Biopharmaceutical Classification System in Invitro/ In-vivo Correlation: Concept and Development Strategies in Drug Delivery

Drug development is a very laborious and expensive process. One of the major reasons for failure during the clinical phases of drug development is inadequate pharmacokinetic data on the drug candidate. Therefore, it would be advantageous if the pharmacokinetic properties of drug candidates be predicted beforehand. One major obstacle in making such  predictions is the inability to appropriately scale the in-vitro data to the in-vivo situation. Results from in-vitro in-vivo correlation (IVIVC) studies have been used to select the appropriate excipients and optimize the manufacturing processes for quality control purposes, and for characterizing the release patterns of newly formulated immediate release, and modified-release products relative to the references. In recent years, the concept and application of the IVIVC for pharmaceutical dosage forms have been a major focus of attention in the pharmaceutical industry, academia and regulatory agencies. Hence, this article highlights the importance of appropriate selection of IVIVC level with respect to the Biopharmaceutical Classification System (BCS) and also covers examples of BCS-based IVIVCs of drugs/products with different types of release profiles.Keywords: In vitro/In vivo correlation, Biopharmaceutical Classification System, Drug Delivery

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Genome-wide analysis of the intrinsic terminators of transcription across the genus Mycobacterium

Termination of transcription in eubacteria is achieved by a region of the nascent transcript. In Escherichia coli, this intrinsic terminator consists of a hairpin followed by a U-stretch. Absence of the typical terminators in several genes of Mycobacterium tuberculosis led us to develop an accurate and efficient algorithm to identify putative terminators in all sequenced microbial genomes. In addition to the typical Escherichia coli type of terminators, several variant terminator structures were predicted by the algorithm and their existence was experimentally verified. We have now analysed 17 Mycobacterium genomes to obtain a comprehensive picture of the transcription terminators in mycobacteria. Our results show that the terminators that lack a U-trail, variant from the typical E. coli intrinsic terminators, are overwhelmingly predominant in all members of the genus. Most terminator structures are concentrated within 50 base pairs downstream of the stop codon. A large number of these terminators occur at the end of experimentally verified or predicted transcription units. We have observed inter-species variations in ΔG and positioning of the terminators downstream of specific genes amongst closely related mycobacterial species suggesting differences in gene expression. The analysis would be useful in furthering our understanding of genome organization and gene expression in mycobacteria, in addition to the improvement in the annotation of the new genomes

Mid-Brunhes strengthening of the Indian Ocean Dipole caused increased equatorial East African and decreased Australasian rainfall

The tropical Indian Ocean is an important component of the largest warm pool, marked by changes in sea surface temperatures and depths of thermocline and mixed layer in its western and eastern extremities leading to the development of a dipole mode - the Indian Ocean Dipole (IOD). A narrow band of westerlies (7°N to 7°S) sweep the equatorial Indian Ocean during the April-May and October-November transitions between the summer- and winter-monsoon seasons. These Indian Ocean equatorial westerlies (IEW) are closely related to the IOD, intensifying the upper ocean Eastward Equatorial current also known as Wyrtki jets. The strength of the IOD/IEW determines the moisture content in East Africa. A major decrease in the strength of the IEW (strengthening or positive mode of the IOD) during the mid-Brunhes epoch (~300-250 Kyr BP) coincides with a wetter equatorial East Africa, a drier Australasia and a stronger Indian summer monsoon, indicating that the IOD/IEW play a significant role in driving climate change in East Africa, Australasia and South Asia