All It Takes for Corruption in Health Systems to Triumph, Is Good People Who Do Nothing; Comment on “We Need to Talk About Corruption in Health Systems”

Numerous investigations demonstrate that the problem of corruption in the health sector is enormous and has grave negative consequences for patients. Nevertheless, the problem of corruption in health systems is far from eminent in the international health policy debate. Hutchinson, Balabanova, and McKee have identifed in their Editorial five reasons why the health policy community has been reluctant to talk about it: (1) Problem of defining corruption; (2) Some corrupt practices are actually ways of making dysfunctional systems work; (3) The serious challenges to researching corruption; (4) Concerns that focus on corruption is a form of victim blaming that ignores larger issues; and (5) Lack of evidence about what works to tackle it. In this commentary, we pay a closer and critical look at these five excuses for doing nothing. We conclude that the vast majority of the world population, being the poor in low and middle-income countries (LMICs) who disproportionately suffer from the problem of corruption in health systems, need good people with high moral and ethical principles who have the courage to disregard these five reasons. The poor need good people who understand that it is crucial to first acknowledge this problem, despite the obvious uncertainties involved, before you can change it. The poor therefore need good editors, good policy-makers, good managers, and good clinicians. We agree with the authors that we first need to talk about corruption. But above all, we need good people who are subsequently willing to walk the talk

Dose-related efficacy and toxicity of gemtuzumab ozogamicin in pediatric acute myeloid leukemia

Gemtuzumab ozogamicin, an anti-tumour antibiotic linked to an anti-CD33 antibody (Mylotarg®), has been well studied in AML in adults but to a lesser extent in children. No review has yet been published on the dose-related toxicity and efficacy of gemtuzumab ozogamicin in pediatric AML patients. Here we looked at 14 studies then scatterplots and linear regressions were used to estimate the relationship between the dose of gemtuzumab and its toxicity and efficacy. A non-significant increase in bilirubin level and in incidence of veno-occlusive disease was seen with higher doses of gemtuzumab ozogamicin when used as single-agent. In terms of efficacy, even a low dose of 3 mg/m2 of gemtuzumab ozogamicin can have antileukemic effect, but available data do not allow conclusions on its dose-dependency. Data indicate that higher doses of gemtuzumab ozogamicin account for more adverse events. The data do not show that a high dose is required for anti-leukemic efficacy of gemtuzumab ozogamicin. This study also indicates that there seems to be a role for gemtuzumab ozogamicin in the treatment of pediatric AML and further studies are required to assess its optimal dose, schedule and balance between efficacy and side-effects

Impaired sleep affects quality of life in children during maintenance treatment for acute lymphoblastic leukemia: an exploratory study

Contains fulltext : 97021.pdf (publisher's version ) (Open Access)BACKGROUND: With the increase of pediatric cancer survival rates, late effects and quality of life (QoL) have received more attention. Disturbed sleep in pediatric cancer is a common clinical observation, but research on this subject is sparse. In general, sleep problems can lead to significant morbidity and are associated with impaired QoL. Information on sleep is essential to develop interventions to improve QoL. METHODS: Children (2-18 years) with acute lymphoblastic leukemia (ALL) were eligible for this multi-center study. The Children's Sleep Habits Questionnaire (CSHQ), Child Health Questionnaire (CHQ) and Pediatric Quality of Life Inventory 3.0 Acute Cancer Version (PedsQL) were used to assess sleep and QoL halfway through maintenance therapy. Sleep and QoL were measured during and after dexamethasone treatment (on-dex and off-dex). RESULTS: Seventeen children participated (age 6.7 +/- 3.3 years, 44% boys). Children with ALL had more sleep problems and a lower QoL compared to the norm. There were no differences on-dex and off-dex. Pain (r = -0.6; p = 0.029) and worry (r = -0.5; p = 0.034) showed a moderate negative association with sleep. Reduced overall QoL was moderately associated with impaired overall sleep (r = -0.6; p = 0.014) and more problems with sleep anxiety (r = -0.8; p = 0.003), sleep onset delay (r = -0.5; p = 0.037), daytime sleepiness (r = -0.5; p = 0.044) and night wakenings (r = -0.6; p = 0.017). CONCLUSION: QoL is impaired in children during cancer treatment. The results of this study suggest that impaired sleep may be a contributing determinant. Consequently, enhanced counseling and treatment of sleep problems might improve QoL. It is important to conduct more extensive studies to confirm these findings and provide more detailed information on the relationship between sleep and QoL, and on factors affecting sleep in pediatric ALL and in children with cancer in general

Effect of Antibacterial Prophylaxis on Febrile Neutropenic Episodes and Bacterial Bloodstream Infections in Dutch Pediatric Patients with Acute Myeloid Leukemia:A Two-Center Retrospective Study

Bloodstream infections (BSIs), especially those caused by Gram-negative rods (GNR) and viridans group streptococci (VGS), are common and potentially life-threatening complications of pediatric acute myeloid leukemia (AML) treatment. Limited literature is available on prophylactic regimens. We retrospectively evaluated the effect of different antibacterial prophylaxis regimens on the incidence of febrile neutropenic (FN) episodes and bacterial BSIs. Medical records of children (0–18 years) diagnosed with de novo AML and treated at two Dutch centers from May 1998 to March 2021 were studied. Data were analyzed per chemotherapy course and consecutive neutropenic period. A total of 82 patients had 316 evaluable courses: 92 were given with single-agent ciprofloxacin, 138 with penicillin plus ciprofloxacin, and 51 with teicoplanin plus ciprofloxacin. The remaining 35 courses with various other prophylaxis regimens were not statistically compared. During courses with teicoplanin plus ciprofloxacin, significantly fewer FN episodes (43% vs. 90% and 75%; p < 0.0001) and bacterial BSIs (4% vs. 63% and 33%; p < 0.0001) occurred than with single-agent ciprofloxacin and penicillin plus ciprofloxacin, respectively. GNR and VGS BSIs did not occur with teicoplanin plus ciprofloxacin and no bacterial BSI-related pediatric intensive care unit (PICU) admissions were required, whereas, with single-agent ciprofloxacin and penicillin plus ciprofloxacin, GNR BSIs occurred in 8% and 1% (p = 0.004), VGS BSIs in 24% and 14% (p = 0.0005), and BSI-related PICU admissions were required in 8% and 2% of the courses (p = 0.029), respectively. Teicoplanin plus ciprofloxacin as antibacterial prophylaxis is associated with a lower incidence of FN episodes and bacterial BSIs. This may be a good prophylactic regimen for pediatric AML patients during treatment

Health-Care Providers' Perspectives towards Childhood Cancer Treatment in Kenya

BACKGROUND: 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

Folates provoke cellular efflux and drug resistance of substrates of the multidrug resistance protein 1 (MRP1)

Cellular folate concentration was earlier reported to be a critical factor in the activity and expression of the multidrug resistance protein MRP1 (ABCC1). Since MRP1 mediates resistance to a variety of therapeutic drugs, we investigated whether the cellular folate concentration inf

Cost-analysis of treatment of childhood acute lymphoblastic leukemia with asparaginase preparations: The impact of expensive chemotherapy

__Abstract__ Asparaginase is an expensive drug, but important in childhood acute lymphoblastic leukemia. In order to compare costs of PEGasparaginase, Erwinia asparaginase and native E. coli asparaginase, we performed a cost-analysis in the Dutch Childhood Oncology Group ALL-10 medium-risk group intensification protocol. Treatment costs were calculated based on patient level data of 84 subjects, and were related to the occurrence of allergy to PEGasparaginase. Simultaneously, decision tree and sensitivity analyses were conducted. The total costs of the intensification course of 30 weeks were $57,893 in patients without PEGasparaginase allergy (n=64). The costs were significantly higher ($113,558) in case of allergy (n=20) necessitating a switch to Erwinia asparaginase. Simulated scenarios (decision tree analysis) using native E. coli asparaginase in intensification showed that the costs of PEGasparaginase were equal to those of native E. coli asparaginase. Also after sensitivity analyses, the costs for PEGasparaginase were equal to those of na

Effect of polymorphisms in folate-related genes on in vitro methotrexate sensitivity in pediatric acute lymphoblastic leukemia

We studied whether common polymorphisms in genes involved in folate metabolism affect methotrexate (MTX) sensitivity. Ex vivo MTX sensitivity of lymphoblasts obtained from pediatric patients with acute lymphoblastic leukemia (ALL; n = 157) was determined by the in situ thymidylate synthase inhibition assay after either continuous (21 hours; TSI(50, cont)) or short-term (3 hours; TSI(50, short)) MTX exposure. DNA was isolated from lymphoblasts obtained from cytospin slides. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR 677C>T, MTHFR 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC 80G>A) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or real-time PCR. Patients with the MTHFR 1298AC variant or the MTRR 66 G-allele showed decreased in vitro MTX sensitivity measured under both test conditions. SHMT1 1420TT homozygotes only showed decreased MTX sensitivity in the TSI(50, cont). In conclusion, polymorphisms in the folate-related genes MTHFR, MTRR, and SHMT1 are related to MTX resistance in pediatric patients with ALL

Parental Sleep, Distress, and Quality of Life in Childhood Acute Lymphoblastic Leukemia:A Longitudinal Report from Diagnosis up to Three Years Later

This study assessed sleep, distress and quality of life (QoL) in parents of children with acute lymphoblastic leukemia (ALL) from diagnosis to three years after, and the impact of sleep and distress on QoL. Additionally, this study explored determinants of sleep and distress. Parents completed the MOS Sleep, Distress Thermometer for Parents and SF-12 at four-five months (T0), one year (T1), two years (T2), and three years (T3) after diagnosis. The course of outcomes and longitudinal impact of clinically relevant sleep problems (>1SD above reference’s mean) and clinical distress (score ≥ 4) on QoL Z-scores were assessed with linear mixed-models. Determinants of sleep and distress were assessed with multinomial mixed-models. Parents (81% mothers) of 139 patients (60% males; 76% medium-risk (MR)) participated. Distress and QoL gradually restored from T0 to T3. Sleep problems improved, but were still elevated at T3: 33% reported clinically relevant sleep problems, of which 48% in concurrence with distress. Over time, presence of sleep problems or distress led to lower mental QoL Z-scores (SD-score −0.2 and −0.5, respectively). Presence of both led to a cumulatively lower Z-score (SD-score −1.3). Parents in the latter group were more likely to report insufficient social support, parenting problems, a chronic illness, pain for their child, having a child with MR-ALL, and being closer to diagnosis. In conclusion, parental well-being improves over time, yet sleep problems persist. In combination with ongoing distress, they cumulatively affect QoL. Special attention should be given to parents who are vulnerable to worse outcomes

The neurovascular unit in diffuse intrinsic pontine gliomas

Aims: Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a median overall survival of eleven months. Lack of chemotherapy efficacy may be related to an intact blood-brain barrier (BBB). In this study we aim to investigate the neurovascular unit (NVU) in DIPG patients. Methods: DIPG biopsy (n = 4) and autopsy samples (n = 6) and age-matched healthy pons samples (n = 20) were immunohistochemically investigated for plasma protein extravasation, and the expression of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1), basement membrane component laminin, pericyte marker PDGFR-β, and efflux transporters P-gp and BCRP. The mean vascular density and diameter were also assessed. Results: DIPGs show a heterogeneity in cell morphology and evidence of BBB leakage. Both in tumor biopsy and autopsy samples, expression of claudin-5, ZO-1, laminin, PDGFR-β and P-gp was reduced compared to healthy pontine tissues. In DIPG autopsy samples, vascular density was lower compared to healthy pons. The density of small vessels (&lt;10 µm) was significantly lower (P&lt;0.001), whereas the density of large vessels (≥10 µm) did not differ between groups (P = 0.404). The median vascular diameter was not significantly different: 6.21 µm in DIPG autopsy samples (range 2.25-94.85 µm), and 6.26 µm in controls (range 1.17-264.77 µm). Conclusion: Our study demonstrates evidence of structural changes in the NVU in DIPG patients, both in biopsy and autopsy samples, as well as a reduced vascular density in end-stage disease. Adding such a biological perspective may help to better direct future treatment choices for DIPG patients