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

Toward an Integrated Ecology and Economics of Land Degradation and Restoration: Methods, Data, and Models

This report assesses existing data, models, and knowledge methods and recommends a way forward for the ELD Initiative. It draws from existing research, publications, and case studies to summarize current practices and identify knowledge gaps. This report begins with a review of the methods to value land-use and management options. It emphasizes the overall development goal of sustainable human well-being, not merely growth of the market economy. To obtain sustainable well-being through improved land management depends on the interaction of four basic types of capital assets: built, human, social, and natural. For example, the value of ecosystem services is the relative contribution of natural capital in combination with the other three types of assets to produce sustainable well-being. Although this report focuses on natural capital and ecosystem services, it recognizes that the understanding, modelling, and valuing of ecosystem services requires an integrated, transdisciplinary approach which includes all four types of capital and their complex interactions. Another central part of this report is a review of computer models that could be useful for analyzing and valuing land management options. This includes farm and site scale models, watershed and regional scale models, climate change models, integrated global models, and ecosystem services models. A major conclusion of this report is that truly integrated models (i.e., models that include all four types of capital and their interactions at multiple scales) are required to meet the goals of the Initiative. Examples of these types of models do exist, but further development is necessary to make them accessible to stakeholders and used in decision-making. For further development and integration of the models themselves, a more participatory approach to model development is recommended along with the possibility of adding advanced gaming interfaces to the models to allow them to be "played" by a large number of interested parties and their trade-off decisions (and the valuations they imply) to be accumulated and compared. This report concludes with a vision of what these integrated assessment and valuation tools might look like and how they would help solve the problems of land degradation, restoration, and sustainable management.This report was commisioned by Economics of Land Degradation (ELD) Initiativ

A review of methods, data, and models to assess changes in the value of ecosystem services from land degradation and restoration

This review assesses existing data, models, and other knowledge-based methods for valuing the effects of sustainable land management including the cost of land degradation on a global scale. The overall development goal of sustainable human well-being should be to obtain social, ecologic, and economic viability, not merely growth of the market economy. Therefore new and more integrated methods to value sustainable development are needed. There is a huge amount of data and methods currently available to model and analyze land management practices. However, it is scattered and requires consolidation and reformatting to be useful. In this review we collected and evaluated databases and computer models that could be useful for analyzing and valuing land management options for sustaining natural capital and maximizing ecosystem services. The current methods and models are not well equipped to handle large scale transdisciplinary analyses and a major conclusion of this synthesis paper is that there is a need for further development of the integrated approaches, which considers all four types of capital (human, built, natural, and social), and their interaction at spatially explicit, multiple scales. This should be facilitated by adapting existing models and make them and their outcomes more accessible to stakeholders. Other shortcomings and caveats of models should be addressed by adding the ‘human factor’, for instance, in participatory decision-making and scenario testing. For integration of the models themselves, a more participatory approach to model development is also recommended, along with the possibility of adding advanced gaming interfaces to the models to allow them to be “played” by a large number of interested parties and their trade-off decisions to be accumulated and compared

Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial

Background Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth.Methods GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 mu L intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366.Findings Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0 center dot 336 mm/year (SE 0 center dot 032) with avacincaptad pegol 2 mg and 0 center dot 392 mm/year (0 center dot 033) with sham, a difference in growth of 0 center dot 056 mm/year (95% CI 0 center dot 016-0 center dot 096; p=0 center dot 0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group.Interpretation Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy.Funding Iveric Bio, An Astellas Company.Copyright (c) 2023 Elsevier Ltd. All rights reserved

Alirocumab and cardiovascular outcomes after acute coronary syndrome

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Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

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