Severe Methotrexate Toxicity Following a Capizzi Cycle in an Obese Adolescent With Acute Lymphoblastic Leukemia and Hepatic Steatosis.

Methotrexate is a major component of pediatric leukemia treatment. While toxicities are common after high-dose methotrexate, escalating dose methotrexate (Capizzi methotrexate) is typically well-tolerated. We report an adolescent Hispanic female with pre-B acute lymphoblastic leukemia, preexisting obesity and hepatic steatosis who developed severe multiorgan failure following an escalating dose of methotrexate with delayed methotrexate excretion of 11 days. We identified one similar report in an obese adult; however, this case is the first to our knowledge involving a pediatric patient. With the rising incidence of obesity and associated comorbidities among children and adolescents with leukemia, attention to potential risks for this population is warranted.

Access to Methotrexate Monitoring in Latin America: A Multicountry Survey of Supportive Care Capacity.

High-dose methotrexate (HDMTX) is used to treat a broad spectrum of cancers. Methotrexate (MTX) monitoring and adequate supportive care are critical for safe drug administration; however, MTX level timing is not always possible in low- and middle-income countries. The aim of this study was to evaluate HDMTX supportive care capacity and MTX monitoring practices in Latin America (LATAM) to identify gaps and opportunities for improvement. A multicenter survey was conducted among LATAM pediatric oncologists. Twenty healthcare providers from 20 institutions answered the online questionnaire. HDMTX was used to treat acute lymphoblastic leukemia (ALL; 100%), non-Hodgkin lymphoma (84.2%), diffuse large B-cell lymphoma (47.4%), osteosarcoma (78.9%), and medulloblastoma (31.6%). Delays in starting HDMTX infusion were related to bed shortages (47.4%) and MTX shortages (21.1%). MTX monitoring was performed at an in-hospital laboratory in 52%, at an external/nearby laboratory in 31.6%, and was not available in 10.5%. Median interval between sampling and obtaining MTX levels was ≤ 2 h in 45% and ≥ 6 h in 30%, related to laboratory location. Sites without access to MTX monitoring reduced the MTX dose for patients with high-risk ALL or did not include MTX in the treatment of patients with osteosarcoma. Respondents reported that implementation of point-of-care testing of MTX levels is feasible. In LATAM, highly variable supportive care capacity may affect the safe administration of MTX doses. Improving accessibility of MTX monitoring and the speed of obtaining results should be prioritized to allow delivery of full doses of MTX required by the current protocols.

Early clinical indicators of acute kidney injury caused by administering high-dose methotrexate therapy to juvenile pigs.

Introduction: Early identification of compromised renal clearance caused by high-dose methotrexate (HDMTX) is essential for initiating timely interventions that can reduce acute kidney injury and MTX-induced systemic toxicity. Methods: We induced acute kidney injury (AKI) by infusing 42 juvenile pigs with 4 g/kg (80 g/m2) of MTX over 4 hours without high-volume alkalinizing hydration therapy. Concentrations of serum creatinine and MTX were measured at 15 time points up to 148 hours, with 10 samples collected during the first 24 hours after the start of the HDMTX infusion. Results: During the first 28 hours, 81% of the pigs had increases in the concentrations of serum creatinine in one or more samples indicative of AKI (i.e., > 0.3g/dL increase). A rate of plasma MTX clearance of less than 90% during the initial 4 hours after the HDMTX infusion and a total serum creatinine increase at 6 and 8 hours after starting the infusion greater than 0.3 g/dL were predictive of AKI at 28 hours (p < 0.05 and p < 0.001, respectively). At conclusion of the infusion, pigs with a creatinine concentration more than 0.3 g/dL higher than baseline or serum MTX greater than 5,000 µmol/L had an increased risk of severe AKI. Conclusions: Our findings suggest that serum samples collected at conclusion and shortly after HDMTX infusion can be used to predict impending AKI. The pig model can be used to identify biological, environmental, and iatrogenic risk factors for HDMTX-induced AKI and to evaluate interventions to preserve renal functions, minimize acute kidney injury, and reduce systemic toxicity.

Time to establish an international vaccine candidate pool for potential highly infectious respiratory disease: a community's view.

In counteracting highly infectious and disruptive respiratory diseases such as COVID-19, vaccination remains the primary and safest way to prevent disease, reduce the severity of illness, and save lives. Unfortunately, vaccination is often not the first intervention deployed for a new pandemic, as it takes time to develop and test vaccines, and confirmation of safety requires a period of observation after vaccination to detect potential late-onset vaccine-associated adverse events. In the meantime, nonpharmacologic public health interventions such as mask-wearing and social distancing can provide some degree of protection. As climate change, with its environmental impacts on pathogen evolution and international mobility continue to rise, highly infectious respiratory diseases will likely emerge more frequently and their impact is expected to be substantial. How quickly a safe and efficacious vaccine can be deployed against rising infectious respiratory diseases may be the most important challenge that humanity will face in the near future. While some organizations are engaged in addressing the World Health Organization's "blueprint for priority diseases", the lack of worldwide preparedness, and the uncertainty around universal vaccine availability, remain major concerns. We therefore propose the establishment of an international candidate vaccine pool repository for potential respiratory diseases, supported by multiple stakeholders and countries that contribute facilities, technologies, and other medical and financial resources. The types and categories of candidate vaccines can be determined based on information from previous pandemics and epidemics. Each participant country or region can focus on developing one or a few vaccine types or categories, together covering most if not all possible potential infectious diseases. The safety of these vaccines can be tested using animal models. Information for effective candidates that can be potentially applied to humans will then be shared across all participants. When a new pandemic arises, these pre-selected and tested vaccines can be quickly tested in RCTs for human populations.

Expert consensus guidelines for the prophylaxis and management of tumor lysis syndrome in the United States: Results of a modified Delphi panel.

INTRODUCTION: Tumor lysis syndrome (TLS), which occurs spontaneously or in response to anticancer treatment, results in the release of intracellular potassium, phosphorus, and nucleic acids into the bloodstream, which results in secondary clinical complications that may be fatal. Prior TLS guidelines do not take into consideration potent novel oncologic agents or contemporary treatment paradigms with increased risk of TLS. Thus, a modified Delphi panel of experts was convened to provide an update for TLS management guidelines based upon a combination of supporting literature and practice consensus. METHODS: A three-round modified Delphi process was implemented. For round 1, nine expert panelists completed a web-based questionnaire developed using published literature. In round 2, panelists were asked to reconsider their answers to questions that did not reach consensus (defined as ≥ 66% agreement among voting panelists). Round 3 was an unblinded, moderated virtual meeting to discuss any remaining questions that did not reach consensus. RESULTS: Detailed recommendations are given for prophylaxis, monitoring, and management of TLS risks and complications, with hydration being a key element of TLS prophylaxis and management. Guidelines for the management of acute effects of TLS and prevention of long-term renal effects include management of hyperkalemia, hypocalcemia, hyperphosphatemia, and hyperuricemia. DISCUSSION: Although the control of uric acid levels is quite effective with currently available agents, panelists emphasize the importance of monitoring and treating other dangerous electrolyte abnormalities such as hyperkalemia and hyperphosphatemia. Guidelines from this modified Delphi panel should aid clinicians in preventing and managing TLS.

Insights from a pharmacometric analysis of HDMTX in adults with cancer: Clinically relevant covariates for application in precision dosing.

AIMS: High-dose methotrexate (HDMTX) is an essential part of the treatment of several adult and paediatric malignancies. Despite meticulous supportive care during HDMTX administration, severe toxicities, including acute kidney injury (AKI), may occur contributing to patient morbidity. Population pharmacokinetics provide a powerful tool to predict time to clear HDMTX and adjust subsequent doses. We sought to develop and validate pharmacokinetic models for HDMTX in adults with diverse malignancies and to relate systemic exposure with the occurrence of severe toxicity. METHODS: Anonymized, de-identified data were provided from 101 US oncology practices that participate in the Guardian Research Network, a non-profit clinical research consortium. Modelled variables included clinical, laboratory, demographic and pharmacological data. Population pharmacokinetic analysis was performed by means of nonlinear mixed effects modelling using MonolixSuite. RESULTS: A total of 693 HDMTX courses from 243 adults were analysed, of which 62 courses (8.8%) were associated with stage 2/3 acute kidney injury (43 stage 2, 19 stage 3). A three-compartment model adequately fitted the data. Time-dependent serum creatinine, baseline serum albumin and allometrically scaled bodyweight were clinically significant covariates related to methotrexate clearance. External evaluation confirmed a satisfactory predictive performance of the model in adults receiving HDMTX. Dose-normalized methotrexate concentration at 24 and 48 hours correlated with AKI incidence. CONCLUSION: We developed a population pharmacometric model that considers weight, albumin and time-dependent creatinine that can be used to guide supportive care in adult patients with delayed HDMTX elimination.

How should childhood acute lymphoblastic leukemia relapses in low-income and middle-income countries be managed: The AHOPCA-ALL study group experience.

BACKGROUND: Children with relapsed acute lymphoblastic leukemia (ALL) in low-income and middle-income countries rarely survive. The Pediatric Hematology-Oncology Association of Central America (AHOPCA) developed the AHOPCA-ALL REC 2014 protocol to improve outcomes in resource-constrained settings without access to stem cell transplantation. METHODS: The AHOPCA-ALL REC 2014 protocol was based on a modified frontline induction phase 1A, a consolidation therapy with six modified R-blocks derived from the ALL-Berlin-Frankfurt-Munster REZ 2002 protocol and intermittent maintenance therapy. Children with B-lineage ALL were eligible after a late medullary relapse, an early or late combined relapse, or any extramedullary relapses. Those with T-lineage ALL were eligible after early and late extramedullary relapses, as were those with both B-lineage and T-lineage relapses occurring at least 3 months after therapy abandonment. RESULTS: The study population included 190 patients with T-lineage (n = 3) and B-lineage (n = 187) ALL. Of those with B-lineage ALL, 25 patients had a very early extramedullary relapse, 40 had an early relapse (32 extramedullary and 8 combined), and 125 had a late relapse (34 extramedullary, 19 combined, and 72 medullary). The main cause of treatment failure was second relapse (52.1%). The 3-year event-free survival rate (± standard error) was 25.9% ± 3.5%, and the 3-year overall survival rate was 36.7% ± 3.8%. The 3-year event-free survival rate was 47.2% ± 4.7% for late relapses. The most frequently reported toxicity was grade 3 or 4 infection. Mortality during treatment occurred in 17 patients (8.9%), in most cases because of infectious complications. CONCLUSIONS: Selected children with relapsed ALL in Central America can be cured with second-line regimens even without access to consolidation with stem cell transplantation. Children in low-income and middle-income countries who have lower risk relapses of ALL should be treated with curative intent.

Multiple Asparaginase Infusions Cause Increasingly Severe Acute Hyperammonemia.

Adverse reactions during and shortly after infusing asparaginase for the treatment of acute lymphoblastic leukemia can increase in severity with later doses, limiting further use and increasing relapse risk. Although asparaginase is associated with hyperammonemia, the magnitude of the increase in serum ammonia immediately after the infusion and in response to multiple infusions has not been examined. The concurrence of hyperammonemia and infusion reactions was studied using weaned juvenile pigs that received 12 infusions of Erwinia asparaginase (Erwinase; 1250 U/kg) over 28 days, with two 5-day recovery periods without asparaginase after the eighth and eleventh doses. Infusion reactions and prolonged hyperammonemia (>50 µM ammonia 48 h after the infusion) began after the fourth dose and increased with later doses. Dense sampling for 60 min revealed an acute phase of hyperammonemia that peaked within 20 min after starting the first infusion (298 + 62 µM) and lasted less than 1 h, without apparent symptoms. A pronounced acute hyperammonemia after the final infusion (1260 + 250 µM) coincided with severe symptoms and one mortality during the infusion. The previously unrecognized acute phase of hyperammonemia associated with asparaginase infusion coincides with infusion reactions. The juvenile pig is a translational animal model for understanding the causes of acute and chronic hyperammonemia, differentiating from hypersensitivity reactions, and for improving infusion protocols to reduce acute hyperammonemia and to allow the continued use of asparaginase.

Defining Essential Childhood Cancer Medicines to Inform Prioritization and Access: Results From an International, Cross-Sectional Survey.

PURPOSE: Access to essential cancer medicines is a major determinant of childhood cancer outcomes globally. The degree to which pediatric oncologists deem medicines listed on WHO's Model List of Essential Medicines for Children (EMLc) essential is unknown, as is the extent to which such medicines are accessible on the front lines of clinical care. METHODS: An electronic survey developed was distributed through the International Society of Pediatric Oncology mailing list to members from 87 countries. Respondents were asked to select 10 cancer medicines that would provide the greatest benefit to patients in their context; subsequent questions explored medicine availability and cost. Descriptive and bivariate statistics compared access to medicines between low- and lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs). RESULTS: Among 159 respondents from 44 countries, 43 (27%) were from LMICs, 79 (50%) from UMICs, and 37 (23%) from HICs. The top five medicines were methotrexate (75%), vincristine (74%), doxorubicin (74%), cyclophosphamide (69%), and cytarabine (65%). Of the priority medicines identified, 87% (27 of 31) are represented on the 2021 EMLc and 77% (24 of 31) were common to the lists generated by LMIC, UMIC, and HIC respondents. The proportion of respondents indicating universal availability for each of the top medicines ranged from 9% to 46% for LMIC, 25% to 89% for UMIC, and 67% to 100% for HIC. Risk of catastrophic expenditure was more common in LMIC (8%-20%), compared with UMIC (0%-28%) and HIC (0%). CONCLUSION: Most medicines that oncologists deem essential for childhood cancer treatment are currently included on the EMLc. Barriers remain in access to these medicines, characterized by gaps in availability and risks of catastrophic expenditure for families that are most pronounced in low-income settings but evident across all income contexts.

Variations of COVID-19 mortality are affected by economic disparities across countries.

BACKGROUND: When the COVID-19 case number reaches a maximum in a country, its capacity and management of health system face greatest challenge. METHODS: We performed a cross-sectional study on data of turning points for cases and deaths for the first three waves of COVID-19 in countries with more than 5000 cumulative cases, as reported by Worldometers and WHO Coronavirus (COVID-19) Dashboard. We compared the case fatality rates (CFRs) and time lags (in unit of day) between the turning points of cases and deaths among countries in different development stages and potential influence factors. As of May 10, 2021, 106 out of 222 countries or regions (56%) reported more than 5000 cases. Approximately half of them have experienced all the three waves of COVID-19 disease. The average mortality rate at the disease turning point was 0.038 for the first wave, 0.020 for the second wave, and 0.023 for wave 3. In high-income countries, the mortality rates during the first wave are higher than that of the other income levels. However, the mortality rates during the second and third waves of COVID-19 were much lower than those of the first wave, with a significant reduction from 5.7% to 1.7% approximately 70%. At the same time, high-income countries exhibited a 2-fold increase in time lags during the second and the third waves compared to the first wave, suggesting that the periods between the cases and deaths turning point extended. High rates in the first wave in developed countries are associated to multiple factors including transportation, population density, and aging populations. In upper middle- and lower middle-income countries, the decreasing of mortality rates in the second and third waves were subtle or even reversed, with increased mortality during the following waves. In the upper and lower middle-income countries, the time lags were about 50% of the durations observed from high-income countries. INTERPRETATION: Economy and medical resources affect the efficiency of COVID-19 mitigation and the clinical outcomes of the patients. The situation is likely to become even worse in the light of these countries' limited ability to combat COVID-19 and prevent severe outcomes or deaths as the new variant transmission becomes dominant.

Global Neuroblastoma Network: An international multidisciplinary neuroblastoma tumor board for resource-limited countries.

BACKGROUND: Tumor boards are part of standard care of patients with complex cancers, but appropriate multidisciplinary expertise and infrastructure are often not available in low- and middle-income countries (LMIC) for pediatric cancers, such as neuroblastoma. Our goal was to review results of a Global Neuroblastoma Network (GNN) tumor board accessible to LMIC. METHODS: De-identified clinical cases presented via internet conference during a weekly GNN virtual tumor board from 2010 through 2020 were evaluated in a standardized format, including diagnostic imaging, pathology, therapy information, resource limitations, and questions for discussion. Information summarized included the presentations, a survey of the impact on care, and a resource questionnaire. RESULTS: Registered GNN participants included 575 individuals from 77 countries, with a median of 39 participants per session. Total 412 cases were presented from 32 countries, including 351 unique neuroblastoma patients, 52 follow-up cases, and nine non-neuroblastoma diagnoses. Twenty-eight educational sessions were presented. Limited critical resources for diagnostics and staging of cases included MYCN analysis (54.7%), metaiodobenzylguanidine (MIBG) scans (38.7%), and International Neuroblastoma Pathology Classification (49%). Therapies were also limited, with markedly decreased use of radiation and autologous stem cell transplant for high-risk cases, and no availability of anti-GD2 antibody in LMIC. Limited sampling with a post-presentation survey showed that 100% found the GNN helpful, and 70% altered the care plan based on the discussion. CONCLUSION: This report shows the utility of an international tumor board for LMIC focused on a challenging solid tumor where local expertise may be limited, with international multidisciplinary expert participation and educational sessions.

Democracy and case fatality rate of COVID-19 at early stage of pandemic: a multicountry study.

Many studies have evaluated factors that influence the course of the COVID-19 pandemic in different countries. This multicountry study assessed the influence of democracy and other factors on the case fatality rate of COVID-19 during the early stage of the pandemic. We accessed the World Health Organization, World Bank, and the Democracy Index 2019 databases for data from the 148 countries. Multiple analyses were conducted to examine the association between the Democracy Index and case fatality rate of COVID-19. Within 148 countries, the percentage of the population aged 65 years and above (p = 0.0193), and health expenditure as a percentage of GDP (p = 0.0237) were positively associated with countries' case fatality rates. By contrast, hospital beds per capita helped to reduce the case fatality rates. In particular, the Democracy Index was positively associated with case fatality rates in a subgroup of 47 high-income countries. This study suggests that enhancing the health system with increased hospital beds and healthcare workforce per capita should reduce case fatality rate. The findings suggest that a higher Democracy Index is associated with more deaths from COVID-19 at the early stage of the pandemic, possibly due to the decreased ability of the government.

Graphical Trajectory Comparison to Identify Errors in Data of COVID-19: A Cross-Country Analysis.

Data from the early stage of a novel infectious disease outbreak provide vital information in risk assessment, prediction, and precise disease management. Since the first reported case of COVID-19, the pattern of the novel coronavirus transmission in Wuhan has become the interest of researchers in epidemiology and public health. To thoroughly map the mechanism of viral spreading, we used the patterns of data at the early onset of COVID-19 from seven countries to estimate the time lag between peak days of cases and deaths. This study compared these data with those of Wuhan and estimated the natural history of disease across the infected population and the time lag. The findings suggest that comparative analyses of data from different regions and countries reveal the differences between peaks of cases and deaths caused by COVID-19 and the incomplete and underestimated cases in Wuhan. Different countries may show different patterns of cases peak days, deaths peak days, and peak periods. Error in the early COVID-19 statistics in Brazil was identified. This study provides sound evidence for policymakers to understand the local circumstances in diagnosing the health of a population and propose precise and timely public health interventions to control and prevent infectious diseases.

From Anti-PD-1/PD-L1 to CTLA-4 and to MUC1-Is the Better Response to Treatment in Smokers of Cancer Patients Drug Specific?

Whether smokers respond to anti-cancer drugs differently than non-smokers remains controversial. The objective of this study is to explore whether the better response of the smokers is specific to therapy of anti-PD-1/PD-L1, anti-checkpoint inhibitor, individual drugs on the cell surface, or lung cancer. Our results showed that among all non-small cell lung cancer (NSCLC) patients, when the data from anti-PD-1/PD-L1, anti-CTLA-4, and anti-MUC1 drugs are combined, the mean hazard ratios (HR) of smokers and non-smokers were 0.751 and 1.016, respectively. A meta-analysis with a fixed effect (FE) model indicated that the smokers have an HR value of 0.023 lower than that of the non-smokers. A stratified subgroup meta-analysis indicated that when treated with anti-CTLA-4 drugs, smokers had reduced HR values of 0.152 and 0.165 on average and FE model meta-analysis, respectively. When treated with an anti-MUC1 drug, smokers had reduced HR values of 1.563 and 0.645, on average and FE model meta-analysis, respectively. When treated with a combination of nivolumab and ipilimumab drugs, smokers had, on average, reduced HR and FE model meta-analysis values (0.257 and 0.141), respectively. Smoking is a clinical response predictor for anti-PD/PD-L1 monotherapy or first-line treatment in lung, urothelial carcinoma, and head and neck cancer. Smokers treated with other drugs have shown worse responses in comparison to non-smokers. These data suggest that, along with the progress in the development of new drugs for cancer, drugs acting on specific genotypes of smokers likely will arise.

Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators.

INTRODUCTION: Inalignment with the World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC), the International Society of Pediatric Oncology initiated a program to map global pediatric oncology services. As survival rates in Africa are low and data are scant, this continent was mapped first to identify areas with greatest need. METHODS: Beginning November 2018, an electronic survey was sent to all known stakeholders, followed by email communications and internet searches to verify data. Availability of pediatric oncologists, chemotherapy, surgical expertise, and radiotherapy was correlated with geographic region, World Bank income status, Universal Health Coverage, population < 15 and < 24 years, percentage of gross domestic product spent on healthcare, and Human Development Index (HDI). RESULTS: Responses were received from 48/54 African countries. All three treatment modalities were reportedly available in 9/48 countries, whereas seven countries reported no pediatric oncology services. Negative correlations were detected between provision of all three services and geographic region (P = 0.01), younger median population age (P = 0.002), low-income country status (P = 0.045), and lower HDI (P < 0.001). CONCLUSION: This study provides a comprehensive overview of pediatric oncology care in Africa, emphasizing marked disparities between countries: some have highly specialized services, whereas others have no services. A long-term strategy to eliminate disparities in African pediatric cancer care should be aligned with the WHO GICC aims and facilitated by SIOP Africa. MEETING ABSTRACTS: SIOP maps pediatric oncology services in Africa to address inequalities in childhood cancer services. Geel J, Ranasinghe N, Davidson A, Challinor J, Howard S, Wollaert S, Myezo K, Renner L, Hessissen L, Bouffet E. 51st Annual Congress of the International Society of Paediatric Oncology (SIOP), Lyon, France, October 2019. Pediatric Blood and Cancer Vol 66 S219-S219. Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators.

Pediatric cancer care in Africa: SIOP Global Mapping process.

In November 2018, theInternational Society of Paediatric Oncology (SIOP) launched a project to map African facilities providing pediatric oncology treatment. A 55-item digital survey was created in English, piloted in India, translated to French and Portuguese, and distributed by email, social media, or personal contacts. December 2019, 48/54 African countries responded (72% surveys completed and analyzed). Issues included incomplete responses, multiple entries for one facility with conflicting data for key services, and repeated entries with varied answers by the same respondent. The facility mapping project, now on-going program will serve as a global registry of global pediatric cancer centers.

Toward a Country-Based Prediction Model of COVID-19 Infections and Deaths Between Disease Apex and End: Evidence From Countries With Contained Numbers of COVID-19.

The complexity of COVID-19 and variations in control measures and containment efforts in different countries have caused difficulties in the prediction and modeling of the COVID-19 pandemic. We attempted to predict the scale of the latter half of the pandemic based on real data using the ratio between the early and latter halves from countries where the pandemic is largely over. We collected daily pandemic data from China, South Korea, and Switzerland and subtracted the ratio of pandemic days before and after the disease apex day of COVID-19. We obtained the ratio of pandemic data and created multiple regression models for the relationship between before and after the apex day. We then tested our models using data from the first wave of the disease from 14 countries in Europe and the US. We then tested the models using data from these countries from the entire pandemic up to March 30, 2021. Results indicate that the actual number of cases from these countries during the first wave mostly fall in the predicted ranges of liniar regression, excepting Spain and Russia. Similarly, the actual deaths in these countries mostly fall into the range of predicted data. Using the accumulated data up to the day of apex and total accumulated data up to March 30, 2021, the data of case numbers in these countries are falling into the range of predicted data, except for data from Brazil. The actual number of deaths in all the countries are at or below the predicted data. In conclusion, a linear regression model built with real data from countries or regions from early pandemics can predict pandemic scales of the countries where the pandemics occur late. Such a prediction with a high degree of accuracy provides valuable information for governments and the public.

The threat of the COVID-19 pandemic on reversing global life-saving gains in the survival of childhood cancer: a call for collaborative action from SIOP, IPSO, PROS, WCC, CCI, St Jude Global, UICC and WHPCA.

The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis.

Impact of computerised physician order entry (CPOE) on the incidence of chemotherapy-related medication errors: a systematic review.

PURPOSE: Computerised prescriber (or physician) order entry (CPOE) implementation is one of the strategies to reduce medication errors. The extent to which CPOE influences the incidence of chemotherapy-related medication errors (CMEs) was not previously collated and systematically reviewed. Hence, this study was designed to collect, collate, and systematically review studies to evaluate the effect of CPOE on the incidence of CMEs. METHODS: A search was performed of four databases from 1 January 1995 until 1 August 2019. English-language studies evaluating the effect of CPOE on CMEs were selected as per inclusion and exclusion criteria. The total CMEs normalised to total prescriptions pre- and post-CPOE were extracted and collated to perform a meta-analysis using the 'meta' package in R. The systematic review was registered with PROSPERO CRD42018104220. RESULTS: The database search identified 1621 studies. After screening, 19 studies were selected for full-text review, of which 11 studies fulfilled the selection criteria. The meta-analysis of eight studies with a random effects model showed a risk ratio of 0.19 (95% confidence interval: 0.08-0.44) favouring CPOE (I2 = 99%). CONCLUSION: The studies have shown consistent reduction in CMEs after CPOE implementation, except one study that showed an increase in CMEs. The random effects model in the meta-analysis of eight studies showed that CPOE implementation reduced CMEs by 81%.

COVID-19 vaccine: Call for employees in international transportation industries and international travelers as the first priority in global distribution.

While countries are in a hurry to obtain SARS-CoV-2 vaccine, we are concerned with the availability of vaccine and whether a vaccine will be available to all in need. We predicted three possible scenarios for vaccine distributions and urge an international united action on the worldwide equitable access. In case the international community does not reach a consensus on how to distribute the vaccine to achieve worldwide equitable access, we call for a distribution plan that includes the employees in international transportation industries and international travelers to halt the disease transmission and promote the recovery of the global economy.