Oral drug delivery: Gastrointestinal tract adaptations, barriers and strategies for delivery enhancement - a review

The mouth is a vital route of drug administration with over 84 % of all medicines reportedly administered through it. The gastrointestinal system is equally imbued with a lot of adaptive features that make the oral route even more conducive for systemic drug delivery. The usefulness of the oral route is, however challenged by the existence of numerous absorption barriers which limit the effective absorption and delivery of drugs to their target sites in the body systems. Understanding these adaptive attributes, systemic barriers and available strategies for overcoming such barriers will not only be helpful in drug development and design but also useful to the formulation scientists desirous of optimizing drug delivery. The objective of this work was to review the gastrointestinal route of drug administration with respect to some biochemical and physio-anatomic features that impede or enhance drug absorption and to highlight current strategies that have been deployed to achieve optimum per oral drug delivery. The current review reveals the emerging roles of nanocarriers in oral drug delivery. Polymeric nanocarriers enhance the solubility, targeting and safety profiles of many important pharmacological agents. Novel systems that offer protection against gastro enzymes and as such, promote oral administration of biologicals are being widely investigated. Mechanical, magnetic, and acoustic energy – induced membrane perturbation are other delivery options receiving research attentions. It may be concluded that, with the avalanche of research efforts in the area, the oral route will maintain its prominence among other routes of drug administration. &nbsp

The potential impact of the COVID-19 pandemic on global antimicrobial and biocide resistance:An AMR Insights global perspective

The COVID-19 pandemic presents a serious public health challenge in all countries. However, repercussions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on future global health are still being investigated, including the pandemic's potential effect on the emergence and spread of global antimicrobial resistance (AMR). Critically ill COVID-19 patients may develop severe complications, which may predispose patients to infection with nosocomial bacterial and/or fungal pathogens, requiring the extensive use of antibiotics. However, antibiotics may also be inappropriately used in milder cases of COVID-19 infection. Further, concerns such as increased biocide use, antimicrobial stewardship/infection control, AMR awareness, the need for diagnostics (including rapid and point-of-care diagnostics) and the usefulness of vaccination could all be components shaping the influence of the COVID-19 pandemic. In this publication, the authors present a brief overview of the COVID-19 pandemic and associated issues that could influence the pandemic's effect on global AMR.</p

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

The potential impact of the COVID-19 pandemic on global antimicrobial and biocide resistance : an AMR Insights global perspective

The COVID-19 pandemic presents a serious public health challenge in all countries. However, repercussions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on future global health are still being investigated, including the pandemic’s potential effect on the emergence and spread of global antimicrobial resistance (AMR). Critically ill COVID-19 patients may develop severe complications, which may predispose patients to infection with nosocomial bacterial and/or fungal pathogens, requiring the extensive use of antibiotics. However, antibiotics may also be inappropriately used in milder cases of COVID-19 infection. Further, concerns such as increased biocide use, antimicrobial stewardship/infection control, AMR awareness, the need for diagnostics (including rapid and point-of-care diagnostics) and the usefulness of vaccination could all be components shaping the influence of the COVID-19 pandemic. In this publication, the authors present a brief overview of the COVID-19 pandemic and associated issues that could influence the pandemic’s effect on global AMR.This study was supported by internal funding.https://academic.oup.com/jacamram2022School of Health Systems and Public Health (SHSPH

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

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Knowledge and Compliance with Standard Precaution Among Healthcare Workers in A South-East Nigerian Tertiary Hospital

Background: Adherence to standard precautions (SP) is critical to reducing the burden of nosocomial infections. Objective: We assessed the knowledge and practice of SP among healthcare workers (HCWs). Methodology: A cross-sectional study was conducted among HCWs in Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi Anambra State, Nigeria using self-administered questionnaire and key informant interview. Results: Mean age and employment duration of subjects were 33.4±11.9 and 6.0 ± 6.7 years, respectively. Majority of the 341 HCWs had heard about SP (82.1%) and agreed that it should be applied to all patient care (78.0%). Only 45.7% of them correctly cited ≥2 components of SP. Two-third of participants reported that SP was poorly practiced in their unit mainly due to inadequate supply of materials (63.1%), inadequate staff training/retraining (62.2%), inadequate support by management (51.4%) and unavailable standard operating procedures (SOPs) on SP (37.8%). Compliance with SP and specifically, personal protective equipment (PPE) use were 65.1% and 76.2%, respectively. Profession (p=0.023), awareness about SP (p&lt;0.001), SOP display in prominent places (p&lt;0.001) and regular supply of running water (p&lt;0.001) were significantly associated with SP compliance. Key informant interview revealed lack of written SP policies or its communication to HCWs, lack of training/retraining of HCWs and lack of materials required for SP practice. Conclusion: Knowledge of basic concept and practice of SP was not satisfactory among HCWs. Major barriers to SP were lack of materials, training and active support by hospital management. Awareness, SOP display in prominent places and regular supply of running water positively influenced SP compliance. Having written policies and communicating such to all HCWs, consistent supply of necessary materials, intensified training, and regular supervision are recommended Keywords: Universal precautions, Nosocomial infections, Tertiary hospitals, Health Personnel, Nigeri

Analysis of perception, reasons, and motivations for COVID-19 vaccination in people with diabetes Across Sub-Saharan Africa: A mixed method approach

Diabetes mellitus (DM) is associated with severe COVID-19 infection and complications. This study assesses COVID-19 vaccine acceptance and hesitancy in people with DM, and explores the reasons for not being vaccinated. This was a web-based cross-sectional survey using a mixed-method approach conducted in March–May 2021, corresponding to most sub-Saharan African (SSA) countries’ early vaccine rollout period. Participants were those aged ≥18 years with self-reported DM in 11 Sub-Saharan African (SSA) countries. Responses to comments on the reasons for vaccine hesitancy and facilitators for vaccine uptake were analyzed. Of the 73 participants with DM, 65.8% were males, older than 35 years (86.3%), had postsecondary education (90%), and a significant proportion were from South Africa (39.7%), Nigeria (28.8%) and Ghana (13.7%). At the time of this study, 64.4% experienced COVID-19 symptoms, 46.6% were tested for COVID-19, of which 19.2% tested positive. Few participants (6.8%) had received a COVID-19 vaccination, 65.8% were willing to take the vaccine when it becomes available in their country, while 26.0% either refused or remained hesitant towards taking the vaccine. The main identified reasons for not taking the vaccine were: advice from religious leaders; concerns about the safety, effects, and efficacy of the vaccines; mistrust of the pharmaceutical companies producing the vaccines and the process of production; the conspiracy theories around the vaccines; and the personal belief of the participants regarding vaccination. However, participants stated they would take the vaccine if they were more educated about it, received positive feedback from those vaccinated, were rewarded for taking the vaccine, or if vaccination became a condition for travel and employment. In conclusion, this study shows that the uptake of the COVID-19 vaccine was very low in this high-risk group. Efforts to increase the uptake of COVID-19 vaccines among people with diabetes are imperative, such as the provision of education and relevant information

The potential impact of the COVID-19 pandemic on global antimicrobial and biocide resistance: An AMR Insights global perspective

The COVID-19 pandemic presents a serious public health challenge in all countries. However, repercussions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections on future global health are still being investigated, including the pandemic's potential effect on the emergence and spread of global antimicrobial resistance (AMR). Critically ill COVID-19 patients may develop severe complications, which may predispose patients to infection with nosocomial bacterial and/or fungal pathogens, requiring the extensive use of antibiotics. However, antibiotics may also be inappropriately used in milder cases of COVID-19 infection. Further, concerns such as increased biocide use, antimicrobial stewardship/infection control, AMR awareness, the need for diagnostics (including rapid and point-of-care diagnostics) and the usefulness of vaccination could all be components shaping the influence of the COVID-19 pandemic. In this publication, the authors present a brief overview of the COVID-19 pandemic and associated issues that could influence the pandemic's effect on global AMR