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The mutational landscape of phylogenetically ultraconserved elements (UCEs), especially those in noncoding DNAs (ncUCEs), and their functional relevance in cancers remain poorly characterized. Here, we perform a systematic analysis of whole-genome and in-house targeted UCE sequencing datasets from more than 3000 patients with cancer of 13,736 UCEs and demonstrate that ncUCE somatic alterations are common. Using a multiplexed CRISPR knockout screen in colorectal cancer cells, we show that the loss of several altered ncUCEs significantly affects cell proliferation. In-depth functional studies in vitro and in vivo further reveal that specific ncUCEs can be enhancers of tumor suppressors (such as ARID1B) and silencers of oncogenic proteins (such as RPS13). Moreover, several miRNAs located in ncUCEs are recurrently mutated. Mutations in miR-142 locus can affect the Drosha-mediated processing of precursor miRNAs, resulting in the down-regulation of the mature transcript. These results provide systematic evidence that specific ncUCEs play diverse regulatory roles in cancer.

Abstract Background The routine diagnostic process increasingly entails the processing of high-volume and high-dimensional data that cannot be directly visualised. This processing may provide scaling issues that limit the implementation of these types of data into research as well as integrated diagnostics in routine care. Here, we investigate whether we can use existing dimension reduction techniques to provide visualisations and analyses for a complete bloodcount (CBC) while maintaining representativeness of the original data. We considered over 3 million CBC measurements encompassing over 70 parameters of cell frequency, size and complexity from the UMC Utrecht UPOD database. We evaluated PCA as an example of a linear dimension reduction techniques and UMAP, TriMap and PaCMAP as non-linear dimension reduction techniques. We assessed their technical performance using quality metrics for dimension reduction as well as biological representation by evaluating preservation of diurnal, age and sex patterns, cluster preservation and the identification of leukemia patients. Results We found that, for clinical hematology data, PCA performs systematically better than UMAP, TriMap and PaCMAP in representing the underlying data. Biological relevance was retained for periodicity in the data. However, we also observed a decrease in predictive performance of the reduced data for both age and sex, as well as an overestimation of clusters within the reduced data. Finally, we were able to identify the diverging patterns for leukemia patients after use of dimensionality reduction methods. Conclusions We conclude that for hematology data, the use of unsupervised dimension reduction techniques should be limited to data visualization applications, as implementing them in diagnostic pipelines may lead to decreased quality of integrated diagnostics in routine care.

Research shows that a cohesive classroom community, or the relationships built between students within a classroom setting, leads to a long list of positive student outcomes in higher education. This research seeks to better understand how to build cohesion in a classroom community, a goal that has become even more urgent given the student isolation caused by the COVID-19 pandemic. It uses the tool of social network analysis, a tool particularly well suited for studying networks of relationships, to examine how two common collaborative learning techniques--small group discussions and team-based projects--affect the structure and strength of the classroom community networks in two public affairs undergraduate courses. The results show that both collaborative learning techniques created a network of denser, more inclusive relationships between students. Teamwork, in particular, had a large impact on the formation of relationships between students. Further, the collaborative teaching strategies were effective in improving student learning outcomes. Students received higher grades and reported higher satisfaction with the course if they were more embedded in the classroom community network. The results of this research reveal the importance of focusing on relationship-building instructional techniques for student success in higher education. [Note: The volume number (34), publication year (2022), and page range (78-89) shown on the PDF is incorrect. The correct volume number is 35, the correct publication year is 2023, and the correct page range is 79-91.]

Advances in therapeutic approaches for melanoma urge the need for biomarkers that can identify patients at risk for recurrence and to guide treatment. The potential use of liquid biopsies in identifying biomarkers is increasingly being recognized. Here, we present a head‐to‐head comparison of several techniques to analyze circulating tumor cells (CTCs) and cell‐free DNA (cfDNA) in 20 patients with metastatic melanoma. In this study, we investigated whether diagnostic leukapheresis (DLA) combined with multimarker flow cytometry (FCM) increased the detection of CTCs in blood compared to the CellSearch platform. Additionally, we characterized cfDNA at the level of somatic mutations, extent of aneuploidy and genome‐wide DNA methylation. Both CTCs and cfDNA measures were compared to tumor markers and extracranial tumor burden on radiological imaging. Compared to the CellSearch method applied on peripheral blood, DLA combined with FCM increased the proportion of patients with detectable CTCs from 35% to 70% (P = 0.06). However, the median percentage of cells that could be recovered by the DLA procedure was 29%. Alternatively, cfDNA mutation and methylation analysis detected tumor load in the majority of patients (90% and 93% of samples successfully analyzed, respectively). The aneuploidy score was positive in 35% of all patients. From all tumor measurements in blood, lactate dehydrogenase (LDH) levels were significantly correlated to variant allele frequency (P = 0.004). Furthermore, the presence of CTCs in DLA was associated with tumor burden (P

Background and purpose: For frail institutionalized hip fracture patients who opt for nonoperative management (NOM), the additional treatment benefits of hospital admission and in-hospital diagnostics are not well evaluated. We aimed to describe and compare treatment satisfaction and quality of dying for patients who refrained from hospitalization after a hip fracture and patients who were treated nonoperatively after a short period of hospitalization. Methods: Both cohorts included very frail institutionalized hip fracture patients. The first group directly started supportive care in their own nursing home after a suspected hip fracture. The second opted for NOM during shared decision-making after admission and diagnostics at the hospital. Primary outcomes were treatment satisfaction and quality of dying measured by the Quality of Dying and Death Questionnaire (QODD). Secondary outcomes included health-related quality of life (EuroQoL-5D-5L and Qualidem), pain, and medication. Results: 20 non-hospitalized and 88 hospitalized patients were included. Overall treatment satisfaction by proxies was high for both the non-hospitalized 9 (interquartile range [IQR] 8–10) and hospitalized patients 8 (IQR 4–9). Quality of dying was rated higher in the non-hospitalized group with QODD 8.3, IQR 6.9–8.6 versus 7.0, IQR 5.7–7.8, and median difference 1.0 (95% confidence interval [CI] 0.1–1.8). Health-related quality of life, measured by the EQ-5D-5L utility score, was low in both groups but higher in non-hospitalized patients (0.30, IQR 0.15–0.32) than in hospitalized patients (0.25, IQR 0.03–0.32, median difference: 0.03, CI –0.03 to 0.09). Both groups reported similar pain levels, but hospitalized patients used higher standardized daily doses of opiates (68 mg vs 39 mg, median difference 24 mg, CI 7–42). Conclusion: Proxies of hospitalized and non-hospitalized patients report high treatment satisfaction after opting for NOM. Non-hospitalization may have a beneficial effect on quality of dying in selected patients who have pre-recorded do-not-hospitalize directives or shared decision-making after a suspected hip fracture.

PurposeTo compare the effectiveness and efficiency of supervised dichoptic action-videogame play to occlusion therapy in children with amblyopia.MethodsNewly diagnosed children with amblyopia aged 4-12 years were recruited, excluding strabismus >30PD. After 16 weeks of refractive adaptation children were randomized to gaming 1 h/week supervised by the researcher, or electronically monitored occlusion 2 h/day. The gaming group played a dichoptic action-videogame using virtual reality goggles, which included the task of catching a snowflake presented intermittently to the amblyopic eye. Contrast for the fellow eye was self-adjusted until 2 identical images were perceived. The primary outcome was visual acuity (VA) change from baseline to 24 weeks.ResultsWe recruited 96 children, 29 declined and 2 were excluded for language or legal issues. After refractive adaptation, 24 of the remaining 65 no longer met the inclusion criteria for amblyopia, and 8 dropped out. Of 16 children treated with gaming, 7 (6.7 years) completed treatment, whereas 9 younger children (5.3 years) did not. Of 17 treated with occlusion, 14 (5.1 years) completed treatment and 3 (4.5 years) did not. Of 5 children with small-angle strabismus, 3 treated with occlusion completed treatment and 2 treated with gaming did not. Median VA improved by 0.30 logMAR (IQR 0.20-0.40) after gaming, 0.20 logMAR (0.00-0.30) after occlusion (p = 0.823). Treatment efficiency was 1.25 logMAR/100 h (range 0.42-2.08) with gaming, 0.08 (-0.19-0.68) with occlusion (p

ABSTRACTBackground This study explored the treatment-related, financial and psychological experiences of caregivers during cancer treatment of their children in South Africa’s (SA) public and private sectors.Methods In this exploratory study, three focus groups were conducted with caregivers of children undergoing cancer treatment in SA’s public healthcare sector. A fourth small focus group with two parents in the private sector was conducted online. A mixed-methods approach was employed using a combination of thematic analysis and grounded theory.Results Of the 20 public sector caregivers, many expressed frustration at the number of visits to primary healthcare clinics before being referred. Caregivers had difficulties coping with and accepting the diagnosis, alongside managing continued care for the child and other children at home. Support received by family and community members was varied. Financial strain was an important concern. The two private sector parents indicated greater levels of support and no financial hardship, but expressed similar levels of emotional stress.Conclusion These caregiver experiences indicate that improvements are urgently needed in the recognition of childhood cancer symptoms at primary healthcare level in SA. They also highlight a need for increased financial support from government through social grants, travel allowances and nutritional support.

Background We sought to identify what barriers and facilitators determine current perceived access to childhood cancer care in South Africa through in-depth interviews with stakeholders in South Africa’s public and private sectors.Methods Qualitative semi-structured interviews were conducted with 29 key health system stakeholders, including policy-makers and regulators, medical insurance scheme informants, medicine suppliers, healthcare providers and civil society stakeholders. Identified barriers and facilitators in access to medicines and broader care were structured according to the pharmaceutical value chain (PVC).Results Barriers and facilitators were identified across all components of the PVC. Key barriers included (1) a lack of political commitment to childhood cancers, (2) discontinuation of essential chemotherapeutics, (3) incomplete insurance coverage for childhood cancers, (4) stock-outs of essential medicines, (5) the inability to access care, including travel to healthcare facilities and (6) low awareness on childhood cancers among primary healthcare (PHC) workers. Proposed priority interventions included pricing flexibilities, increased transparency and consistency in decision-making and healthcare spending, and improved training of PHC staff, nurses and pharmacists on childhood cancers.Conclusion This first comprehensive study of determinants of access to medicines used in childhood cancer in South Africa provides context-specific evidence for targeted policy development.

Introduction Asthma control is often suboptimal, which is associated with incorrect medication use and poor asthma management by patients. Astmakompas, a digital self-management intervention, comprises a mobile app for patients, a web portal for healthcare professionals (HCP), and a wireless spirometer. Together, these components are intended to facilitate symptom monitoring, patient-HCP communication and assist in asthma-related self-management. Objective The pilot study primarily aims to assess the feasibility, acceptability, usability and safety of Astmakompas from patient and HCP perspectives, and secondarily to explore potential effects on asthma control, medication use, Quality of Life, self-efficacy and (in)direct costs. Methods A mixed-method, multi-center, pre-post study design was conducted in two Dutch hospitals, involving patients with uncontrolled asthma and four HCPs. Primary outcomes were assessed post-intervention using questionnaires and in-depth interviews. Secondary outcomes were assessed at baseline and post-intervention using questionnaires, and post-intervention using in-depth interviews. Results In general, the data show that Astmakompas was considered feasible, acceptable, usable and safe by both patients ( n = 14) and HCPs ( n = 4). Furthermore, qualitative data of 11 patients and all HCPs showed the importance of guidance from HCPs and tailoring of Astmakompas to care needs. Astmakompas helped patients recognise symptoms and provided valuable insights into asthma control while being easy to use. Asthma control improved from baseline ( M = 2.1, SD = 1.3) to post-intervention ( M = 1.3, SD = 1.0, t (13) = 2.61; p = .02). Conclusion Astmakompas shows promise for further implementation and research. Future randomized studies with longer evaluation periods are crucial to assess the tool's impact on asthma outcomes and workload. It is important that HCPs guide and tailor interventions to meet the patient's individual needs and circumstances.

Objective Acute kidney injury (AKI) is easily missed and underdiagnosed in routine clinical care. Timely AKI management is important to decrease morbidity and mortality risks. We recently implemented an AKI e-alert at the University Medical Center Utrecht, comparing plasma creatinine concentrations with historical creatinine baselines, thereby identifying patients with AKI. This alert is limited to data from tertiary care, and primary care data can increase diagnostic accuracy for AKI. We assessed the added value of linking primary care data to tertiary care data, in terms of timely diagnosis or excluding AKI. Methods With plasma creatinine tests for 84,984 emergency department (ED) visits, we applied the Kidney Disease Improving Global Outcome guidelines in both tertiary care-only data and linked data and compared AKI cases. Results Using linked data, the presence of AKI could be evaluated in an additional 7886 ED visits. Sex- and age-stratified analyses identified the largest added value for women (an increase of 4095 possible diagnoses) and patients ≥60 years (an increase of 5190 possible diagnoses). We observed 398 additional visits where AKI was diagnosed, as well as 185 cases where AKI could be excluded. We observed no overall decrease in time between baseline and AKI diagnosis (28.4 days vs. 28.0 days). For cases where AKI was diagnosed in both data sets, we observed a decrease of 2.8 days after linkage, indicating a timelier diagnosis of AKI. Conclusions Combining primary and tertiary care data improves AKI diagnostic accuracy in routine clinical care and enables timelier AKI diagnosis.

Background and purpose Recent research has highlighted non-operative management (NOM) as a viable alternative for frail older adults with hip fractures in the final phase of life. This study aims to guide Dutch physicians and hospitals nationwide in a standardised implementation of shared decision-making regarding surgery or NOM in selected frail older adults with a hip fracture.Methods and analysis The patient population for implementation includes frail older adults aged ≥70 years with an acute proximal femoral fracture, nursing home care or a similar level of care elsewhere and at least one additional criterion (ie, malnutrition, severe mobility impairment or ASA≥4). The 2-year implementation study will be conducted in four phases. In phases 1 and 2, barriers and facilitators for implementation will be identified and an implementation protocol, educational materials and patient information will be developed. Phase 3 will involve an implementation pilot in 14 hospitals across the Netherlands. The protocol and educational material will be improved based on healthcare provider and patient experiences gathered through interviews. Phase 4 will focus on upscaling to nationwide implementation and the effect of the implementation on NOM rate will be measured using data from the Dutch Hip Fracture Audit.Ethics and dissemination The study was exempted by the local Medical Research Ethics Committee (MEC-2023-0270, 10 May 2023) and Medical Ethics Committee United (W23.083, 26 April 2023). The study’s results will be submitted to an open access international peer-reviewed journal. Its protocols, tools and results will be presented at several national and international academic conferences of relevant orthogeriatric (scientific) associations.Trial registration number NCT06079905.

Centrosomal Protein 55 (CEP55) exhibits various oncogenic activities; it regulates the PI3K-Akt-pathway, midbody abscission, and chromosomal instability (CIN) in cancer cells. Here, we analyzed the mechanism of how CEP55 controls CIN in ovarian and breast cancer (OvCa) cells. Down-regulation of CEP55 reduced CIN in all cell lines analyzed, and CEP55 depletion decreased spindle microtubule (MT)-stability in OvCa cells. Moreover, recombinant CEP55 accelerated MT-polymerization and attenuated cold-induced MT-depolymerization. To analyze a potential relationship between CEP55-controlled CIN and its impact on MT-stability, we identified the CEP55 MT-binding peptides inside the CEP55 protein. Thereafter, a mutant with deficient MT-binding activity was re-expressed in CEP55-depleted OvCa cells and we could show that this mutant did not restore reduced CIN in CEP55-depleted cells. This finding strongly indicates that CEP55 regulates CIN by controlling MT dynamics.

Abstract Background Sustainable Development Goal (SDG) indicator 3.b.3 monitors progress in medicines’ accessibility for adults and has significant limitations when applying to medicines for children. An adapted indicator methodology was developed to fill this gap, but no proof of its robustness exists. We provide this evidence through sensitivity analyses. Methods Data on availability and prices of child medicines from ten historical datasets were combined to create datasets for analysis: Dataset 1 (medicines selected at random) and Dataset 2 (preference given to available medicines, to better capture affordability of medicines). A base case scenario and univariate sensitivity analyses were performed to test critical components of the methodology, including the new variable of number of units needed for treatment (NUNT), disease burden (DB) weighting, and the National Poverty Line (NPL) limits. Additional analyses were run on a continuously smaller basket of medicines to explore the minimum number of medicines required. Mean facility scores for access were calculated and compared. Results The mean facility score for Dataset 1 and Dataset 2 within the base case scenario was 35.5% (range 8.0–58.8%) and 76.3% (range 57.2–90.6%). Different NUNT scenarios led to limited variations in mean facility scores of + 0.1% and -0.2%, or differences of + 4.4% and -2.1% at the more critical NPL of $5.50 (Dataset 1). For Dataset 2, variations to the NUNT generated differences of + 0.0% and -0.6%, at an NPL of $5.50 the differences were + 5.0 and -2.0%. Different approaches for weighting for DB induced considerable fluctuations of 9.0% and 11.2% respectively. Stable outcomes with less than 5% change in mean facility score were observed for a medicine basket down to 12 medicines. For smaller baskets, scores increased more rapidly with a widening range. Conclusion This study has confirmed that the proposed adaptations to make SDG indicator 3.b.3 appropriate for children are robust, indicating that they could be an important addition to the official Global Indicator Framework. At least 12 child-appropriate medicines should be surveyed to obtain meaningful outcomes. General concerns that remain about the weighting of medicines for DB and the NPL should be considered at the 2025 planned review of this framework.

Abstract Red blood cell distribution width (RDW) is a biomarker associated with a variety of clinical outcomes. While anemia and subclinical inflammation have been posed as underlying pathophysiology, it is unclear what mechanisms underlie these assocations. Hence, we aimed to unravel the mechanisms in silico using a large clinical dataset and validate our findings in vitro. We retrieved complete blood counts (CBC) from 1,403,663 measurements from the Utrecht Patient Oriented Database, to model RDW using gradient boosting regression. We performed (sex-stratified) analyses in patients with anemia, patients younger/older than 50 and validation across platforms and care settings. We then validated our hypothesis regarding oxidative stress using an in vitro approach. Only percentage microcytic (pMIC) and macrocytic (pMAC) erythrocytes and mean corpuscular volume were most important in modelling RDW (RMSE = 0.40, R2 = 0.96). Subgroup analyses and validation confirmed our findings. In vitro induction of oxidative stress underscored our results, namely increased RDW and decreased erythrocyte volume, yet no vesiculation was observed. We found that erythrocyte size, especially pMIC, is most informative in predicting RDW, but no role for anemia or inflammation. Oxidative stress affecting the size of the erythrocytes may play a role in the association between RDW and clinical outcomes.

Introduction The importance of access to available and affordable essential medicines for all is embodied in targets 3.8 and 3.b of the sustainable development goals (SDGs) and remains a priority [...], Child-appropriate medicines are essential for the safe and effective treatment of children, yet we have observed a large gap in the data required to adequately monitor access to these medicines. We have examined data on the availability and pricing of child-appropriate medicines across 50 surveys. Child-appropriate medicines for nine out of 12 priority diseases in children were infrequently surveyed or not at all. A similar data deficit on age-appropriate medicines is detectable in the broader scientific literature. We also note that existing instruments for collecting data on the availability or prices of medicines are limited in their ability to generate the required data for children. We have identified four priorities as key for improved monitoring of access to medicines for children: (i) dedicated child medicine surveys are needed on availability and prices of child-appropriate medicines; (ii) standardized survey instruments should include age-appropriate medicines and dosages; (iii) health facility service readiness survey tools should include the collection of data on the price of child-appropriate medicines in addition to the availability of medicines; and (iv) sustainable development goal indicator 3.b.3 should be modified to enable the monitoring of access to medicines for children. These deficiencies need to be addressed to ensure the monitoring of access to child medicines as part of the sustainable development goal agenda for 2030 and to implement appropriate interventions for improving access for this vulnerable population. Disposer de medicaments adaptes aux enfants est essentiel a l'administration d'un traitement sur et efficace. Pourtant, nous avons observe de vastes lacunes dans les donnees requises pour evaluer l'acces a ces medicaments. Nous avons passe 50 enquetes au crible, a la recherche d'informations sur la disponibilite et le prix des medicaments pediatriques. Dans le cas de neufmaladies infantiles prioritaires sur douze, les medicaments adaptes aux enfants n'etaient pas ou peu etudies. Meme constat dans le contexte plus large de la litterature scientifique. Nous avons egalement remarque que les instruments servant a recolter des donnees sur la disponibilite ou le prix des medicaments avaient leurs limites et ne permettaient pas d'obtenir les informations requises concernant les enfants. Nous avons identifie quatre priorites majeures en vue d'ameliorer la surveillance de l'acces aux medicaments pediatriques: (i) la realisation d'enquetes sur les medicaments pediatriques afin d'en connaitre la disponibilite et le prix; (ii) l'integration des medicaments et dosages adequats dans les instruments d'enquete standard; (iii) outre la disponibilite, la prise en compte du prix des medicaments a usage pediatrique dans les outils d'evaluation de l'etat de preparation des services au sein des etablissements de sante; et enfin, (iv) la modification de l'indicateur 3.b.3 des objectifs de developpement durable, qui prevoirait des lors un controle de l'acces aux medicaments adaptes aux enfants. Ces lacunes doivent etre comblees pour assurer un suivi en matiere d'acces aux medicaments pediatriques dans le cadre du Programme de developpement durable a l'horizon 2030, mais aussi pour adopter les mesures correspondantes afin d'ameliorer la prise en charge de cette population vulnerable. Los medicamentos indicados para los ninos son esenciales para su tratamiento seguro y eficaz, pero se ha observado un gran vacio en los datos necesarios para supervisar de manera adecuada el acceso a estos medicamentos. Se han analizado los datos sobre la disponibilidad y el precio de los medicamentos indicados para los ninos en 50 encuestas. Estos medicamentos para nueve de las 12 enfermedades prioritarias infantiles se encuestaron con poca frecuencia o no se encuestaron en absoluto. En la literatura cientifica mas general, se detecta un deficit de datos similar sobre los medicamentos adecuados para la edad. Tambien se observa que los instrumentos existentes para recopilar los datos sobre la disponibilidad o los precios de los medicamentos son limitados en su capacidad para generar los datos necesarios en el caso de los ninos. Se han identificado cuatro prioridades para mejorar el seguimiento del acceso a los medicamentos pediatricos: (i) se necesitan encuestas especificas sobre la disponibilidad y los precios de los medicamentos indicados para los ninos; (ii) los instrumentos de encuesta estandarizados deben incluir medicamentos y dosis adecuados para la edad; (iii) las herramientas de encuesta sobre la disponibilidad de los servicios sanitarios deben incluir la recopilacion de los datos sobre el precio de los medicamentos indicados para los ninos, ademas de la disponibilidad de los medicamentos; y (iv) el indicador 3.b.3 del Objetivo de Desarrollo Sostenible se debe modificar para permitir el seguimiento del acceso a los medicamentos pediatricos. Es preciso solucionar estas deficiencias para garantizar el seguimiento del acceso a los medicamentos pediatricos como parte de la agenda de los objetivos de desarrollo sostenible para 2030 y aplicar las intervenciones adecuadas para mejorar el acceso de esta poblacion vulnerable.

This article offers embodied, phenomenological descriptions of the disorientation project, a solo work by dance artist P. Megan Andrews. From the position of an ongoing witness of Megan’s practice, the author reflects on how experiences of perceptual disorientation can be potent and productive, opening space for relations of care.

Introduction The effectiveness of a health system in providing access to medicines is in part determined by the alignment of several core pharmaceutical processes. For South Africa’s public health sector, these include the registration of medicines, selection and subsequent procurement through national tenders. Registration, selection and reimbursement are key processes in the private sector. This study assessed the alignment of forementioned processes for essential paediatric oncology medicines in South Africa.Methods A selection of priority chemotherapeutics, antiemetics and analgesics in the treatment of five prevalent childhood cancers in South Africa was compared with those listed in 1) the WHO Essential Medicines List for Children (WHO EMLc) 2021, 2) the registered health products database of South Africa, 3) the relevant South African National Essential Medicines Lists (NEML), 4) bid packs and awarded tenders for oncology medicines for 2020 and 2022 and 5) oncology formularies from the leading Independent Clinical Oncology Network (ICON) and two private sector medical aid schemes. Consistency between these sources was assessed descriptively.Results There was full alignment for 25 priority chemotherapeutics for children between the NEML, the products registered in South Africa and those included on tender. Due to unsuccessful procurement, access to seven chemotherapeutics was potentially constrained. For antiemetics and analgesics, eight of nine active ingredients included on the WHO EMLc were also registered in South Africa and on its NEML. An exploratory assessment of private sector formularies showed many gaps in ICON’s formulary and two medical scheme formularies (listing 33% and 24% of the chemotherapeutics, respectively).Conclusion Despite good alignment in public sector pharmaceutical processes, access constraints to essential chemotherapeutics for children may stem from unsuccessful tenders. Private sector formularies show major gaps; however, it is unclear how this translates to access in clinical practice.