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

Battling Biofilm Forming Nosocomial Pathogens Using Chitosan and Pluronic F127

Biofilm represents a potential strut in bacterial treatment failure. It has a dual action; it affords microbial resistance against antibiotics and facilitate transmission of pathogenic bacteria. Nosocomial bacteria pose a serious problem in healthcare units; it prolongs patient hospital stay and increases the mortality rates beside other awful economical effect. This study was planned for targeting nosocomial bacterial biofilm using natural and biologically safe compounds like Chitosan and/or Pluronic F127. Ninety-five isolates were recovered from 107 nosocomial clinical samples. Different bacterial and fungal species were detected, from which Klebsiella pneumonia (23%), Pseudomonas aeruginosa (19%), Acinetobacter baumannii (18%) and E.coli (17%) were the predominate organisms. Pseudomonas aeruginosa, Acinetobacter baumanni and Klebsiella pneumonia were the abundant antibiotic resistant strains with multi-resistance pattern of 72%, 65% and 59%, respectively. A significant percentage of these isolates were strong biofilm forming. Herein, we investigate the effect of Chitosan and Pluronic F127 alone and in combination with each other against biofilm production. Chitosan show variable degree of biofilm inhibition, while Pluronic F127 was able to retard biofilm formation by 80% to 90% in most strain. There is no significant difference (P< 0.05) between Pluronic F127 alone and its effect in combination with Chitosan

Effect of DPI's training-device on inhalation technique and clinical efficacy in asthmatics

The aim of this work was to study the effect of using training device (In-Check DIAL) along with traditional dry powder inhaler (DPI) counseling on inhalation technique and pulmonary functions test (PFT) in asthmatics.Adult asthmatics >18 years old were recruited in 3months study of investigation and training. They were divided into control and investigation groups.DPI inhalation technique was checked and mistakes were noted and corrected at every monthly visit. Their peak expiratory flow and forced expiratory volume in 1second as percentage of forced vital capacity were checked at each visit followed by showing patients the correct inhalation technique and how to use In-Check DIAL (investigation group).29 patients (14 females) and 57 patients (30 females) in control and investigation groups respectively completed the study. Mean number of mistakes was significantly decreased (p < .001) as the counseling session increased in both groups. Significant decrease in crucial mistake (inhalation quickly and forcefully until complete filling up of the lungs) that was very hard to be learned via only verbal counseling was noticed after the addition of In-Check DIAL. The improvement of the PFT results were significant from the second visit in the investigation group (p < .05) and from the third visit in the control group (p < .001). The decrease in the rate of rescue medication consumption was faster in investigation group than control group.Using training device along with verbal counseling has proven a beneficial role in inhalation technique resulting in optimum dosage delivery and yielding reasonable improvement in PFT. Keywords: DPI, In-Check DIAL, Dose delivery, Traditional verbal counseling, Pulmonary function

Effect of DPI's training-device on inhalation technique and clinical efficacy in asthmatics

The aim of this work was to study the effect of using training device (In-Check DIAL) along with traditional dry powder inhaler (DPI) counseling on inhalation technique and pulmonary functions test (PFT) in asthmatics.Adult asthmatics >18 years old were recruited in 3months study of investigation and training. They were divided into control and investigation groups.DPI inhalation technique was checked and mistakes were noted and corrected at every monthly visit. Their peak expiratory flow and forced expiratory volume in 1second as percentage of forced vital capacity were checked at each visit followed by showing patients the correct inhalation technique and how to use In-Check DIAL (investigation group).29 patients (14 females) and 57 patients (30 females) in control and investigation groups respectively completed the study. Mean number of mistakes was significantly decreased (p < .001) as the counseling session increased in both groups. Significant decrease in crucial mistake (inhalation quickly and forcefully until complete filling up of the lungs) that was very hard to be learned via only verbal counseling was noticed after the addition of In-Check DIAL. The improvement of the PFT results were significant from the second visit in the investigation group (p < .05) and from the third visit in the control group (p < .001). The decrease in the rate of rescue medication consumption was faster in investigation group than control group.Using training device along with verbal counseling has proven a beneficial role in inhalation technique resulting in optimum dosage delivery and yielding reasonable improvement in PFT. Keywords: DPI, In-Check DIAL, Dose delivery, Traditional verbal counseling, Pulmonary function

Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice

To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers

Microelimination of hepatitis C in patients with chronic hemolytic anemias: a single-center experience

Abstract Background Patients with chronic hemolytic anemias (CHA) are at a high risk for transfusion-transmitted infections. Various studies in Egypt have shown a prevalence of hepatitis C virus (HCV) infection in 24–37% of those patients. Elimination of hepatitis C virus (HCV) in patients with CHA would prevent early progression of liver disease. In this study, we aimed to assess the efficacy, safety, and tolerability of sofosbuvir (SOF) and daclatasvir (DAC) in the special population of HCV-infected patients with CHA. In this prospective study, 21 consenting hepatitis C patients were recruited and treated using ribavirin-free SOF/DAC regimen for either 12 or 24 weeks according to categorization of patients into easy or hard-to-treat in accordance with the national protocols. Sustained virological response was assessed by RT-PCR for HCV-RNA at 12 weeks post-treatment (SVR12). Any treatment-related adverse events were noted. Results All patients were adherent to treatment with no discontinuation of therapy. SVR12 was achieved in 19 out of 21 patients (90.5%). There was a significant improvement in levels of ALT (p<0.009) after completion of therapy. On the other hand, the hemoglobin, total bilirubin, and ferritin levels showed a non-significant difference (p<0.501, p<0.542, and p<0.339, respectively). Moderate adverse events were observed in 2 out of 21 patients (9.5%), including sickling crisis and hepatic decompensation. Conclusion The results of this study substantiate the favorable efficacy, safety, and tolerability of ribavirin-free direct-acting antivirals (DAAs) in the special population of HCV-infected patients with CHA. Micro-elimination of HCV in special patient populations allows for pragmatic delivery of care to patients with co-morbid conditions who are in most need for treatment and allows for achievement of global elimination of HCV worldwide

Brain Targeting of Quetiapine Fumarate via Intranasal Delivery of Loaded Lipospheres: Fabrication, In-Vitro Evaluation, Optimization, and In-Vivo Assessment

A liposphere system for intranasal delivery of quetiapine fumarate (QTF) was created to assess the potential for enhanced drug delivery. We investigated the effects of particle size, entrapment effectiveness, poly dispersibility index, and pluronic incorporation percentage on these variables. The optimal formula was examined using a TEM, and investigations into DSC, XRD, and FTIR were made. Optimized liposphere formulation in vitro dissolution investigation with a mean diameter of 294.4 &plusmn; 18.2 nm revealed about 80% drug release in 6 h. The intranasal injection of QTF-loaded lipospheres showed a shorter Tmax compared to that of intranasal and oral suspension, per the findings of an in vivo tissue distribution investigation in Wistar mice. Lipospheres were able to achieve higher drug transport efficiency (DTE %) and direct nose-to-brain drug transfer (DTP %). A potentially effective method for delivering QTF to specific brain regions is the liposphere system

Dinebra retroflexa Herbal Phytotherapy: A Simulation Study Based on Bleomycin-Induced Pulmonary Fibrosis Retraction Potential in Swiss Albino Rats

Background and Objectives: Fibrotic lung disease is one of the main complications of many medical conditions. Therefore, the use of anti-fibrotic agents may provide a chance to prevent, or at least modify, such complication. The aim of this study was to evaluate the protective pulmonary anti-fibrotic and anti-inflammatory effects of Dinebra retroflexa. Materials and methods: Dinebra retroflexa methanolic extract and its synthesized silver nanoparticles were tested on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/5 mL/kg-Saline) as a supposed model for induced lung fibrosis. The weed evaluation was performed by intratracheal instillation of Dinebra retroflexa methanolic extract and its silver nanoparticles (35 mg/100 mL/kg-DMSO, single dose). Results: The results showed that both Dinebra retroflexa methanolic extract and its silver nanoparticles had a significant pulmonary fibrosis retraction potential, with Ashcroft scores of three and one, respectively, and degrees of collagen deposition reduction of 33.8 and 46.1%, respectively. High-resolution UHPLC/Q-TOF-MS/MS metabolic profiling and colorimetrically polyphenolic quantification were performed for further confirmation and explanation of the represented effects. Such activity was believed to be due to the tentative identification of twenty-seven flavonoids and one phenolic acid along with a phenolic content of 57.8 mg/gm (gallic acid equivalent) and flavonoid content of 22.5 mg/gm (quercetin equivalent). Conclusion: Dinebra retroflexa may be considered as a promising anti-fibrotic agent for people at high risk of complicated lung fibrosis. The results proved that further clinical trials would be recommended to confirm the proposed findings