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

Novel iron oxide nanocarriers loading finasteride or dutasteride : enhanced skin penetration for topical treatment of alopecia

In the present study, iron oxide nanoparticles, in the form of maghemite core coated with lauric acid (ION), were synthesized and loaded with finasteride (FIN) or dutasteride (DUT) as a novel drug delivery system for the topical treatment of alopecia. Additionally, developed formulations (FIN-ION and DUT-ION) were completely elaborated with components involved in the follicle metabolism, i.e., lauric acid, which acts as a 5α-reductase inhibitor, and iron which deficiency has been related to hair loss aggravation. Stability assessment conducted over the course of 90 days showed they are highly stable, with pH 7.4, constant EE% (>99%), and practically unchanged particle size and zeta potential. Besides drug distribution, the actual number of iron oxide nanoparticles, through a newly developed method using ferromagnetic resonance, was determined in each skin layer following permeation experiments. Despite the same donor concentration of colloids, nanoparticle distribution in the skin varied according to the loaded molecule. While DUT did not interfere with the nanoparticle natural tendency to accumulate within the hair follicle shafts, FIN presence hampered nanosystem interaction with the skin. Still, both formulations provided a higher skin drug penetration, compared to each respective control solution. Additionally, iron nanocarriers present a desirable visual characteristic, as the dark color aspect might instantly help disguise scarce hair follicle areas. These findings suggest the nanoformulations are highly promising for alopecia therapies

A sociodental approach in prosthodontic treatment decision making Uma abordagem social nas tomadas de decisão no tratamento com prótese dentária

A critical problem in the decision making process for dental prosthodontic treatment is the lack of reliable clinical parameters. This review discusses the limits of traditional normative treatment and presents guidelines for clinical decision making. There is a need to incorporate a sociodental approach to help determine patient's needs. Adoption of the evidence-based clinical practice model is also needed to assure safe and effective clinical practice in prosthetic dentistry.<br>Um problema crítico no processo de tomadas de decisão em prótese dentária é a falta de parâmetros clínicos confiáveis nas condutas clínicas de tratamento. A presente revisão descreve e discute alguns aspectos desse problema e apresenta diretrizes para as decisões clínicas a partir do levantamento de limitações inerentes ao tratamento normativo tradicional. Conclui-se que há necessidade de incorporação de uma abordagem sócio-odontológica na determinação de necessidades dos pacientes. A adoção de um modelo de práticas baseadas em evidências é essencial para assegurar práticas clínicas seguras e efetivas em prótese dentária