The Characteristics and Follow-Up of SARS-CoV-2 Infection in Pediatric Oncology Patients.

Introduction Clinical data about the first and second most prominent waves of SARS-CoV-2 among pediatric cancer patients were inconsistent. This study aims to retrospectively report the clinical characteristics and outcomes of SARS-CoV-2 infection in pediatric oncology patients. Methods This is an observational, retrospective study conducted in a tertiary care oncology center from March 2020 to May 2022. We reviewed the prevalence, severity of symptoms, and duration of positivity in relation to blood count laboratory data and mortality with a follow-up of 30 days post-infection for SARS-CoV-2. Results A total of 396 PCR tests were performed on 342 pediatric cancer patients. The overall rate of SARS-CoV-2 positivity was 43.1% (2.7% in the first wave and 95.4% in the second wave). Among 342 screened pediatric cancer patients, 72 patients had confirmed SARS-CoV-2 positivity in 92 different episodes. Nearly 59% had a mild or moderate infection, with fever and cough as the predominant presentations. The mean duration of positivity was 18.4±7.76 days. Comparing the laboratory values before and after acquiring the COVID-19 infection, only monocytes, hemoglobin, hematocrit, and platelets were statistically significantly affected, with P-values of 0.002, 0.03, 0.02, and 0.01, respectively. More than 18% of patients had grade 3 to 4 neutropenia (absolute neutrophil count=0.39±0.35) before COVID-19 infection and remained neutropenic throughout the disease, regardless of symptom severity. The mean recovery time was 13.67±8 days, which resulted in a delay in cancer treatment delivery of up to four weeks in 42.2% of patients. Conclusion Our data demonstrated that pediatric cancer patients with SARS-CoV-2 infection have a mild to moderate course of COVID-19 disease, with the majority being symptomatic, yet a great portion of our study population experienced treatment interruptions reaching up to four weeks caused by COVID-19.

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation.

The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC0-24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Clvan, the volume of distribution at a steady-state Vdss, the volume of distribution for peripheral compartment Vdp, half-life for the elimination phase t½ß, and the first-order rate constant for the elimination process ß in FN compared to non-FN patients. Furthermore, AUC0-24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC0-24, which may require specific consideration during the treatment initiation.

A Retrospective Single-Center Study of Sevelamer Hydrochloride for the Treatment of Hyperphosphatemia in Children With Tumor Lysis Syndrome.

Introduction Tumor lysis syndrome (TLS) is a life-threatening metabolic abnormality. The incidence of TLS depends on the underlying malignancy. In a recent analysis of hematological malignancy, the incidence of clinical TLS in children was 3.8%, laboratory TLS 46.2%, and hyperphosphatemia 32.7%. Sevelamer is effective for the treatment of hyperphosphatemia associated with renal failure; however, there is no clear data that it has the same effect in treating hyperphosphatemia with TLS. Methods This was a retrospective study among children aged ≤14 years with hematological malignancy who developed TLS and received sevelamer to treat hyperphosphatemia at Princess Norah Oncology Center, King Abdulaziz Medical City (KAMC) in Jeddah from January 2012 to December 2016. Results A total of 34 patients received sevelamer. The majority was male (64%), with a median age of six years. The median sevelamer dose per day was 1600 mg, while the median duration of use was two days. Phosphate level was significantly decreased at different times (24 hours, 48 hours, and 72 hours) during sevelamer usage, p-value <0.001. Conclusion In our study, the use of sevelamer resulted in a significant decrease in phosphate levels. This finding further consolidates the efficacy of sevelamer in treating hyperphosphatemia with TLS. However, further research into the drug's kinetics is recommended.

Augmented Renal Clearance and Hypoalbuminemia-Induced Low Vancomycin Trough Concentrations in Febrile Neutropenic Patients With Hematological Malignancies.

INTRODUCTION: Vancomycin administration in individuals with hematological malignancy or neutropenia is associated with a suboptimal trough concentration. Nonetheless, most studies did not distinguish whether low vancomycin trough concentrations were due to hematological malignancies or neutropenia. This study aimed to determine the association between types of hematological malignancy and febrile neutropenia with low vancomycin concentrations. METHODS: The present retrospective chart review study was conducted by using clinical data adopted from computerized physician order entries (BestCare®) for all of the patients who received intravenous vancomycin treatment between January 2017 and December 2020 at King Abdulaziz Medical City in Jeddah. RESULTS: Out of the 296 patients, 217 were included. There was no significant association between the type of hematological malignancy and the incidence of a low trough concentration (p > 0.05), while a significant association between febrile neutropenia and the incidence of a low trough concentration was observed (p < 0.05). Furthermore, the predictors for a low trough among febrile neutropenic patients were creatinine clearance (CrCI) and a low albumin concentration. In addition, there was a significant association between febrile neutropenia and augmented renal clearance (p < 0.05). CONCLUSIONS: The findings of this study conclude that febrile neutropenia is associated with low vancomycin concentrations. Interestingly, augmented renal clearance was observed in most of the febrile neutropenia patients with a significant association, which is considered the main driver for a low trough in neutropenic patients.

Off-Label Drug Use in Pediatric Out-Patient Care: A Multi-Center Observational Study.

OBJECTIVE: Prescribing a drug for a child is not an easy task and requires using the best available evidence as a guide, especially when a drug is used off-label. The practice of prescribing a drug for off-label use is fairly widespread worldwide. The FDA does not regulate prescribing patterns or practices of individual practitioners and, therefore, allows off-label use. The main objective of this study is to evaluate off-label prescribing among the pediatric population in the Kingdom of Saudi Arabia (KSA). METHOD: This is a retrospective, simple random selection observational study of children (≤15 years) who visited pediatric clinics and had at least 1 drug prescribed over a 12-month period (January to December 2018). RESULTS: A total of 865 drugs (mean 1 and SD 0.24) were prescribed to 326 children. Off-label was identified in 39.4% of the drugs with a frequency of 512 (as 1 drug may belong to more than 1 off-label category). The most common reason for off-label prescribing was related to doses that were "higher or lower than the recommended use" (48.6%), and the most frequently identified drug class prescribed for off-label use was anti-infective drugs for systemic use (39.9%). The percentage of off-label drug use was found to be higher in girls and in the age group of 1 month to 2 years (P = .001) for both variables. In addition, a significant association was found between off label drug use and the total number of drugs prescribed, P < .001. CONCLUSION: The findings of this study showed a high incidence of off-label prescribing mainly related to dosing and indication. The results of this observational study support the need to establish a unified national pediatric dosing formulary guide to ensure safe drug use in pediatrics.

Predicting Patients' Intention to Use a Personal Health Record Using an Adapted Unified Theory of Acceptance and Use of Technology Model: Secondary Data Analysis.

BACKGROUND: With the rise in the use of information and communication technologies in health care, patients have been encouraged to use eHealth tools such as personal health records (PHRs) for better health and well-being services. PHRs support patient-centered care and patient engagement. To support the achievement of the Kingdom of Saudi Arabia's Vision 2030 ambitions, the National Transformation program provides a framework to use PHRs in meeting the 3-fold aim for health care-increased access, reduced cost, and improved quality of care-and to provide patient- and person-centered care. However, there has been limited research on PHR uptake within the country. OBJECTIVE: Using the Unified Theory of Acceptance and Use of Technology (UTAUT) as the theoretical framework, this study aims at identifying predictors of patient intention to utilize the Ministry of National Guard-Health Affairs PHR (MNGHA Care) app. METHODS: Using secondary data from a cross-sectional survey, data measuring the intention to use the MNGHA Care app, along with its predictors, were collected from among adults (n=324) visiting Ministry of National Guard-Health Affairs facilities in Riyadh, Jeddah, Dammam, Madinah, Al Ahsa, and Qassim. The relationship of predictors (main theory constructs) and moderators (age, gender, and experience with health apps) with the dependent variable (intention to use MNGHA Care) was tested using hierarchical multiple regression. RESULTS: Of the eligible population, a total of 261 adult patients were included in the analysis. They had a mean age of 35.07 (SD 9.61) years, 50.6 % were male (n=132), 45.2% had university-level education (n=118), and 53.3% had at least 1 chronic medical condition (n=139). The model explained 48.9% of the variance in behavioral intention to use the PHR (P=.38). Performance expectancy, effort expectancy, and positive attitude were significantly associated with behavioral intention to use the PHR (P<.05). Prior experience with health apps moderated the relationship between social influence and behavioral intention to use the PHR (P=.04). CONCLUSIONS: This study contributes to the existing literature on PHR adoption broadly as well as in the context of the Kingdom of Saudi Arabia. Understanding which factors are associated with patient adoption of PHRs can guide future development and support the country's aim of transforming the health care system. Similar to previous studies on PHR adoption, performance expectancy, effort expectancy, and positive attitude are important factors, and practical consideration should be given to support these areas.

Prescriber behaviours that could be targeted for change: An analysis of behaviours demonstrated during prescription writing in children.

BACKGROUND: The prescribing process for children with cancer is complex, and errors can occur at any step. As a result, many interventions have been used to reduce errors. However, few of them have been designed based on an understanding of the prescriber behaviour that can lead to errors. In order to design effective behaviour change interventions, it is important first to understand the prescribing process and identify prescriber behaviours that could be targeted for change. OBJECTIVES: To describe the prescribing process in a paediatric oncology ward and to identify prescriber behaviours during prescription writing that could be targeted to reduce errors. METHODS: This study employed two sequential phases. First, the prescribing process was observed and then described using the hierarchical task analysis (HTA) method. Second, prescriber tasks identified from the HTA were analysed using the behaviour change wheel (BCW) approach to identify promising behaviours for change. These identified behaviours were prioritised based on information collected from four focus groups with prescribers and chart review of errors made in the ward. RESULTS: The prescribing process was complex and involved multiple tasks performed in varying orders. Applying the BCW identified thirty-two candidate behaviours for potentially reducing prescribing errors. However, after prioritization, only two emerged as promising candidate behaviours for intervention: writing drug indications at the time of prescribing and using a pre-written order when ordering medications through electronic prescribing. CONCLUSIONS: This research suggests that two behaviours could be promising in reducing errors. Having identified these behaviours, future work could explore what needs to change with respect to individuals and their work environments to achieve the desired change in these identified behaviours.

Evaluation of handling, storage, and disposal practices of oral anticancer medications among cancer patients and their caregivers at home setting in the Princess Noorah Oncology Center.

BACKGROUD: Oral medications are commonly prescribed for many cancer patients. Unfortunately, most of them are dispensed without proper counseling about handling practices. We aimed to evaluate the handling, storage, and disposal practices of oral anticancer medications among cancer patients and their caregivers at home. METHODS: A cross-sectional questionnaire was filled in by adult cancer patients or caregivers who received oral anticancers and/or visited an outpatient pharmacy over two months. RESULTS: A total of 201 participants were interviewed, 67% were female, and nearly 44% were between 40 and 60 years of age. The majority of participants were educated (78%). The top five medications involved were: tamoxifen, capecitabine, letrozole, dasatinib, and imatinib. More than 95% of participants reported that medications were kept away from children and pets in the original container and stored away from extreme heat, cold, and humidity. Hand washing and wearing gloves were not consistently practiced. Only 5% reported "Always" wearing gloves, while 24% reported "Always" washing hands after handling anticancer medications. The participants reported that they had been informed about safe handling and storage by their physician (39%) and pharmacist (25%), while 34% had not been informed. In terms of disposal practices, 66% of patients have not had any unused or expired medications, 29% disposed them in the trash, and 27% returned them. CONCLUSIONS: Our findings suggest that patients and caregivers' handling practices of oral anticancer medications are inconsistent with the published recommendations. Hence, appropriate and comprehensive education is needed to mitigate the risk of exposure to these agents in the home setting.

A clinical approach to non-neutropenic fever in children with cancer.

BACKGROUND: There are a limited number of studies that address non-neutropenic fever episodes in children with cancer, and no standard approach exists. METHOD: We opt to retrospectively analyze the efficacy of the current clinical approach for management of non-neutropenic fever episodes and the associated risk factors among children with cancer at the Princess Noorah Oncology Center from May 2016 through December 2017. RESULTS: A total of 480 non-neutropenic fever episodes were identified in 131 children, of which 62 episodes were triaged as high-risk non-neutropenic fever and 418 as low-risk non-neutropenic fever. Of those 480 non-neutropenic fever, 361 episodes (75.2%) were associated with the presence of central venous catheters. The overall failure rate of ceftriaxone mono-therapy was observed in 75.6% (11.7% in high-risk non-neutropenic fever with a mean C-reactive protein level of 21.1 (±23.2) mmol/L and 63.9% in low-risk non-neutropenic fever with a mean C-reactive protein level of 17.6 (±53.9) mmol/L). The overall bacteremia rate was 14.4%. The type of organisms isolated was mainly high-risk organisms in 59 non-neutropenic fever episodes (85.5%), OR 1.78 (95% CI: 0.45-7.04) p = 0.41. Of note, all bacteremia were associated with the presence of central venous catheter (100%). Of all the examined risk factors of outpatient treatment failure in low-risk non-neutropenic fever, only prolonged fever of more than three days were significantly associated with bacteremia OR 8.107 [95% CI: 1.744-37.691], p = 0.008. Noteworthy is that almost 43% of non-neutropenic fever episodes were associated with respiratory symptoms. This study provides a baseline for future prospective research assessing the pattern of non-neutropenic fever by focusing on associated risk factors.

Coping with the residency program during COVID-19: Hematology oncology pharmacy residents' perspective.

INTRODUCTION: The COVID-19 pandemic has led to significant changes in all governmental activities in Saudi Arabia including training and teaching, with the majority of such activities suspended in response to the COVID-19 pandemic. We aim to share the challenges that Hematology Oncology Pharmacy (HOP) residents faced during the quarantine period and provide recommendations on how to cope with the residency journey. METHOD: We followed a qualitative methodological approach in March 2020 using a structured virtual group discussion for data generation. RESULTS: All six PGY2 hematology oncology pharmacy (HOP) residents were included in the group discussion. The group agreed that the need for HOP services during this pandemic is beyond the scope of oncology pharmacists' normal daily practice. The group recognized two fundamental points. First, the goal of the current training should be customized to the most pressing need and recognized at the national level. Second, the current training system should be improved to ensure efficient use of current resources. On this basis, the group developed six main recommendations for action. CONCLUSION: The current situation is a challenge for all healthcare providers, and the majority of the nation's current generation never dealt with such a situation in days gone by. This paper presents the challenges that should be addressed at the national level and provide a fundamental consensus recommendation for practical approaches to maximize learning and minimize disruption to trainees' progression while maintaining patient-pharmacy quality of care.

Adoption of a Personal Health Record in the Digital Age: Cross-Sectional Study.

BACKGROUND: As health care organizations strive to improve health care access, quality, and costs, they have implemented patient-facing eHealth technologies such as personal health records to better engage patients in the management of their health. In the Kingdom of Saudi Arabia, eHealth is also growing in accordance with Vision 2030 and its National Transformation Program framework, creating a roadmap for increased quality and efficiency of the health care system and supporting the goal of patient-centered care. OBJECTIVE: The aim of this study was to investigate the adoption of the personal health record of the Ministry of National Guard Health Affairs (MNGHA Care). METHODS: A cross-sectional survey was conducted in adults visiting outpatient clinics in hospitals at the Ministry of National Guard Health Affairs hospitals in Riyadh, Jeddah, Dammam, Madinah, and Al Ahsa, and primary health care clinics in Riyadh and Qassim. The main outcome measure was self-reported use of MNGHA Care. RESULTS: In the sample of 546 adult patients, 383 (70.1%) reported being users of MNGHA Care. MNGHA Care users were more likely to be younger (P<.001), high school or university educated (P<.001), employed (P<.001), have a chronic condition (P=.046), use the internet to search for health-related information (P<.001), and use health apps on their mobile phones (P<.001). CONCLUSIONS: The results of this study show that there is substantial interest for the use of MNGHA Care personal health record with 70% of participants self-reporting use. To confirm these findings, objective data from the portal usage logs are needed. Maximizing the potential of MNGHA Care supports patient engagement and is aligned with the national eHealth initiative to encourage the use of technology for high-quality, accessible patient-centered care. Future research should include health care provider perspectives, incorporate objective data, employ a mixed-methods approach, and use a theoretical framework.

Practical strategies to manage cancer patients during the COVID-19 pandemic: Saudi Oncology Pharmacy Assembly Experts recommendations.

PURPOSE: During COVID-19 pandemic, cancer patients are considered one of the most vulnerable to infection since they tend to have advanced age, multiple comorbidities, and are often immunosuppressed by their cancer or therapy. Hence, the Saudi Oncology Pharmacy Assembly has issued recommendations to reduce the frequency of cancer patients' visits to oncology centers during the pandemic while maintaining the access to cancer therapy and minimize the risk of exposure to coronavirus disease. MATERIALS AND METHODS: A qualitative methodological approach was conducted in April 2020 using a virtual panel discussion for collection of recommendations. RESULTS: A total of 12 expert oncology pharmacy practitioners shared their knowledge and experiences in managing oncology patients during the COVID-19 pandemic. The participants recognized many fundamental recommendations that were already applied in many cancer centers since the start of the COVID-19 outbreak. On that basis, the panelists developed eight practice-related recommendations for action, with a main focus on cancer treatment modification. CONCLUSIONS: In conclusion, delivering cancer care during the COVID-19 pandemic carries significant challenges. This paper addressed suggestions to properly manage cancer patients during difficult times. Implementing changes in practice mandates a national collaborative effort from different sectors to guarantee the quality and continuity of care. The SOPA expert panel developed these recommendations, to ultimately contribute in maintaining access to cancer therapy while minimizing the risk of COVID-19 exposure.

Addressing Cancer Treatment Shortages in Saudi Arabia: Results of a National Survey and Expert Panel Recommendations.

PURPOSE: Cancer treatment shortages are complex and a persistent problem worldwide. Patients with cancer are most vulnerable to drug shortages, which provides opportunities to examine the extent of the challenge(s) facing Saudi Arabia and to provide recommendations toward mitigating the impact of cancer treatment shortages on patient outcomes. MATERIALS AND METHODS: A qualitative methodologic approach was conducted in April 2019 using a validated questionnaire and structured panel discussion for data generation. RESULTS: Overall, 55 responses were received from practicing oncology health care professionals (26 pharmacists and 29 physicians). The annual average number of treated patients with cancer per institution was 640 (adults [n = 400] and pediatric [n = 240]). All respondents (100%) reported that cancer treatment shortages constitute a current problem in their center, with an average of 5 (range, 1-9) per month. The panelists recognized 2 fundamental points. First, the definition of cancer drug shortages should be standardized and recognized at the national level. Second, the current system must be improved to ensure proper and efficient use of the current resources. On that basis, the panelists developed 9 recommendations for action. CONCLUSION: Cancer drug shortage is a significant problem in all health centers in Saudi Arabia. This study presents challenges that should be addressed at the national level and essential consensus recommendations for a coordinated action developed by a panel of experts to tackle the current national problem of cancer treatment shortages. Implementing these recommendations will provide a blueprint for management of national drug shortages in general and cancer treatment shortages in particular.

Epidemiology of Preventable Drug-Related Problems (DRPs) Among Hospitalized Children at KAMC-Jeddah: a Single-Institution Observation Study.

AIM: Drug-related problems (DRPs) "are the unwanted effects of drugs that potentially lead to a harmful outcome" thereby requiring considerable attention. Hospitalized pediatric patients, in particular, represent a population at risk of DRPs. The epidemiology of preventable DRPs among children in Saudi Arabia remains scarce, which thus poses distinct challenges to all healthcare professionals. We aim to characterize preventable DRPs among hospitalized children at KAMC-Jeddah. METHODS: A prospective observational study of children (≤15 years) admitted to pediatric units (excluding cancer units) at KAMC-Jeddah over a 3-month period (May 29 to August 30, 2016) is carried out to determine the incidence of preventable DRPs and investigate the possible associated factors (gender, age, admission location, type of admission, and number of medications). RESULTS: A total of 319 DRPs were identified among 235 patients, of which 280 DRPs (87.8%, 280/319) were deemed preventable. The majority of preventable DRPs were related to dose selection (78%, 219/280). None of the preventable DRPs were life threatening or fatal, and the majority were assessed as moderate in severity (94.3%, 264/280). There was no significant difference between DRP incidences with age mean 3.5 (P=0.389), gender mean (P=0.436), and weight mean 13.47 (P=0.323). Younger children (age ≤2years) admitted to PICU were more likely to have DRP (OR 4.44, 95% CI, 1.87 to 10.52, P=0.00001). Scheduled admissions were 2.89 times more likely to be exposed to DRP compared to transferred admissions (OR 2.8, 95% CI, 1.83 to 4.70, P=0.005). Additionally, DRP incidences increased proportionally to the number of medications. CONCLUSION: Our data suggest that establishing appropriate prevention strategies towards improvement and safety in medicine use among this vulnerable patient population is a high priority.

Medication Exchange and Sharing Network Program (MESNP) initiative to cope with drug shortages in the Kingdom of Saudi Arabia (KSA).

BACKGROUND: Drug shortages are a major public health concern and remain a persistent problem worldwide. At present, there are no unified existing strategies for managing medicine stocks in the Kingdom of Saudi Arabia (KSA). Here, the aim is to describe our experience with creating a non-profit voluntary national Medication Exchange and Sharing Network Program (MESNP) throughout the KSA. METHODS: A quality improvement process map method was used in this project. The baseline evaluation included a review of possible reasons and strategies for managing medication shortages and recognizing potential associated safety issues. To that end, at the national level, we developed MESNP as a novel project to cope with medication shortages using Telegram social media as the preferred program for connecting with the member institution. RESULTS: A total of 500 requests were received over one year. Three hundred and fifteen (315) constituted requests for drug supplies due to shortages while the number of reports indicating the availability of overstock drug for re-distribution is (185). Almost 98% of overstocking drug reports was re-distributed in which it covers 75% of drug shortage requests. CONCLUSION: This novel project aims to use our current resources by facilitating the medication exchange and sharing between the organizations at national level. The optimistic goal is to proactively mitigate drug wastages and prevent drug shortages toward better patient care.

Impact of the e-prescribing system on the incidence and nature of drug-related problems in children in a Saudi hospital.

OBJECTIVES: To determine the impact of a computerised physician order entry (CPOE) system on the drug-related problems' (DRPs) incidence and characteristics in hospitalised children in a Saudi hospital, and to compare DRPs incidence pre-/post-CPOE implementation. METHODS: An observational study. DRPs were identified by pharmacists, reviewing children's (0-14 years) medical records on CPOE system, in paediatric wards and/or attending emergency department. DRPs preventability and severity were assessed. RESULTS: A total of 657 paediatric patients were included, with 235 (35.8%) experienced 328 DRPs, majority were preventable (99.7%, 327). Difference in DRP incidence pre- and post-CPOE implementation (44.8% versus 35.8%, P < 0.01) was significant. CONCLUSION: The CPOE system has significantly reduced DRPs incidence in children in the study hospital.

Intrathecal dose intensification by CNS status at diagnosis in the treatment of children with acute lymphoblastic leukemia.

OBJECTIVES: Acute lymphoblastic leukemia (ALL) with CNS2 status predicts inferior outcome and a high rate of CNS relapse, similar to overt CNS leukemia (CNS3). The purpose of this study was to determine if intrathecal (IT) dose intensification during induction would improve outcomes and reduce CNS relapse for CNS2 disease. METHODS: From January 2001 to December 2014, children (1-14 years) with newly diagnosed ALL were treated at the Princess Noorah Oncology Centre (PNOC) following modifications of the Children's Oncology Group (COG) protocols. We intensified IT methotrexate (ITM) during induction for patients with CNS2 disease. Patients were evaluated for overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR). RESULTS: 449 children with T-cell (14.3%) or B-cell (85.7%) ALL were treated using PNOC-SR or PNOC-HR regimens (Jan 2001- Dec 2007) or CALL08 regimens (Arm A [SR], Arm B [IR], and Arm C [HR]) (Jan 2008 - Dec 2014). The 5-year OS, DFS, and CIR were 87.2 ± 1.6%, 81.7 ± 1.9%, and 13.0 ± 1.7%, respectively. The OS and DFS of patients with CNS2 were significantly superior to that of patients with CNS3 (P = 0.025 and P = 0.019, respectively). Patients with CNS2 had similar OS and DFS to those with CNS1. None of the patients with CNS2 at initial diagnosis experienced CNS relapse. CONCLUSIONS: ITM intensification during induction was associated with elimination of CNS recurrence in patients with CNS2 disease and childhood ALL. Controlled studies are needed to confirm this observation.

Understanding the causes of prescribing errors from a behavioural perspective.

INTRODUCTION: While many attempts have been made to reduce prescribing errors (PEs), they persist. PE is not in itself a behaviour, but a consequence of a prescribing behaviour. Interventions aimed at prescribers should focus on understanding prescribers' behaviours. OBJECTIVES: The aim of this study was to use the capability, opportunity, motivation - behaviour (COM-B) model to explore the behaviours that could have caused PEs made by senior doctors in a speciality paediatric inpatient ward. METHODS: A qualitative approach was used to investigate prescribers' behaviours in a 26-bed paediatric oncology ward. Error data were collected over a two-month period and were presented during focus groups with prescribers, which were audio-recorded and transcribed verbatim. Thematic analysis was used to identify contributory factors to errors, which was used to identify sources of behaviours using the COM-B model. RESULTS: Behaviours related to prescribers' capabilities were: prescribers' improper use of the software because of insufficient skills, and prescribers' inability to prescribe correctly because of lack of knowledge. Behaviours related to opportunities in the environment were: prescribers' inability to make an informed decision because of poor access to patient information, inability to properly complete a task because of heavy workload and interruption, and having to re-check doses frequently because of frequent change in patients' weight and surface area. Those related to motivation were: prescribers unquestioningly following recommendations and not communicating with other specialists because they over-trusted them or feared a negative reaction, and prescribers inability to complete a task because of other competing and preferable tasks at the same time. CONCLUSION: Employing COM-B helped in identifying causes of PEs from a new perspective. Future work could focus on mapping identified sources of behaviour and errors against appropriate intervention functions and policies in order to design more successful interventions.

FLAG/FLAG-IDA regimen for children with relapsed/refractory acute leukemia in the era of targeted novel therapies.

BACKGROUND: Outcomes of relapsed/refractory childhood acute leukemia remain poor. We analyzed the safety/efficacy of fludarabine, cytarabine, and granulocyte colony stimulating factor, with/without idarubicin (FLAG ± IDA) as salvage therapy compared with recent published results of novel therapies. METHODS: This retrospective study included children aged 1 to 15 years with relapsed/refractory acute leukemia who received FLAG ± IDA salvage therapy from January 2000 to December 2014. Patients with infant leukemia, mixed lineage leukemia, Philadelphia-positive acute leukemia, or secondary leukemia were excluded. RESULT: Fifty patients were identified: 25 with acute lymphoblastic leukemia and 25 with acute myeloid leukemia. The median age at initiation of FLAG ± IDA was seven years. Site of relapse was the bone marrow in 29, isolated central nervous system in 11, and combined in 10 patients. FLAG ± IDA was used after first relapse in 68% and after multiple relapses in 32%. Complete remission was achieved in 34 (68%) patients. No variables predictive of complete remission were identified. Grade 3 or greater toxicity was observed in 96% and 6% died from toxicity. Toxicities included hematologic toxicity (96%), infection (52%), and enterocolitis (28%). Twenty-four of 50 (48%) patients achieved a sustained complete remission and survived to bone marrow transplantation. The five-year overall survival was 23.9% ± 6.9%. Patients achieving second complete remission and patients proceeding to bone marrow transplantation following second complete remission demonstrated significantly improved overall survival (p = 0.001). CONCLUSION: Despite a 68% complete remission rate using FLAG ± IDA, only 48% of patients survived to bone marrow transplantation. The regimen was associated with 96% toxicity and only one in four patients was alive at five years. This underscores the need to find more effective lower toxicity salvage regimens.

Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia.

BACKGROUND: Refinement of risk-based treatment stratification by minimal residual disease (MRD) at different time points has improved outcomes of childhood acute lymphoblastic leukemia (ALL). In this prospective study we evaluated effects of such stratification, including intensification of therapy based on response assessment at day-15 and MRD at day-29 of induction to test if treatment intensification would improve outcomes. METHODS: 241 patients, 1-14 years old, newly diagnosed with ALL, were recruited and stratified by risk and MRD response into three treatment Arms (A, B, or C). Arm A was modified from COG AALL0331, B from AALL0232, and C from AALL0232 and AALL0434. Assignments were according to NCI risk, phenotype, rapid vs. slow early response (SER), steroid pretreatment, MLL rearrangement (MLLR), CNS3, and testicular involvement. Patients on Arm A had treatment intensified early based on day-15 marrow results or late based on end-of-induction MRD. RESULTS: 5-year OS, EFS, and CIR were 89.5% ± 4.0%, 87.6% ± 4.3%, and 7.1% ± 3.5%. No significant difference was found by B- vs. T cell phenotype. 5-year OS, EFS, and CIR for B-cell ALL were 90.5% ± 2.4%, 88.7% ± 2.6%, and 6.4% ± 2.0%. Outcomes for patients with t(1;19)/TCF3-PBX1 and MLLR were significantly (p ≤ 0.05) worse than for other patients. MRD level at end-of-induction associated with outcomes, but association with a specific MRD value at end-of-induction varied significantly by NCI-risk group. Late treatment intensification based on end-of-induction MRD significantly improved survival outcomes for NCI-SR patients, however, patients with NCI-HR and positive MRD at end-of-induction had significantly inferior outcomes despite intensification. MRD transitions between day-15 and day-29 of induction associated with differences for OS and EFS. CONCLUSIONS: Arm switching to a more intensive protocol had mixed results. Assigning patients by end-of-induction MRD-risk alone did not reflect response kinetics of the different NCI-risk groups. Although late treatment intensification improved outcomes of NCI-SR patients with positive MRD at end-of-induction, further refinement is needed to improve outcomes of NCI-HR with SER. Integration of NCI-risk group with specific MRD value and time point allows more refined treatment stratification.Trial Registration Protocols were approved by King Abdullah International Medical Research Center and Ethics Review Committee RC08053J.