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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Bovine herpesvirus (BoHV-1 e/ou BoHV-5): the process of elimination, viremia and serology of naturally infected dairy cows

A fim de esclarecer dados da dinâmica da infecção pelos Bovine herpesvirus 1 (BoHV-1) e/ou Bovine herpesvirus 5 (BoHV-5), este trabalho visou comparar a eliminação dos referidos agentes virais em duas fases distintas da lactação (cinco meses antes e na época do parto) de vacas leiteiras naturalmente infectadas. Isso, de modo a relacionar a eliminação viral ao estresse periparto, tomando como parâmetro de análise dosagens do hormônio cortisol. Também foi investigada, através da Nested-PCR, a eliminação do DNA viral no colostro/leite, secreção nasal, viremia e, através da soroneutralização, a resposta sorológica de vacas leiteiras naturalmente infectadas. Foi demonstrado não haver diferenças dos níveis de cortisol entre as fases produtivas estudadas. Consequentemente, não houve diferenças na detecção do genoma viral e na resposta humoral das amostras clínicas focadas, considerando as duas fases estudadas. O leite se apresentou como uma alternativa amostral eficaz de diagnóstico da presença genômica do BoHV-1 e/ou BoHV-5. Em uma das propriedades de trabalho, praticamente 100% dos animais infectados estavam eliminando material genômico dos agentes, e houve uma média de 52% de frequência de positividade desse material eliminado no leite das vacas das demais propriedades. A frequência positiva de viremia se assemelhou àquela do leite em animais infectados, enquanto que a eliminação via secreção nasal apresentou baixa frequência de positividade, comparando ao leite. Isso sugere um prolongamento da época de eliminação via leite quando comparada à secreção nasal, concordando com a eficácia do leite como alternativa de material para diagnóstico viral. Sendo assim, conclui-se que a Nested-PCR é um método eficiente para o diagnóstico dos vírus deste estudo em leite e que essa amostra é promissora para o foco dos profissionais de campo, pois, além do diagnóstico ser possível na fase de infecção produtiva, há maior facilidade em sua coleta, quando comparada à coleta de sangue.In order to clarify data on the dynamics of infection by Bovine herpesvirus 1 (BoHV-1) and / or Bovine herpesvirus 5 (BoHV-5), the aim of this study was to compare the viral clearance of BoHV-1 and/or BoHV-5 in two distinct phases of lactation (five months before and at parturition) of naturally infected dairy cows. Measurements of the cortisol hormone were used as an analysis parameter in order to relate viral shedding to post partum stress., The elimination of viral DNA in colostrum / milk, nasal secretions and viremia was investigated by nested PCR. The antibody response of cattle naturally infected was investigated by neutralization. There was no difference in cortisol levels between the two lactation phases. Therefore, there was no difference in viral genome detection and antibody responses of the tested samples, considering the two studied phases. Milk was an effective sample alternative for genomic diagnosis of BoHV-1 and/or BoHV-5. In one of the properties studied, close to 100% of infected animals were shedding viral DNA, and the mean frequency of milk shedding in cows from other properties was only 52%. The positive viremia rate was similar to the one observed in the milk of infected animals, while viral clearance in nasal discharges had low positivity rate, compared to milk. This suggests an extended shedding time in the milk, when compared to other dissemination routes. This information corroborates with milk efficacy as a sample alternative for viral diagnosis. Thus, in this study, Nested- PCR is an efficient tool for the viral diagnosis in milk. Milk is a promising sample for field practitioners because not only does it allow for productive infection diagnosis, it is easier to collect compared to blood

Detecção de peptídeos importantes para o diagnóstico da cisticercose bovina no immunoblot

A dificuldade de se localizar cisticercos em bovinos com infecção discreta torna o diagnóstico tradicional da cisticercose bovina em matadouros um recurso de baixa sensibilidade, o que gera uma demanda de diagnóstico por métodos alternativos como o immunoblot. Para tanto, neste trabalho, foram realizados ensaios de immunoblot a fim de analisar os peptídeos responsáveis pela reação do antígeno vesicular de Taenia crassiceps. Foram utilizadas 28 amostras de soro de bovinos comprovadamente negativos e 28 amostras coletadas de bovinos infectados experimentalmente com ovos de Taenia saginata. Os resultados dos ensaios de immunoblot com as amostras de soros-controle mencionadas indicaram que os peptídeos de 4-6, 14 e 18kDa destacaram-se entre os demais, mostrando altas taxas de desempenho no diagnóstico da cisticercose bovina e uma aparência diferenciada, com área e largura maiores, ao contrário dos peptídeos de média e alta massa molecular, que se apresentaram sob a forma de linha e com reações inespecíficas. O immunoblot mostrou ter um potencial como uma alternativa de diagnóstico da cisticercose bovina, incluindo sua aplicação em animais vivos, como método auxiliar de diagnóstico em estudos epidemiológicos da doença.The diagnosis of cysticercosis in bovines that presents discreet infection is committed by the conventional methodology of detection employed in slaughterhouses. This deficiency leads to the development of alternative methods, such as immunoblot, in order to improve the detection of this disease. An immunoblot assay was developed to detect peptides from Taenia crassiceps antigenand it was used to test 56 samples of bovine serum (28 confirmed as negative and 28 from experimentally infected animals with Taenia saginata eggs). The peptides 4-6, 14 and 18 kDa showed better performance in bovine cysticercosis diagnosis due to an enhanced appearance, once they showed higher area and wide, contrasting with medium and high molecular weight peptides, that showed unspecific reactions and discreet appearance. The obtained results indicated that immunoblot can represent a potential alternative in bovine cysticercosis diagnosis, including its use in live animals, improving the detection of this disease even in epidemiological studies

Detecção de peptídeos importantes para o diagnóstico da cisticercose bovina no immunoblot Detection of important peptides for bovine cysticercosis diagnosis in immunoblot

A dificuldade de se localizar cisticercos em bovinos com infecção discreta torna o diagnóstico tradicional da cisticercose bovina em matadouros um recurso de baixa sensibilidade, o que gera uma demanda de diagnóstico por métodos alternativos como o immunoblot. Para tanto, neste trabalho, foram realizados ensaios de immunoblot a fim de analisar os peptídeos responsáveis pela reação do antígeno vesicular de Taenia crassiceps. Foram utilizadas 28 amostras de soro de bovinos comprovadamente negativos e 28 amostras coletadas de bovinos infectados experimentalmente com ovos de Taenia saginata. Os resultados dos ensaios de immunoblot com as amostras de soros-controle mencionadas indicaram que os peptídeos de 4-6, 14 e 18kDa destacaram-se entre os demais, mostrando altas taxas de desempenho no diagnóstico da cisticercose bovina e uma aparência diferenciada, com área e largura maiores, ao contrário dos peptídeos de média e alta massa molecular, que se apresentaram sob a forma de linha e com reações inespecíficas. O immunoblot mostrou ter um potencial como uma alternativa de diagnóstico da cisticercose bovina, incluindo sua aplicação em animais vivos, como método auxiliar de diagnóstico em estudos epidemiológicos da doença.The diagnosis of cysticercosis in bovines that presents discreet infection is committed by the conventional methodology of detection employed in slaughterhouses. This deficiency leads to the development of alternative methods, such as immunoblot, in order to improve the detection of this disease. An immunoblot assay was developed to detect peptides from Taenia crassiceps antigenand it was used to test 56 samples of bovine serum (28 confirmed as negative and 28 from experimentally infected animals with Taenia saginata eggs). The peptides 4-6, 14 and 18 kDa showed better performance in bovine cysticercosis diagnosis due to an enhanced appearance, once they showed higher area and wide, contrasting with medium and high molecular weight peptides, that showed unspecific reactions and discreet appearance. The obtained results indicated that immunoblot can represent a potential alternative in bovine cysticercosis diagnosis, including its use in live animals, improving the detection of this disease even in epidemiological studies

Molecular Methodology for the Detection of the Leishmania Genus in Different Biological Samples Extracted from Dogs

Background: The leishmaniases are a group of parasitic diseases caused by trypanosomatids belonging to the genus Leishmania, members of the class Kinetoplastida, order Trypanosomatidae, family Trypanosomatidae. Despite innumerous wild species that are infected, the domestic dog is a potential reservoir of Leishmania infantum in urban areas, which expands the transmission pathway to humans. When infected, the dog becomes Visceral Canine Leishmaniasis (CVL), which is characterized by a diverse clinical picture that ranges from asymptomatic to non-specific signs, such as skin lesions, lymphadenomegaly, weight loss, splenomegaly, and/or ocular lesions, thus impairing accurate and rapid diagnosis.In Brazil, it is considered a public health problem since it is endemic in certain regions. Therefore, parasitological, serological, and molecular methods can be used for the detection of the disease. However, the possibility of serological cross-reaction and the occurrence of co-infection with other trypanosomatids decreases the specificity rate to below 100%, which suggests the use of more accurate diagnostic tools. Several molecular targets and starting samples for leishmaniasis diagnosis are already standardized, but there is lack of data allowing the evaluation of the target, as well as which biological material is more efficient for the molecular diagnosis of CVL. The sensitivity of PCR may vary with DNA quality, primer type, parasitemia level, and number of target copies per cell. The spleen, blood, liver, aspirate of bone marrow and lymph nodes are the most frequently used for molecular diagnosis of CVL. The present study aimed to evaluate and compare three protocols of the polymerase chain reaction (PCR) for the molecular diagnosis of CVL in different biological samples removed from animals with different clinical and anatomopathological signs.Materials, Methods & Results: Fifty seropositive dogs for CVL were used, their clinical and anatomopathological signs were evaluated, and were classified as asymptomatic, oligosymptomatic, and polysymptomatic. The PCR was conducted with specific primers for each region of the smaller subunit of rRNA, ITS-1, and KDNA genes. The four types of biological samples (spleen, blood, lymph nodes, and liver) were analyzed. Among the 50 dogs studied, 19 (38%) were in the asymptomatic group; all the animals showed healthy appearance, 15/50 (30%) of the dogs presented up to two symptoms, being classified as oligosymptomatic. The polysymptomatic dogs [16/50 (32%)] presented with a compromised clinical status. The study showed that all dogs had a positive result in at least one analyzed PCR methodology. Comparing the results of the three types of tests in the four types of studied samples, the nested-PCR was the one which presented a greater frequency of amplifications. Of a total of 200 samples, 124 showed amplification, showing a 62% sensitivity.Discussion: The results revealed that, when 50 dogs were analyzed, the spleen tissue samples had a better performance in all the tests, but the sensitivity of blood samples was also satisfactory in Nested SSU rRNA-PCR and MC-PCR. The blood samples can be easily accessed with minimal invasion. One of the limitations around the use of biopsy of the spleen or its aspirate is the risk of serious bleeding or even death of the animal. Taking into consideration the practicality and because it has a lower grade of invasiveness, the combination of peripheral blood with Nested SSU rRNA-PCR becomes the methodology of first choice

Antibodies against Bovine herpesvirus 1 in dairy herds in the state of Espirito Santo, Brasil

Bovine herpesvirus 1 (BoHV-1) causes major losses in worldwide livestock, affecting the respiratory and reproductive tracts of bovine. In the past decades, the number of cases in Brazil has been gradually increasing. Therefore, it is important to assess the distribution of infection in different regions of the country. In the state of Espírito Santo (ES) the BoHV 1 infection rate in dairy cattle herds is unknown. Thus, the aim of this study was to detect neutralizing antibodies against BoHV-1 in serum samples from 1,161 non-vaccinated cows from 59 dairy cattle herds in 23 municipalities of the Metropolitan, North, Northwest and South macro-regions. The identification of seropositive cows was evaluated by the virus neutralization test. The results showed that of all serum samples evaluated 775 (66.75%) had neutralizing antibodies against BoHV-1. Moreover, all herds were found positive; however, the percentage of positive cows varied among regions; 49.06%, 62.15%, 67.21% and 80.04% for the Metropolitan, South, North and Northwest macro-regions, respectively. In this study, the results clearly indicate the dissemination of the viral agent in dairy cattle in the ES state, requiring the monitoring and control of diseases related to BoHV-1 infection

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit