Post-marketing authorisation safety and efficacy surveillance of advanced therapy medicinal products in Brazil, the European Union, the United States and Japan.

BACKGROUND AIMS: Advanced therapy medicinal products (ATMPs) are a class of biological products for human use that are based on gene, tissues or cells. ATMPs have peculiar characteristics when compared with traditional medicines. In this regard, long-term safety and efficacy follow-up systems of individuals treated with ATMPs have become necessary and may present unique challenges, because unlike conventional drugs and biologics, these products can exert their effects for years after administration. This work seeks to assess the requirements foreseen in the regulatory frameworks for the post-marketing authorization safety and efficacy surveillance for ATMPs in Brazil, European Union (EU), Japan and United States, which are some of the members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. METHODS: We reviewed the scientific literature and official documents of regulatory agencies (RAs) in Brazil, the EU, Japan and the United States. RESULTS AND CONCLUSIONS: RAs in the EU, US and Japan have developed regulatory guidelines for the post-marketing surveillance of ATMPs. These guidelines aim at implementing surveillance plans for monitoring adverse events, including late ones, after marketing authorization. All the ATMPs authorized by the RAs studied, submitted some type of post-marketing requirement to supplement safety and efficacy data, according to the regulations and terminology used by those jurisdictions.

Reflections on recruiting healthcare professionals as research participants: Learning from the ONSPres Study.

The involvement of healthcare professionals (HCPs) as research participants is essential to generate high quality evidence for enhancing health services and practice.  Research teams face many challenges in recruiting HCPs for research, and barriers and enablers for interdisciplinary research are not well described in the literature.  The Oral Nutritional Supplement Prescribing Malnutrition Research Study (ONSPres Study) examined malnutrition identification, management, and appropriate oral nutritional supplement prescribing in primary care in Ireland.  The ONSPres Study offers a unique view of recruiting HCPs for research because a range of disciplines were sought for participation in a mixed methods study.  The purpose of this open letter is to describe the experiences of recruitment and participation.  Sixteen general practitioners (GPs) were recruited to participate in one-to-one interviews, eighty health and social care professionals working in community care (including nurses, pharmacists, dietitians, physiotherapists, speech and language therapists, and occupational therapists) were recruited to take part in 12 focus groups, and 31 GPs and trainee GPs were recruited to participate in an education programme developed by the study team.   Strategies required to gain access and reach HCPs differed between disciplines.   Professional networks enhanced access to HCPs working in practice and recruitment was slower and more tailored when those networks were less available to the team.  An interest in malnutrition, to assist in research, to advance patient care, and the opportunity for learning were incentives for the participating HCPs.  Limitations in the diversity of the sample arose, with a bias towards female participants and GPs motivated by an interest in the topic.  It is recommended that study teams collaborate early with relevant HCP disciplines so they can contribute to recruitment planning at project concept and design stages.  To enhance and incentivise HCP participation in research, dedicated time and acknowledgement of participation as continuous professional development is proposed.

Colonoscopy: an evidence-based approach.

Colonoscopy is an invasive, endoscopic procedure undertaken to visualise the inner lumen of the colon and is used for a variety of diagnostic purposes. The procedure is increasingly performed by nurse endoscopists. This article provides an overview of the indications and contraindications for colonoscopy and describes various elements of the procedure, including consent, sedation and bowel preparation within the context of the evidence base. The article also discusses patient care before, during and after the procedure.

Comparison of new Brazilian legislation for the approval of advanced therapy medicinal products with existing systems in the USA, European Union and Japan.

BACKGROUND AIMS: Advanced therapy medicinal products (ATMPs) are a class of biological products for human use that are based on genes, cells and tissues. The first ATMP received marketing authorization in Europe in 2009, whereas Brazil granted the first authorization in 2020. The objective of this study was to compare the regulatory models adopted by Brazil, the USA, Japan and the European Union, which comprise the member countries of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, with regard to the marketing authorization of ATMPs. METHODS: The authors performed a review of the scientific literature and official documents of the regulatory agencies in the aforementioned countries. RESULTS: The legislation and regulatory guidelines adopted by the regulatory agencies exhibit similarities and differences. It was not possible to assess whether these differences can be translated into divergent final recommendations by regulatory authorities upon a request for marketing authorization. CONCLUSIONS: In the future, it will be appropriate to start a progressive process of harmonization between these agencies in terms of terminology, legal recommendations and characterization requirements. This is particularly important for emerging countries such as Brazil. In this sense, some measures can be taken to achieve alignment between regulators.

Malnutrition: A Misunderstood Diagnosis by Primary Care Health Care Professionals and Community-Dwelling Older Adults in Ireland.

BACKGROUND: Language and communication have an impact on how a clinical condition is treated and experienced, from both the health care professional (HCP) and patient perspective. Malnutrition is prevalent among community-dwelling older adults, yet perceptions of patient understanding of the term malnutrition to date remain underexplored. OBJECTIVE: This qualitative study explored the use and perceptions of the term malnutrition among HCPs and older adults at risk of malnutrition. DESIGN: Semi-structured interviews and focus groups were conducted with HCPs and older adults with a prescription for oral nutritional supplements (ONS) in the community, to explore perspectives. PARTICIPANTS AND SETTING: HCPs with experience of working with older adults were recruited in primary care centers, general practitioner practices, community health organizations, and community pharmacies in County Dublin, Ireland, between 2018 and 2019. Older adults, aged ≥60 years, with a current or previous prescription for ONS were recruited from daycare centers. One-to-one interviews were conducted with general practitioners (n = 16) and patients (n = 13), and focus groups were conducted with other HCPs, including dietitians (n = 22), nurses (n = 22), pharmacists (n = 9), physiotherapists (n = 12), occupational therapists (n = 6), and speech and language therapists (n = 4). DATA ANALYSIS: Data from interviews and focus groups were transcribed verbatim and analyzed using thematic analysis. RESULTS: There was mutual agreement between HCPs and patients on the main theme, "malnutrition is a term to be avoided." There were three subthemes with varying input from the different HCP groups and patients: "Malnutrition is a term a patient doesn't want to hear"-malnutrition has negative connotations that imply neglect and stigma; "malnutrition is a clinical term which patients don't understand"-with perceptions that it is better to substitute the term with simpler motivating messages; and "lack of confidence identifying malnutrition"-expressed by non-dietetics HCPs who believed they had insufficient expertise on malnutrition to communicate effectively with patients. CONCLUSIONS: HCPs and patients perceived negative connotations with the term malnutrition, and HCPs used alternatives in practice. Additional consultation with HCPs and patients is recommended to explore appropriate language for conveying health risks associated with malnutrition. Future research should also address how current communication challenges can be addressed as part of strategic management programs or interventions to prevent and treat malnutrition.

Healthcare professionals' perceptions of malnutrition management and oral nutritional supplement prescribing in the community: A qualitative study.

BACKGROUND & AIM: Protein-energy malnutrition is under-recognised in the community despite being common in older adults due to physiological and social changes which are often compounded by chronic disease. This qualitative study aimed to explore the opinions of healthcare professionals (HCPs) working in the primary care and community settings about the management of malnutrition and the prescription of oral nutritional supplements (ONS), often included in the treatment of malnutrition. METHODS: Twelve healthcare professional (HCP) focus groups with 75 participants were conducted: community dietitians (n = 17), registered dietitians working in industry (n = 5), community and residential care nurses (n = 22), physiotherapists (n = 12), pharmacists (n = 9), occupational therapists (n = 6) and speech and language therapists (n = 4). Focus group discussions were audio-recorded and transcribed verbatim. The data were coded and analysed using thematic analysis and key themes with illustrative quotes extracted are presented. RESULTS: Similar views on malnutrition management existed across professions. 'Gaps in Primary Care Management' was the first key theme wherein HCPs identified limitations in malnutrition management in the community. Barriers included limited or no dietetic services available in primary care and poor communication between general practitioners and wider primary care team members which resulted in inappropriate or delayed treatment. The second key theme, 'Challenges with ONS use in the Community', encapsulated several issues HCPs experienced with ONS usage including inappropriate prescribing and lack of monitoring of treatment goals. Conflicts of interest regarding dietitians working in industry assessing and treating older adults in residential care settings was highlighted by participants. CONCLUSIONS: This study highlights that more emphasis is needed to identify patients when they are at risk of malnutrition to avoid advanced or severe malnutrition presentations currently seen. Community dietitians for older people are required to address many of the issues raised including the need for awareness, education and training, resources, and malnutrition care pathway structures.

The Human Gut Phageome: Origins and Roles in the Human Gut Microbiome.

The investigation of the microbial populations of the human body, known as the microbiome, has led to a revolutionary field of science, and understanding of its impacts on human development and health. The majority of microbiome research to date has focussed on bacteria and other kingdoms of life, such as fungi. Trailing behind these is the interrogation of the gut viruses, specifically the phageome. Bacteriophages, viruses that infect bacterial hosts, are known to dictate the dynamics and diversity of bacterial populations in a number of ecosystems. However, the phageome of the human gut, while of apparent importance, remains an area of many unknowns. In this paper we discuss the role of bacteriophages within the human gut microbiome. We examine the methods used to study bacteriophage populations, how this evolved over time and what we now understand about the phageome. We review the phageome development in infancy, and factors that may influence phage populations in adult life. The role and action of the phageome is then discussed at both a biological-level, and in the broader context of human health and disease.

Isolation and Characterization of Klebsiella Phages for Phage Therapy.

Introduction: Klebsiella is a clinically important pathogen causing a variety of antimicrobial resistant infections in both community and nosocomial settings, particularly pneumonia, urinary tract infection, and sepsis. Bacteriophage (phage) therapy is being considered a primary option for the treatment of drug-resistant infections of these types. Methods: We report the successful isolation and characterization of 30 novel, genetically diverse Klebsiella phages. Results: The isolated phages span six different phage families and nine genera, representing both lysogenic and lytic lifestyles. Individual Klebsiella phage isolates infected up to 11 of the 18 Klebsiella capsule types tested, and all 18 capsule-types were infected by at least one of the phages. Conclusions: Of the Klebsiella-infecting phages presented in this study, the lytic phages are most suitable for phage therapy, based on their broad host range, high virulence, short lysis period and given that they encode no known toxin or antimicrobial resistance genes. Phage isolates belonging to the Sugarlandvirus and Slopekvirus genera were deemed most suitable for phage therapy based on our characterization. Importantly, when applied alone, none of the characterized phages were able to suppress the growth of Klebsiella for more than 12 h, likely due to the inherent ease of Klebsiella to generate spontaneous phage-resistant mutants. This indicates that for successful phage therapy, a cocktail of multiple phages would be necessary to treat Klebsiella infections.

Collaboration during a crisis - the Lighthouse Lab volunteers.

As a group of early-career researchers, we recount our experiences of volunteering at one of the national Lighthouse Labs based at the UK Biocentre in Milton Keynes. We worked together as part of a multidisciplinary team to support the large-scale processing of coronavirus disease 2019 (COVID-19) swabs from across the whole of the UK.

Implementing skin-to-skin contact at birth using the Iowa model: applying evidence to practice.

Prolonged skin-to-skin contact (SSC) between mothers and newborns in the hour after birth is associated with physiologic and psychological benefits for both mothers and infants, yet this is not a standard practice at all birthing facilities. The purpose of the project described in this article was to implement SSC immediately aft er birth for healthy term newborns as a routine, evidence-based practice in a labor and delivery unit at a Midwestern U.S. academic medical center. When incorporated into routine newborn care, SSC promotes key maternal-infant health outcomes of importance to quality nursing care.

Outcome of clinical nurse specialist-led hyperbilirubinemia screening of late preterm newborns.

PURPOSE/OBJECTIVE: The purpose of this project was to implement universal screening of all late preterm newborns for hyperbilirubinemia in a level I newborn nursery. RATIONALE/BACKGROUND: Late preterm newborns have traditionally received the same level of care and monitoring as term newborns despite being at increased risk for morbidity and mortality. DESCRIPTION OF THE PROJECT: An interdisciplinary clinical nurse specialist-led team guided by the Iowa Model of Evidence-Based Practice developed, piloted, and evaluated a standardized, coordinated approach to universal screening, assessment, and management of hyperbilirubinemia for late preterm newborns. OUTCOMES: The readmission rate of late preterm newborns with hyperbilirubinemia in the 30 days after birth was reduced to zero, providing evidence of programmatic effectiveness. INTERPRETATION/CONCLUSION: Universal screening of late preterm newborns for hyperbilirubinemia significantly improved outcomes in this vulnerable population. IMPLICATIONS: Detection of hyperbilirubinemia through universal screening of late preterm newborns is recommended in newborn nurseries.