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

Wash Resistance and Bioefficacy of Alpha-cypermethrin Long Lasting Impregnated Nets (LLIN-Interceptor(®)) against Anopheles stephensi using Tunnel Test.

Background: The Long-lasing insecticide impregnated nets (LLINs) is considered as an effective tools for malaria vector control. The aim of this study was to evaluate the residual efficacy of alpha-cypermethrin long lasting im- pregnated nets (LLIN-Interceptor®) against Anopheles stephensi using tunnel test. Methods: The wash-resistance of Interceptor® nets were assessed under laboratory conditions using tunnel test. Females of An. stephensi were released into the tunnel and then they were provided blood meals from guinea pigs.Bed nets were washed according to the standard procedure up to 20 times. The bioefficacy indicators such as inhi- bition of bloodmeal from experimental animal, knockdown, irritancy rate, survival rate, entry index and mortality were calculated. Results: It induced 90–100% mortalities in the population of An. stephensi up to 15 washes. The KT50 values re- duced from 73.47 to 26.30 minutes in unwashed in comparison to one washed, respectively. The mean of mortality rate of blood-feeding inhibition and entry indexes was reached to 91.6%±2.8, 87.0±3.4 and 24.9±2.8 respectively after 20 washing. Conclusion: This net could provide a good personal protection against malaria vectors and could induce relatively high mortality, inhibit the blood-feeding as well as reduce the entry rates of female mosquitoes even after several washes

Irritability Levels of Field and Laboratory Population of Culex pipiens Complex in Tehran to Different Groups of Insecticides

Background: The irritant effect of some insecticides can cause a proportion of mosquitoes to leave the sprayed rooms before acquiring a lethal dose, so the repeated contact al sub-lethal dose may lead to extent the resistance. Methods: Larvae and pupae of Culex pipiens complex were collected in mass from open canals of waste water in capital city Tehran and reared to obtain the first generation at laboratory. Sugar-fed 2–3 days female mosquitoes were used for the experiments and compared with laboratory strain. The irritability tests of insecticides impregnated pa­pers were measured in plastic conical exposure chambers placed which implemented at controlled conditions ac­cording  to  the  method  described  by WHO .Number of take-offs were counted during 15  minutes of exposure  time. Results: DDT had the most irritancy effect against field population of Cx. pipiens. DDT, permethrin and deltamethrin was moderately irritable against laboratory strain, whereas, addition to three previous insecticides, malathion, cyfluthrin and propoxur should be also considered as moderately irritable insecticides for field population of. Irritability level of etofenprox, fenithrothion, bendiocarb, and lambdacyhalothrin did not differ from control group. Conclusion: The irritability response of mosquitoes may have a negative impact on control measures. Periodical execution of irritability tests with insecticides that routinely used in vector control program is highly recommended

Molecular Identification of ESBLs Genes (blaTEM, blaSHV and blaCTX) among Non-fermenting Gram-negative Bacteria Isolated from Hospitalized Patients in Mazandaran Province, Iran

Background and purpose: Production of beta-lactamase enzymes by bacteria, especially Extended-spectrum β-lactamases (ESBLs) is one of the major problems worldwide. ESBLs are mostly located on bacterial plasmids and it is recognized that SHV, TEM, and CTX-M are prevailing among them. The aim of this study was to determine the ability to produce ESBLs genes based on molecular method among non-fermenting Gram-negative bacteria (Pseudomonas aeruginosa and Acinetobacter baumannii) isolated from hospitalized patients in Mazandaran province, Iran. Materials and methods: In this cross-sectional descriptive study, 81 non-fermenting bacterial isolates were collected. The isolates were tested for antibiotic susceptibility according to CLSI guidelines. Molecular identification of blaSHV, blaTEM, and blaCTX-M genes was performed using specific primers and polymerase chain reaction (PCR) method. Results: Of 81 non-fermentative bacteria isolated, 49 (60.5%) isolates of A. baumannii were detected and 32 (39.5%) isolates were confirmed as P. aeruginosa. The prevalence of identified genes in these isolates was as follows: 26% blaSHV, 19% blaTEM, and 12% blaCTX-M in P. aeruginosa and 11% blaTEM, 8% blaCTX-M, and 4% blaSHV in A. baumannii. Conclusion: ESBL positive strains of P. aeruginosa and A. baumannii are increasingly found in hospital isolates. Their high ability to pass resistant genes to other clinical strains requires their quick detection in clinical laboratories

Evaluation of the TXNIP gene expression in gastric adenocarcinoma and its relationship with overall survival of patients

Background. Gastric Cancer (GC) is a common gastrointestinal tumor, and its incidence is increasing. The pathogenesis of GC is very complex and remains unclear. Recent basic studies of GC have focused on gene expression dysregulation. Accumulating evidence has demonstrated that thioredoxin-interacting protein (TXNIP) is abnormally expressed in a variety of malignant tumors but it is obscure in GC. This study aimed to compare the expression of the TXNIP gene in cancerous and adjacent tissue of gastric cancer and evaluate its clinical significance in the prognosis and survival analysis of gastric cancer patients. Methods. A total of 50 tumor tissues and marginal non-tumor control tissues were obtained from GC patients. Also, TXNIP gene expression levels were evaluated by real-time PCR. Meanwhile, bioinformatic approaches were used to evaluate TXNIP expression in two different cohorts of GC patients. A data mining study was also performed to determine the prognostic role of TXNIP expression in the overall survival of GC. Furthermore, a pan-cancer analysis of TXNIP expression was performed using TCGA data. Results. The TXNIP gene was down-regulated in tumor samples with a fold change of 0.33, and the same results were repeated in bioinformatics analysis. Decreased expression of TXNIP was significantly associated with metastasis, poor differentiation, and drug abuse. Our results provided evidence that TXNIP gene expression level is positively correlated with the overall survival of GC patients. Pan-cancer analysis of TCGA data revealed down-regulated TXNIP in a variety of malignant tumors. Conclusion. This study established low TXNIP expression as a prognostic biomarker in GC. It also revealed that the decrease in TXNIP expression likely favors metastatic GC. Practical Implications. Evaluation of TXNIP expression is informative in the prognosis of GC patients

Chemical Composition, Larvicidal and Repellency Properties of Cionura erecta (L.) Griseb. Against Malaria Vector, Anopheles stephensi Liston (Diptera: Culicidae).

Background: Application of plant derivatives have been suggested as alternative sources for mosquito control. Methods: The root essential oil and methanol extract of Cionura erecta (L.) Griseb was tested under laboratory conditions for larvicidal and skin repelleny activities against Anopheles stephensi. The chemical compositions of essential oils were analyzed using gas chromatography- mass spectrometry. Results: Among the five concentrations tested, the 320 ppm of essential oil and 1280 ppm of methanolic extract had the most toxic effects yielding 100% mortality. The LC50 values of C. erecta for both essential oil and methanolic extract were 77.30 and 250.38 ppm, respectively. A total of 19 compounds were identified in essential oil of root. The major components were detected in root essential oil including Cedren-9-one (7.89%), alpha cadinol (5.67%), eugenol (4.02%) and alpha muurolene (3.58%). The protection time of 50% solution of essential oil against bites of An. stephensi was 2.28 hour on white rabbit and the ED50 and ED90 values of the essential oil were 10.12 and 23.01 ppm respectively. Conclusion: The findings suggest that C. erecta oil has a potential source as larvicidal and repellency properties against An.stephensi

Current Susceptibility Status of Anopheles stephensi (Diptera: Culicidae) to Different Imagicides in a Malarious Area, Southeastern Iran

Background: Anopheles mosquitoes are an important group of arthropods due to their role in transmission of ma­laria. The present study was conducted for determination of susceptibility status of Anopheles stephensi to different imagicides collected from malarious area in Chabahar city, Iran. Methods: In the present study seven insecticides including: DDT 4%, lambdacyhalothrin 0.05%, deltamethrin 0.05%, permethrin 0.75%, cyfluthrin 0.15% and etofenprox 0.5% were tested based on WHO method. Regression line was plotted for each insecticide using mortality of different exposure times. Bioassay data were analyzed using Probit software and the lethal time for 50% and 90% mortality (LT50 and LT90) values were calculated. Results: The susceptibility levels of field strain of An. stephensi to the discriminative dose of different imagicides were determined 100, 98, 96, 89, 82 and 62% for etofenprox, permethrin, deltamethrin, lambdacyhalothrin, cyfluth­rin and DDT, respectively. Our finding indicated that An. stephensi is resistant to DDT, lambdacyhalothrin and cyfluthrin, and susceptible to etofenprox and permethrin and candidate of resistant to deltamethrin based on WHO criteria. Conclusion: Our findings indicated that An. stephensi is resistant to DDT and some pyrethroid insecticides which can be developed due to application of insecticides in health and agriculture. These results can provide a clue for future chemical control program in the study area

Baseline Susceptibility of Different Geographical Strains of Anopheles stephensi (Diptera: Culicidae) to Temephos in Malarious Areas of Iran

Background: Malaria still remains a public health problem in Iran. There are different vector control interventions such as insecticide spraying. The present study was carried out to determine the susceptibility status of Anopheles stephensi larvae to temephos as a national plan for monitoring and mapping of insecticide resistanceMethods: Eight different localities in two main malarious provinces were determined as field collecting sites. Mos­quitoes were collected from the field and reared in an insectray. Susceptibility assays were carried out according to the WHO method. The laboratory reared susceptible Beech-Lab strain was used for comparison. Data were analyzed using Probit analysis to determine LC50 and LC90 values.Results: Susceptibility of An. stephensi to temephos indicated that the LC50 ranged from 0.0022 mg/l to 0.0141 mg/l. Although all field strains were susceptible to temephos, considerable variations in temephos resistance ratios of field strains were noticed from all the localities studied in comparison with the susceptible strain. A low level of resistance ratio was noticed in An. stephensi populations except for the Chabahar strain (RR= 4.27 fold). All field-collected An. stephensi populations exhibited homogeneity to the larvicide except for Bandar Abbas and Hormoodar village strains (P> 0.05%).Conclusion: Due to intensive use of temephos in the neighboring countries and occurrence of resistant to this insec­ticide in the main malaria vector in the region, insecticide resistance gene may evolve in the populations of An. stephensi. If temephos be applied as a larvicide it should be used judiciously for resistance management, as rotation strateg