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

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

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

Effects of Oral Administration of Atorvastatin or Fenofibrate on Hyperlipidemia Induced by Betamethasone Dipropionate Injection in Rabbits

Betamethasone, a fluorinated and synthetic steroid, is a commonly used glucocorticoid. To our knowledge, no available studies exist concerning the hyperlipidemic effect of betamethasone dipropionate (BDP) in rabbits. Therefore, the current study was conducted to highlight the effects of intramuscular injection of BDP on lipid profile in rabbits, investigate the possible mechanism underlying the produced effects and evaluate the possible antihyperlipidemic effect of atorvastatin (ATR) and fenofibrate (FFB). For this purpose, twenty male New Zealand rabbits were classified into control, BDP (0.5 ml/kg B.wt/ IM/day/single dose), BDP+ATR; rabbits were IM injected with BDP, then they were orally given ATR (1.9 mg./kg. B.wt./ once/ day/ month) and group IV (BDP+FFB); rabbits were IM injected with BDP then they were orally given FFB (7.5 mg/kg B.wt/ once/ day/ month). The obtained result revealed that single IM injection of BDP produced a significant elevation in triglycerides, total cholesterol, LDL level with a significant decline in HDL in comparison to control group on the 3rd,7th,14th, 21st, 30th day of the experiment. On the 30th day of the experiment there was an increase in the ALT, AST, MDA, VCAM-1 as well as a significant decrease in TAC. Furthermore, BDP induced a significant increase in HMG-COA reductase gene expression and a significant decrease in lipoprotein lipase gene expression. Oral administration of ATR or FFB concurrently with BDP for a month succeeded in reducing the hyperlipidemia induced by BDP in rabbits

Eucalyptus oil abrogated liver damage, oxidant /antioxidant imbalance, inflammation and apoptosis stimulated by acetaminophen in rats: biochemical, molecular and histological approaches

Acetaminophen is an analgesic antipyretic commonly used. Hepatotoxicity is one of the most common obstacles to acetaminophen therapy. Eucalyptus oil is an antioxidant with potent free radical-capturing activities. This research was designed to evaluate the inhibitory impact of Eucalyptus oil versus acetaminophen-triggered hepatotoxicity. The composition of Eucalyptus was detected utilizing gas chromatography mass spectroscopy. Forty-eight rats were assigned into six groups; control group, acetaminophen group (500mg/kg I.P twice on the 17th and, 20th of the experiment), silymarin group (50mg/kg, I.P once daily for three weeks), Eucalyptus oil group (30mg/kg orally once daily for three weeks), acetaminophen +silymarin group and Eucalyptus +acetaminophen group. gas chromatography mass spectroscopy discovered four compounds in Eucalyptus with eucalyptol representing the main compound. revealed that acetaminophen remarkably elevated serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels, whereas it declined serum albumin and total protein levels. In addition, hepatic oxidant/antioxidant imbalance was evident in acetaminophen-intoxicated rats by the rising of lipid peroxidation biomarker; malondialdehyde and the downregulation of nuclear factor erythroid 2-related factor 2 and its transcriptional mediators; superoxide dismutase, glutathione peroxidase, and reduced glutathione. Furthermore, following acetaminophen injection, there was a remarkable increase in transforming growth factor-β gene expression, tumor necrosis factor-α and interleukin1-β levels along with a decline in interleukin-10 levels. Immunohistochemical and histopathological examinations were in parallel with the abovementioned results. However, all these abnormalities were significantly abrogated in rats pretreated with Eucalyptus. We conclude that prior administration of Eucalyptus oil counteracted acetaminophen-mediated hepatotoxicity via powerful antioxidant, anti-inflammatory, and anti-apoptotic impacts

Long-Term Feeding with Curcumin Affects the Growth, Antioxidant Capacity, Immune Status, Tissue Histoarchitecture, Immune Expression of Proinflammatory Cytokines, and Apoptosis Indicators in Nile Tilapia, <i>Oreochromis niloticus</i>

The impact of dietary curcumin (CUR) on the growth, antioxidant activity, histomorphology of certain organs, proinflammatory cytokine production, and immune status of Oreochromis niloticus was evaluated. The fingerlings (n = 225, 41.60 ± 0.09 g/fish) were randomly allotted into five experimental groups in triplicate. Fish were fed basal diets complemented with 0, 200, 400, 600, or 800 mg curcumin/kg diet (CUR0, CUR200, CUR400, CUR600, and CUR800, respectively) for 10 weeks. An increase in fish growth was reported in the CUR200 and CUR400 groups. The feed conversion ratio was enhanced by 15% in the CUR400 group. Fish body protein content was increased in the CUR600 group (p ≤ 0.01). Body fat was decreased, and ash content was increased by CUR supplementation in a level-related way (p O. niloticus challenged with Aeromonas hydrophila was highest in the CUR200-CUR600 groups (100%) and decreased in the CUR800 group (80%). This study concluded that CUR could be added to Nile tilapia diets up to 400 mg·kg−1 to achieve better growth, antioxidant capacity, immune response, and intestinal histology. Long feeding periods on high levels of CUR (600 and 800 mg·kg−1) stimulate inflammatory reactions in fish tissues

Alhagi maurorum Ethanolic Extract Rescues Hepato-Neurotoxicity and Neurobehavioral Alterations Induced by Lead in Rats via Abrogating Oxidative Stress and the Caspase-3-Dependent Apoptotic Pathway

This work investigated the probable protective effect of an Alhagi maurorum ethanolic extract on the hepatotoxicity and neurotoxicity accompanied by neurobehavioral deficits caused by lead in rats. Rats in four groups were orally administered distilled water, ethanolic extract of A. maurorum (300 mg/kg BW daily), lead (100 mg/kg BW daily for 3 months), and lead + A. maurorum extract. The results demonstrated that lead exposure resulted in elevated locomotor activities and sensorimotor deficits associated with a decrease in brain dopamine levels. Moreover, lead exposure significantly increased liver function markers. In addition, the lead-treated rats exhibited extensive liver and brain histological changes and apoptosis. The lead treatment also triggered oxidative stress, as demonstrated by the increase in malondialdehyde (MDA) concentrations with a remarkable reduction in the activities of antioxidant enzymes, reduced glutathione (GSH) levels, and transcriptional mRNA levels of antioxidant genes in the liver and brain. Nevertheless, co-treatment with the A. maurorum extract significantly ameliorated the lead-induced toxic effects. These findings indicate that the A. maurorum extract has the ability to protect hepatic and brain tissues against lead exposure in rats through the attenuation of apoptosis and oxidative stress

Pseudomonas putida infection induces immune-antioxidant, hepato-renal, ethological, and histopathological/immunohistochemical disruptions in Oreochromis niloticus: the palliative role of titanium dioxide nanogel

Abstract Background Pseudomonas putida is a pathogenic bacterium that induces great losses in fishes, including Nile tilapia (Oreochromis niloticus). Currently, the application of nanomaterials in aquaculture practices has gained more success as it endows promising results in therapies compared to traditional protocols. Objective Therefore, the current perspective is considered the first report to assess the anti-bacterial efficacy of titanium dioxide nanogel (TDNG) against Pseudomonas putida (P. putida) in Nile tilapia. Methods The fish (n = 200; average body weight: 47.50±1.32 g) were allocated into four random groups (control, TDNG, P. putida, and TDNG + P. putida), where 0.9 mg/L of TDNG was applied as bath treatment for ten days. Results Outcomes revealed that P. putida infection caused ethological alterations (surfacing, abnormal movement, and aggression) and depression of immune-antioxidant variables (complement 3, lysozyme activity, total antioxidant capacity, superoxide dismutase, and reduced glutathione content). Additionally, a substantial elevation in hepatorenal biomarkers (aspartate and alanine aminotransferases and creatinine) with clear histopathological changes and immuno-histochemical alterations (very weak BCL-2 and potent caspase-3 immuno-expressions) were seen. Surprisingly, treating P. putida-infected fish with TDNG improved these variables and obvious restoration of the tissue architectures. Conclusion Overall, this report encompasses the key role of TDNG as an anti-bacterial agent for controlling P. putida infection and improving the health status of Nile tilapia

Olive Leaf Extract Attenuates Chlorpyrifos-Induced Neuro- and Reproductive Toxicity in Male Albino Rats

Chlorpyrifos (CPF) is a common organophosphorus insecticide. It is associated with negative consequences such as neurotoxicity and reproductive injury. This study aimed to observe the ability of olive leaf extract to attenuate chlorpyrifos toxicity, which induced neuro- and reproductive toxicity in male albino rats. Olive leaf extract (OLE) exhibits potent antioxidant and antiapoptotic properties. Twenty-two mature male rats were divided into four groups: control (saline), CPF (9 mg/kg), OLE (150 mg/kg), and CPF + OLE. Treatment was administered orally for 80 days. The CPF significantly reduced serum sex hormones, sperm counts and motility, high oxidants (MDA), and depleted antioxidants (GSH, SOD, TAC) in the brain and testes homogenate; additionally, it decreased serum AChE and brain neurotransmitters, increased Bax, decreased Bcl-2, and boosted caspase-3 immune expression in neural and testicular cells. Immunological expression of Ki 67 in the cerebrum, cerebellum, choroid plexus, and hippocampus was reduced, and α-SMA in testicular tissue also decreased. Histopathological findings were consistent with the above impacts. OLE co-administration significantly normalized all these abnormalities. OLE showed significant protection against neural and reproductive damage caused by CPF

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially