Browsing by Author "Skiles, Jodi"
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Item Biomarkers for Diagnosis and Prognosis of Sinusoidal Obstruction Syndrome after Hematopoietic Cell Transplantation.(Elsevier, 2015-10) Akil, Ayman; Zhang, Qing; Mumaw, Christen L.; Raiker, Nisha; Yu, Jeffrey; de Mendizabal, Nieves Velez; Haneline, Laura S.; Robertson, Kent A.; Skiles, Jodi; Diaz-Ricart, Maribel; Carreras, Enric; Renbarger, Jamie; Hanash, Samir; Bies, Robert R.; Paczesny, Sophie; Department of Pediatrics, IU School of MedicineReliable, non-invasive methods for diagnosing and prognosing sinusoidal obstruction syndrome (SOS) early after hematopoietic cell transplantation (HCT) are needed. We used a quantitative mass spectrometry-based proteomics approach to identify candidate biomarkers of SOS by comparing plasma pooled from 20 patients with and 20 patients without SOS. Of 494 proteins quantified, we selected six proteins [L-Ficolin, vascular-cell-adhesion-molecule-1 (VCAM1), tissue-inhibitor of metalloproteinase-1, von Willebrand factor, intercellular-adhesion-molecule-1, and CD97] based on a differential heavy/light isotope ratio of at least 2 fold, information from the literature, and immunoassay availability. Next, we evaluated the diagnostic potential of these six proteins and five selected from the literature [suppression of tumorigenicity-2 (ST2), angiopoietin-2 (ANG2), hyaluronic acid (HA), thrombomodulin, and plasminogen activator inhibitor-1] in samples from 80 patients. The results demonstrate that together ST2, ANG2,Item Childhood acute lymphoblastic leukemia treatment in an academic hospital in Kenya: Treatment outcomes and health‐care providers’ perspectives(Wiley, 2021-12) Olbara, Gilbert; van der Wijk, Thyra; Njuguna, Festus; Langat, Sandra; Mwangi, Henry; Skiles, Jodi; Vik, Terrry A.; Kaspers, Gertjan J.L.; Mostert, Saskia; Pediatrics, School of MedicineBackground Early deaths and treatment nonadherence are major reasons for low childhood acute lymphoblastic leukemia (ALL) survival in low- and middle-income countries. This study assessed treatment outcomes of children presenting with ALL and evaluated perspectives of health-care providers (HCP) on ALL treatment at a Kenyan academic hospital. Methods This was a combined retrospective medical records and cross-sectional questionnaire study. Treatment outcomes of 136 children diagnosed with ALL between 2010 and 2016 were collected. Questionnaires were completed by 245 HCP (response rate, 86%) between September and October 2016. Results Childhood ALL treatment outcomes were death (30%), progressive or relapsed disease (26%), abandonment (24%), and event-free survival (20%). Of all deaths, 80% were early deaths (prior or during induction), whereas 20% occurred in remission. Probability of event-free survival at three years was 18%. Only 57% of HCP believed childhood ALL can be cured, with more doctors (96%) than other HCP (45%) believing in curability of ALL (P < 0.001). The majority of HCP (96%) thought that experienced doctors should put more time and effort into making parents understand the diagnosis and necessity to complete treatment. According to HCP, reasons for protocol nonadherence included parental financial difficulties (94%) and use of alternative treatment (79%). Conclusions Event-free survival for ALL in Kenya is low. The primary reason for treatment failure is early death from treatment-related complications. More efforts should be directed toward improving supportive care strategies. In the opinion of HCPs, improved communication with parents and supervision of junior staff will improve ALL treatment outcomes.Item Factors influencing survival among Kenyan children diagnosed with endemic Burkitt lymphom between 2003 and 2011: a historical cohort study(Wiley, 2016-09-15) Buckle, Geoffrey; Maranda, Louise; Skiles, Jodi; Ong'echa, John Michael; Foley, Joslyn; Epstein, Mara; Vik, Terry A.; Schroeder, Andrew; Lemberger, Jennifer; Rosmarin, Alan; Remick, Scot C.; Bailey, Jeffrey A.; Vulule, John; Otieno, Juliana A.; Moormann, Ann M.; Pediatrics, School of MedicineDiscovering how to improve survival and establishing clinical reference points for children diagnosed with endemic Burkitt lymphoma (eBL) in resource-constrained settings has recaptured international attention. Using multivariate analyses, we evaluated 428 children with eBL in Kenya for age, gender, tumor stage, nutritional status, hemoglobin, lactate dehydrogenase (LDH), Epstein-Barr virus (EBV) and Plasmodium falciparum prior to induction of chemotherapy (cyclophosphamide, vincristine, methotrexate, and doxorubicin) to identify predictive and prognostic biomarkers of survival. During this ten year prospective study period, 22% died in-hospital and 78% completed six-courses of chemotherapy. Of those, 16% relapsed or died later; 31% achieved event-free-survival; and 31% were lost to follow-up; the overall one-year survival was 45%. After adjusting for co-variates, low hemoglobin (<8g/dL) and high LDH (>400 mU/ml) were associated with increased risk of death (adjusted Hazard Ratio (aHR)=1.57 [0.97 to 2.41]) and aHR=1.84, [0.91 to 3.69], respectively). Anemic children with malaria were 3.55 times more likely to die [1.10 to 11.44] compared to patients without anemia or malarial infection. EBV load did not differ by tumor stage nor was it associated with survival. System-level factors can also contribute to poor outcomes. Children were more likely to die when inadvertently overdosed by more than 115% of the correct dose of cyclophosphamide (aHR=1.43 [0.84 to 2.43]), or doxorubicin (aHR=1.25, [0.66 to 2.35]), compared to those receiving accurate doses of the respective agent in this setting. This study codifies risk factors associated with poor outcomes for eBL patients in Africa and provides a benchmark by which to assess improvements in survival for new chemotherapeutic approaches.Item Factors influencing time to diagnosis and treatment among pediatric oncology patients in Kenya(Taylor & Francis, 2016) Njuguna, F.; Martijn, H.; Langat, S.; Musimbi, J.; Muliro, H.; Skiles, Jodi; Vik, Terry; Sitaresmi, M. N.; van de Ven, P. M.; Kaspers, G. J. L.; Mostert, S.; Department of Pediatrics, IU School of MedicineEarly diagnosis and start of treatment are fundamental goals in cancer care. This study determines the time lag and the factors that influence the time to diagnosis and start of treatment. Study participants were parents of childhood cancer patients diagnosed between August 2013 and July 2014 in a hospital in Kenya. Patient, physician, diagnosis, treatment, health care system, and total delay were explored using a questionnaire. Demographic and medical data were collected from the patients' medical records. Parents of 99 childhood cancer patients were interviewed (response rate: 80%). Median total delay was 102 (9–1021) days. Median patient delay (4 days) was significantly shorter than health care system delay (median 87 days; P < .001). Diagnosis delay (median 94 days) was significantly longer than treatment delay (median 6 days; P < .001). days. Lack of health insurance at diagnosis and use of alternative medicine before attending conventional health services were associated with a significantly longer patient delay (P = .041 and P = .017, respectively). The type of cancer had a significant effect on treatment delay (P = .020). The type of health facility attended affected only patient delay (P = .03). Gender, age at diagnosis, stage of disease, parents' education level or income, and distance from hospital did not have a significant effect on the length of any type of delay. Training on childhood cancer should be included in the curricula for medical training institutes. In-service workshops should be held for the health workers already working. Families must be obligated to get health insurance. Families should be encourage to attend conventional health facilities and informed on symptoms of cancer through mass media.Item Glutathione-S-transferase P1 may predispose children to a decline in pulmonary function after stem cell transplant(Wiley, 2017-07) Stark, Julie; Renbarger, Jamie; Slaven, James; Yu, Zhangsheng; Then, Jenny; Skiles, Jodi; Davis, Stephanie; Pediatrics, School of MedicineRATIONALE: Pulmonary complications after hematopoietic stem cell transplant (SCT) are associated with increased mortality. Genetic markers for those at risk for pulmonary impairment post-SCT have not been widely investigated. METHODS: Forty-nine patients were retrospectively selected from a single institution's biorepository with linked clinical data. All subjects performed pre-SCT PFTs. Genotyping was conducted using the Infinium Exome-24 BeadChip. Four single nucleotide polymorphisms (SNPs) were selected (rs1800871, rs1695, rs1800629, rs12477314) and evaluated for association with PFT parameters as change over time from baseline. Associations between SNPs and PFT parameters were assessed and adjusted for the following confounding variables: age, gender, and race. RESULTS: Using the recessive genetic model, patients with one or two minor alleles for the glutathione S-transferase P1 (GSTP1) SNP rs1695 had a lower decline in FEV1 and FEF25-75 at 1-year post-SCT compared to patients who were homozygous for the ancestral allele (adjusted P-values <0.01 and 0.02, respectively). No other SNPs were significantly associated with other PFT parameters. CONCLUSIONS: Our findings suggest that GSTP1 genotype may be associated with lung function during the first year post-SCT. Identifying and investigating genes that predispose patients to pulmonary complications after SCT may allow for more personalized patient management based on pre-emptive genetic testing. The glutathione S-transferase gene merits further investigation.Item Health-Care Providers' Perspectives towards Childhood Cancer Treatment in Kenya(2016-09) Njuguna, Festus; Van der Burgt, Renske; Seijfert, Anneloes; Musimbi, Joyce; Langat, Sandra; Sitaresmi, Mei Neni; van de Ven, Peter; Kaspers, Gertjan; Mostert, Saskia; Skiles, Jodi; Department of Pediatrics, School of MedicineBACKGROUND: This study explored perspectives of health-care providers on childhood cancer treatment in Kenya. MATERIALS AND METHODS: A self-administered questionnaire was completed by 104 health-care providers in January and February 2013. RESULTS: Seventy six percent of the health-care providers believed cancer to be curable. More doctors than other health-care providers had this positive opinion (p=0.037). The majority of health-care providers (92%) believed that most children with cancer will not be able to finish their treatment due to financial difficulties. They considered that prosperous highly-educated parents adhere better with treatment (88%) and that doctors adhere better with treatment for prosperous highly-educated parents (79%). According to 74% of health-care providers, quality of care is better for prosperous highly-educated parents (74%). Most health-care providers reported giving more explanation (71%), work with greater accuracy (70%) and use less difficult vocabulary (55%) to prosperous more educated families. Only 34% of health-care providers reported they feel more empathy towards patients from prosperous families. Reasons for non-adherence with the protocol according to health-care providers are: family refuses drugs (85%), inadequate supply of drugs at pharmacy (79%), child looks ill (75%), and financial difficulties of parents (69%). CONCLUSIONS: Health-care providers' health beliefs and attitudes differ for patients with families having high versus low socio-economic backgrounds.Item Influence of health insurance status on paediatric non-Hodgkin's lymphoma treatment in Kenya(BMJ Publishing Group, 2017-08-11) Martijn, Hugo A.; Njuguna, Festus; Olbara, Gilbert; Langat, Sandra; Skiles, Jodi; Martin, Stephen; Vik, Terry; Ven, Peter M. van de; Kaspers, Gertjan JL; Mostert, Saskia; Pediatrics, School of MedicineObjective: Non-Hodgkin's lymphoma (NHL) is the most common childhood malignancy in sub-Saharan Africa. Survival rates for NHL are higher than 80% in high-income countries.This study explores treatment outcomes of children with NHL in Kenya, a sub-Saharan low-income country, and the association between health insurance status at diagnosis and treatment outcomes. Design: This was a retrospective medical records study. All children diagnosed with NHL in 2010, 2011 and 2012 were included. Data on treatment outcomes and health insurance status at diagnosis were collected. Results: Of all 63 patients with NHL, 35% abandoned treatment, 22% had progressive or relapsed disease, 14% died and 29% had event-free survival. Most patients (73%) had no health insurance at diagnosis. Treatment outcomes in children with or without health insurance at diagnosis differed significantly (p=0.005). The most likely treatment outcome in children with health insurance at diagnosis was event-free survival (53%), whereas in children without health insurance at diagnosis it was abandonment of treatment (44%). Crude HR for treatment failure was 3.1 (95% CI 1.41 to 6.60, p=0.005) for uninsured versus insured children. The event-free survival estimate was significantly higher in children with health insurance at diagnosis than in patients without health insurance at diagnosis (p=0.003). Stage of disease at diagnosis was identified as a confounder of this association (adjusted HR=2.4, 95% CI 0.95 to 6.12, p=0.063). Conclusions: Survival of children with NHL in Kenya is much lower compared with high-income countries. Abandonment of treatment is the most common cause of treatment failure. Health insurance at diagnosis was associated with better treatment outcomes and survival.Item Multiple Organ Dysfunction and Critically Ill Children with Acute Myeloid Leukemia: single-center retrospective cohort study(Wolters Kluwer, 2023) Gaugler, Mary; Swinger, Nathan; Rahrig, April L.; Skiles, Jodi; Rowan, Courtney M.; Pediatrics, School of MedicineObjectives: To describe the prevalence of multiple organ dysfunction syndrome (MODS) and critical care utilization in children and young adults with acute myeloid leukemia (AML) who have not undergone hematopoietic cell transplantation (HCT). Design: Retrospective cohort study of MODS (defined as dysfunction of two or more organ systems) occurring any day within the first 72 hours of PICU admission. Setting: Large, quaternary-care children's hospital. Patients: Patients 1 month through 26 years old who were treated for AML from 2011-2019. Interventions: None. Measurements and main results: Eighty patients with AML were included. These 80 patients had a total of 409 total non-HCT-related hospital and 71 PICU admissions. The majority 53 of 71 of PICU admissions (75%) were associated with MODS within the first 72 hours. MODS was present in 49 of 71 of PICU admissions (69%) on day 1, 29 of 52 (56%) on day 2, and 25 of 32 (78%) on day 3. The organ systems most often involved were hematologic, respiratory, and cardiovascular. There was an increasing proportion of renal failure (8/71 [11%] on day 1 to 8/32 [25%] on day 3; p = 0.02) and respiratory failure (33/71 [47%] to 24/32 [75%]; p = 0.001) as PICU stay progressed. The presence of MODS on day 1 was associated with a longer PICU length of stay (LOS) (β = 5.4 [95% CI, 0.7-10.2]; p = 0.024) and over a six-fold increased risk of an LOS over 2 days (odds ratio, 6.08 [95% CI, 1.59-23.23]; p = 0.008). Respiratory failure on admission was associated with higher risk of increased LOS. Conclusions: AML patients frequently require intensive care. In this cohort, MODS occurred in over half of PICU admissions and was associated with longer PICU LOS. Respiratory failure was associated with the development of MODS and progressive MODS, as well as prolonged LOS.Item Posterior Reversible Encephalopathy Syndrome: Incidence and Clinical Characteristics in Children with Cancer Katherine(Wolters Kluwer, 2022) Sommers, Katherine R.; Skiles, Jodi; Lelan, Brian; Rowan, Courtney M.; Pediatrics, School of MedicineThe etiology and outcomes of posterior reversible encephalopathy syndrome (PRES) in children with cancer are not well understood. We aim to determine the incidence of PRES, describe associated morbidity and mortality, and better understand risk factors in this patient population. 473 children with a hematologic malignancy or post-allogeneic hematopoietic cell transplantation (HCT) between June 2015 and June 2020 were screened for PRES to determine incidence and whether age or underlying diagnosis are associated with development of PRES. We conducted a case-control study to evaluate whether comorbidities or chemotherapeutic agents are associated with PRES. Children with PRES were matched with two controls based on age and underlying diagnosis to identify additional risk factors. Fourteen patients developed PRES, with an incidence of 5.9/1000 people/year. Those diagnosed with PRES had commonly described PRES symptoms: hypertension, seizures, nausea/vomiting, altered mental status, and headaches. All patients received an MRI, and most had findings consistent with PRES. HCT was associated with the development of PRES. The use of Etoposide was associated with PRES but comorbidities, steroids and calcineurin inhibitors were not. While PRES was infrequent in this population, it is associated with high morbidity and mortality, with ICU admissions and an overall hospital mortality, due to secondary causes, of 29%.Item Wilms Tumor Treatment Outcomes: Perspectives From a Low-Income Setting(American Society of Clinical Oncology, 2016-12-21) Njuguna, Festus; Martijn, Hugo A.; Kuremu, Robert Tenge; Saula, Peter; Kirtika, Patel; Olbara, Gilbert; Langat, Sandra; Martin, Steve; Skiles, Jodi; Vik, Terry; Kaspers, Gertjan J.L.; Mostert, Saskia; Medicine, School of MedicinePurpose Wilms tumor is the commonest renal malignancy in childhood. Survival in high-income countries is approximately 90%, whereas in low-income countries, it is less than 50%. This study assessed treatment outcomes of patients with Wilms tumor at a Kenyan academic hospital. Patients and Methods We conducted a retrospective medical record review of all children diagnosed with Wilms tumor between 2010 and 2012. Data on treatment outcomes and various sociodemographic and clinical characteristics were collected. Results Of the 39 patients with Wilms tumor, 41% had event-free survival, 31% abandoned treatment, 23% died, and 5% had progressive or relapsed disease. Most patients presented at an advanced stage: stage I (0%), II (7%), III (43%), IV (40%), or V (10%). The most likely treatment outcome in patients with low-stage (I to III) disease was event-free survival (67%), whereas in those with high-stage (IV to V) disease, it was death (40%). No deaths or instances of progressive or relapsed disease were recorded among patients with low-stage disease; their only reason for treatment failure was abandonment of treatment. Stage of disease significantly affected treatment outcomes (P = .014) and event-free survival estimates (P < .001). Age at diagnosis, sex, duration of symptoms, distance to hospital, and health insurance status did not statistically significantly influence treatment outcomes or event-free survival estimates. Conclusion Survival of patients with Wilms tumor in Kenya is lower compared with that in high-income countries. Treatment abandonment is the most common cause of treatment failure. Stage of disease at diagnosis statistically significantly affects treatment outcomes and survival.