jwara by ancient Ayurvedic seers, and it was thought to be the most serious ofall diseases. Fever is described as a separate illness, a symptom, and a complication of many ailments in Ayurveda classics. Jwara is the first and most serious of all diseases, so it needs special attention. In this article, we will attempt to compile and evaluate Rasa yogas in jwara chikithsa from various Ayurvedic classics. Rasendra Sara Sangraha, Bhaishjya Rathnavali, Rasa Ratna Samucchaya, Rasa Tharangini and other works are reviewed in detail. In Rasasastra classics, these formulations are indicated separately for navajwara chikitsa, nirama jwara chikitsa, jeerna jwara chikitsa, vishama jwara chikitsa, and sannipatha jwara chikitsa. This article includes 112 formulations from various sources that have been classified based on their indications. There are certain peculiarities in the ingredients based on jwara avasthas that can be discovered by studying these formulations. The majority of these formulations are herbo-mineral compounds that come in tablet form, making dosage, administration, and palatability more convenient. A few of these formulations are commercially available for common clinical practise. Antipyretic use is excessive in everyday life in the present pandemic situation. The aim of this study is to raise awareness of these particular formulations in the health-care system so that they can be applied to community needs. Key words: fever, jwara, navajwara, vishama jwara, nirama jwara, sannipatha jwara, herbo mineral formulations, rasa yogas.