Drugs in Context

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Authors: Martina Burlando, Riccardo Castelli, Emanuele Cozzani, Aurora Parodi

The authors wish to make the following corrections to their article: Burlando M, Castelli R, Cozzani E, Parodi A. Treatment of moderate-to-severe plaque psoriasis with tildrakizumab in the real-life setting. Drugs in Context 2021; 10: 2021-2-6. DOI: 10.7573/dic.2021-2-6

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Authors: Daniele Orsucci, Marco Vista

Letter to the Editor in response to Finsterer J, Scorza FA, Scorza CA. Presentation and pathophysiology of neuro-COVID. Drugs Context. 2021;10:2021-6-5. https://doi.org/10.7573/dic.2021-6-5

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Authors: Sergey V Efimov, Natallia V Matsiyeuskaya, Olga V Boytsova, Lyudmila Yu Akhieva, Elena I Kvasova, Francisco Harrison, Yulia S Karpova, Anton Tikhonov, Nadezhda F Khomyakova, Tim Hardman, Jean-François Rossi

The authors wish to make the following corrections to their article: Efimov SV, Matsiyeuskaya NV, Boytsova OV, et al. Corrigendum: The effect of azoximer bromide (Polyoxidonium®) in patients hospitalized with coronavirus disease (COVID-19): an open-label, multicentre, interventional clinical study. Drugs in Context 2021; 10: 2021-11-1. DOI: 10.7573/dic.2020-11-1

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Authors: Xavier Garcia-Moll, Vivencio Barrios, Josep Franch-Nadal

Traditionally, patients with type 2 diabetes have been stratified according to cardiovascular (CV) risk to requiring either primary prevention (those without atherosclerotic CV disease) or secondary prevention (those with atherosclerotic CV disease in any of the vascular beds). However, this classification is misleading and arbitrary, as not all patients requiring secondary prevention have the same risk for such events, which also holds true for those requiring primary prevention (i.e. CV risk ranges from moderate to very high). In addition, in some cases, the definitions of primary and secondary prevention do not rely on symptoms but rather on the results of supplementary tests. Furthermore, patients with type 2 diabetes may also develop heart failure or chronic kidney disease. Importantly, reducing CV risk stratification to primary and secondary prevention does not provide a comprehensive approach for the management of patients with diabetes, leading to an underuse of drugs with proven CV benefit regardless of the presence of atherosclerotic CV disease. Therefore, patients with diabetes should be treated according to their CV risk considered as a continuum and not simply as falling within primary or secondary prevention.

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Authors: Kristin M Holland, Lara DePadilla, Derrick W Gervin, Erin M Parker, Marcienne Wright

The United States drug overdose epidemic has reached an all-time high, with 2020 provisional mortality data indicating that over 90,000 lives were lost to drug overdose in the 12-months ending in December 2020. The overdose epidemic has evolved over time with respect to the substances involved in overdose deaths and also with respect to the geographic distribution and epidemiology of deaths involving specific substances. Thus, a nimble approach to addressing the epidemic and preventing future overdoses is needed. CDC’s response to the overdose epidemic supports implementation efforts at the state and local levels, where partners can better detect and respond to the evolving drug overdose landscape and implement prevention measures that meet their needs. CDC’s framework for responding to the overdose epidemic focuses on five areas: (1) conducting surveillance and research; (2) building state, local and tribal capacity; (3) supporting providers, health systems and payers; (4) partnering with public safety; and (5) empowering consumers to make safe choices. Central to informing the implementation of evidence-based strategies to prevent drug overdose is rigorous research that undergirds the evidence. This Commentary describes recent investments in overdose prevention research and outlines opportunities for ensuring that future research efforts allow for the flexibility necessary to effectively respond to the continually evolving epidemic.

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Authors: Martina Burlando, Riccardo Castelli, Emanuele Cozzani, Aurora Parodi

Background: Tildrakizumab is a high-affinity, humanized IgG1κ monoclonal antibody targeting the p19 subunit of IL-23, which is a key regulatory cytokine in psoriasis. Based on evidence from clinical trials, tildrakizumab is approved for the treatment of moderate-to-severe plaque psoriasis in patients eligible for systemic therapy. Methods: We report our clinical experience with 26 patients followed up to 24 weeks. Results: No adverse event was observed and no patient discontinued tildrakizumab. Whilst no patient had a Psoriasis Area and Severity Index (PASI) score of <5 at baseline, at week 4, 8 (32%) patients had a PASI score of <3 and 6 of these had a PASI score of 0. At week 12, 19 (79%) patients had a PASI score of <5 and, among these, 18 had a PASI score of <3 of whom 16 had a PASI score of 0. At week 24, 22 (96%) patients had a PASI score of <3 and 20 (87%) had a PASI score of 0. Quality of life was improved after 4 weeks and through the whole period of observation. Conclusion: Our experience in the real-life setting confirms the efficacy and safety of tildrakizumab as demonstrated by clinical trials.

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Authors: Sarah L Anderson, Matteo Bassetti, Arduino A Mangoni

The year 2020 was dominated by the COVID-19 pandemic, bringing with it unprecedented advancements in the fields of healthcare and therapeutic interventions as well as in vaccine and drug development. Nevertheless, several other advancements in various fields of medicine also deserve attention. Herein, the Senior Editors of Drugs in Context provide us with their expert opinion on the events of 2020 and what lies ahead in 2021.

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Authors: Sarah M Michienzi, Mikayla Johnson, Thomas D Chiampas, Eric Wenzler, Rodrigo M Burgos, Renata O Smith, Melissa E Badowski

Although tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) have been evaluated in various clinical trials, limited safety and efficacy data exist in real-world settings. The goal of this retrospective analysis is to assess changes in virological suppression, immunological status, renal function, weight and body mass index (BMI) amongst people living with HIV who switched from a TDF-based to a TAF-based regimen. Of 130 patients included in the final analysis, 53 patients experienced an increase in their viral load upon switching from TDF to TAF therapy whilst 62 patients remained undetectable. For those who experienced a viral blip, 33 (62%) resuppressed by the time of last follow-up, 15 (28%) patients did not have additional labs beyond the last follow-up and concern for failure occurred in 5 (9%) patients. No differences in immunological function, renal function, weight or BMI were observed from before switching to the last follow-up. Although a loss of virological suppression was found upon switching to TAF at subsequent follow-up visits, resuppression ultimately occurred in most patients.

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Authors: Ana Victoria Carro Martínez, Lydia Montolio Chiva, Montserrat Robustillo Villarino

Drug therapy of immune-mediated inflammatory arthropathies is not always satisfactory, and there is a risk of adverse events. Granulocyte and monocyte/macrophage apheresis (GMA) is a non-pharmacological therapeutic option that is beneficial and very well tolerated. GMA involves passing blood through a column with cellulose acetate beads to remove increased and activated myeloid lineage cells and improve the cytokine profile. The technique reduces pain and inflammation. We present four clinical reports that illustrate the clinical uses of GMA with the medical device Adacolumn® in patients with different backgrounds and immune-mediated inflammatory arthritis. The results were positive, and no adverse events were reported.

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Authors: Anna R Morgan, Michelle A Hendricks, Sanae El Ibrahimi, Sara E Hallvik, Brigit Hatch, Caitlin Dickinson, Dagan Wright, Michael A Fischer

The United States faces an opioid crisis with an unprecedented and increasing death rate from opioid overdose. Successfully reducing the rates of opioid use disorder (OUD) and overdose will require the engagement of frontline clinicians to prescribe opioids more safely and to build their capacity to treat patients with OUD using evidence-based approaches. The COVID-19 pandemic has created significant challenges for patients, clinicians and health systems and has been associated with increasing risks of overdoses and deaths. Herein, we review a multidisciplinary project designed to implement and evaluate clinic-based interventions in Oregon, USA, to improve pain management, opioid prescribing and treatment of OUD. The intervention, called Improving PaIn aNd OPiOId MaNagemenT in Primary Care (PINPOINT), combines practice facilitation, academic detailing and education through the Oregon ECHO Network. Implementation of PINPOINT has occurred across the Oregon Rural Practice-based Research Network and has involved 49 clinic sites to date. To evaluate the impact of the intervention, the research team created the Provider Results of Opioid Management and Prescribing Training (PROMPT), a dataset that links information from the state prescription drug monitoring program, all-payer claims database, emergency medical services, vital records and substance use disorder treatment system. The PROMPT dataset will allow evaluation of the impact of the intervention at both the clinician and clinic levels. Due to the constraints of the COVID-19 pandemic, elements of both implementation and evaluation required significant adaptations to continue to meet the original project goals.

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Authors: Giovanna Malara, Gabriella Fabbrocini, Caterina Trifirò, Martina Burlando

Background: Dimethyl fumarate (DMF) is an oral systemic agent approved for the treatment of moderate-to-severe psoriasis vulgaris. It has a favourable tolerability profile, but it is associated with a high incidence of mild and reversible adverse events. The aim of the article is to describe a clinical experience aimed at increasing tolerability. Patients and methods: A group of patients was treated with DMF with a titration schedule, according to clinical practice, although a personalization of the step-up timing was allowed. The highest dose was the minimal effective dose or the maximal tolerated doses. Results: DMF treatment was effective in reducing the disease severity and improving the quality of life. DMF was well tolerated as only mild, mainly gastrointestinal, adverse events occurred in these patients. In addition, the up-titration schedule seemed to provide a reduced incidence of adverse events compared with the fixed dose. Conclusion: Our experience suggested that the recommended up-titration schedule of DMF, adjusted and personalized according to patient needs and physician opinion, provided a relevant clinical benefit and was well tolerated.

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Authors: Rajesh R Tampi, Brent P Forester, Marc Agronin

Alzheimer’s disease (AD) is the most common cause for dementia worldwide. Until recently, all approved treatments for AD were symptomatic and not disease modifying. On 7 June 2021, the US FDA approved aducanumab, a human IgG1 anti-Aβ monoclonal antibody selective for Aβ aggregates, as the first disease-modifying treatment for AD. Aducanumab is approved in the United States for the treatment of mild cognitive impairment or mild-dementia stage of AD. In this Editorial, we review the trial data for aducanumab in the treatment of AD and the controversies that its approval has generated.

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Authors: Peter MB English

The vaccination campaign in the United Kingdom has been extremely successful. Bold decisions were made to order vaccines early, before we knew if they would be effective, and to vary from the manufacturers’ recommendations by extending the ‘prime-boost’ interval between the first and second doses of the AstraZeneca and Pfizer-BioNTech vaccines. These decisions were controversial at the time but have contributed enormously to the effectiveness of the vaccination programme. This is a personal perspective on the approach to COVID-19 vaccination in the United Kingdom.

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Authors: Valeria Nucera MD, Elisabetta Gerratana MD, Manuela Giallanza MD, Laura La Corte MD, Donatella Sangari MD, Fabiola Atzeni MD, PhD

Interstitial lung diseases (ILDs) are some of the first and most serious complications of connective tissue diseases (CTDs). However, the pathogenesis of CTD-related ILDs (CTD-ILDs) is still unclear and their treatment often depends on functional and radiographic disease progression as well as on patient age and comorbidities. It can be difficult to manage CTD-ILDs due to their heterogeneous nature, the lack of robust therapeutic data, and the few well-defined outcome measures. This review focuses on cyclophosphamide due to its crucial role in the treatment of systemic sclerosis-related ILD, particularly in the case of patients with progressive ILD. This narrative review was performed using PubMed, Medline, and Cochrane Library databases to retrieve English language papers published between 2000 and April 2020 concerning the treatment of CTD-ILDs with cyclophosphamide.

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Authors: Kam Lun Hon, Wun Fung Hui, Alexander KC Leung

Background: Poisoning causes significant morbidity and sometimes mortality in children worldwide. The clinical skill of toxidrome recognition followed by the timely administration of an antidote specific for the poison is essential for the management of children with suspected poisoning. This is a narrative review on antidotes for toxidromes in paediatric practice. Methods: A literature search was conducted on PubMed with the keywords “antidote”, “poisoning”, “intoxication”, “children” and “pediatric”. The search was customized by applying the appropriate filters (species: humans; age: birth to 18 years) to obtain the most relevant articles for this review article. Results: Toxidrome recognition may offer a rapid guide to possible toxicology diagnosis such that the specific antidote can be administered in a timely manner. This article summarizes toxidromes and their respective antidotes in paediatric poisoning, with an emphasis on the symptomatology and source of exposure. The antidote and specific management for each toxidrome are discussed. Antidotes are only available for a limited number of poisons responsible for intoxication. Antidotes for common poisonings include N-acetyl cysteine for paracetamol and sodium thiosulphate for poisoning by cyanide. Conclusion: Poisoning is a common cause of paediatric injury. Physicians should be familiar with the recognition of common toxidromes and promptly use specific antidotes for the management of childhood toxidromes.

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Authors: Rodrigo M Burgos, Melissa E Badowski, Emily Drwiega, Samaneh Ghassemi, Nikki Griffith, Fischer Herald, Mikayla Johnson, Renata O Smith, Sarah M Michienzi

The unprecedented toll of severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus 2019 disease (COVID-19), jumpstarted the race towards the development and distribution of effective treatment and prevention options. With an urgent need to slow viral transmission, lessen disease severity, and reduce mortality, biopharmaceutical companies rapidly began investigating potential COVID-19 vaccinations. While typical vaccine development can take upwards of 10–15 years, COVID-19 vaccines were developed in less than a year after the identification of COVID-19. To accomplish this feat, clinical development, manufacturing scale-up and distribution are occurring in parallel for the four COVID-19 vaccine front-runners. This remarkable opportunity will forever change the drug development process and would not be possible without tremendous dedication from the public and private sectors, researchers, and clinical trial volunteers. However, many challenges still lie ahead. Comprehensive plans for equitable vaccine education, distribution, administration and post-marketing surveillance must be implemented successfully to overcome vaccine hesitancy, supply-chain obstacles and healthcare provider shortages in an already overburdened healthcare system. We are moving forward at a remarkable pace but worldwide immunity through vaccination will take time to achieve. Thus, current prevention efforts of masking, hand hygiene and social distancing must remain in effect for the foreseeable future. We must remain diligent and not fatigue in our efforts. Ending the COVID-19 pandemic cannot rest on the promise of vaccination alone – it will require a continued, robust and multi-faceted approach to disease treatment and prevention.

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Authors: Kam Lun Hon, Karen Ka Yan Leung, Felix Oberender, Alexander KC Leung

Background: Septic shock is a common critical illness associated with high morbidity and mortality in children. This article provides an updated narrative review on the management of septic shock in paediatric practice. Methods: A PubMed search was performed using the following Medical Subject Headings: “sepsis”, “septic shock” and “systemic inflammatory response syndrome”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies and reviews. The search was limited to the English literature and specific to children. Results: Septic shock is associated with high mortality and morbidity. The outcome can be improved if the diagnosis is made promptly and treatment initiated without delay. Early treatment with antimicrobial therapy, fluid therapy and vasoactive medications, and rapid recognition of the source of sepsis and control are the key recommendations from paediatric sepsis management guidelines. Conclusion: Most of the current paediatric sepsis guideline recommendations are based on the adult population; therefore, the research gaps in paediatric sepsis management should be addressed.

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Authors: Tiago Torres, Margarida Gonçalo, Maria João Paiva Lopes, Cristina Claro, Leonor Ramos, Manuela Selores, Pedro Mendes Bastos, Joana Rocha, Rodrigo Carvalho, Alberto Mota, Paulo Filipe on Behalf of the Atopic Dermatitis Group of the Portuguese Society of Dermatology and Venereology

Atopic dermatitis is a highly prevalent chronic, immune-mediated inflammatory skin disease with a significant burden on patients, families and healthcare systems. This article presents recommendations developed by the Atopic Dermatitis Group of the Portuguese Society of Dermatology and Venereology addressing several clinical questions that arise in the management and care of moderate-to-severe atopic dermatitis with biologic agents and Janus kinase (JAK) inhibitors based on the available evidence. The recommendations were generated after a thorough evaluation of existing guidelines on the treatment of atopic dermatitis, publications concerning new biologics and JAK inhibitors not yet incorporated into existing guidelines, and expert-based recommendations. It also includes considerations on atopic dermatitis severity, indications for initiating biologic agents and JAK inhibitors, parameters to be considered in the treatment choice, in particular treatment goals, and recommendations for the use, screening and monitoring of these therapies.

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Authors: Omar Castaneda-Puglianini, Julio C Chavez

Immunotherapy has revolutionized the treatment of cancers. There are several approaches, including naked monoclonal antibodies, antibody–drug conjugates, immune-checkpoint inhibitors and chimeric antigen receptor T cell therapies with important success. Bispecific antibodies represent a novel immunotherapeutic approach for the treatment of several malignancies, in particular non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). Early-phase studies have shown encouraging clinical activity in poor-risk B cell NHL and MM. Several constructs are currently available and in clinical development for the treatment of these malignancies. Here, we present a narrative review of the most current data on bispecific antibodies in B cell NHL and MM.

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Authors: Karen Ka Yan Leung, Kam Lun Hon, Wun Fung Hui, Alexander KC Leung, Chi Kong Li

Background: With advancements in the field of oncology, cancer survival rates have improved dramatically but modern cancer treatments also come with an increasing number of disease and treatment-associated complications. This article provides an updated narrative review on the pathophysiology, clinical presentations and latest management strategies for common paediatric oncological emergencies. Methods: An extensive PubMed® search of all human studies in the English literature was performed in Clinical Queries for different oncology syndromes and conditions using the following Medical Subject Headings: “tumour lysis syndrome”, “hyperleukocytosis”, “disseminated intravascular coagulation”, “superior mediastinal syndrome”, “superior vena cava syndrome”, “sepsis”, “severe inflammatory response syndrome”, “acute respiratory distress syndrome”, “posterior reversible encephalopathy syndrome” and “reversible posterior leukoencephalopathy syndrome”. Categories were limited to clinical trials and reviews for ages from birth to 18 years. Results: The general description, presentation and management of these oncologic emergencies are systematically described. Early recognition along with prompt and proactive treatment can reduce the chances of potential complications and improve the clinical outcomes, thereby improving not only survival rates in oncology patients but also their clinical outcomes and quality of life. Conclusions: Oncologic emergencies are associated with significant mortality and morbidity. Healthcare professionals involved with the care of oncology patients must be vigilant of these emergencies.

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Authors: Rajesh R Tampi, Pallavi Joshi, Gargi Bhattacharya, Sheila Gupta

Objectives: This narrative review aims to synthesize information from the literature regarding older-age bipolar disorder (OABD) in order to provide up-to-date information on this important illness. Methods: We searched Ovid (Medline, Embase and PsychInfo) on October 1, 2020, using the keywords “bipolar disorder”, “older adults” and “elderly” to identify relevant articles on OABD. Additionally, the bibliography of identified articles was reviewed for pertinent studies. Discussions: OABD is a term that is used to describe bipolar disorder (BD) occurring amongst individuals ≥50 years of age. Evidence indicates that OABD accounts for a quarter of all cases of BD. When compared to individuals with early-onset BD, individuals with OABD have a greater association with cerebrovascular disease and other neurological disorders, less family history of mood disorders, and utilize almost four times the total amount of mental health services. In addition, they are four times more likely to have psychiatric hospitalizations when compared to age-matched controls. Despite a dearth of controlled studies on the use of pharmacotherapy amongst individuals with OABD, available evidence from mixed-age studies indicates the efficacy of commonly used medications in individuals with early-onset BD. Additionally, psychosocial treatments have been found to be effective as adjunctive management strategies amongst individuals with OABD. Furthermore, electroconvulsive therapy may be effective in the treatment of refractory cases of OABD. Conclusions: There is a great need for an improved understanding of the phenomenology and neurobiology of OABD. Additionally, research into effective treatments for this serious psychiatric disorder will mitigate the suffering of individuals with OABD.

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Authors: Caterina Vacchi PhD, Andreina Manfredi MD, Giulia Cassone PhD, Gian Luca Erre MD, Carlo Salvarani MD, Marco Sebastiani MD

Interstitial lung disease (ILD) represents a severe pulmonary complication of connective tissue diseases, rheumatoid arthritis (RA), and antineutrophil cytoplasmic antibodyassociated vasculitis. Treatment of ILD, mainly based on immunosuppression, remains challenging. Rituximab (RTX), a monoclonal antibody binding to CD20, is considered a valuable therapeutic choice in cases of refractory ILD. Here, we review the available efficacy and safety data on the use of RTX in the treatment of rheumatic disease-related ILD. Despite controversial efficacy data, RTX seems to be able to stabilize or improve ILD related to RA and antisynthetase syndrome and in established and severe ILD complicating systemic sclerosis. Fewer data are available regarding ILD related to Sjögren syndrome, systemic lupus erythematosus, and antineutrophil cytoplasmic antibody-associated vasculitis. To date, few prospective studies are available and randomized trials are still ongoing with the purpose of exploring the role of RTX in this condition, including the supposed relationship between efficacy and ILD radiologic patterns and safety data, up to now derived mainly from RA studies. Despite an overall acceptable safety profile, concerns remain regarding an increased infectious disease risk in patients with ILD as well as possible lung toxicity and the increased rate of immune-mediated reactions in patients with connective tissue diseases. In conclusion, RTX is a relevant therapeutic option for rheumatic disease-related ILD despite the existing uncertainties; ongoing trials are expected to clarify its use.

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Authors: Jason HS Kim, Joseph M Lam

Infantile haemangiomas (IHs) are relatively common benign vascular tumours found in the paediatric population. They have varying sizes and involve different depths in the skin leading to various colours, shapes and textures. Although considered harmless in most cases, they may lead to life-threatening complications or cause permanent disfigurations and organ dysfunction. For problematic IHs, the treatment options include oral and topical beta-blockers, systemic corticosteroids, laser treatment, and surgery. In this narrative review, the treatment options for problematic IH are compared and delivered concisely to facilitate the clinical decisions from practitioners, including those in primary care settings. Oral propranolol is currently considered the first-line intervention for problematic IHs. For superficial lesions, there is robust evidence for the use of topical timolol maleate. Systemic corticosteroids are sometimes used in specific situations such as resistance or contraindications to beta-blockers. Surgical excision can be considered in cases requiring urgent intervention such as airway obstruction; this can be done alongside laser therapies for the removal of residual tissue or when reconstructing areas of deformity. The combination of multiple treatment modalities may lead to a more rapid clinical response.

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Authors: Gian Luca Erre MD, PhD, Marco Sebastiani PhD, Andreina Manfredi MD, Elisabetta Gerratana MD, Fabiola Atzeni MD, Giuseppe Passiu MD, Arduino A Mangoni MD

Fibrosing interstitial lung disease (ILD) is one of the most important causes of morbidity and mortality in patients with connective tissue diseases (CTDs), which include systemic sclerosis, rheumatoid arthritis, Sjögren’s syndrome, idiopathic inflammatory myositis and systemic lupus erythematosus. The treatment of CTD-ILDs is challenging due to the paucity of proven effective treatments. Recently, two antifibrotic drugs conditionally approved for use in patients with idiopathic pulmonary fibrosis, nintedanib and pirfenidone, have been trialled in CTD-ILDs based on overlapping pathological and clinical features between the two diseases. In this narrative review, we discuss the experimental evidence and clinical trials investigating the efficacy and safety of antifibrotic drugs in patients with CTD-ILDs and the potential mechanisms of action involved. Results from clinical trials suggest that nintedanib use retards lung function decline in progressive fibrotic CTD-ILDs. By contrast, the evidence for the efficacy of pirfenidone in these groups is not equally compelling. Further, well-designed randomized clinical trials are needed to evaluate the efficacy and safety of individual antifibrotic drugs in specific CTD-ILD subgroups.

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Authors: Silvia Natoli

Objective: Ketamine is an anaesthetic agent with a unique dissociative profile and pharmacological effects ranging from the induction and maintenance of anaesthesia to analgesia and sedation, depending on the dose. This article provides information for the clinical use of ketamine in anaesthesia, in both conventional and special circumstances. Methods: This is a non-systematic review of the literature, through a PubMed search up to February 2021. Results: With a favourable pharmacokinetic profile, ketamine is used in hospital and prehospital settings for emergency situations. It is suitable for patients with many heart conditions and, unlike other anaesthetics, its potential for cardiorespiratory depression is low. Furthermore, it may be used when venous access is difficult as it may be administered through various routes. Ketamine is the anaesthetic of choice for patients with bronchospasm thanks to its bronchodilatory and anti-inflammatory properties. Conclusion: With a favourable pharmacokinetic profile, ketamine is used in hospital and prehospital settings for emergency situations and is suitable for patients with many cardiac and respiratory conditions.

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Authors: Theresa NH Leung, James WCH Cheng, Anthony KC Chan

Obstructive sleep apnoea syndrome (OSAS) is defined as the intermittent reduction or cessation of airflow due to partial or complete obstruction of the upper airway during sleep. Paediatric OSAS has specific contributing factors, presenting symptoms and management strategies in various age groups. Untreated OSAS can lead to detrimental effects on neurocognitive development and cardiovascular and metabolic functions of a growing child. In the past decade, practice guidelines have been developed to guide the evaluation and management of OSAS. This article provides a narrative review on the current diagnostic and treatment options for paediatric OSAS. Alternative diagnostic tools other than the standard polysomnography are discussed. Adenotonsillectomy is considered the first-line therapy yet it is not suitable for treatment of all OSAS cases. Nocturnal non-invasive positive airway pressure ventilation is effective and could be the priority treatment for patients with complex comorbidities, residual OSAS post-adenotonsillectomy or obesity. However, intolerance and non-adherence are major challenges of positive airway pressure therapy especially in young children. There is increasing evidence for watchful waiting and other gentler alternative treatment options in mild OSAS. The role of anti-inflammatory drugs as the primary or adjunctive treatment is discussed. Other treatment options, including weight reduction, orthodontic procedures and myofunctional therapy, are indicated for selected patients. Nevertheless, the successful management of paediatric OSAS often requires a multidisciplinary team approach.

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Authors: Amalia Leceta, Aintzane García, Ander Sologuren, Cristina Campo

Background: Bilastine, a non-sedating H1-antihistamine, is indicated to treat the symptoms of allergic disorders (e.g. rhinoconjunctivitis and urticaria) in adults and adolescents and, more recently, in children. Following its marketing approval, many questions regarding the ideal use of bilastine in various clinical practice situations have been received by the Medical Information Department (MID) of Faes Farma Spain. This article is an update of a previous review, with a focus on recent clinical information on the use of bilastine in paediatric and other populations. Methods: Results of recent clinical studies in paediatric and other populations as well as questions received and responses provided by the Faes Farma MID. Results: The information regarding the use of bilastine in paediatric patients is the most relevant aspect of this updated review. The stepwise approval of the paediatric formulations in various countries started with the European Medicines Agency approval in 2017 in accordance with a 2009 Paediatric Investigation Plan, followed by approval in other countries. The queries that are most commonly received by the Faes Farma MID include the potential for drug interactions involving bilastine and other frequently used drugs, and the use of bilastine in special populations or to treat specific symptoms related to allergic conditions. As the concomitant use of many medications is not permitted during clinical trials, the advice provided regarding the concomitant use of other medications with bilastine considers the pharmacological properties of both the drug in question and bilastine, as well as expert opinion. Likewise, advice regarding the use of bilastine in special populations (e.g. patients with renal impairment, obesity, lactose intolerance, and elderly or pregnant individuals) or to treat specific symptoms (e.g. treatment-resistant urticaria, pruritus or BASCULE syndrome) considers the best evidence from a variety of sources, including clinical studies, real-world experience, guideline recommendations and expert opinion. Conclusion: This updated review provides current data regarding the best use of bilastine in specific situations and patients and identifies areas in which further knowledge is required. Although decisions regarding the use of bilastine may be aided by expert opinion that relies on knowledge of the underlying science, additional research and evidence are required to answer certain queries regarding the use of bilastine.

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Authors: James S Leung

Background: Asthma is the most common chronic disease of childhood and a major source of childhood health burden worldwide. These burdens are particularly marked when children experience characteristic ‘symptom flare-ups’ or acute asthma exacerbations (AAEs). AAE are associated with significant health and economic impacts, including acute Emergency Department visits, occasional hospitalizations, and rarely, death. To treat children with AAE, several medications have been studied and used. Methods: We conducted a narrative review of the literature with the primary objective of understanding the evidence of their efficacy. We present this efficacy evidence in the context of a general stepwise management pathway for paediatric AAEs. This framework is developed from the combined recommendations of eight established (inter)national paediatric guidelines. Discussion: Management of paediatric AAE centres around four major care goals: (1) immediate and objective assessment of AAE severity; (2) prompt and effective medical interventions to decrease respiratory distress and improve oxygenation; (3) appropriate disposition of patient; and (4) safe discharge plans. Several medications are currently recommended with varying efficacies, including heliox, systemic corticosteroids, first-line bronchodilators (salbutamol/albuterol), adjunctive bronchodilators (ipratropium bromide, magnesium sulfate) and second-line bronchodilators (aminophylline, i.v. salbutamol, i.v. terbutaline, epinephrine, ketamine). Care of children with AAE is further enhanced using clinical severity scoring, pathway-driven care and after-event discharge planning. Conclusions: AAEs in children are primarily managed by medications supported by a growing body of literature. Continued efforts to study the efficacy of second-line bronchodilators, integrate AAE management with long-term asthma control and provide fair/equitable care are required.

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Authors: Francisca Gonçalves, Egídio Freitas, Tiago Torres

Background: Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases worldwide. AD pathogenesis is multifactorial, involving environmental and genetic factors. IL-13 stands out as one of the main cytokines in the pathophysiology of AD. Currently, dupilumab, which targets both IL-4 and IL-13 signalling, is the only biologic agent approved for the treatment of moderate-to-severe AD. New targeted biologic therapies are being developed, such as lebrikizumab and tralokinumab, two selective IL-13 inhibitors. This article reviews the role of IL-13 in AD and the most recent data on lebrikizumab and tralokinumab. Methods: A narrative review of the literature was written after retrieving relevant articles in the PubMed database (up until December 2020) using the following keywords present in the title, abstract or body: atopic dermatitis; interleukin 13; IL-13; tralokinumab; lebrikizumab, biologic therapy. Discussion: A phase IIb trial showed that all three dosing regimens evaluated (lebrikizumab 125 mg every 4 weeks (Q4W), 250 mg Q4W or 250 mg every 2 weeks) achieved rapid and dose-dependent efficacy concerning the signs and symptoms of AD, with a statistically significant improvement, at week 16. Tralokinumab was studied in three phase III clinical trials and reached its primary endpoints at week 16 (ECZTRA 1 and 2 in monotherapy and ECZTRA 3 with concomitant topical corticosteroids), with response maintained over time. Both lebrikizumab and tralokinumab exhibited good safety profiles in AD trials, with adverse effects usually being comparable between the control and treatment groups. Conclusion: The evidence supports the hypothesis that selective antagonism of IL-13 is sufficient to control AD, providing an improvement in the patient’s quality of life. Therefore, the development of lebrikizumab and tralokinumab represents a new and exciting phase in the management of AD.

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Authors: Alexander KC Leung, Benjamin Barankin, Joseph M Lam, Kin Fon Leong, Kam Lun Hon

Background: Acne vulgaris is the most common skin disease that can lead to disfigurement and psychological distress. This article aims to provide a narrative updated review on the management of acne vulgaris. Methods: A PubMed search was performed with Clinical Queries using the key term “acne”. The search strategy included clinical trials, meta-analyses, randomized controlled trials, observational studies and reviews. The search was restricted to articles published in English. Results: Treatments of acne include proper skin care, topical medications, oral medications and procedural therapies. Topical agents are the first-line treatment for mild-to-moderate acne and can be used as combination therapy for more severe acne. Systemic therapies are usually prescribed for the initial treatment of moderate-to-severe acne as well as for acne that is refractory to topical therapies. Conclusion: Topical retinoids are the drugs of choice for the treatment and maintenance therapy of patients with mild-to-moderate acne vulgaris. Depending on the severity of the acne, topical retinoids may be used alone or in combination with benzoyl peroxide and topical or oral antibiotics. Oral antibiotics are an important therapy for inflammatory acne unresponsive to topical therapy. Neither topical nor oral antibiotics should be used as monotherapy. Oral contraceptives and/or spironolactone are useful for many women with acne. Oral isotretinoin is the drug of choice for severe, extensive, nodular acne vulgaris but is also often used in moderate cases where scarring is evident, acne-related psychosocial distress is significant or other treatment modalities have failed.

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Authors: Constantine E Kosmas, Dafni Pantou, Andreas Sourlas, Evangelia J Papakonstantinou, Rogers Echavarria Uceta, Eliscer Guzman

Cardiovascular disease (CVD) represents the leading cause of death worldwide. The role of low-density lipoprotein-cholesterol (LDL-C) in the pathophysiology of atherosclerosis and CVD has been well recognized. Statins are the standard of care for the management of hypercholesterolaemia, and their effectiveness in lowering LDL-C and reducing CVD risk in both primary and secondary prevention has been well established. However, several patients fail to attain optimal LDL-C goals or are intolerant to statins, especially at high doses. PCSK9 inhibitors, bempedoic acid, inclisiran, ANGPTL3 inhibitors, PPARβ/δ agonists and LXR agonists are novel or upcoming LDL-C-lowering agents that have shown promising beneficial results. This review aims to present and discuss the current clinical and scientific data pertaining to the new and emerging lipid-modifying LDL-C-lowering drugs.

29

Authors: Xenophon Kassianides BSc (Hons), MBBS, MRCP(UK), Sunil Bhandari MBChB, MRCP, FRCP, PhD, M Clin Edu, FHEA

Third-generation intravenous (i.v.) iron preparations are safe and efficacious and are increasingly used in the treatment of iron-deficiency anaemia. Hypophosphataemia is emerging as an established side-effect following the administration of certain compounds. Symptoms of hypophosphataemia can be masked by their similarity to those of iron-deficiency anaemia and both acute and chronic hypophosphataemia can be detrimental. Hypophosphataemia appears to be linked to imbalances in the metabolism of the phosphatonin fibroblast growth factor 23. In this narrative review, we discuss the possible pathophysiology behind this phenomenon, the studies comparing third-generation i.v. iron compounds, and the potential implications of the changes in fibroblast growth factor 23 and hypophosphataemia. We also present an algorithm of how to approach such patients requiring i.v. iron in anticipation of hypophosphataemia and how the impact related to it can be minimized.