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

COVID-19: Second Wave or Multiple Peaks, Natural Herd Immunity or Vaccine – We Should be Prepared

Between December 31, 2019, and August 30, 2020 (date of this article), the novel coronavirus and its corresponding infection, coronavirus disease (COVID-19), increased to more than 25 million cases, and 843 158 deaths have been registered. Countries around the world have been affected, albeit in different levels and intensities. Despite implementations of preventive public health measures, most countries are seriously preparing for 1 or more waves. The threat of this surge is likely to persist until herd immunity is acquired either by natural infection or through vaccination. However, given the time frame needed for herd immunity to occur and the low probability that a vaccine will be available on a global scale by the coming fall and winter seasons, contingency preparedness plans should be established and put in place for the coming days or months. These plans should help mitigate new peaks of the pandemic while relaxing the social isolation rules, patient, public health, and hospital levels. In this article, we discuss recommendations that practicing physicians and public health agencies should provide to individuals, especially those at risk of infection, to take and implement pre-emptive measures in anticipation of the potential next peak of the pandemic

The 2018 Lebanese Society of Infectious Diseases and Clinical Microbiology Guidelines for the use of antimicrobial therapy in complicated intra-abdominal infections in the era of antimicrobial resistance

Abstract Background The Lebanese Society of Infectious Diseases and Clinical Microbiology (LSIDCM) is involved in antimicrobial stewardship. In an attempt at guiding clinicians across Lebanon in regards to the proper use of antimicrobial agents, members of this society are in the process of preparing national guidelines for common infectious diseases, among which are the guidelines for empiric and targeted antimicrobial therapy of complicated intra-abdominal infections (cIAI). The aims of these guidelines are optimizing patient care based on evidence-based literature and local antimicrobial susceptibility data, together with limiting the inappropriate use of antimicrobials thus decreasing the emergence of antimicrobial resistance (AMR) and curtailing on other adverse outcomes. Methods Recommendations in these guidelines are adapted from other international guidelines but modeled based on locally derived susceptibility data and on the availability of pharmaceutical and other resources. Results These guidelines propose antimicrobial therapy of cIAI in adults based on risk factors, site of acquisition of infection, and clinical severity of illness. We recommend using antibiotic therapy targeting third-generation cephalosporin (3GC)-resistant gram negative organisms, with carbapenem sparing as much as possible, for community-acquired infections when the following risk factors exist: prior (within 90 days) exposure to antibiotics, immunocompromised state, recent history of hospitalization or of surgery and invasive procedure all within the preceding 90 days. We also recommend antimicrobial de-escalation strategy after culture results. Prompt and adequate antimicrobial therapy for cIAI reduces morbidity and mortality; however, the duration of therapy should be limited to no more than 4 days when adequate source control is achieved and the patient is clinically stable. The management of acute pancreatitis is conservative, with a role for antibiotic therapy only in specific situations and after microbiological diagnosis. The use of broad-spectrum antimicrobial agents including systemic antifungals and newly approved antibiotics is preferably restricted to infectious diseases specialists. Conclusion These guidelines represent a major step towards initiating a Lebanese national antimicrobial stewardship program. The LSIDCM emphasizes on development of a national AMR surveillance network, in addition to a national antibiogram for cIAI stratified based on the setting (community, hospital, unit-based) that should be frequently updated

Variable Neighborhood Search Algorithm for the Single Assignment Incomplete Hub Location Problem with Modular Capacities and Direct Connections

In distribution systems such as airlines and express package delivery, the use of hub-and-spoke networks is common, and flow consolidation at hub facilities is essential for cost reduction. While a constant discount factor is typically used to model cost reduction in interhub links, this paper explores an extension of the incomplete hub location problem with modular capacity that enables direct connections between non-hub nodes. The modified approach, called MHLPDC, aims to locate a set of hub facilities, connect each non-hub node to a hub, and activate hub facility links, access arc links, and direct links between non-hub nodes to minimize network costs. The MHLPDC integrates link activation decisions into the decision-making process and utilizes modular arc costs to model the flow dependence of transportation costs in all arcs. To solve the problem, the paper presents a mixed-integer mathematical programming formulation and heuristic algorithm based on a greedy randomized adaptive search and variable neighborhood search approach. The proposed algorithm produces high-quality solutions, as demonstrated through computational experiments on benchmark instances with up to 40 nodes. Furthermore, a sensitivity analysis of the optimal network structure indicates that increasing the discount factor, by varying hub and access arc capacities as well as the associated variable costs, results in fewer hubs being established and more direct shipments between non-hub nodes being permitted

Immunogenicity and Effectiveness of Primary and Booster Vaccine Combination Strategies during Periods of SARS-CoV-2 Delta and Omicron Variants

In this study involving a cohort of employees of the National Airline company in Lebanon, we assessed humoral immunity levels and the effectiveness of two COVID-19 vaccines, Gam-COVID-Vac versus BNT162b2, after two doses and after a homologous and heterologous BNT162b2 booster, in addition to the impact of hybrid immunity. Vaccine effectiveness (VE) was retrospectively determined against laboratory-confirmed SARS-CoV-2 infection during the periods of Delta and Omicron variants&rsquo; predominance, separately, and was calculated based on a case&ndash;control study design. The humoral immune response, measured by a SARS-CoV-2 anti-spike receptor-binding domain (RBD) IgG titer, was prospectively assessed after the aforementioned vaccination schemes at different time points. This study showed higher effectiveness of BNT162b2 after two doses (81%) compared to two doses of Gam-COVID-Vac (41.8%) against the Delta variant of SARS-CoV-2, which correlated with anti-spike antibody levels. Regarding the Omicron variant, protection against infection and antibody levels were severely compromised and the correlation between an anti-spike IgG titer and effectiveness was lost, unlike the situation during the Delta wave. Considering the booster vaccination schemes, a homologous BNT162b2 booster after a BNT162b2 primary vaccination induced a higher humoral immune response when compared to that induced by a heterologous BNT162b2 booster after a Gam-COVID-Vac primary vaccination. However, the VE of both booster regimens against the Omicron variant was almost equal (64% in the homologous regimen and 57% in heterologous regimen). Hybrid immunity evidenced a better humoral response and a greater and longer protection against Delta and Omicron infections compared to vaccination-induced immunity in COVID-19-na&iuml;ve individuals. Finally, the findings show that VE waned with time during the same wave, highlighting the importance of reinforcing primary and booster COVID-19 vaccination mainly at the beginning of each wave during the surge of a new variant of concern

Retrospective analysis on the use of amphotericin B lipid complex in neutropenic cancer patients with suspected fungal infections in Lebanon, a single center experience and review of international guidelines

Introduction: Immunocompromised patients carry a high risk for invasive fungal disease (IFD), which is associated with high mortality. Materials and Methods: This is a retrospective chart review of a 4 years’ experience of ABLC utilization for the management of suspected IFD at the Hematology/Oncology and Bone Marrow Transplantation unit at Makassed General Hospital, Beirut, Lebanon between January 2011 and December 2014. We focused on treatment strategy, response rate and adverse drug events associated with ABLC therapy. We also reviewed ABLC indications in international guidelines beyond its Food and Drug Administration approval. Results: A total of 89 patients received ABLC therapy for suspected fungal infection. Forty eight percent (48%) were treated for a possible fungal infection, 19% for a problable fungal infection, 12% based on hospital guidelines, and 20% based on treating physician’s recommendations. The overall response rate was 71%. Nephrotoxicity occurred in 24% of patients and serum creatinine improved in 10% of these patients. Moderate hypokalemia was observed in 61% of the patients and severe hypokalemia in 10% but was corrected in both cases. Hepatotoxicity was observed in 12% of the patients throughout ABLC therapy. Drug delivery reactions were observed in 36% of the patients. There was a decrease in the incidence of these reactions upon using combination of premedication drugs. Conclusion: In this study, ABLC proved to be an effective and safe option in the management of suspected IFD in immunocompromised patients failing previous therapies

Correlation between antifungal consumption and the distribution of Candida species in different hospital departments of a Lebanese medical Centre

Abstract Background In recent years, there has been a significant increase in the incidence of fungal infections attributed to Candida species worldwide, with a major shift toward non-albicans Candida (NAC). In this study, we have described the distribution of Candida species among different hospital departments and calculated the antifungal consumption in our facility. We also correlated the consumption of certain antifungals and the prevalence of specific Candida species. Methods This was a retrospective review of all the Candida isolates recovered from the computerised microbiology laboratory database of Makassed General Hospital, a tertiary care centre in Beirut, Lebanon, between January 2010 and December 2015. Data on antifungal consumption between January 2008 and December 2015 were extracted from the hospital pharmacy electronic database. We used Spearman’s coefficient to find a correlation between Candida species distribution and antifungal consumption. Results Between 2008 and 2015, we observed that the highest antifungal consumption was in the haematology/oncology department (days of therapy/1000 patient days = 348.12 ± 85.41), and the lowest was in the obstetrics/gynaecology department (1.36 ± 0.47). In general, the difference in antifungal consumption among various departments was statistically significant (P < 0.0001). Overall, azoles were the most common first-line antifungals in our hospital. Echinocandins and amphotericin B were mostly prescribed in the haematology/oncology department. As for Candida species distribution, a total of 1377 non-duplicate isolates were identified between 2010 and 2015. A non-homologous distribution of albicans vs. non-albicans was noted among the different departments (P = 0.02). The most commonly isolated NAC was Candida glabrata, representing 14% of total Candida species and 59% of NAC. Candida famata (9% of NAC), Candida parapsilosis (3.6% of NAC) and Candida krusei (3% of NAC) were recovered unequally from the different departments. The total antifungal consumption correlated positively with the emergence of NAC. The use of azoles correlated positively with Candida glabrata, while amphotericin B formulations correlated negatively with it. None of these correlations reached statistical significance. Conclusion Different Candida species were unequally distributed among different hospital departments, and this correlated with consumption of antifungals in respective departments, highlighting the need for antifungal stewardship