Erratum: SARS-CoV-2 Main Protease Inhibitors: Structure-Based Enhancement to Anti-Viral Pre-Clinical GC376 Encourages Further Development (Journal of Computational Biophysics and Chemistry (2023) (2350014) DOI: 10.1142/S273741652350014X)

The email address for Elliot D. Perry has been corrected to edperry1@hotmail.co.uk. © 2023 World Scientific Publishing Company.

OECD health working paper no. 137: shortages of medicines in OECD countries

. Medicine shortages have become increasingly common in a number of countries in recent years and the COVID-19 pandemic has exacerbated the situation. The aim of this paper was to develop further insights into the extent and nature of medicine shortages in OECD countries (pre COVID-19). However, absent both a common nomenclature and harmonised notification systems for reporting shortages, intercountry comparisons, and an overarching global perspective remain challenging. Notwithstanding these challenges, the number of shortage notifications increased by 60% over the period 2017 to 2019 in a sample of 14 OECD countries. . In OECD's analysis, more than half of all notifications were concentrated in three main therapeutic areas: medicines targeting the nervous system, cardiovascular system and antiinfectives. In nearly two-thirds of cases, a shortage of a given active substance was reported in more than one country. Shortages affected predominantly older, off-patent molecules. However, the impact on patient health is largely unknown, given that a notification does not necessarily impact patients adversely if appropriate alternatives remain available and accessible. . The multifactorial nature of this issue and complexity of this industrial sector confound root cause analysis, with different stakeholder perceptions, poor data quality, and general misconceptions further complicating understanding of the issue. Pharmaceutical supply chains are highly complex, involving multiple stakeholders, often with different procedural steps occurring in multiple countries and/or locations. Nevertheless, in general, shortages may be considered as arising from exogenous factors that increase demand (such as in the case of COVID-19), or exogenous or endogenous factors that limit or reduce supply. . Several analyses have noted that shortages, as reported by marketing authorisation holders, are predominantly due to (exogenous) manufacturing and quality issues (in about 60% of cases). Manufacturing and quality problems include, for example, production quality issues or defects in any component of a product;shortages of inputs;inventory and storage practices;temporary and permanent suspension of production due to e.g. technical issues with production or non-compliance with Good Manufacturing Practice, or manufacturing site closure or relocation. Linked to this, policy debates also point to the issues of concentration of manufacturing, or limited availability of manufacturing facilities to produce certain categories or components of medicines, as additional sources of supply vulnerability. While the contributions of these factors are challenging to assess based on available information, in general, ensuring that the manufacturing of particular components is not highly concentrated at one or few manufacturing sites or in small geographic areas, could reduce the overall vulnerability of medicines' supply to these types of risks. . Beyond manufacturing and quality issues, (endogenous) commercial factors, and the policy settings that influence them, may play important underlying roles in propagating shortages, particularly for off-patent products, although further analysis is needed. Regulation and reimbursement policies, such as those that favour unsustainably low prices, may influence commercial decisions, putting supply at risk. In the United States, for example, an empirical analysis identified three root causes, key among them a lack of incentive for the continued production of less profitable drugs in a setting of highly competitive tendering and contracting practices. The analysis also cited a lack of incentives to upgrade production facilities or maintain quality management systems as another root cause. There have also been suggestions that similar issues are implicated in Europe, but the links between production problems and market attractiveness warrant further exploration. . Many OECD countries are pursuing policies aimed at improving the monitoring, mitigating the impact, and/or preventing the future occurrence of shortages. For

Adenine quadruplexes show surprising stability: Potential implications for SARS-CoV-2

SARS-CoV-2 is an endemic positive-sense RNA virus naturally transmissible between numerous species with notable infectivity and associated mortality. It is characterized by a poly-adenylated structure capping the genomic terminus. This poly(A) tail is crucial to a cascade of viral replicative activity occurring both extra- and intra-cellular during infection. As a route to proposing potential chemotherapy, this study suggests simple biplanar adenine quadruplexes (A4s) which may fold in specific sequences of the viral genome. To the best of our knowledge, uniquely biplanar A4s have not been previously described in any context. Using molecular modeling techniques and molecular dynamics simulations, some of these non-canonical structures show reasonable stability in a biological context. Notably, mRNA configured as a biplanar A4, shows less dynamic activity than DNA equivalents. This observation may be especially relevant in a physiological context. Furthermore, in contrast to well-characterized guanine quadruplexes, co-ordination with cations appears not to impact on stability. Our molecular dynamics simulations and analyses demonstrate that some A4s are stable in biologically relevant terms. These conclusions may apply to SARS-CoV-2, its variants and other pathogenic RNA viruses. © 2021 World Scientific Publishing Company.

Assessing patient satisfaction with the cystic fibrosis telehealth service

Objectives: Telehealth (via videocall) was rapidly implemented by the South Australian Adult Cystic Fibrosis (CF) Service in March 2020 due to the Novel Coronavirus 2019 pandemic. Home spirometers were distributed as part of objective patient assessment. Our aim was to assess patient satisfaction with the telehealth service in CF multidisciplinary clinic via online survey. Methods: All patients of the CF service were invited to complete an online survey designed to assess satisfaction with telehealth, which was undertaken through the consumer organisation Cystic Fibrosis South Australia. A quantitatively driven concurrent mixed-methods design was chosen, with statistical analysis of symmetrical five-point Likert responses using IBM SPSS Statistics for Windows v.26 and coding of unstructured responses for thematic analysis. Results: To date 57/160 patients (35.6%) completed the survey, with some item non-responses. 37/57 (64.9%) participants were aged ≤35 years of age, 42/53 (79.2%) had ≥2 telehealth appointments, and 46/53 (86.7%) found it easy/very easy to access. 18/48 (37.5%) of participants had technical issues. Despite this 48/52 (92.3%) felt satisfied/very satisfied with engagement of CF team via telehealth. 38/50 (76%) found telehealth more convenient with significant time saved. The thematic analysis added depth to quantitative analysis by identification of six key themes: convenience, ease of access, maintaining the therapeutic relationship, comprehensive care, safety, and patient centred care. Conclusion: Most patients reported high satisfaction with telehealth and would like a hybrid clinic with the option of telehealth or in person review for clinics into the future.

Assessing patient satisfaction with the cystic fibrosis telehealth service

Introduction/Aim: Telehealth (via videocall) was rapidly implemented by the South Australian Adult Cystic Fibrosis (CF) Service in March 2020 due to the Novel Coronavirus 2019 pandemic (COVID-19). Home spirometers were distributed as part of objective patient assessment. Our aim was to assess patient satisfaction with the telehealth service in CF multidisciplinary clinic via online survey. Methods: All patients of the CF service were invited to complete an online survey designed to assess satisfaction with telehealth, which was undertaken through the consumer organization Cystic Fibrosis South Australia. A quantitatively driven concurrent mixed-methods design was chosen, with statistical analysis using IBM SPSS Statistics for Windows v.26 and coding of unstructured responses to generate themes for thematic analysis. Results: To date 57 from a cohort of 160 patients (35.6%) completed the survey, with some item non-responses. 37/57 (64.9%) of participants were aged ≤35yo, 42/53 (80.7%) had 2 telehealth appointments, and 46/53 (86.7%) found it easy/very easy to access. 18/48 (37.5%) of participants had problems with audio/visual dropout. Despite this 48/52 (92.3%) felt satisfied or very satisfied that the CF team were engaged in their care via telehealth, with just under half utilizing a home spirometer at the time of the survey. 38/50 (76%) found that telehealth was more convenient than an in-person appointment with significant time saved. The thematic analysis added context and depth to analysis of the quantitative data by identification of six key themes of convenience, ease of access, maintaining the therapeutic relationship, comprehensive care, safety, and patient centred care. Conclusion: Most patients reported high satisfaction with telehealth and would like a hybrid clinic with the option of telehealth or in person review for clinics into the future.

The impact of the coronavirus disease 2019 (covid-19) pandemic on young people with diabetes and preferences for future care: A patient survey

Aims: Covid-19 restrictions have impacted social interaction, work, education and care provision for young people with diabetes. Furthermore, people with diabetes have increased morbidity and mortality from covid-19. We aimed to explore the impact of the pandemic on young people's diabetes care and management;their psychosocial well-being;and identify preferences for future diabetes care. Methods: A survey was emailed to all patients aged 16-23 with diabetes attending two London (UK) hospital-based diabetes clinics. Descriptive and content analyses were conducted. Results: Response rate was 33% (n = 74/222). Respondents reflected clinic population in age, ethnicity and area-level deprivation, although males were underrepresented (34%, n = 25). Since the pandemic 55% (n = 41) felt well supported by their diabetes team;35% (n = 26) felt more confident and 40% (n = 29) more motivated to manage their diabetes. Conversely 22% (n = 16) felt less confident or motivated, which they attributed to decreased physical activity, disrupted diabetes routines and a lack of support. Mental well-being was reportedly negatively impacted in 57% (n = 42) of patients, with no differences by area-level deprivation or ethnicity. 31% (n = 23) and 41% (n = 30) of respondents felt more negatively about their diabetes and future health, respectively. Face-to- face care in the future remained the most popular option (69%, n = 51), despite increased virtual appointments during the pandemic. Conclusion: Negative impacts on mental well-being, feelings about diabetes and future health need to be considered when providing care for young people with diabetes. Variable experiences and views on care provision indicate the need for a flexible approach to future care delivery models.

Virtual hackathon to tackle COVID-19 unmet needs

What are the new findings? ►► The COVID-19 pandemic prevented physical innovation formats and virtual innovation strategies such as the virtual hackathon proposed in this article may address this challenge. ►► Virtual interdisciplinary collaboration between students and early career professionals can ead to rapid innovations to address urgent unmet clinical needs in times of global emergencies. How might it impact on healthcare in the future? ►► Innovation pathways should be augmented with virtual innovation strategies to break down barriers to engagement in healthcare innovation, improve global interdisciplinary collaboration and enhance rapid innovation adoption moving into the future. ►► Particular healthcare technologies likely to be positively impacted by this include those in digital health, global health and medical device sectors. © 2021 Georg Thieme Verlag. All rights reserved.