World Health Organization Expert Research Articles

Emergency care and treatment of cerebral stroke at the stages of hospitalisation

According to the World Health Organization experts, about 7 million deaths due to cerebrovascular disease are recorded annually worldwide, and the number of stroke deaths is projected to reach 7.8 million by 2030. The main causes of stroke and its growth are population ageing, urbanisation, unhealthy lifestyles, insufficient control of risk factors (hypertension, atherosclerosis, diabetes, stressful situations, etc.). It is also associated with untimely provision of emergency medical care at the pre-hospital stage and ineffective treatment of strokes at the hospital stage, as well as a low efficiency of preventive treatment for recurrent stroke and rehabilitation measures. The lecture presents modern methods and techniques for treating patients with acute cerebrovascular accident at different stages: pre-hospital, hospital, and rehabilitation.

User-experience testing of an evidence-to-decision framework for selecting essential medicines.

Essential medicine lists (EMLs) are important medicine prioritization tools used by the World Health Organization (WHO) EML and over 130 countries. The criteria used by WHO's Expert Committee on the Selection and Use of Essential Medicines has parallels to the GRADE Evidence-to-Decision (EtD) frameworks. In this study, we explored the EtD frameworks and a visual abstract as adjunctive tools to strengthen the integrate evidence and improve the transparency of decisions of EML applications. We conducted user-experience testing interviews of key EML stakeholders using Morville's honeycomb model. Interviews explored multifaceted dimensions (e.g., usability) on two EML applications for the 2021 WHO EML-long-acting insulin analogues for diabetes and immune checkpoint inhibitors for lung cancer. Using a pre-determined coding framework and thematic analysis we iteratively improved both the EtD framework and the visual abstract. We coded the transcripts of 17 interviews with 13 respondents in 103 locations of the interview texts across all dimensions of the user-experience honeycomb. Respondents felt the EtD framework and visual abstract presented complementary useful and findable adjuncts to the traditional EML application. They felt this would increase transparency and efficiency in evidence assessed by EML committees. As EtD frameworks are also used in health practice guidelines, including those by the WHO, respondents articulated that the adoption of the EtD by EML applications represents a tangible mechanism to align EMLs and guidelines, decrease duplication of work and improve coordination. Improvements were made to clarify instructions for the EtD and visual abstract, and to refine the design and content included. 'Availability' was added as an additional criterion for EML applications to highlight this criterion in alignment with WHO EML criteria. EtD frameworks and visual abstracts present additional important tools to communicate evidence and support decision-criteria in EML applications, which have global health impact. Access to essential medicines is important for achieving universal health coverage, and the development of essential medicine lists should be as evidence-based and trustworthy as possible.

Paracetamol and ibuprofen in the treatment of pain and fever in children: modern views on the choice of a drug

Paracetamol (acetaminophen) and ibuprofen are commonly used to relieve fever and pain in children. Their effects are similar, but differ in strength and mechanisms of action on the body. Acetaminophen, a para-aminophenol derivative, has antipyretic and analgesic properties. Despite the fact that paracetamol has been officially used as a drug for more than 75 years, its mechanism of biological action has not been sufficiently studied. In paediatric practice, paracetamol is more often used as an antipyretic, but in recent years, with the development of technology and emergence of new dosage forms on the market, it came into common use as an analgesic in many diseases, including oncological, rheumatological, etc. Ibuprofen is the most commonly used non-steroidal anti-inflammatory drug with pronounced analgesic and antipyretic properties. Ibuprofen, a non-selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), affects the hypothalamic thermoregulatory center via inhibition of prostaglandin synthesis. In the paediatric population, the most common indications for the use of ibuprofen are fever, sore throat, ear pain, headache and toothache, post-traumatic and musculoskeletal pain, and inflammatory joint diseases. Paracetamol and ibuprofen are safe for use in paediatric practice, if dosing rules are observed, and are approved for use by the World Health Organization, FDA and other expert organizations. In addition, the emergence of new presentation forms of these drugs is most important in paediatrics.

An ethics framework for social listening and infodemic management

Abstract Issue Successful response to an infodemic requires social listening and integrated analysis to produce infodemic insights by identifying questions, concerns, information voids and circulating narratives including health misinformation. There is currently a wide variation in social listening and infodemic insights generation practices, and a lack of frameworks to be applied on ethical values and standards. Description of the problem In the context of infodemic management, infodemic insights are generated based on social listening, health system and data from online and offline sources. Where there is a difference between health guidance and behaviors during an emergency, rapid infodemic insights can help understand the underlying drivers of this divergence. Integrated analysis of this data informs infodemic management strategies generate insights that advise a wide range of public health interventions. Present ethical challenges influence data processing and use. Results The World Health Organization (WHO) convened a group of experts to develop an ethical framework for social listening and infodemic management. It will guide health authorities and practitioners in planning and setting up infodemic insights teams and implementing infodemic management activities. To support the deliberation of the WHO expert group, a systematic review has been conducted to understand present ethical concerns and challenges. Lessons Infodemic management strategies raise ethical concerns that relate to data control, commercialization, transparency, accountability and implications. Power and power imbalances, human rights, privacy and dignity, trust and respect for cultural practices may arise during data collection, analysis, interpretation, and intervention design. Without proper ethical oversight and guidance, the implementation of infodemic management strategies could harm individuals and communities, erode trust, and undermine the effectiveness of responses to a public health emergency. Key messages • Social listening and infodemic management by health authorities require consideration of ethical principles and guidance. • WHO ethics guidance will help public health authorities establish infodemic management practices, policies and strategies.

Perspectives on recent reviews of aspartame cancer epidemiology

Aspartame is a dipeptide non-sugar sweetener that was first marketed in the US in carbonated beverages in 1983, before gaining prominence globally. The Joint Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) and the WHO International Agency for Research on Cancer (IARC) completed evaluations of aspartame and cancer in July 2023. JECFA reaffirmed the safety of aspartame, stating that epidemiology evidence is “not convincing,” and that there are no consistent associations between aspartame and cancer (JECFA/IARC, 2023; JECFA, 2023). JECFA also noted “reverse causality, chance, bias and confounding by socioeconomic or lifestyle factors, or consumption of other dietary components, could not be completely ruled out” in relevant epidemiology studies (JECFA/IARC, 2023). In contrast, IARC stated that there are three “high quality” studies on liver cancer (Riboli, 2023), but that the evidence is limited because “chance, bias or confounding could not be ruled out as an explanation for the positive findings” (JECFA/IARC, 2023). IARC does not provide an explanation as to how these studies can be both high quality and have these weaknesses, most notably potential exposure misclassification, or how inconsistent associations from studies with these weaknesses constitute limited evidence. Further, when IARC concludes an agent has limited or inadequate human evidence (and no sufficient animal or strong mechanistic evidence), it classifies that agent as either Group 2B, a possible human carcinogen, or Group 3, not classifiable as to its carcinogenicity. Ultimately, the interpretations of Group 2B and Group 3 classifications are intended to be similar. However, a Group 2B designation may make it appear to scientists and non-scientists alike that the evidence is pointing in the direction of causality. This can lead to unnecessary confusion with respect to the evidence, as well as a perception of a disagreement within WHO regarding aspartame. This apparent contradiction could have been avoided by assigning the IARC classification most consistent with the conclusion that the human evidence for cancer is inadequate: Group 3.

Non-standard nature. Venoms, serum and serpentariums in the uneven fabrication of global health

Envenomation challenges international public health, and antivenom serum is a strategic tool in the management of this condition. However, although antivenom serum has been in use since the late 19th century, the accessibility, quality and safety of this essential health product are still causes for concern in the most affected areas. The reasons for such a situation are multiple and include the poverty of snakebite victims, the high production costs of serum, the logistical difficulties pertaining to the mostly rural location of envenomation events, however one root cause has been the recurring difficulty to standardize antivenom serum as a health commodity. This paper, grounded in “Science and Technology Studies” (STS) focuses on this standardization issue, and argues that it can be explained in two complementary ways: on one hand, the difficulty to standardize serum relates to the nature of venom itself, and on the other hand, it relates to the social and institutional characteristics of envenomation as a neglected disease. The argument is supported by the analysis of reports published by the World Health Organization expert committee on biological standardization from 1947 to 2022 and dealing with the standardization of venom and antivenom. The paper describes the successive standardization strategies implemented by international public health actors. This analysis shows that standardization procedures are shaped by a series of interactions between objects (venom and antivenom), scientific bodies of knowledge that characterize them (eg. toxinology or venomics), organizational and financial public health regimes that frame their circulation. The difficulties raised by the standardization of antivenom reveal the problematic articulation between these domains. Acknowledging this problematic articulation, the discussion emphasizes its consequences for the understanding of relations between medical technologies, global markets and so-called “natural resources”. One conclusion drawn from these findings is to call for a “One Health” approach that would take into greater account the diversity and complexity of non-human life.

Real-time face mask position recognition system based on MobileNet model.

COVID-19 is a highly contagious disease that was first identified in 2019, and has since taken more than six million lives world wide till date, while also causing considerable economic, social, cultural and political turmoil. As a way to limit its spread, the World Health Organization and medical experts have advised properly wearing face masks, social distancing and hand sanitization, besides vaccination. However, people wear masks sometimes uncovering their mouths and/or noses consciously or unconsciously, thereby lessening the effectiveness of the protection they provide. A system capable of automatic recognition of face mask position could alert and ensure that an individual is wearing a mask properly before entering a crowded public area and putting themselves and others at risk. We first develop and publicly release a dataset of face mask images, which are collected from 391 individuals of different age groups and gender. Then, we study six different architectures of pre-trained deep learning models, and finally propose a model developed by fine tuning the pre-trained state of the art MobileNet model. We evaluate the performance (accuracy, F1-score, and Cohen's Kappa) of this model on the proposed dataset and MaskedFace-Net, a publicly available synthetic dataset created by image editing. Its performance is also compared to other existing methods. The proposed MobileNet is found as the best model providing an accuracy, F1-score, and Cohen's Kappa of 99.23%, 99.22%, and 99.19%, respectively for face mask position recognition. It outperforms the accuracy of the best existing model by about 2%. Finally, an automatic face mask position recognition system has been developed, which can recognize if an individual is wearing a mask correctly or incorrectly. The proposed model performs very well with no drop in recognition accuracy from real images captured by a camera.

Collaborative study for the calibration of a replacement International Standard for Diphtheria Antitoxin Equine

The International Standard for Diphtheria Antitoxin Equine is essential for the standardisation of assays used to determine the potency of therapeutic diphtheria antitoxin products produced from equine serum. This paper describes the production and characterization of the 2nd International Standard for Diphtheria Antitoxin Equine and its calibration in International Units. Calibration was performed by toxin neutralization test in vivo and in vitro (Vero cell assay), and potency was expressed relative to the 1st International Standard to ensure continuity of the International Unit. The candidate standard (NIBSC product code 18/180) was assigned a unitage of 57 IU/ampoule based on results from 14 laboratories in 9 different countries and was established by the World Health Organisation Expert Committee on Biological Standardization in 2021.

The development and establishment of a heat inactivated preparation of Mycobacterium tuberculosis (H37Rv) as the first international standard for nucleic acid amplification techniques

A need to develop an inactivated Mycobacterium tuberculosis (Mtb) preparation, to be used as a DNA standard, as an important and urgent requirement for Tuberculosis (TB) diagnostics standardization was identified in 2018. A candidate material was generated using a heat inactivated culture of Mtb strain H37Rv. A lyophilised preparation was evaluated for its suitability as an International Standard for molecular detection of Mtb DNA in an international collaborative study. Together with the use of quantitative PCR assays and rapid diagnostic tests, this candidate standard was demonstrated to be fit-for-purpose. Based on the results from this collaborative study, it is proposed this lyophilised heat inactivated Mtb preparation (NIBSC code: 20/152) to be established by the World Health Organization Expert Committee on Biological Standardization, as the First WHO International Standard for Mycobacterium tuberculosis (H37Rv) for nucleic acid amplification techniques with an assigned unitage of 6.3 log10 or 2 × 106 International Units per vial.The intended uses of this IS are for calibration of secondary or in-house reference preparations used in the assays for the molecular detection of Mtb DNA. It may also be used for assay validation and monitoring the performance in terms of limit of detection of rapid diagnostic tests.

Results evaluation of the implementation of the “Program for Optimizing Feeding of Children in the First Year of Life in the Russian Federation” dated 2009

Background. Appropriate prescribing of complementary food allows to optimize the intake of macro- and micronutrients, provides adequate indicators of growth and development of the child, reduces the risk of non-infectious pathology. Taking into account the significance of this problem, World Health Organization (WHO) experts, together with The European Society for Paediatric Gastroenterology Hepatology and Nutrition, carried out a research where they studied issues related to the appointment of complementary food for children in the European Region and their compliance with existing recommendations.
 Aim. To study the features of the introduction of complementary food in the Russian Federation on the basis of an assessment of the implementation of the recommendations of the "National program for optimizing the feeding of children in the first year of life in the Russian Federation", 2009 and to conduct a comparative analysis of the results obtained and the data presented in the study carried out by WHO experts.
 Materials and methods. A multicenter retrospective, uncontrolled, non-randomized study was conducted in 7 cities of the Russian Federation.
 Results. The median age at which complementary foods were introduced was 5 [46] months; vegetables (51.0%) and cereals (31.2%) were the first complementary food products; children began to receive fruit mainly (77.3%) in the second half of life; the age of introduction of meat puree was 7 [68] months, while every 4th child by 9 months did not receive meat; juices were introduced at 7 [69] months, but in 8.8% of children juices became the first product of complementary foods; median age for yolk administration was 8 [710] months, fish 9 [810] months. Only 14.0% of mothers used products of exclusively industrial production in the nutrition of their children, 33.9% prepared it themselves. Correlation analysis did not revealed any relationship between the body weight of a child at the age of 12 months and the time of introduction of the first complementary food product, as well as with the age of introduction of each of the introduced products. A connection was established between the body weight of a child at the age of 12 months and the volume of individual products that children receive between the age of 6 and 12 months. The recommendations of the National program for optimizing the feeding of children in the first year of life in the Russian Federation were generally implemented. Our analyses revealed the most frequent violations during the introduction and use of complementary food products: late start of their introduction (after the age of 6 months) in 41.3% of children, delayed prescription of meat, frequent use of home-made cereals not enriched with micronutrients, dilution of dairy-free porridge with water, irregular inclusion in the diet of egg yolk.
 Conclusion. The results obtained confirm the importance of implementation of the Program for Optimizing Feeding of Children in the First Year of Life in the Russian Federation updated in 2019 and approved by the Ministry of Health of Russia and indicate the need for further work on its improvement.

Iron deficiency in children: modern aspects of the problem, possibilities of primary prevention: A review

Iron deficiency (ID) is common in the pediatric population, primarily due to inadequate iron intake from food and a high requirement due to rapid growth. The most significant for pediatric practice are latent iron deficiency and iron deficiency anemia. Hyposiderosis significantly impacts a child's physical and cognitive development and immunological reactivity. It can be an independent condition and complicate the course of several other diseases. The article presents data on the most significant factors contributing to the ID, risk groups, clinical presentation features (sideropenic and anemic syndromes), criteria of laboratory diagnostics of iron deficiency anemia according to the clinical guidelines "Iron deficiency anemia" approved by the Russian Ministry of Health in 2021, and the latent iron deficiency developed by the World Health Organization experts. Also, the algorithm of ID primary prevention, diet therapy approaches, and the use of functional products and dietary supplements to meet the iron requirement of a child's organism are discussed.

Points to consider in the development of national human genome editing policy.

Clustered regularly interspaced short palindromic repeats and other genome editing technologies have the potential to transform the lives of people affected by genetic disorders for the better. However, it is widely recognised that they also raise large ethical and policy questions. The focus of this article is on how national genome editing policy might be developed in ways that give proper recognition to these big questions. The article first considers some of the regulatory challenges involved in dealing these big ethical and social questions, and also economic issues. It then reviews the outcomes of a series of major reports on genome editing from international expert bodies, with a particular focus on the work of the World Health Organization's expert committee on genome editing. The article then summarises five policy themes that have emerged from this review of the international reports together with a review of other literature, and the authors' engagement with members of the Australian public and with a wide range of experts across multiple disciplines. Each theme is accompanied by one to three pointers for policymakers to consider in developing genome editing policy.

Analysis of antibacterials for systemic use recommended for the treatment of patients with community-acquired pneumonia in Ukraine according to the modern approach to preventing the development of antimicrobial resistance

BACKGROUND. According to a 2019 epidemiological study, antibiotic resistance (AR) caused about 1.27 million deaths worldwide, with lower respiratory tract infections (particularly pneumonia) dominating the global disease burden caused by resistant microorganisms.
 OBJECTIVE. To determine the compliance of antibiotics (J01), which are recommended by the guidelines of the National Academy of Medical Sciences of Ukraine for the empiric therapy of community-acquired pneumonia (CAP) in adults, with World Health Organization (WHO) recommendations based on the prevention of the development of AR.
 MATERIALS AND METHODS. Objects – antibiotics (J01) recommended by the guideline and their belonging to the access, watch and reserve groups according to the WHO AWaRe classification of antibiotics. Methods: system overview, analytical, comparison and generalization.
 RESULTS AND DISCUSSION. In the guidelines for empiric therapy of CAP in adults, antibiotics of 7 groups are recommended, from which 36 international non-proprietary names (INNs) were selected and analyzed. Of these, 7 INNs belong to the access group, of which only 4 antibiotics (amoxicillin, amoxicillin / clavulanic acid, gentamicin, doxycycline) are recommended by WHO experts for empiric treatment of CAP in adults; 26 INNs belong to the watch group, but only 3 antibiotics (cefotaxime, ceftriaxone, clarithromycin) according to the WHO database are recommended as empiric therapy for the severe CAP in adults. Ceftaroline, according to the WHO AWaRe antibiotic classification, belongs to the reserve group and should be used to fight multiresistant microorganisms. No antibiotic of the reserve group is recommended by WHO for empiric therapy of CAP.
 CONCLUSIONS. The results of the analysis can be used in updating the recommendations for rational empiric antibiotic therapy of CAP, taking into account the mechanisms of resistance to the development and spread of AR.

Modern algorithms of geno-phenotypic diagnosis of tuberculosis in Ukraine

BACKGROUND. To ensure timely and accurate detection of tuberculosis (TB), including TB with multiple drug resistance in Ukraine, the document “Health Standards for TB” (Order of the Ministry of Health of Ukraine № 2161 of 06.10.2021), which the basis of laboratory diagnosis of TB is the use of modern molecular genetic methods and tested in the Central Reference Laboratory of Ukraine for microbiological diagnosis of TB.
 RESULTS AND DISCUSSION. The article presents complex algorithms for the diagnosis and monitoring treatment of pulmonary TB using rapid molecular genetic methods. The basic principles and approaches to the diagnostic process, on which the domestic normative document is based, corresponds to those recommended by World Health Organization experts for the countries of the European region. When testing for TB, a molecular genetic test must be performed to detect the presence of Mycobacterium tuberculosis DNA in the diagnostic sample. Then (depending on the capabilities of the laboratory) one or another technology is used to detect mutations associated with the resistance of M. tuberculosis to the maximum possible range of AMBP I and II lines. After receiving the results of seeding in the automated system BACTEC MGIT, which is currently the gold standard for the study of drug sensitivity of M. tuberculosis to AMBP I and II lines, the treatment regimen is adjusted if necessary according to the phenotypic test of drug sensitivity.
 CONCLUSIONS. According to the latest international guidelines for the diagnosis of TB, preference should be given to molecular genetic diagnostic tests and culture studies in liquid nutrient media. Microscopic and cultural studies are important and remain necessary to monitor treatment.

Можливості впливу засобів фізичної терапії на перебіг цукрового діабету та розвиток діабетичних ускладнень

According to the latest data from the World Health Organization experts, the incidence of diabetes mellitus in economically developed countries of the world is up to 6% of the population. Throughout the world and in Ukraine in particular, diabetes mellitus is one of the most common chronic non-infectious diseases. Complications of diabetes mellitus occupy the third place among various causes of death. The use of modern pharmacological agents in the treatment of diabetes mellitus does not solve all the problems of this difficult and multifaceted pathology, therefore the search for non-pharmacological methods of physical therapy and rehabilitation of such patients remains relevant and has been studied insufficiently. In addition, an effective combination of drug and physical treatment methods can accelerate the achievement of diabetes compensation, prevent or cause regression of the development of neurovascular complications. The purpose of the study was to discuss the possibilities of the influence of physical therapy on the course of diabetes mellitus and the development of diabetic complications at the current stage. Results. In accordance with modern requirements, rehabilitation of patients with diabetes mellitus and diabetic complications is carried out in acute, subacute and long-term rehabilitation periods at the inpatient and outpatient stages of treatment. Properly dosed physical activity has a positive effect on all types of metabolism; this may allow to reduce the level of glycemia, increase the number of insulin receptors and their sensitivity, as well as reduce the doses of hypoglycemic drugs. Physical therapy has a positive effect on the condition of the central and peripheral nervous system, the disorders of which are important in the development of diabetic complications. The level of physical exertions should correspond to the patient's state of health, his/her physical capabilities, taking into account the stage and state of compensation of the disease, the presence of diabetic complications. The probability of success in physical therapy for such patients depends on the complex of physical therapy tools in combination with physiotherapeutic methods and massage. The effectiveness and safety of the physical therapy should be monitored by the dynamics of glycemia, glycosuria, and body weight. Conclusion. Therefore, the modern strategy of complex management of diabetic patients from the standpoint of physical and rehabilitation medicine involves a multidisciplinary approach with the inclusion of effective means of physical therapy, rehabilitation technologies, physiotherapeutic methods, as well as ergotherapeutic measures aimed at increasing functional reserves, compensation of impaired vascular and innervation mechanisms, regeneration capabilities, secondary prevention of diabetic complications, social adaptation and restoration of working capacity of patients

Phân tích việc áp dụng chức năng y tế công cộng thông qua văn bản chỉ đạo được ban hành nhằm ứng phó với COVID-19 trong bốn giai đoạn dịch tại Việt Nam

The Government, the National Steering Committee, and the Ministry of Health are the agencies that play an important role in deciding, leading and operating in the entire process of responding to the COVID-19 pandemic in Vietnam. Through issued documents, these agencies showed their concerns and directions to relevant departments and sectors at all levels. Collecting and analyzing such documents will allow lessons to be learned from both successes and failures in each and all four phases of the pandemic. The analysis is mainly through a comparative comparison of these documents with the basic functions of public health, a basic theoretical framework developed by the World Health Organization experts based on fundamental principles agreed upon by member countries of the United Nations. Vietnam is one of those consensus countries. That theoretical framework is standardized in each participating country accordingly before being promulgated. In Vietnam, that stage was completed in 2001 with the approval of the Ministry of Health. The research conducted during this particular pandemic allowed the team to make initial observations on how these basic public health functions were applied in a factual and specific event. The research has shown the concept in an objective way that those public health functions are specifically understood and applied in each different epidemic wave and in emergency response situations during the pandemic. From there, the relevant lessons learned will serve as suggestions for future complete plans before similar situations may happen in the future.

Relationships Weight Loss Mother With Hormonal Birth Control Usage

Family planning, according to WHO (world health organization) expert commite 1970 is action that helps couples to avoid unwanted pregnancies, getting birth highly desired, set the interval between pregnancies and determine the number of children in the family (Sulistyawati, 2018). Objective To determine the relationship research Mom Weight Loss with use of hormonal birth control in the village Pekan Tebih Puskesmas Rokan Hulu. The research method used is Analytical Survey and the type of cross-sectional study. The population in the study were all women taking hormonal birth control as many as 129 people and the sample is saturated sample as many as 129 people. Results of research on the relationship of maternal weight with the use of hormonal birth control only get 69 respondents who are willing to be investigated, while the rest are not willing to study for a variety of reasons given by the respondents. Based on the data obtained is processed using computerized women taking birth control pills that there were 18 respondents (23.1%) and taking injections were 51 people (73.9%). Conclusion There is a relationship Weight Mom With Hormonal birth Pemakian Pekan Tebih Village Puskesmas Kepenuhan Hulu. Expected advice for other researchers can continue research on the use of mother Weight Loss Hormonal birth control and be used as a reference / reading especially things related about hormonal birth control.
 Keywords: Hormonal Birth Control, Birth Control, Weight Loss

The morphologic spectrum of lobular carcinoma in situ (LCIS) observations on clinical significance, management implications and diagnostic pitfalls of classic, florid and pleomorphic LCIS.

Lobular carcinoma in situ (LCIS) is a non-invasive proliferation of atypical dyscohesive epithelial cells characterized by loss or functional alteration of E-cadherin-mediated cell adhesion. The morphologic spectrum of LCIS encompasses classic (C-LCIS), florid (F-LCIS) and pleomorphic LCIS (P-LCIS), as recently defined by the World Health Organization (WHO) Expert Consensus Group. Atypical lobular hyperplasia (ALH) is also part of this spectrum.This article highlights the morphologic and immunohistochemical features of the three forms of LCIS and summarizes their management implications and prognosis, with emphasis on F-LCIS and P-LCIS.

Regulatory Evaluation of Biosimilars: Refinement of Principles Based on the Scientific Evidence and Clinical Experience.

The World Health Organization (WHO) guidelines on evaluation of similar biotherapeutic products (SBPs; also called biosimilars) were adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2009. In 2019, the ECBS considered that a more tailored and potentially reduced clinical data package may be acceptable in cases where this was clearly supported by the available scientific evidence. The goal of this publication is to review the current clinical experience and scientific evidence and to provide an expert perspective for updating the WHO guidelines to provide more flexibility and clarity. As the first step, the relevant guidelines by other regulatory bodies were reviewed in order to identify issues that might help with updating the WHO guidelines. Next, a literature search was conducted for information on the long-term efficacy, safety, and immunogenicity of biosimilars to identify possible long-term problems. Finally, a search for articles concerning the role of clinical studies in the benefit–risk evaluation of biosimilars was conducted. The analysis of other guidelines suggested that the WHO guidelines may need more emphasis on the importance of the state-of-the-art physicochemical and structural comparability exercise and in vitro functional testing. The use of “foreign” reference product will also need clarifications. The value of in vivo toxicological tests in the development of biosimilars is questionable, and the non-clinical part needs revisions accordingly. The concepts of “totality of evidence,” “stepwise development,” and “residual uncertainty” were applied in the evaluation of the clinical sections of the guideline. The review of long-term safety and efficacy demonstrated the robustness of the current biosimilar development concept. The analysis of the roles of different development phases suggested that the large efficacy, safety, and immunogenicity studies are, in most cases, redundant. The residual uncertainty of safety, immunogenicity, and efficacy of biosimilars that has shaped the current regulatory guidelines is now substantially reduced. This will allow the re-evaluation of the non-clinical and clinical requirements of the current WHO main guideline. The shift of the relative impact of the development phases towards physico-chemical and in vitro functional testing will provide a relief to the manufacturers and new challenges to the regulators.

In It Together

In It Together