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

Pharmacokinetic evaluation of D-ribose after oral and intravenous administration to healthy rabbits

Karem H Alzoubi,1 Zuhair Bani Ismail,2 Mohamed K AL-Essa,3 Osama Y Alshogran,1 Reem F Abutayeh,4 Nareman Abu-Baker5 1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Physiology, Faculty of Medicine, University of Jordan, Amman, Jordan; 4Department of Medicinal Chemistry and Phytochemistry, Applied Science Private University, Amman, Jordan; 5Philadelphia Biomedical Products Development Center, Amman, Jordan Introduction: This study explored d-ribose pharmacokinetics after intravenous (IV) and oral administration to healthy rabbits. Materials and methods: D-ribose was administered once as 420 mg/kg (N=4) or 840 mg/kg (N=6) dose intravenously, or as an oral dose of 420 mg/kg (N=3) or 840 mg/kg (N=3). Serum was obtained at various time points, up to 210 minutes after administration. Urine was also collected after IV administration. Pharmacokinetic parameters were determined from drug concentration&ndash;time data using Kinetica software. Results: The findings showed that D-ribose follows a dose-dependent kinetic profile. With doubling the IV dose, AUCtotal was significantly increased by threefold, while the clearance was decreased by 44%. The half-life was 1.7-fold longer at the higher dose. Similar nonsignificant trends were also observed at oral administration. D-ribose was rapidly absorbed (Tmax=36&ndash;44 minutes) and rapidly disappeared from plasma (within &lt;140 minutes). Additionally, D-ribose was partially (18&ndash;37.5%) recovered from urine. Conclusion: Collectively, D-ribose showed a dose-dependent kinetic profile, where parameters change according to dosing levels. D-ribose clearance seems to follow first-order kinetics at low dose. Thereafter, elimination systems are saturated, and elimination continues in a fast manner. Urine recovery was partial, which could be attributed to the several metabolic pathways that pentose can undergo. Keywords: D-ribose, single dose, pharmacokinetics, rabbits, oral, intravenou

Nutraceutical Potential of Apiaceae

Apiaceae family is large, with over 3.000 species worldwide cultivated for many purposes. Some plants in this family such as carrots, parsley, parsnip and celery are common vegetable crops, while other members like anise, caraway, coriander, cumin, fennel, lovage, angelica and dill are famous for their medicinal and aromatic properties. Usage of these plants is very popular in everyday diet because of their documented health benefits. Apiaceae are a very important source of phytochemicals – chemicals with biological activity. However, phytochemicals are non-nutritive plant chemicals, also called nutraceuticals. They are widely used for prevention, treatment or cure of conditions or diseases. Bioactive compounds with nutraceutical potential are polyphenolic compounds, polyacetylenes and terpenoids. The aim of this review is to represent selected plants of Apiaceae family currently used as nutraceuticals and describe their nutritional benefits

Medicinal plants - prophylactic and therapeutic options for gastrointestinal and respiratory diseases in calves and piglets? A systematic review.

BACKGROUND Gastrointestinal and respiratory diseases in calves and piglets lead to significant economic losses in livestock husbandry. A high morbidity has been reported for diarrhea (calves ≤ 35 %; piglets ≤ 50 %) and for respiratory diseases (calves ≤ 80 %; piglets ≤ 40 %). Despite a highly diverse etiology and pathophysiology of these diseases, treatment with antimicrobials is often the first-line therapy. Multi-antimicrobial resistance in pathogens results in international accordance to strengthen the research in novel treatment options. Medicinal plants bear a potential as alternative or additional treatment. Based on the versatile effects of their plant specific multi-component-compositions, medicinal plants can potentially act as 'multi-target drugs'. Regarding the plurality of medicinal plants, the aim of this systematic review was to identify potential medicinal plant species for prevention and treatment of gastrointestinal and respiratory diseases and for modulation of the immune system and inflammation in calves and piglets. RESULTS Based on nine initial sources including standard textbooks and European ethnoveterinary studies, a total of 223 medicinal plant species related to the treatment of gastrointestinal and respiratory diseases was identified. A defined search strategy was established using the PRISMA statement to evaluate 30 medicinal plant species starting from 20'000 peer-reviewed articles published in the last 20 years (1994-2014). This strategy led to 418 references (257 in vitro, 84 in vivo and 77 clinical trials, thereof 48 clinical trials in veterinary medicine) to evaluate effects of medicinal plants and their efficacy in detail. The findings indicate that the most promising candidates for gastrointestinal diseases are Allium sativum L., Mentha x piperita L. and Salvia officinalis L.; for diseases of the respiratory tract Echinacea purpurea (L.) MOENCH, Thymus vulgaris L. and Althea officinalis L. were found most promising, and Echinacea purpurea (L.) MOENCH, Camellia sinensis (L.) KUNTZE, Glycyrrhiza glabra L. and Origanum vulgare L. were identified as best candidates for modulation of the immune system and inflammation. CONCLUSIONS Several medicinal plants bear a potential for novel treatment strategies for young livestock. There is a need for further research focused on gastrointestinal and respiratory diseases in calves and piglets, and the findings of this review provide a basis on plant selection for future studies