Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Native plant diversity for ecological reclamation in Moroccan open-pit phosphate mines

Mining activities have significant impacts on the environment, particularly in terms of the destruction of natural habitats, biodiversity loss. With the increasing awareness of the importance of ecological restoration and conservation, there is a growing need to study and understand the flora that thrives in mining sites for successful reclamation efforts. This study aimed to investigate the floristic composition and plant diversity of four phosphate mine sites (PMSs) in Morocco, namely Bou Craa mine (BCM), Ben Guerir mine (BGM), Youssoufia mine (YSM), and Khouribga mine (KHM).The study found a total of 215 vascular plant species from 166 genera and 49 taxonomic families across the four sites. BGM was the most diverse site with 120 plant species, followed by KHM with 75, YSM with 57, and BCM with 54. Compositae family species were the most common at BGM and KHM, while Amaranthaceae species were dominant at BCM, and Poaceae and Compositae at YSM. Therophytes (annual species) were the most common functional group (45.0%), followed by chamaephytes (19.6%) and hemicryptophytes (15.9%).Atriplex nummularia and Chenopodium album were the most common species found at all four sites, while Atriplex semibaccata, Bassia muricata, Haloxylon scoparium, and 12 other species were common at three sites. However, 156 plant species were found at only one site. The findings of this study highlight the significant abundance of plant species in Moroccan PMSs and provide a basis for successful ecological engineering rehabilitation plans. The study emphasizes the importance of studying the indigenous plant species that naturally populate these marginal lands to ensure successful reclamation efforts

Native plant diversity for ecological reclamation in Moroccan open-pit phosphate mines

Mining activities have significant impacts on the environment, particularly in terms of the destruction of natural habitats andbiodiversity loss. With the increasing awareness of the importance of ecological restoration and conservation, there is a growing need to study and understand the flora that thrives in mining sites in order to facilitate successful reclamation efforts. This study aimed to investigate the floristic composition and plant diversity of four phosphate mine sites (PMSs) in Morocco, namely Bou Craa mine (BCM), Ben Guerir mine (BGM), Youssoufia mine (YSM), and Khouribga mine (KHM).The study found a total of 215 vascular plant species from 166 genera and 49 taxonomic families across the four sites. BGM was the most diverse site with 120 plant species, followed by KHM with 75, YSM with 57, and BCM with 54. Compositae family species were the most common at BGM and KHM, while Amaranthaceae species were dominant at BCM, and Poaceae and Compositae at YSM. Therophytes (annual species) were the most common functional group (45.0%), followed by chamaephytes (19.6%) and hemicryptophytes (15.9%).Atriplex nummularia and Chenopodium album were the most common species found at all four sites, while Atriplex semibaccata, Bassia muricata, Haloxylon scoparium, and 12 other species were common at three sites. However, 156 plant species were found at only one site. The findings of this study highlight the significant abundance of plant species in Moroccan PMSs and provide a basis for successful ecological engineering rehabilitation plans. The study emphasizes the importance of studying the indigenous plant species that naturally populate these marginal lands to ensure successful reclamation efforts

Medicines in the kitchen: Gender roles shape ethnobotanical knowledge in marrakshi households

Differences in gendered knowledge about plants are contingent on specific cultural domains. Yet the boundaries between these domains, for example food and medicine, are sometimes blurred, and it is unclear if and how gender plays a role in creating a continuum between them. Here, we present an in-depth evaluation of the links between gender, medicinal plant knowledge, and culinary culture in Marrakech, Morocco. We interviewed 30 women and 27 men with different socio-demographic characteristics and evaluated how gender and cooking frequency shape their food and medicinal plant knowledge. We documented 171 ethno-taxa used in Marrakshi households as food, medicine, or both, corresponding to 148 botanical taxa and three mixtures. While no clear differences appear in food plant knowledge by gender, women have a three-fold greater knowledge of medicinal plants, as well as plants with both uses as food and medicine. Women¿s medicinal and food plant knowledge increases with their reported frequency of cooking, whereas the opposite trend is observed among men. Men who cook more are often single, have university-level degrees, and may be isolated from the channels of knowledge transmission. This demonstrates that the profound relations between the culinary and health domains are mediated through gender.This study has received funding from the Evolution, eDNA, Genomics and Ethnobotany research group at the Natural History Museum, University of Oslo (Norway) through a personal grant to I.T.-T.Introduction Materials and Methods Results Discussion Conclusions Author Contributions Funding Institutional Review Board Statement Informed Consent Statement Data Availability Statement Acknowledgments Conflicts of Interest Reference

Comparative Oil Composition Study of the Endemic Moroccan Olive (Olea europaea subsp. maroccana) and Wild Olive (var. Sylvestris) in Central West Morocco

Six wild olive subspecies (Olea europaea L.) are currently recognised globally, with two taxa cooccurring in the argan tree area in Central West Morocco: the widespread Mediterranean subspecies europaea var. Sylvestris (the so-called oleaster) and the microendemic subspecies maroccana. Despite its taxonomic and ecological importance, the chemical composition of subsp. maroccana oil remains poorly known. Therefore, the aim of this study is to investigate the oil content and the chemical composition of subsp. maroccana and var. Sylvestris as well as comparing their proprieties during two consecutive years (2017 and 2018) from the same geographical area. The fatty acid and the sterol compositions were analysed using gas chromatography. Additionally, the tocopherol content was determined using high-performance liquid chromatography. The total amount of unsaturated fatty acids was higher in maroccana (85.24%) than that in oleasters (79.05%). Additionally, the tocopherol and phytosterol content of the maroccana oil (1232.35 mg/kg and 312.75 mg/100 g, resp.) was approximately twofold higher than in oleasters (661.35 mg/kg and 210.06 mg/100 g, resp.). Analysis of variance and principal component analysis (PCA) of the chemical composition highlighted a significant difference between the quantitative and qualitative properties of their oil. Finally, these findings suggest that maroccana oil could be considered as a potential source of vitamin E, essential fatty acids, and sterols and can provide a nutraceutical oil for the local population. While this work contributes to the study of olive tree biodiversity, further investigations are still necessary to guide the putative nutraceutical use of subspecies maroccana

Glutathione Is Essential For Early Embryogenesis - Analysis of a Glutathione Synthetase Knockout Mouse

Glutathione (GSH) is present in all mammalian tissues and plays a crucial role in many cellular processes. The second and final step in the synthesis involves the formation of GSH from gamma-glutamylcysteine (γ-GC) and glycine and is catalyzed by glutathione synthetase (GS). GS deficiency is a rare autosomal recessive disorder, and is present in patients with a range of phenotypes, from mild hemolytic anemia and metabolic acidosis to severe neurologic disorders or even death in infancy. The substrate for GS, γ-GC, has been suggested as playing a protective role, by substituting for GSH as an antioxidant in GS deficient patients. To examine the role of GS and GSH metabolites in development, we generated mice deficient in GSH by targeted disruption of the GS gene (Gss). Homozygous mice died before embryonic day (E) 7.5, but heterozygous mice survived with no distinct phenotype. GS protein levels and enzyme activity, as well as GSH metabolites, were investigated in multiple tissues. Protein levels and enzyme activity of GS in heterozygous mice were diminished by 50%, while GSH levels remained intact. γ-GC could not be detected in any investigated tissue. These data demonstrate that GSH is essential for mammalian development, and GSH synthesis via GS is an indispensable pathway for survival

ACCELERATE and European Medicines Agency Paediatric Strategy Forum for medicinal product development of checkpoint inhibitors for use in combination therapy in paediatric patients

The third multistakeholder Paediatric Strategy Forum organised by ACCELERATE and the European Medicines Agency focused on immune checkpoint inhibitors for use in combination therapy in children and adolescents. As immune checkpoint inhibitors, both as monotherapy and in combinations have shown impressive success in some adult malignancies and early phase trials in children of single agent checkpoint inhibitors have now been completed, it seemed an appropriate time to consider opportunities for paediatric studies of checkpoint inhibitors used in combination. Among paediatric patients, early clinical studies of checkpoint inhibitors used as monotherapy have demonstrated a high rate of activity, including complete responses, in Hodgkin lymphoma and hypermutant paediatric tumours. Activity has been very limited, however, in more common malignancies of childhood and adolescence. Furthermore, apart from tumour mutational burden, no other predictive biomarker for monotherapy activity in paediatric tumours has been identified. Based on these observations, there is collective agreement that there is no scientific rationale for children to be enrolled in new monotherapy trials of additional checkpoint inhibitors with the same mechanism of action of agents already studied (e.g. anti-PD1, anti-PDL1 anti-CTLA-4) unless additional scientific knowledge supporting a different approach becomes available. This shared perspective, based on scientific evidence and supported by paediatric oncology cooperative groups, should inform companies on whether a paediatric development plan is justified. This could then be proposed to regulators through the available regulatory tools. Generally, an academic-industry consensus on the scientific merits of a proposal before submission of a paediatric investigational plan would be of great benefit to determine which studies have the highest probability of generating new insights. There is already a rationale for the evaluation of combinations of checkpoint inhibitors with other agents in paediatric Hodgkin lymphoma and hypermutated tumours in view of the activity shown as single agents. In paediatric tumours where no single agent activity has been observed in multiple clinical trials of anti-PD1, anti-PDL1 and anti-CTLA-4 agents as monotherapy, combinations of checkpoint inhibitors with other treatment modalities should be explored when a scientific rationale indicates that they could be efficacious in paediatric cancers and not because these combinations are being evaluated in adults. Immunotherapy in the form of engineered proteins (e.g. monoclonal antibodies and T cell engaging agents) and cellular products (e.g. CAR T cells) has great therapeutic potential for benefit in paediatric cancer. The major challenge for developing checkpoint inhibitors for paediatric cancers is the lack of neoantigens (based on mutations) and corresponding antigen-specific T cells. Progress critically depends on understanding the immune macroenvironment and microenvironment and the ability of the adaptive immune system to recognise paediatric cancers in the absence of high neoantigen burden. Future clinical studies of checkpoint inhibitors in children need to build upon strong biological hypotheses that take into account the distinctive immunobiology of childhood cancers in comparison to that of checkpoint inhibitor responsive adult cancers

Global Incidence and Risk Factors Associated With Postoperative Urinary Retention Following Elective Inguinal Hernia Repair

Importance Postoperative urinary retention (POUR) is a well-recognized complication of inguinal hernia repair (IHR). A variable incidence of POUR has previously been reported in this context, and contradictory evidence surrounds potential risk factors.Objective To ascertain the incidence of, explore risk factors for, and determine the health service outcomes of POUR following elective IHR.Design, Setting, and Participants The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) study, an international, prospective cohort study, recruited participants between March 1 and October 31, 2021. This study was conducted across 209 centers in 32 countries in a consecutive sample of adult patients undergoing elective IHR.Exposure Open or minimally invasive IHR by any surgical technique, under local, neuraxial regional, or general anesthesia.Main Outcomes and Measures The primary outcome was the incidence of POUR following elective IHR. Secondary outcomes were perioperative risk factors, management, clinical consequences, and health service outcomes of POUR. A preoperative International Prostate Symptom Score was measured in male patients.Results In total, 4151 patients (3882 male and 269 female; median [IQR] age, 56 [43-68] years) were studied. Inguinal hernia repair was commenced via an open surgical approach in 82.2% of patients (n = 3414) and minimally invasive surgery in 17.8% (n = 737). The primary form of anesthesia was general in 40.9% of patients (n = 1696), neuraxial regional in 45.8% (n = 1902), and local in 10.7% (n = 446). Postoperative urinary retention occurred in 5.8% of male patients (n = 224), 2.97% of female patients (n = 8), and 9.5% (119 of 1252) of male patients aged 65 years or older. Risk factors for POUR after adjusted analyses included increasing age, anticholinergic medication, history of urinary retention, constipation, out-of-hours surgery, involvement of urinary bladder within the hernia, temporary intraoperative urethral catheterization, and increasing operative duration. Postoperative urinary retention was the primary reason for 27.8% of unplanned day-case surgery admissions (n = 74) and 51.8% of 30-day readmissions (n = 72).Conclusions The findings of this cohort study suggest that 1 in 17 male patients, 1 in 11 male patients aged 65 years or older, and 1 in 34 female patients may develop POUR following IHR. These findings could inform preoperative patient counseling. In addition, awareness of modifiable risk factors may help to identify patients at increased risk of POUR who may benefit from perioperative risk mitigation strategies