Phytochemical and antioxidant investigations of a Clausena anisata hook, a South African medicinal plant

Background: Clausena anisata (Willd). Hook (Rutaceae), also known as Iperepesi in Xhosa language is a medicinal plant widely used by herbalists for the treatment and/or management of several ailments such as chronic cough, tuberculosis and lung ulceration in Eastern Cape, South Africa. With reference to the information gathered in our previous study, we investigated the plant’s phyto-constituents, as well as its inhibitory effects using aqueous and two different organic solvent of extractions in order to justify its folkloric usage.Methods: Antioxidant activity of the plant was screened through 1,1- diphenyl-2-picrylhydrazyl (DPPH), 2,2’-azino-bis(3-ethylbenzthiazoline-6- sulfonic acid) (ABTS) diammonium salt, nitric oxide (NO), and ferric reducing power. Total phenols, flavonoids, flavonols, proanthocyanidins, tannins, alkaloids and saponins were investigated using spectroscopic techniques.Results: There were no significant differences in the flavonoid and proanthocyanidins contents between the leaves and bark extracts of C.  anisata respectively, while the total phenolic content of the bark extract of C. anisata was significantly higher than that of the C. anisata leaf. The acetone extracts of both the leaf and bark indicated strong antioxidant activities.Conclusion: The observed activities of the plant extracts could be attributed to the high contents of the phenolics, alkaloids, flavonoids, saponins, proanthocyanidins and tannin. The acetone extracts of the plants have also exhibited strong antioxidant activities in vitro. It has been established scientifically that oxidative stress is linked with several degenerative conditions and diseases; the inhibitory effects of these plant extracts on the free radicals could logically justify the folkloric usage of C. anisata leaf and bark in the Eastern Cape for the treatment of respiratory infection diseases.Key words: Antioxidants, Clausena anisata phytochemical contents, solvent extraction antiradica

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

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

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 middle-income 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 low-income 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 low-income, 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

The antibacterial activity of Clausena anisata hook, a South African medicinal plant

Background: Clausena anisata Hook also known as Iperepesi in Xhosa language is a medicinal plant used traditionally for the treatment of various ailments and some opportunistic infections associated with tuberculosis (TB). Patients in South Africa based on the phytotherapeutic information on this species in the Eastern Cape, use this medicinal plant. Hence, the antibacterial activity of various solvent extracts of the leaves and barks were respectively, evaluated using selected bacterial strains.Method: The leaves and stem bark were tested against 10 selected strains of Gram - positive and Gram - negative bacteria through the agar dilution method. Acetone, dichloromethane and water extracts were used for the extraction. MIC was determined at different concentrations (0.1mg/ml, 0.5mg/ml, 1mg/ml and 5mg/ml) and the results obtained were compared to that of standard antibiotics.Result: The acetone extract of the leaves were more active against both Gram-positive and Gram –negative bacteria with MIC ranging from 0.1 mg/ml - 0.5 mg / ml. The dichloromethane extract of the bark showed appreciable activities against Staphylococcus aureus (ATCC 6538) (MIC: 0.1mg /ml) Escherichia coli and, Streptococcus pyogenes with an MIC of 5mg/ml respectively. On the other hand, the aqueous extract of the leaves showed no activity against the tested organisms with the exception of the aqueous bark extract which inhibited Staphylococcus aureus (MIC: 0.5mg/ml) and Pseudomonas aeruginosa (MIC: 5mg/ml).Conclusion: This study confirmed the antibacterial activities of acetone extract of the leaves of Clausena anisata. The capability of this extract to inhibit both Gram positive and negative bacteria is an indication that the extract is a potential broad spectrum antibacterial. The result of this study further justified its indigenous use for the treatment of bacteria commonly associated with TB especially among the people of Nkonkobe Municipality.Key words: Clausena anisata; tuberculosis; antibacterial activity; herbal medicineAbbreviations: DCM = dichlormethane; ACT =acetone; MIC =minimum inhibitory concentration; na: not investigated beyond 5mg/ml; Cipro:Ciprofloxacin; Amox: Amoxicilli

Efficacy of opioids versus placebo in chronic pain: a systematic review and meta-analysis of enriched enrollment randomized withdrawal trials

Diana S Meske,1 Oluwadolapo D Lawal,1 Harrison Elder,1 Valerie Langberg,2 Florence Paillard,1 Nathaniel Katz1,3 1Analgesic Solutions, Natick, MA, USA, 2The Center for Evidence Synthesis in Health, Brown University, Providence, RI, USA, 3Department of Anesthesiology and Perioperative Medicine, Tufts University School of Medicine, Boston, MA, USA Introduction: Opioids have been used for millennia for the treatment of pain. However, the long-term efficacy of opioids to treat chronic non-cancer pain continues to be debated. To evaluate opioids&rsquo; efficacy in chronic non-cancer pain, we performed a meta-analysis of published clinical trials for &mu;-opioid receptor agonists performed for US Food and Drug Administration approval. Methods: MEDLINE and Cochrane trial register were searched for enriched enrollment randomized withdrawal studies (before June 2016). Selection criteria included: adults, &ge;10 subjects per arm, any chronic pain condition, double-blind treatment period lasting &ge;12 weeks, and all &mu;-agonist opioids approved in the USA. Results: Fifteen studies met criteria. Opioid efficacy was statistically significant (p&lt;0.001) versus placebo for pain intensity (standardized mean difference: &minus;0.416), &ge;30% and &ge;50% improvement in pain (risk difference: 0.166 and 0.137), patient global impression of change (0.163), and patient global assessment of study medication (0.194). There were minor benefits on physical function and no effect on mental function. Conclusion: Opioids are efficacious in the treatment of chronic non-cancer pain for up to 3 months in randomized controlled trials. This should be considered, alongside data on opioid safety, in the use of opioids for the treatment of chronic pain. Keywords: opioid analgesics, non-cancer pain, long-term efficacy, EERW trials, opioid efficacy; evidence-based medicin