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.

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.

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.

Venetoclax for the treatment of multiple myeloma: Outcomes outside of clinical trials.

Multiple myeloma (MM) remains an incurable disease despite incorporation of novel agents. Venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor is approved for some hematologic malignancies but not yet for MM, although clinical trials have shown efficacy in patients with MM, particularly those harboring t(11;14). We reviewed the medical records of relapsed and/or refractory MM patients to study the efficacy and safety of venetoclax used outside of clinical trials at Mayo Clinic between December, 2016 and March, 2019. The data cut-off date was August 06, 2020. We identified 56 patients of whom 42 (75%) harbored t(11;14). The median number of prior therapies was six (range 1-15) and 14% of patients had received ≥10 prior lines of therapy. Fifty-three (95%) patients were refractory to an immunomodulatory drug and proteasome inhibitor. Venetoclax was used as monotherapy or doublet, in combination with dexamethasone in 55% (n = 31) and a triplet or quadruplet in 45% of patients. No patient experienced tumor lysis syndrome. Overall response rate in 52 evaluable patients was 44%. The median time to best response was 2 months and median duration of response was 13.6 months. The median PFS for the entire cohort was 5.8 (95% CI 4.9-10.3) months and median OS was 28.4 (95% CI 14.6-not reached) months. The presence of t(11;14) was associated with improved PFS (median 9.7 months vs. 4.2 months, p = 0.019) and OS (median not reached vs. 10.8 9 months, p = 0.015). Venetoclax demonstrates encouraging activity in heavily-treated patients with relapsed/refractory MM, particularly the t(11;14) patient-population.

Trauma Training Courses and Programs in Low- and Lower Middle-Income Countries: A Scoping Review.

BACKGROUND: Injury is the leading cause of morbidity and mortality in low- and lower middle-income countries (LMICs). Trauma training is a cost-effective way to improve injury outcomes. Several trauma programs have been implemented in LMICs; however, their scope and effectiveness remain unclear. In this review, we sought to describe and assess the current state of trauma training in LMICs. METHODS: We searched MEDLINE, Embase, Global Health, Cochrane Library, and ProQuest Dissertations & Theses Global for trauma training courses in LMICs. An additional gray literature search was conducted on university, governmental, and non- governmental organizations' websites to identify trauma-related postgraduate medical education (PGME) opportunities. RESULTS: Most studies occurred in sub-Saharan Africa and participants were primarily physicians/surgeons, medical students/residents, and nurses. General and surgical trauma management courses were most common, followed by orthopedic trauma or plastic surgery trauma/burn care courses. 32/45 studies reported on participant knowledge and skills, 27 of which had minimal follow-up. Of the four studies commenting on cost of courses, only one demonstrated cost-effectiveness. Three articles evaluated post-course effects on patient outcomes, two of which failed to demonstrate significant improvements. Overall, 43.0% of LMICs have PGME programs with defined trauma competency requirements. CONCLUSIONS: Current studies on trauma training in LMICs do not clearly demonstrate sustainability, cost-effectiveness, nor improved outcomes. Trauma training programs should be in response to a need, championed locally, and work within a cohesive system to demonstrate concrete benefits. We recommend standardized and contextualized trauma training with recertifications in LMICs for lasting and improved trauma care.

Prognostic Role of Beta-2 Microglobulin in Patients with Light Chain Amyloidosis Treated with Autologous Stem Cell Transplantation.

The prognostic impact of increased beta-2 microglobulin (B2M) in patients with light chain (AL) amyloidosis undergoing autologous stem cell transplantation (ASCT) is unknown. The Mayo 2012 stage and increased bone marrow plasma cell (BMPC) percentage are known predictors for survival. Increased B2M is predictive of survival in patients with multiple myeloma. We evaluated the prognostic role of B2M in patients with newly diagnosed AL undergoing ASCT. We retrospectively reviewed patients with a diagnosis of AL amyloidosis who were treated with ASCT between July 1996 and September 2017. Patients with a creatinine level >1.2 mg/dL were excluded, because that affects B2M levels. The receiver operator characteristic curve was used to determine the best cutoff for B2M before ASCT in predicting survival, which was 2.5 µg/mL, which was also the upper limit of normal in our laboratory. Baseline characteristics were compared between patients with B2M >2.5 µg/mL and ≤2.5 µg/mL. Progression-free survival (PFS) was defined as the time from ASCT to relapse or death, whichever occurred first. Overall survival (OS) was calculated from the time of ASCT to death of any cause. Univariate and multivariate analyses were done for OS. Five hundred and ten patients were identified, 222 of whom (44%) had a B2M >2.5 µg/mL. These patients were more likely to be older (median age, 61 versus 57 years; P = .0002), to have Mayo 2012 stage III/IV disease (33% versus 8%; P < .0001), to have more than 2 organs involved (25% versus 14%; P = .001), and to have ≥10% BMPCs (56% versus 40%; P = .0002) compared with patients with B2M ≤2.5 µg/mL. The median PFS and OS were shorter in patients with B2M >2.5 µg/mL (median PFS, 64 months versus 80 months [P = .03]; median OS, 104.9 months versus 175.5 months [P < .0001]). On univariate analysis, predictors for OS included age >60 years (hazard ratio [HR], 1.61; P = .001), Mayo 2012 stage III/IV (HR, 3.36; P < .0001), more than 2 organs involved (HR, 1.36; P = .07), ≥10% BMPCs (HR, 1.5; P = .005), melphalan conditioning with 200 mg/m2 (HR, .29; P < .0001), B2M >2.5 µg/mL (HR, 1.82; P < .0001), and transplantation during or after 2010 (HR, .4; P = .0006). On multivariate analysis, only Mayo 2012 stage III/IV (HR, 1.89; P = .005), melphalan conditioning with 200 mg/m2 (HR, .39; P < .0001), B2M >2.5 µg/mL (HR, 1.84; P = .003), and transplantation performed during or after 2010 (HR, .58; P = .03) remained independent predictors of OS. Our findings identify B2M >2.5 µg/dL before ASCT as an independent predictor for OS in patients with AL amyloidosis and normal kidney function and should be routinely measured.

Hematopoietic score predicts outcomes in newly diagnosed multiple myeloma patients.

Risk stratification of multiple myeloma (MM) at diagnosis is critical. We examined the ability of hematopoietic indices including mean corpuscular volume (MCV), hemoglobin (Hgb), and platelet (Plt) to predict outcomes. This was a retrospective study of patients treated at Mayo Clinic between January 2004 and April 2018. We incorporated three variables (Hgb < 10 g/dL, Plt < 150 × 109 /L, and MCV > 96 fL), assigning a score of 1 to each. We identified 1540 newly diagnosed MM patients, of whom 707 (46%) had a score of 0, 513 (33%) had a score of 1, 260 (17%) had a score of 2, and 60 (4%) had a score of 3. The score risk stratified patients into four groups with differing survivals. The median PFS was 32.3 months for score 0, 24.8 months for score 1, 21.7 months for score 2, and 18.3 months for score 3, for P < .001. The median OS was 80.7 months for score 0, 59.9 months for score 1, 51.7 months for score 2, and 31.3 months for score 3, P < .0001. Predictors of OS on the multivariable analysis were age ≥ 65 (HR, 1.93; P < .0001), R-ISS stage (1-2 vs 3) (HR, 0.48; P < .0001), and hematopoietic score (0-2 vs 3) (HR, 0.51; P = .006). A hematopoietic score can predict survival in newly diagnosed myeloma patients.

Multiple Myeloma in the Time of COVID-19.

We provide our recommendations (not evidence based) for managing multiple myeloma patients during the pandemic of COVID-19. We do not recommend therapy for smoldering myeloma patients (standard or high risk). Screening for COVID-19 should be done in all patients before therapy. For standard-risk patients, we recommend the following: ixazomib, lenalidomide, and dexamethasone (IRd) (preferred), cyclophosphamide lenalidomide and dexamethasone (CRd), daratumumab lenalidomide and dexamethasone (DRd), lenalidomide, bortezomib, and dexamethasone (RVd), or cyclophosphamide, bortezomib, and dexamethasone (CyBorD). For high-risk patients we recommend carfilzomib, lenalidomide, and dexamethasone (KRd) (preferred) or RVd. Decreasing the dose of dexamethasone to 20 mg and giving bortezomib subcutaneously once a week is recommended. We recommend delaying autologous stem cell transplant (ASCT), unless the patient has high-risk disease that is not responding well, or if the patient has plasma cell leukemia (PCL). Testing for COVID-19 should be done before ASCT. If a patient achieves a very good partial response or better, doses and frequency of drug administration can be modified. After 10-12 cycles, lenalidomide maintenance is recommended for standard-risk patients and bortezomib or ixazomib are recommended for high-risk patients. Daratumumab-based regimens are recommended for relapsed patients. Routine ASCT is not recommended for relapse during the epidemic unless the patient has an aggressive relapse or secondary PCL. Patients on current maintenance should continue their therapy.

Non-pharmacological Interventions for Intractable Epilepsy.

In 30% of epileptic individuals, intractable epilepsy represents a problem for the management of seizures and severely affects the patient's quality of life due to pharmacoresistance with commonly used antiseizure drugs (ASDs). Surgery is not the best option for all resistant patients due to its post-surgical consequences. Therefore, several alternative or complementary therapies have scientifically proven significant therapeutic potential for the management of seizures in intractable epilepsy patients with seizure-free occurrences. Various non-pharmacological interventions include metabolic therapy, brain stimulation therapy, and complementary therapy. Metabolic therapy works out by altering the energy metabolites and include the ketogenic diets (KD) (that is restricted in carbohydrates and mimics the metabolic state of the body as produced during fasting and exerts its antiepileptic effect) and anaplerotic diet (which revives the level of TCA cycle intermediates and this is responsible for its effect). Neuromodulation therapy includes vagus nerve stimulation (VNS), responsive neurostimulation therapy (RNS) and transcranial magnetic stimulation therapy (TMS). Complementary therapies such as biofeedback and music therapy have demonstrated promising results in pharmacoresistant epilepsies. The current emphasis of the review article is to explore the different integrated mechanisms of various treatments for adequate seizure control, and their limitations, and supportive pieces of evidence that show the efficacy and tolerability of these non-pharmacological options.

Outcomes of Patients with Light Chain Amyloidosis Who Had Autologous Stem Cell Transplantation with 3 or More Organs Involved.

Prior reports have suggested that 3 or more organs involved is a contraindication for autologous stem cell transplant (ASCT) in amyloid light chain (AL) amyloidosis. Therefore, most centers limit transplantation to patients who have no more than 2 organs significantly involved. We retrospectively reviewed all patients with AL amyloidosis with ≥3 involved organs and who had ASCT between 1996 and 2015 at Mayo Clinic, Rochester, Minnesota to assess transplant safety and outcomes. Seventy-five patients with ≥3 organs involved underwent ASCT. Median age at diagnosis was 54 years, and 67% were men. The heart was involved in 95%, followed by the kidneys (84%). Thirty-eight patients (51%) had no induction treatment before ASCT. Full-dose melphalan (200 mg/m2) was given in 45%, and the remainder received 140 mg/m2. Overall hematologic response rate was 75%. The median progression-free survival (PFS) and overall survival (OS) were 16 and 68 months, respectively. The 100-day mortality was 16%, and 44 patients (59%) died during follow-up. The most common causes of death were cardiovascular events (32%) and progressive amyloidosis (25%). On multivariable analysis, predictors for PFS were Mayo 2012 stage III/IV (relative risk [RR], 3.3; P = .0012) and hematologic response (at least very good partial response; RR, .4; P = .012). An N-terminal pro-brain natriuretic peptide (NT-proBNP) level of ≥2000 pg/mL was an independent predictor for shorter PFS (RR, 2.6; P = .013). Predictors for OS included any hematologic response (RR, .12; P = .0015), melphalan 200 mg/m2 (RR, .2; P = .014), and Mayo 2012 stage III/IV (RR, 7.7; P = .0002). An NT-proBNP level ≥ 2000 pg/mL was a powerful predictor of OS (RR, 4; P = .013). The number of organs involved (3 versus >3) did not significantly impact PFS or OS. We conclude that the high prevalence and severity of cardiac involvement are the main drivers for the poor outcome in patients who have ≥3 organs involved. Using selection criteria defined for safe transplantation in cardiac amyloidosis should result in low therapy-related mortality independent of the number of organs involved. The severity of cardiac involvement should be the major criterion for transplanting patients with AL amyloidosis that have ≥3 organs involved and not merely the number of organs involved.

Impact of consolidation therapy post autologous stem cell transplant in patients with light chain amyloidosis.

The role of consolidation post autologous stem cell transplant in light chain amyloidosis is not well defined. We retrospectively identified patients who had light chain amyloidosis and underwent autologous stem cell transplant at the Mayo Clinic. Consolidation was defined as any treatment given after the day 100 evaluation post-transplant to maintain or deepen the response. We identified 471 patients, of whom 72 (15%) received consolidation. Patients receiving consolidation had more advanced disease (Mayo 2012 stage ≥II in 67% vs 52%, P = .02), and had lower day 100 response rates (very good partial response or better: 35% vs 84%, P < .001). After consolidation, rates of very good partial response improved from 24% to 28%, and rates of complete response improved from 11% to 40%. Patients with less than very good partial response who received consolidation, had better progression-free survival (median of 22.4 vs 8.8 months, P < .001), and the benefit was greater in those who deepened their response (median of 41 vs 8.8 months, P < .001). In patients with less than very good partial response, there was a trend for better overall survival in patients who responded to consolidation (median of 125.8 vs 74.4 months, P = .07). In patients who achieved very good partial response, or better, at day 100 post autologous stem cell transplant, consolidation did not improve progression-free or overall survival. Consolidation after autologous stem cell transplant for light chain amyloidosis improves progression-free survival for patients who achieve less than very good partial response.

Knowledge and attitude towards antibiotic use within consumers in Alkharj, Saudi Arabia.

BACKGROUND: The World Health Organization (WHO) has made the problem of solving antibiotic resistance one of its priorities. The present study was designed to determine knowledge and attitude towards antibiotic use in Alkharj, Saudi Arabia. MATERIALS AND METHODS: A cross-sectional survey was conducted in Alkharj, Saudi Arabia in the period of July 2017 to October 2017. A self-administered questionnaire included question on demographic characteristics, antibiotic usage, knowledge and attitude towards antibiotics use. The data were analyzed using Statistical Package For the Social Science (SPSS). RESULTS: A total of 405 questionnaires were randomly distributed to the general public in Al-Kharj, Saudi Arabia. However, only 387 of the participants completed the questionnaire making the response rate 95.5%. The majority of the participants (64.3%) know antibiotics effective against bacterial infections while (46.8%) of participants believed that antibiotics can be used to treat viral infections. A significant positive correlation was noted between the respondents' antibiotic knowledge score and their attitude score (r = 0.523, p = 0.000). Significantly higher mean knowledge score of antibiotics was observed among study participants who were married, employed, participants working in health sector, high educational and high monthly income groups. Mean attitude score was found to be significantly high for females, participants working in health sector, high educational and high monthly income groups. CONCLUSION: The participants who have good knowledge towards antibiotics use showed positive attitude towards antibiotics use. Some specific groups should to be targeted for educational intervention in terms of appropriate antibiotic use, such as those who have received a low level of education and are in receipt of a low monthly income.

Selective removal of dibenzothiophene from commercial diesel using manganese dioxide-modified activated carbon: a kinetic study.

With a total concentration of 7055 mgS/kgfuel, the content of organosulphur compounds (OSCs) in local diesel is 20 times higher than the regulated value. Analysis revealed that 30% of OSC is originated from dibenzothiophene (DBT). It is known that DBT is a hardly removable compound and selective adsorbents are often needed for its removal with low affinity for other diesel components. In this work, a selective adsorbent based on surface modification of activated carbon (AC) by MnO2 is prepared for DBT removal from diesel. The porous nature of AC enabled carrying large amounts of MnO2 particles to end up with a selective adsorber for DBT. The best performance was observed at a surface loading of 26.8% of Mn and DBT is favourably removed over mono- and diaromatics hydrocarbons in diesel. Adsorption kinetics of DBT is studied under a high initial concentration of 835-11,890 mg/kg and at a ratio of 11 cm3/g (diesel:carbon). The results indicated a fast removal process after surface modification where 96% of the surface is occupied within 30 min of interaction. Kinetic data were best presented by reaction-based models with low prediction error sum of squares values 0.5-47.0, while, diffusion-based models showed limited application for modelling DBT adsorption. Accordingly, adsorption process is controlled by surface reactions and pore diffusion has a minor role in the overall process. The modified adsorbent is satisfactorily regenerated using n-hexane at 65°C.

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%.

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.