Solar-powered O2 delivery for the treatment of children with hypoxaemia in Uganda: a stepped-wedge, cluster randomised controlled trial.

BACKGROUND: Supplemental O2 is not always available at health facilities in low-income and middle-income countries (LMICs). Solar-powered O2 delivery can overcome gaps in O2 access, generating O2 independent of grid electricity. We hypothesized that installation of solar-powered O2 systems on the paediatrics ward of rural Ugandan hospitals would lead to a reduction in mortality among hypoxaemic children. METHODS: In this pragmatic, country-wide, stepped-wedge, cluster randomised controlled trial, solar-powered O2 systems (ie, photovoltaic cells, battery bank, and O2 concentrator) were sequentially installed at 20 rural health facilities in Uganda. Sites were selected for inclusion based on the following criteria: District Hospital or Health Centre IV with paediatric inpatient services; supplemental O2 on the paediatric ward was not available or was unreliable; and adequate space to install solar panels, a battery bank, and electrical wiring. Allocation concealment was achieved for sites up to 2 weeks before installation, but the study was not masked overall. Children younger than 5 years admitted to hospital with hypoxaemia and respiratory signs were included. The primary outcome was mortality within 48 h of detection of hypoxaemia. The statistical analysis used a linear mixed effects logistic regression model accounting for cluster as random effect and calendar time as fixed effect. The trial is registered at ClinicalTrials.gov, NCT03851783. FINDINGS: Between June 28, 2019, and Nov 30, 2021, 2409 children were enrolled across 20 hospitals and, after exclusions, 2405 children were analysed. 964 children were enrolled before site randomisation and 1441 children were enrolled after site randomisation (intention to treat). There were 104 deaths, 91 of which occurred within 48 h of detection of hypoxaemia. The 48 h mortality was 49 (5·1%) of 964 children before randomisation and 42 (2·9%) of 1440 (one individual did not have vital status documented at 48 h) after randomisation (adjusted odds ratio 0·50, 95% CI 0·27-0·91, p=0·023). Results were sensitive to alternative parameterisations of the secular trend. There was a relative risk reduction of 48·7% (95% CI 8·5-71·5), and a number needed to treat with solar-powered O2 of 45 (95% CI 28-230) to save one life. Use of O2 increased from 484 (50·2%) of 964 children before randomisation to 1424 (98·8%) of 1441 children after randomisation (p<0·0001). Adverse events were similar before and after randomisation and were not considered to be related to the intervention. The estimated cost-effectiveness was US$25 (6-505) per disability-adjusted life-year saved. INTERPRETATION: This stepped-wedge, cluster randomised controlled trial shows the mortality benefit of improving O2 access with solar-powered O2. This study could serve as a model for scale-up of solar-powered O2 as one solution to O2 insecurity in LMICs. FUNDING: Grand Challenges Canada and The Women and Children's Health Research Institute.

Gaps and priorities in innovation for children's surgery.

Lack of access to pediatric medical devices and innovative technology contributes to global disparities in children's surgical care. There are currently many barriers that prevent access to these technologies in low- and middle-income countries (LMICs). Technologies that were designed for the needs of high-income countries (HICs) may not fit the resources available in LMICs. Likewise, obtaining these devices are costly and require supply chain infrastructure. Once these technologies have reached the LMIC, there are many issues with sustainability and maintenance of the devices. Ideally, devices would be created for the needs and resources of LMICs, but there are many obstacles to innovation that are imposed by institutions in both HICs and LMICs. Fortunately, there is a growing interest for development of this space, and there are many examples of current technologies that are paving the way for future innovations. Innovations in simulation-based training with incorporated learner self-assessment are needed to fast-track skills acquisition for both specialist trainees and non-specialist children's surgery providers, to scale up access for the larger population of children. Pediatric laparoscopy and imaging are some of the innovations that could make a major impact in children's surgery worldwide.

A Ventriculoperitoneal Shunt With Anal Protrusion Causing Meningitis in A Child.

The ventriculoperitoneal (VP) shunt has been one of the primary methods for treating hydrocephalus for many years and is one of the most frequent surgical interventions performed in neurosurgery using a variety of techniques and different VP shunt types. Consequently, shunt insertion is associated with many complications, including insertion failure, functional failure, and mechanical failure such as shunt migration. Shunt migration to the gastrointestinal or urogenital tract is a rare and one of the most distressing complications, which can lead to ascending infection and even meningitis. We report a rare case of a 24-month-old male with a VP shunt tube that migrated and protruded from the anus, subsequently causing meningitis.

Implications of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Hospitalised Patients with Co-Infections and Clinical Outcomes.

The clinical severity of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may rise because of acquiring a co-infection during the hospital stay of the patients. The rate of hospital co-infection alongside COVID-19 infection remains low. However, the mortality rates and intensive care unit (ICU) admission remains ambiguous. The present study investigates the implications of COVID-19 hospitalised infected patients with co-infection and the clinical outcomes. In this study, 142 patients were included. The eligible patients who tested positive for COVID-19 infection were hospitalised for more than two days. Each patient's characteristics and laboratory results were collected, such as who was admitted to the intensive care unit and who was discharged or expired. The results revealed that out of the 142 hospitalised patients, 25 (17.6%) were co-infection positive, and 12 identified types of co-infection: two Gram-positive bacterial infections, one fungal infection and nine Gram-negative bacterial infections. In addition, 33 (23.2%) were ICU admitted, 21 were co-infection negative and 12 were co-infection positive. Among the 12 ICU admitted with co-infection, 33.4% were discharged. The death rate and ICU admission had a p-value < 0.05, indicating statistical significance for co-infected patients compared to non-co-infected patients. It was concluded that co-infection remains very low within hospitalised COVID-19-infected patients but can have severe outcomes with increased ICU admission and increased mortality rates. Thus, implementing infection preventive measures to minimize the spread of hospital-acquired infections among COVID-19 hospitalised patients.

A balanced communication-avoiding support vector machine decision tree method for smart intrusion detection systems.

The Internet of Things field has created many challenges for network architectures. Ensuring cyberspace security is the primary goal of intrusion detection systems (IDSs). Due to the increases in the number and types of attacks, researchers have sought to improve intrusion detection systems by efficiently protecting the data and devices connected in cyberspace. IDS performance is essentially tied to the amount of data, data dimensionality, and security features. This paper proposes a novel IDS model to improve computational complexity by providing accurate detection in less processing time than other related works. The Gini index method is used to compute the impurity of the security features and refine the selection process. A balanced communication-avoiding support vector machine decision tree method is performed to enhance intrusion detection accuracy. The evaluation is conducted using the UNSW-NB 15 dataset, which is a real dataset and is available publicly. The proposed model achieves high attack detection performance, with an accuracy of approximately 98.5%.

Comparison of a modified pediatric protocol versus a hyper-CVAD protocol in adolescents and young adults with Philadelphia-negative acute lymphoblastic leukemia: A multicenter retrospective analysis.

BACKGROUND: The outcomes of Pediatric acute lymphoblastic leukemia (ALL) have improved dramatically whereas outcomes for ALL amongst adolescents and young adults (AYA) have lagged behind. The introduction of pediatric-like regimens to manage adult ALL has shown promising outcomes across several analyses. MATERIALS AND METHODS: In this analysis, we aimed to retrospectively compare the differences in outcomes among patients aged 14-40 years with Philadelphia-negative ALL treated with a Hyper-CVAD protocol versus a modified pediatric protocol. RESULTS: A total of 103 patients were identified with 58 (56.3%) in the modified ABFM group and 45 (43.7%) in the hyper-CVAD group. The median duration of follow-up for the cohort was 39 months (range 1-93). There were significantly lower rates of MRD persistence after consolidation (10.3% vs. 26.7%, P = 0.031) and transplantation (15.5% vs. 46.6%, P < 0.001) in the modified ABFM group. 5-year OS rates (83.9% vs. 65.3%, P = 0.036) and DFS rates (67.4% vs. 44%, P = 0.014) were higher in the modified ABFM groups. The incidence of grade 3 and 4 hepatotoxicity (24.1% vs. 13.3%, P < 0.001) and osteonecrosis (20.6% vs. 2.2%, P = 0.005) were higher in the modified ABFM group. CONCLUSION: Our analysis demonstrates that the use of a pediatric modified ABFM protocol demonstrated superior outcomes compared to the hyper-CVAD regimen in the treatment of Philadelphia-negative ALL amongst AYA patients. However, the modified ABFM protocol was associated with an increased risk of certain toxicities including high grade liver toxicity and osteonecrosis.

Tiagabine suppresses pentylenetetrazole-induced seizures in mice and improves behavioral and cognitive parameters by modulating BDNF/TrkB expression and neuroinflammatory markers.

Tiagabine (Tia), a new-generation antiseizure drug that mimics the GABAergic signaling by inhibiting GABA transporter type-1, is the least studied molecule in chronic epilepsy models with comorbid neurobehavioral and neuroinflammatory parameters. Therefore, the current study investigated the effects of Tia in a real-time manner on electroencephalographic (EEG) activity, behavioral manifestations and mRNA expression in pentylenetetrazole (PTZ)-kindled mice. Male BALB/c mice were treated with tiagabine (0.5, 1 and 2 mg/kg) for 21 days with simultaneous PTZ (40 mg/kg) injection every other day for a total of 11 injections and monitored for seizure progression with synchronized validation through EEG recordings from cortical electrodes. The post-kindling protection from anxiety and memory deficit was verified by a battery of behavioral experiments. Isolated brains were evaluated for oxidative alterations and real-time changes in mRNA expression for BDNF/TrkB, GAT-1 and GAT-3 as well as neuroinflammatory markers. Experimental results revealed that Tia at the dose of 2 mg/kg maximally inhibited the development of full bloom seizure and reduced epileptic spike discharges from the cortex. Furthermore, Tia dose-dependently exerted the anxiolytic effects and protected from PTZ-evoked cognitive impairment. Tia reduced lipid peroxidation and increased superoxide dismutase and glutathione levels in the brain via augmentation of GABAergic modulation. PTZ-induced upregulated BDNF/TrkB signaling and pro-inflammatory cytokines were mitigated by Tia with upregulation of GAT-1 and GAT-3 transporters in whole brains. In conclusion, the observed effects of Tia might have resulted from reduced oxidative stress, BDNF/TrkB modulation and mitigated neuroinflammatory markers expression leading to reduced epileptogenesis and improved epilepsy-related neuropsychiatric effects.

Examining need and capacity for the development of a pediatric liver transplantation program in Kenya.

BACKGROUND: In Africa, pediatric liver transplantation (PLT) is currently only performed in Egypt and South Africa, leaving those who require treatment in Kenya to travel abroad. The aim of this study was to determine whether sufficient capacity and need exists in Kenya to establish a safe and sustainable PLT program. METHODS: A descriptive analysis of the intensive care unit (ICU) beds, surgical workforce, current hepatobiliary volume, and estimated prevalence of pediatric liver disease (PLD) was conducted across 17 hospitals in Kenya between July and September 2020. Data were collected from medical superintendents, directors of surgical departments, or nominated proxies at Kenyan Level 5 and 6 hospitals via a web-based survey. RESULTS: A total of 165 ICU beds were reported at 17 facilities, with 15 facilities reporting five or more beds. About 39% of general surgeons at responding hospitals performed hepatobiliary procedures, and 30% performed pediatric surgeries. Only 10% of surgeons had pediatric training. Over half (57%) of hospitals performed hepatobiliary procedures; at the maximum, 1-5 cases were performed per week including cholecystectomy to Kasai portoenterostomy and hepatectomy. Across 13 hospitals, there were an estimated 192-570 cases of PLD seen per month. The most common PLDs were hepatitis B, neonatal hepatitis, cirrhosis, and acute hepatic failure. Overall, two hospitals possessed the minimum workforce and resources to attempt PLT. CONCLUSIONS: In Kenya, ICU bed availability, pediatric surgical training, and hepatobiliary volume are limited. However, the high prevalence of PLD demonstrated a significant need for PLT across all Kenyan hospitals.

Antibiotic Exposure Concurrently with Anti-PD1 Blockade Therapy Reduces Overall Survival in Patients with Child-Pugh Class A Advanced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide with a poor prognosis. Treatment with immune checkpoint inhibitors (ICIs) has improved overall survival in patients with HCC. However, not all patients benefit from the treatment. In this study, 59 patients with HCC were enrolled from two medical centers in Saudi Arabia, with 34% using antibiotics concurrently with their Nivolumab (anti-PD1 blockade). The impact of antibiotic use on the clinical outcomes of patients with HCC undergoing treatment with anti-PD1 blockade was examined. The patients' overall survival (OS) was 5 months (95% CI: 3.2, 6.7) compared to 10 months (95% CI: 0, 22.2) (p = 0.08). Notably, patients with Child-Pugh A cirrhosis receiving anti-PD1 blockade treatment without concurrent antibiotic use showed a significantly longer median OS reaching 22 months (95% CI: 6.5, 37.4) compared to those who were given antibiotics with a median OS of 6 months (95% CI: 2.7, 9.2) (p = 0.02). This difference in overall survival was particularly found in Child-Pugh class A patients receiving anti-PD1 blockade. These findings suggest that antibiotic use may negatively affect survival outcomes in HCC patients undergoing anti-PD1 blockade, potentially due to antibiotic-induced alterations to the gut microbiome impacting the anti-PD1 blockade response. This study suggests the need for careful consideration when prescribing antibiotics to patients with HCC receiving anti-PD1 blockade.

Trends in methicillin-resistant Staphylococcus aureus in the Gulf Cooperation Council countries: antibiotic resistance, virulence factors and emerging strains.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a ubiquitous pathogen that is increasing in Gulf Cooperation Council (GCC) countries. It is implicated in a wide range of infections, from superficial skin infections to lifethreatening syndromes. MRSA has moved beyond healthcare facilities, affecting individuals in the community without substantial risk factors. Aims: To review the prevalence and molecular characterization of MRSA in GCC countries during 2011-2021. Methods: We comprehensively searched PubMed using the following keywords: MRSA, Staphylococcus aureus, GCC, Kuwait, Saudi Arabia, Bahrain, Oman, Qatar, UAE, prevalence, and molecular characterization for articles published after 2011. Results: Thirty-nine of 111 articles examined, fulfilled the purpose of this review. Most studies were in Kuwait (44%), Saudi Arabia (28%) and United Arab Emirates (10%). Studies from other GCC countries were sporadic. Several studies demonstrated a clear emergence in antibiotic resistance especially against fusidic acid, ciprofloxacin and clindamycin. Regional prevalence of MRSA is reported as 25-35%, with clear dominance of community-acquired (CA)-MRSA. Panton- Valentine leucocidin (PVL)-producing strains accounted for 35-45%, with clear association with CA-MRSA emergence, but there were some sporadic reports of incorporation of PVL in healthcare-associated (HA)-MRSA. The reported dominant strains included EUST80, USA1100 and WA-MRSA-51. Novel strains are more likely to produce PVL and show fusidic acid resistance. Conclusion: There is a need for national and regional MRSA surveillance programmes, especially with the emergence of strains that require no underlying risk factors to cause illness, as well as the propagation of chimeric resistance elements in both HA-MRSA and CA-MRSA.

Implementation of solar powered oxygen delivery in a conflict zone: preliminary findings from Somalia on feasibility and usefulness.

Access to therapeutic oxygen in low-resource settings remains a significant global problem. Solar powered oxygen (SPO2) delivery is a reliable and cost-effective solution. We followed implementation research methodology to gather data on engineering parameters (remote monitoring), nurse training (before and after knowledge questionnaire), patients treated with SPO2 (descriptive case series), and qualitative user feedback (focus group discussions). In January 2021, SPO2 was installed at Hanano General Hospital in Dusamareb, Galmudug State, Somalia, in a conflict-affected region. Daily photovoltaic cell output (median 8.0 kWh, interquartile range (IQR) 2.6-14) exceeded the electrical load from up to three oxygen concentrators (median 5.0 kWh, IQR 0.90-12). Over the first six months after implementation, 114 patients (age 1 day to 89 years, 54% female) were treated for hypoxaemic illnesses, including COVID-19, pneumonia, neonatal asphyxia, asthma, and trauma. Qualitative end user feedback highlighted SPO2 acceptability. Violent conflict was identified as a contextual factor affecting local oxygen needs. We provide the preliminary findings of this implementation research study and describe the feasibility, fidelity, rapid adoption, usefulness, and acceptability of SPO2 in a low-resource setting characterized by violent conflict during the COVID-19 pandemic. Our findings demonstrated the lifesaving feasibility of SPO2 in volatile settings.

Outcomes and predictors of early emergency department discharge among children with acute gastroenteritis and moderate dehydration.

Background: Gastroenteritis is one of the most common diseases that affects children and remains a leading cause of morbidity and mortality around the world. There is conflicting evidence regarding the effect of rapid intravenous fluid regimen on the clinical outcome of patients with acute gastroenteritis. This study aimed to assess the current practice of intravenous hydration on the clinical outcomes of pediatric patients with acute gastroenteritis and determine the predictive factors for early discharge and emergency department (ED) revisit. Methods: A cohort study was carried out among children aged from 1 month to 14 years who presented to the ED in a tertiary care hospital between September 2015 and September 2017. Children diagnosed with acute gastroenteritis and moderate dehydration who require intravenous hydration were included in the study. The patients were followed up until discharge from ED, admission to the hospital or revisit to the ED. Collected variables were demographics, presenting symptoms, biochemical marker, amount of intravenous fluid (IVF) received and prescription of anti-emetics. Descriptive statistics were summarized as mean, standard deviation for continuous variables and proportions for categorical variables. Logistic regression was used to identify risk factors. Results: Out of 284 patients, 148 (52%) were males, 20 (7%) were infants, 80 (28%) were toddlers, 90 (32%) were in preschool, 88 (31%) were in school and 6 (2.1%) were adolescents. No significant difference was observed in the admission rate, discharge within 12 h or less and ED revisits for those who received IVF ≥40 ml/kg as compared to those who received <40 ml/kg. Patients with bicarbonate level closer to normal are more likely to be discharged after 4 h (odds ratio (OR) 1.2 and 95% CI 1.12-1.43). Patients presenting only with vomiting/diarrhoea were less likely to revisit ED (OR 0.33 (95% CI 0.143 - 0.776), while patients with an increase in CO2 level (OR 1.19 and 95% CI 1.0 -1.436) and anion gap (OR 1.29 and 95% CI 1.08-1.54) were more likely to revisit within 1 week post discharge. Conclusion: This study did not show any additional benefits of receiving IVF ≥ 40 ml/kg over 4 h neither in early discharge nor in reducing the ED revisit. CO2 closer to normal was a significant predictor for early discharge in 4 h where the closer level of CO2 and AGAP were associated with an increase in the chance of a revisit to the ED within 1 week after discharge.

Treatment and outcomes of patients with light chain amyloidosis who received a second line of therapy post autologous stem cell transplantation.

We retrospectively reviewed 292 patients who received a second line of therapy post ASCT for their light chain amyloidosis. Most patients (40%) were treated with an alkylator + PI ± dex or PI ± dex followed by an alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex (26%), an alkylator ± steroid or steroid monotherapy (19%), a 2nd-gen IMiD + PI ± dex (6%), an alkylator + thalidomide ± dex (5%), or daratumumab-based therapy (4%). The rate of CR or VGPR was 70% among the daratumumab-based group, 62% in the alkylator + PI ± dex or PI ± dex group, 55% in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 47% in the 2nd-gen IMiD + PI ± dex group, 24% in the alkylator ± steroid or steroid monotherapy group, and 18% in the alkylator + thalidomide ± dex group. The median OS was NR for the 2nd-gen IMiD + PI ± dex group and the daratumumab group, 130.4 months in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 100 months for the alkylator + PI ± dex or PI ± dex group, 36 months for the alkylator ± steroid or steroid monotherapy group, and 21 months for the alkylator + thalidomide ± dex group (P < 0.0001). The median OS was 100 months in patients who received melphalan 200 mg/m2 compared to 41 months in the 140 mg/m2 group (P < 0.0001). In conclusion, patients receiving novel therapy post ASCT and melphalan conditioning dosing at 200 mg/m2 at diagnosis had better outcomes.

Effect of COVID-19 on pediatric appendicitis presentations and complications.

PURPOSE: Appendicitis is the most common surgical emergency in children. This study aims to examine how the COVID-19 pandemic affected pediatric patients with acute appendicitis with regards to presentation and complications. METHODS: After obtaining ethics approval, we performed a chart review of pediatric patients admitted with a diagnosis of appendicitis from March 1, 2019 to June 30, 2019 and March 1, 2020 to June 30, 2020. Data collection included a post-operative period of 30 days. The primary outcome of interest was complication rates post-appendectomy. Secondary outcomes included time to presentation, symptoms, time to surgery, and rate of perforation. RESULTS: Overall, 205 patients were included with 115 in the pre-pandemic group and 90 in the pandemic group. There was no significant difference in complication rates (16% pre-pandemic vs. 13.3% pandemic). In the pandemic group, time from symptom onset to presentation was significantly longer (1.87 days vs. 2.42 days, p = 0.01), more patients presented with emesis (70% vs. 55%, p<0.05), more patients had perforated appendicitis (47% vs. 32%, p<0.05), more patients were likely to be tachycardic (46% vs. 32%, p = 0.05)  and waited less time for surgery (5.75 h vs. 4.15 h, p = 0.05) which both approached significance. CONCLUSION: Significant delays in pediatric appendicitis presentation, and higher rates of tachycardia and perforation were seen during the pandemic. This did not result in increased complication rates but could suggest pandemic patients were more ill than their pre-pandemic counterparts.

What makes global healthcare partnerships successful? A systematic review.

Academic communities are increasingly involved in efforts to address the overwhelming burden of disease in low-middle income countries. There is, however, little research dedicated to understanding the best approach to creating a successful and sustainable global healthcare project. Our objective was to review the shared characteristics of successful healthcare partnerships between high- and low-middle income countries. Two independent reviewers conducted a systematic review. Articles, describing collaborative, healthcare partnerships between a high- and low-middle income countries between 1910 and September 2018, were included. Twenty-six articles were included. The majority of collaborations were initiated by either the host institution or as a joint decision between institutions. The primary goal of these collaborations revolved around medical education/training and curriculum development. Two partnerships, after more than a decade of collaboration, had achieved a self-sustaining programme. Lack of funding was identified as a major barrier to sustainability. Successful global healthcare partnerships require true collaboration and equal participation of all partners. Funding should be secured prior to programme development in anticipation of a minimum 10-year project. A minimum list of guidelines has been proposed to improve the chances of both a successful and sustainable collaboration.