Current state of biologic pharmacovigilance in the European Union: improvements are needed

Introduction: Pharmacovigilance is essential to monitoring the safety profiles of authorized medicines. Compared with small-molecule drugs, biological drugs are more complex, more susceptible to structural variability due to manufacturing processes, and have the potential to induce immune-related reactions, underscoring the importance of safety monitoring for these products. Although highly similar to reference products, biosimilars are not expected to be structurally identical. For these reasons, proper reporting of potential adverse drug reactions (ADRs) using distinguishable names and batch numbers is essential for accurate tracing of all biological drugs. To address the need for robust pharmacovigilance, the European Parliament and Council of the European Union provided legislation regarding pharmacovigilance of biologics in 2010.

Areas covered: This narrative review examines the current state of pharmacovigilance for biologics in the European Union (EU) and discusses relevant information on pharmacovigilance of biosimilars, the current EU pharmacovigilance system, and areas that could be improved.

Expert opinion: Although steps have been taken to improve pharmacovigilance of biologics in the EU, several enhancements can still be made, including additional training for healthcare professionals on ADR reporting, the use of 2D barcodes that enhance traceability, and an open discussion of potentially missed opportunities in the pharmacovigilance of biosimilars.     

Recall of emotional and neutral words and paragraphs in traumatic brain injury

Background: Traumatic brain injury (TBI) results in verbal recall deficits and impaired processing of emotion encoded in facial appearance, prosody and the linguistic content of messages. Emotion facilitates memory (emotional memory advantage) for non-brain injured (NBI) individuals but the impact of emotion on verbal recall for linguistically encoded stimuli in TBI has not been explored.

Aims: The purpose of this study was to determine the effects of stimulus emotional content on verbal recall of words and paragraphs in TBI compared to NBI individuals.

Methods and procedures: Six 10-item lists, each with five emotional and five neutral words, and six paragraphs (three emotional, three neutral) were counterbalanced and presented in random order to 20 individuals with TBI and 44 NBI. The number of words from lists and the number of content units from paragraphs were compared for the two groups.

Outcomes and results: The NBI participants recalled more words from the lists and content units from the paragraphs than the individuals with TBI. Both groups recalled significantly more emotional than neutral words. NBI but not TBI participants had significantly greater recall for information in paragraphs with emotional content.

Conclusions: Participants with TBI showed impaired recall of words and paragraph content. Emotion facilitated word and paragraph content recall for neurotypical individuals but emotional memory advantage was limited to words for the TBI participants.     

Correction to: Influence of oral anticoagulation on success rates and risk of bleeding events after iStent inject implantation combined with phacoemulsification

Graefe's Archive for Clinical and Experimental Ophthalmology - The published online version contains mistake as the author's first name and last name have been interchanged as "Hild...     

Managing healthcare worker well‐being in an Australian emergency department during the COVID‐19 pandemic

Emergency Medicine staff in Australia and New Zealand are at the forefront of the healthcare response to COVID‐19. This article describes a well‐being plan for ED staff that has been devised to mitigate against the negative psychological impact of the COVID‐19 pandemic.     

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours:A systematic review

BACKGROUND Approximately 20% of patients with neuroendocrine tumours(NETs) develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library) were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies) were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7% of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%) and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75) acid(Se HCAT) scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.     

Treatment of classical Hodgkin’s lymphoma in children and adolescents

Introduction: The treatment of classical Hodgkin lymphoma (cHL) in children is a story of success. Nowadays, more than 90% of patients are cured and overall survival is nearly 100% at 5 years. Efforts have been made to avoid related effects of therapies; therefore, children are treated using different chemotherapy schemes in comparison with adults.

Areas covered: This review includes a view of the clinical classification and risk assessment in children suffering from HL. The chemotherapy more commonly employed is revisited. The use of PET/CT to evaluate the disease in order to guide therapy is analyzed. New options of chemotherapy and emerging immunotherapy are also included.

Expert opinion: In order to make the right treatment choice, a proper initial assessment of risk is mandatory. The choice of therapy in these kinds of patients must be done according to the experience of the team, and also, the cost and logistics related to the eligible scheme are very important. If possible, efforts must be made to include PET/CT in guiding therapy and avoiding overtreatment and long-term adverse effects in children. New options in immunotherapy are emerging and must be considered with caution in selected patients.