Addressing the mental health needs of children affected by HIV in Rwanda: validation of a rapid depression screening tool for children 7-14 years old.

BACKGROUND: Depression in children presents a significant health burden to society and often co-exists with chronic illnesses, such as human immunodeficiency virus (HIV). Research has demonstrated that 10-37% of children and adolescents living with HIV also suffer from depression. Low-and-middle income countries (LMICs) shoulder a disproportionate burden of HIV among other health challenges, but reliable estimates of co-morbid depression are lacking in these settings. Prior studies in Rwanda, a LMIC of 12 million people in East Africa, found that 25% of children living with HIV met criteria for depression. Though depression may negatively affect adherence to HIV treatment among children and adolescents, most LMICs fail to routinely screen children for mental health problems due to a shortage of trained health care providers. While some screening tools exist, they can be costly to implement in resource-constrained settings and are often lacking a contextual appropriateness. METHODS: Relying on international guidelines for diagnosing depression, Rwandan health experts developed a freely available, open-access Child Depression Screening Tool (CDST). To validate this tool in Rwanda, a sample of 296 children with a known diagnosis of HIV between ages 7-14 years were recruited as study participants. In addition to completing the CDST, all participants were evaluated by a mental health professional using a structured clinical interview. The validity of the CDST was assessed in terms of sensitivity, specificity, and a receiver operating characteristic (ROC) curve. RESULTS: This analysis found that depression continues to be a co-morbid condition among children living with HIV in Rwanda. For identifying these at-risk children, the CDST had a sensitivity of 88.1% and specificity of 96.5% in identifying risk for depression among children living with HIV at a cutoff score of 6 points. This corresponded with an area under the ROC curve of 92.3%. CONCLUSIONS: This study provides evidence that the CDST is a valid tool for screening depression among children affected by HIV in a resource-constrained setting. As an open-access and freely available tool in LMICs, the CDST can allow any health practitioner to identify children at risk of depression and refer them in a timely manner to more specialized mental health services. Future work can show if and how this tool has the potential to be useful in screening depression in children suffering from other chronic illnesses.

Fatty acid metabolism underlies venetoclax resistance in acute myeloid leukemia stem cells.

Venetoclax with azacitidine (ven/aza) has emerged as a promising regimen for acute myeloid leukemia (AML), with a high percentage of clinical remissions in newly diagnosed patients. However, approximately 30% of newly diagnosed and the majority of relapsed patients do not achieve remission with ven/aza. We previously reported that ven/aza efficacy is based on eradication of AML stem cells through a mechanism involving inhibition of amino acid metabolism, a process which is required in primitive AML cells to drive oxidative phosphorylation. Herein we demonstrate that resistance to ven/aza occurs via up-regulation of fatty acid oxidation (FAO), which occurs due to RAS pathway mutations, or as a compensatory adaptation in relapsed disease. Utilization of FAO obviates the need for amino acid metabolism, thereby rendering ven/aza ineffective. Pharmacological inhibition of FAO restores sensitivity to ven/aza in drug resistant AML cells. We propose inhibition of FAO as a therapeutic strategy to address ven/aza resistance.