Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products – a PEARRL review.

Objectives: In this review, the current biopharmaceutical approaches for evaluation of oral formulation performance in paediatrics are discussed. Key findings: The paediatric gastrointestinal (GI) tract undergoes numerous morphological and physiological changes throughout its development and growth. Some physiological parameters are yet to be investigated, limiting the use of the existing in vitro biopharmaceutical tools to predict the in vivo performance of paediatric formulations. Meals and frequencies of their administration evolve during childhood and affect oral drug absorption. Furthermore, the establishment of a paediatric Biopharmaceutics Classification System (pBCS), based on the adult Biopharmaceutics Classification System (BCS), requires criteria adjustments. The usefulness of computational simulation and modeling for extrapolation of adult data to paediatrics has been confirmed as a tool for predicting drug formulation performance. Despite the great number of successful physiologically based pharmacokinetic models to simulate drug disposition, the simulation of drug absorption from the GI tract is a complicating issue in paediatric populations. Summary: The biopharmaceutics tools for investigation of oral drug absorption in paediatrics need further development, refinement and validation. A combination of in vitro and in silico methods could compensate for the uncertainties accompanying each method on its own

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Pleadings and depositions in the Duchy Court of Lancaster

Includes index.Vol. 3 contains the report of the Record Society for the year 1895/96.No more published.[v. 1.] Time of Henry VII and Henry VIII.--[v. 2.] Time of Henry VIII.--[v. 3.] Time of Edward VI and Philip and Mary.Mode of access: Internet

Recognising the challenges of collaborative, multi-site research

Background: Collaborative multi-site research is gaining recognition. In particular, across stakeholders in the health and social care professions, there has been an increase in the documentation of such approaches, with the majority acknowledging the strengths and few identifying the pitfalls. Four universities in the south west of England collaborated on the design, analysis and implementation of a project scoping the staff development needs of nursing and midwifery academics to meet the National Health Service Modernisation Agenda in the United Kingdom. Aim: This paper highlights the challenges and the lessons learned from each stage of the process of this large multi-site collaborative study. Consideration has been given to addressing the site-specific differences as well as the politics of the processes and power relations across the research team. Discussion: From an analytical reflection across the team, there were a number of lessons learned from the process of collaboration. Initially, the main challenge was the selection of the team and lead researcher and these were its greatest success. Nevertheless, managing each individual's competing roles within the organisation remained problematic. Particular challenges included gaining consensus on the research design, the chosen sample and data collection to reflect the site-specific differences and were overcome through discussion and effective leadership. Towards the end of the study, adequately representing each institution in the findings, as well as dissemination have remained the greatest challenges. Conclusions: While collaboration has been lauded as a way forward, this analysis of the process highlights some of the difficulties of working as a multi-site virtual team who are widely spread geographically and who have no previous connection. At different stages of the process there has been acknowledgement of the political dimensions affecting such an approach and a need to avoid the pitfalls of collaborative working in order to harness the potential of all team members, if success is to be achieved

Food safety and quality considerations for cassava, a major staple containing a natural toxicant

This chapter discusses the food safety and quality considerations for cassava (Manihot esculenta), a major staple across the developing world and one that is attracting increasing interest from developed country markets and consumers, as well as policy makers. It includes discussions on the agronomy and agricultural production, the types of cassava products in different continents, how they are traditionally and commercially made, nutritional considerations and how the products are used. Production of different cassava products and the attendant considerations for products for domestic consumption (e.g. gari), the export products from cassava (bammies, flour, others) and cassava toxicology, including the role of the cyanogenic glycosides and aflatoxin, and food safety. Discussion involve mitigating natural toxicants, quality considerations, implementation FSQS, and considerations for future growth and utilization of this important staple

Using creativity to achieve an entrepreneurial future for arts marketing

The marketing concept fails to explain marketing behaviour of small firms. Similar comments are now being made of large firms. This gap between theory and practice is even more significant in non-profit and arts organisations where sector specific philosophies often determine how marketing is embraced, with its underlying notions of the customer and profitability. Many of these organisations must overcome severe resource constraints by thinking creatively. This paper investigates the relationship between art, marketing, entrepreneurship and creativity in order to reach a clearer understanding of how creativity can assist both the arts organisation and those involved in researching the sector. There have been increasing calls within the academic marketing community to instil a creative philosophy within the research process. This call has not resulted in much research on the phenomenon within marketing, and certainly not from a nonprofit perspective. This paper discusses creativity as a concept drawing on a diverse range of literatures outside the management discipline. The link between creativity, marketing, entrepreneurship and art is analysed. Justification of the incorporation of creativity in the research process is presented for practitioners and theorists in marketing and the arts, so that they can learn from each others\u27 disciplines. Implications for future research are presented, where creativity is viewed as the centre of a non-linear, free thinking understanding of artistic truth