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

Somaclonal Variation for Genetic Improvement of Starch Accumulation in Potato (Solanum tuberosum) Tubers

Starch content is one of the major quality criteria targeted by potato breeding programs. Traditional potato breeding is a laborious duty due to the tetraploid nature and immense heterozygosity of potato genomes. In addition, screening for functional genetic variations in wild relatives is slow and strenuous. Moreover, genetic diversity, which is the raw material for breeding programs, is limited due to vegetative propagation used in the potato industry. Somaclonal variation provides a time-efficient tool to breeders for obtaining genetic variability, which is essential for breeding programs, at a reasonable cost and independent of sophisticated technology. The present investigation aimed to create potato somaclones with an improved potential for starch accumulation. Based on the weight and starch content of tubers, the somaclonal variant Ros 119, among 105 callus-sourced clones, recorded a higher tuberization potential than the parent cv Lady Rosetta in a field experiment. Although this somaclone was similar to the parent in the number of tubers produced, it exhibited tubers with 42 and 61% higher fresh and dry weights, respectively. Additionally, this clone recorded 10 and 75% increases in starch content based on the dry weight and average content per plant, respectively. The enhanced starch accumulation was associated with the upregulation of six starch-synthesis-related genes, namely, the AGPase, GBSS I, SBE I, SBE II, SS II and SS III genes. AGPase affords the glycosyl moieties required for the synthesis of amylose and amylopectin. GBSS is required for amylose elongation, while SBE I, SBE II, SS II and SS III are responsible for amylopectin

Boosting Polyamines to Enhance Shoot Regeneration in Potato (<i>Solanum tuberosum</i> L.) Using AgNO₃

Advancements in shoot regeneration systems support biotechnology-based tools used in the genetic improvement of plant crops. This study aims to enhance shoot regeneration in potatoes by boosting polyamine content by adding AgNO3 to the shoot regeneration medium (MS medium supplemented with 30 g L−1 sucrose, 100 mg L−1 myoinositol, and 2.25 BA mg L−1). Five concentrations of AgNO3 (2, 4, 6, 8, and 10 mg L−1) were used in addition to a control. The effect of AgNO3 on regeneration assumed a more or less concentration-dependent bell-shaped curve peaking at 4 mg L−1. Enhancements in shoot regeneration were attributed to the known role of AgNO3 as an ethylene action blocker in addition to improvements in polyamine accumulation without an increase in H2O2 content, lipid peroxidation, or DNA damage. The uncoupling of shoot regeneration and polyamine content recorded at high AgNO3 concentrations can be attributed to the consumption of polyamines to counteract the synchronized oxidative stress manifested by increases in H2O2 content, lipid peroxidation, and DNA damage

Boosting Polyamines to Enhance Shoot Regeneration in Potato (Solanum tuberosum L.) Using AgNO3

Advancements in shoot regeneration systems support biotechnology-based tools used in the genetic improvement of plant crops. This study aims to enhance shoot regeneration in potatoes by boosting polyamine content by adding AgNO3 to the shoot regeneration medium (MS medium supplemented with 30 g L&minus;1 sucrose, 100 mg L&minus;1 myoinositol, and 2.25 BA mg L&minus;1). Five concentrations of AgNO3 (2, 4, 6, 8, and 10 mg L&minus;1) were used in addition to a control. The effect of AgNO3 on regeneration assumed a more or less concentration-dependent bell-shaped curve peaking at 4 mg L&minus;1. Enhancements in shoot regeneration were attributed to the known role of AgNO3 as an ethylene action blocker in addition to improvements in polyamine accumulation without an increase in H2O2 content, lipid peroxidation, or DNA damage. The uncoupling of shoot regeneration and polyamine content recorded at high AgNO3 concentrations can be attributed to the consumption of polyamines to counteract the synchronized oxidative stress manifested by increases in H2O2 content, lipid peroxidation, and DNA damage

Somaclonal Variation for Genetic Improvement of Starch Accumulation in Potato (<i>Solanum tuberosum</i>) Tubers

Starch content is one of the major quality criteria targeted by potato breeding programs. Traditional potato breeding is a laborious duty due to the tetraploid nature and immense heterozygosity of potato genomes. In addition, screening for functional genetic variations in wild relatives is slow and strenuous. Moreover, genetic diversity, which is the raw material for breeding programs, is limited due to vegetative propagation used in the potato industry. Somaclonal variation provides a time-efficient tool to breeders for obtaining genetic variability, which is essential for breeding programs, at a reasonable cost and independent of sophisticated technology. The present investigation aimed to create potato somaclones with an improved potential for starch accumulation. Based on the weight and starch content of tubers, the somaclonal variant Ros 119, among 105 callus-sourced clones, recorded a higher tuberization potential than the parent cv Lady Rosetta in a field experiment. Although this somaclone was similar to the parent in the number of tubers produced, it exhibited tubers with 42 and 61% higher fresh and dry weights, respectively. Additionally, this clone recorded 10 and 75% increases in starch content based on the dry weight and average content per plant, respectively. The enhanced starch accumulation was associated with the upregulation of six starch-synthesis-related genes, namely, the AGPase, GBSS I, SBE I, SBE II, SS II and SS III genes. AGPase affords the glycosyl moieties required for the synthesis of amylose and amylopectin. GBSS is required for amylose elongation, while SBE I, SBE II, SS II and SS III are responsible for amylopectin