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

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

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

In Vitro and In Vivo Evaluation of the Effectiveness and Safety of Amygdalin as a Cancer Therapy

Cancer is one of the most important causes of death worldwide. Several studies have shown the efficacy of apricot kernel seed as a cancer therapy due to the presence of amygdalin. These studies have demonstrated amygdalin&rsquo;s cytotoxicity, antioxidant activity, and apoptosis in vitro using human cancer cell lines. However, no studies have demonstrated their cancer activity in vivo. The aim of this study is to develop an amygdalin-loaded niosomes (ALN) gel formulation as a drug delivery system in order to investigate the selectivity, efficacy, and toxicity of amygdalin as a cancer therapy in vivo using the 7,12-dimethylbenz (a) anthracene (DMBA) carcinoma rat model. Based on pre-formulation studies, the ALN formulation composed of Tween 60: cholesterol: dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation because it has a percent of EE of 66.52% with a particle size of 269.3 nm and a reflux of 3.54 &micro;g.cm&minus;2.h&minus;1. The ALN gel formulation was integrated into carbopol gel to be evaluated in vivo. Compared to DMBA control, treatment with ALN gel showed a reduction in the carcinoma volume and in the hyperplasia of the epidermis with no signs of edema. In conclusion, the ALN gel formulation could be an efficient cancer therapy

Molecular detection of multidrug-resistant Pseudomonas aeruginosa of different avian sources with pathogenicity testing and in vitro evaluation of antibacterial efficacy of silver nanoparticles against multidrug-resistant P. aeruginosa

ABSTRACT: Pseudomonas aeruginosa (P. aeruginosa) is a serious zoonotic pathogen threaten the poultry industry causing severe economic losses therefor, this study aimed to isolation, phenotypic, molecular identification of P. aeruginosa from different avian sources (chickens, turkey, pigeons, table eggs, and dead in shell chicken embryos), from different Egyptian governorates (Giza, Qalubia, Beheira, El-Minya, and Al-Sharqia) with applying of antibiotic sensitivity test on all P. aeruginosa isolates. Highly resistant isolates (n = 49) were subjected to molecular identification of P. aeruginosa with detection of resistant genes including carbapenemase-encoding genes blaKPC, blaOXA-48, and blaNDM. On the base of molecular results, a highly resistant P. aeruginosa strain was tested for its pathogenicity on day old specific pathogen free (SPF) chicks. Also, in vitro experiment was adopted to evaluate the efficacy of silver nanoparticles (Ag-NPs) against highly antibiotic-resistant P. aeruginosa strains. The overall isolation percentage was from all examined samples were 36.2% (571/1,576) representing 45.2% (532/1,176) from different birds' tissues and 39/400 (9.7%) from total egg samples. Some of isolated strains showed multidrug resistance (MDR) against kanamycin, amoxicillin, amoxicillin-clavulanic acid, neomycin, chloramphenicol, vancomycin, cefotaxime clavulanic acid, lincomycin-spectinomycin, co-trimoxazole, cefoxitin, gentamycin, and doxycycline. These MDR strains were also molecularly positive for ESBL and carbapenemase-encoding genes. MDR strain showed high pathogenicity with histopathological alterations in different organs in challenged birds. Main histopathological lesions were necrosis of hepatocytes, renal tubular epithelium, and heart muscle bundles. The MDR strain showed in vitro sensitivity to Ag-NPs. In conclusion, MDR P. aeruginosa is a serious pathogen causing high morbidity, mortality, and pathological tissue alterations. Ag NPs revealed a promising in vitro antimicrobial sensitivity against MDR P. aeruginosa and further in vivo studies were recommended

Evaluation of Salicylic Acid Effects on Growth, Biochemical, Yield, and Anatomical Characteristics of Eggplant (<i>Solanum melongena</i> L.) Plants under Salt Stress Conditions

Salt stress is a major issue in agriculture and crop production that influences global food security. Mitigation options to address salt stress through agronomic practices can help manage this issue. Experiments were performed in two summer seasons in an experimental farm to test the impact of three salinity levels (S): 300 (control), 1000, 2000, and 3000 ppm, and two salicylic acid (SA) levels, including 1.0 and 1.50 mM, and their interaction on growth and yield of eggplant (Solanum melongena L.) hybrid Suma. The results showed that increasing S levels up to 3000 ppm reduced plant and fruit physical characteristics, as well as leaf and fruit chemical characteristics, especially leaf total chlorophyll, carotenoids, relative water, fruit nitrogen, phosphorus, and potassium contents, which led to a reduction in total yield per plant. However, an insignificant effect was observed in the control level and 1000 ppm saline water in leaf area, fruit length, leaf total chlorophyll content, fruit phosphorus content, and total yield per plant. In contrast, leaf sugars, proline contents, electrolyte leakage, fruit TSS (total soluble solids), and ascorbic acid contents were improved with S levels up to the concentration of 3000 ppm compared to the control. However, tested parameters were significantly higher due to the SA foliar spray of 1.0 mM besides photosynthetic pigments of leaves enhanced by using 1.0 and 1.50 mM. Using 1.0 mM SA concentration alleviated the adverse impact of S on eggplant plants until 1000 ppm saline water, reflecting an increase in eggplant yield. The anatomical structure of eggplant leaves revealed positive variations in mature leaf blades in both the stressed and SA-treated plants. Based on these results, the use of SA at a concentration of 1.0 mM may lessen the negative impacts of salt on the growth of eggplant, which increases the overall yield