Different Levels Of Risk Research Articles

Provisional Prognostic Score for Plasmablastic Lymphoma

Background Plasmablastic Lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin's lymphoma. It tends to be associated with immunosuppressive clinical contexts, such as HIV infection and immunosuppressive therapies for autoimmune disorders and organ transplants. However, due to the rarity of the disease, which needs to be better understood, varied treatment approaches have been implemented, and no optimal data or guidelines for managing PBL are available. Therefore, we conducted this study to develop a provisional PBL prognostic score (PBLPS) for this rare disease. Methods We used our constructed PBL database, which contains retrospective data on 300 cases. Such data included demographics such as sex, age, and race. It also included disease presentation symptoms, duration of symptoms before diagnosis, site(s) of the disease, blood counts, coexisting comorbidities, disease immunohistochemical and molecular phenotype, types of treatment, and survival outcomes. Of the 300 cases, 291 had complete survival and outcomes data, the sample chosen for this study. Cox proportional-hazards model and Log-rank tests were used to assess the influence of clinicopathologic factors on overall survival (OS). We included factors that statistically impacted OS and scored them by the impact of their hazard ratios. Results The median OS of the cohort was 25 months. The following dichotomous variables were identified as impactful prognostic factors in this cohort: LDH>500 (p=0.04), CD4<100 (p=0.006), bone marrow (BM) involvement (p<0.0001), EBER-negative (p=0.01), HHV8+ (p=0.02), and involvement of liver (p=0.003), lungs/pleura (p<0.0001), and upper GI tract (p=0.001). A prognostic model was devised using these variables to identify different levels of risk. Involvement of BM and involvement of any of the worse prognosis organs (liver, lung/pleura, and/or upper GI tract) were each assigned a score of 2 when present. CD4<100, EBER-negative, and LDH>500 were assigned 1 point each as they had the lowest hazard ratios of all the other variables. In this exploratory cohort, we assigned low risk a score of 0, intermediate risk a score of 1-2, and high risk a score of 3-7. This prognostic score system led to our cohort's most optimal risk discriminatory model, where low, intermediate, and high risk had a median OS of NR, 15, and 4 months, respectively (p<0.0001). Conclusion This PBLPS is a promising new tool for risk-stratifying patients with PBL. However, it still requires prospective validation.

Provisional Prognostic Score for Blastic Plasmacytoid Dendritic Cell Neoplasm

Background BPDCN is an aggressive hematologic malignancy which often involves the skin. This disorder has gone through many iterations over the years, being classified initially as a blastic NK-cell lymphoma, then a subset of AML, and finally recognized as a unique myeloid neoplasm. While BPDCN often follows an aggressive course, its outcomes vary considerably. We conducted this study to develop a provisional BPDCN prognostic score (BPS) for this rare disease. Methods We used our constructed BPDCN database, which contains retrospective data on 273 cases. Such data included demographics such as sex, age, and race. It also included disease presentation symptoms, duration of symptoms before diagnosis, site(s) of the disease, blood counts, coexisting comorbidities, disease immunohistochemical and molecular phenotype, types of treatment, and survival outcomes. Of the 273 cases, only 218 had complete survival and outcomes data, the sample chosen for this study. Cox proportional-hazards model and Log-rank tests were used to assess the influence of clinicopathologic factors on overall survival (OS). We included factors that statistically impacted OS and scored them by the impact of their hazard ratios. Results The median OS of the cohort was 16 months. The following dichotomous variables were identified as impactful prognostic factors in this cohort: Age>60 (10 vs. 30 months), lymphadenopathy (14 vs. 42 months), bone marrow involvement (14 vs. NR months), splenomegaly (10 vs. 16 months), and disseminated skin disease (13 vs. NR months). A prognostic model was devised using these variables to identify different levels of risk. Each variable was assigned a score of 1 when present, except for age>60, splenomegaly, and disseminated skin disease, that were assigned 2 points each as they had the highest hazard ratios of all the other variables. In this exploratory cohort, low risk was assigned a score of 0-2, intermediate risk a score of 3-4, and high risk a score of 5-8. This prognostic score system led to our cohort's most optimal risk discriminatory model, where low, intermediate, and high risk had a median OS of NR, 24, and 10 months, respectively (p<0.0001). Conclusion This BPS is a promising new tool for risk-stratifying patients with BPDCN. However, it still requires prospective validation.

Unsupervised cluster analysis of clinical and metabolite characteristics in patients with chronic complications of T2DM: an observational study of real data.

The aim of this study was to cluster patients with chronic complications of type 2 diabetes mellitus (T2DM) by cluster analysis in Dalian, China, and examine the variance in risk of different chronic complications and metabolic levels among the various subclusters. 2267 hospitalized patients were included in the K-means cluster analysis based on 11 variables [Body Mass Index (BMI), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Glucose, Triglycerides (TG), Total Cholesterol (TC), Uric Acid (UA), microalbuminuria (mAlb), Insulin, Insulin Sensitivity Index (ISI) and Homa Insulin-Resistance (Homa-IR)]. The risk of various chronic complications of T2DM in different subclusters was analyzed by multivariate logistic regression, and the Kruskal-Wallis H test and the Nemenyi test examined the differences in metabolites among different subclusters. Four subclusters were identified by clustering analysis, and each subcluster had significant features and was labeled with a different level of risk. Cluster 1 contained 1112 inpatients (49.05%), labeled as "Low-Risk"; cluster 2 included 859 (37.89%) inpatients, the label characteristics as "Medium-Low-Risk"; cluster 3 included 134 (5.91%) inpatients, labeled "Medium-Risk"; cluster 4 included 162 (7.15%) inpatients, and the label feature was "High-Risk". Additionally, in different subclusters, the proportion of patients with multiple chronic complications was different, and the risk of the same chronic complication also had significant differences. Compared to the "Low-Risk" cluster, the other three clusters exhibit a higher risk of microangiopathy. After additional adjustment for 20 covariates, the odds ratios (ORs) and 95% confidence intervals (95%CI) of the "Medium-Low-Risk" cluster, the "Medium-Risk" cluster, and the"High-Risk" cluster are 1.369 (1.042, 1.799), 2.188 (1.496, 3.201), and 9.644 (5.851, 15.896) (all p<0.05). Representatively, the "High-Risk" cluster had the highest risk of DN [OR (95%CI): 11.510(7.139,18.557), (p<0.05)] and DR [OR (95%CI): 3.917(2.526,6.075), (p<0.05)] after 20 variables adjusted. Four metabolites with statistically significant distribution differences when compared with other subclusters [Threonine (Thr), Tyrosine (Tyr), Glutaryl carnitine (C5DC), and Butyryl carnitine (C4)]. Patients with chronic complications of T2DM had significant clustering characteristics, and the risk of target organ damage in different subclusters was significantly different, as were the levels of metabolites. Which may become a new idea for the prevention and treatment of chronic complications of T2DM.

Polygenic risk scores and the prediction of onset of mood and psychotic disorders in adolescents and young adults.

To examine whether polygenic risk scores (PRS) for neuroticism, depression, bipolar disorder and schizophrenia are higher in individuals manifesting trans-diagnostic risk factors for the development of major mental disorders and whether PRS enhance prediction of early onset full-threshold disorders. Using data from the Brisbane Longitudinal Twin Study, we examined individual PRS for neuroticism, depression, bipolar disorder and schizophrenia, recorded evidence of subthreshold syndromes and family history of mood and/or psychotic disorders and noted progression to trans-diagnostic clinical caseness (onset of major mental disorders) at follow-up. We undertook multivariate, receiver operating curve and logistic regression analyses that were adjusted for known variables of influence (age, twin status, and so on). Of 1473 eligible participants (female = 866, 59%; mean age 26.3 years), 28% (n = 409) met caseness criteria for a mood and/or psychotic disorder. All PRS were higher in cases versus non-cases but associations with different levels of risk were inconsistent. The prediction of caseness (reported as area under the curve with 95% confidence intervals [CI]) improved from 0.68 (95% CI: 0.65, 0.71) when estimated using clinical risk factors alone up to 0.71 (95% CI: 0.69, 0.73) when PRS were added to the model. Logistic regression identified five variables that optimally classified individuals according to caseness: age, sex, individual risk characteristics, PRS for depression and mental health case status of cotwins or siblings. The findings need replication. However, this exploratory study suggests that combining PRS with other risk factors has the potential to improve outcome prediction in youth.

Risk of Further Progression or Death Among Durable Progression-Free Survivors With Melanoma or Non-Small-Cell Lung Cancer in PD-1 Blockade Trials: Implications for Imaging Surveillance.

Durable progression-free survivors (dPFSors) over 2 years have been reported among patients with melanoma or non-small-cell lung cancer (NSCLC) who received PD-(L)1 therapy. However, risk of progression still exists and the optimal imaging surveillance interval is unknown. Individual patient data for progression-free survival (PFS) were extracted from PD-1 blockade clinical trials with a follow-up of at least 5 years. Patients with a PFS of at least 2 years were considered as dPFSors. Conditional risks of progression/death (P/D) every 3, 4, 6, and 12 months in each subsequent year were calculated. We prespecified three different levels of risk between scans (10%, 15%, or 20%) to allow clinicians and patients to decide on the scanning interval on the basis of considerations of imaging frequency and risk tolerance. An interval is considered acceptable if the upper bound of the 95% CI of the risk at each scan is lower than a prespecified level. Of 1,495 and 3,752 patients with melanoma and NSCLC, 474 (31.7%) and 586 (15.6%) were dPFSors, respectively. Among them, the PFS probability for an additional 3 years was 76.4% and 48.1%, respectively. Not more than 8% of patients had P/D in any quarter in the 3 years. With a risk threshold of 10%, melanoma dPFSors can be scanned every 6 months during the third year and then every 12 months in years 4 and 5. The interval for NSCLC would be every 3 months in the third year and every 4 months in years 4 and 5. The higher risk tolerance of 15% and 20% would allow for less frequent scans. On the basis of their own risk tolerance level, our findings allow clinicians and dPFSors make data-driven decisions regarding the imaging surveillance schedule beyond every 3 months.

Decision Support Model for Allocating Maintenance Budgets for Bridges

This paper introduces a newly developed decision support model for allocating a budget for bridge maintenance. The model is built based on capturing the experts’ knowledge for the prioritization of criteria for selecting a bridge maintenance plan. A literature review and interviews with a group of nine local experts were carried out to identify the criteria for bridge prioritization for maintenance. A questionnaire survey was then designed and administered, utilizing multi-criteria decision-making techniques through face-to-face meetings with local bridge maintenance managers to determine the weights of the identified criteria and develop the utility curves for each criterion. The developed model consists of four major modules: (1) bridge ranking module; (2) prioritization module of bridge structural elements; (3) optimization-based simulation module; and (4) the outputs module. The model was validated in a hypothetical network of four bridges. The validation reveals that the model can assist bridge maintenance managers in setting a bridge maintenance plan, with a high level of confidence using efficient frontier analysis technique. Utilizing frontier analysis enables comparisons of mean costs of different bridge maintenance plans against different levels of risk to enable decision-makers to make informed decisions. The result of this study indicated that bridge structural condition was the most important criterion amongst all the criteria influencing the decision of bridge prioritization for maintenance, followed by traffic and bridge location. Moreover, bridge deck and parapet, followed by bearing pads, were found to be the most important of the bridge’s structural elements.

Type of Exchange Sex and Associated Behaviors and Outcomes Among Cisgender Men and Women at Increased Risk for HIV via Heterosexual Transmission in Six U.S. Metropolitan Areas.

Exchange sex is associated with sexual risk behaviors and poor outcomes and different types may incur different levels of risk. We assessed risk profiles of different types of exchange sex among non-injecting cisgender men and women who participated in the 2019 National HIV Behavioral Surveillance project at six sites. Six percent of men and 19% of women reported exchange sex in the past year; most engaged in non-commercial exchange sex for drugs/money with smaller percentages reporting formal sex work or non-commercial exchange sex for goods or services other than drugs/money. Exchange sex was associated with sexual risk and prevention behaviors and psychosocial and sexual health outcomes and associations varied by type of exchange sex. Efforts to improve access to STI/HIV testing and PrEP may benefit from tailoring based on type of exchange sex. Findings indicate value in a broader definition of exchange sex with follow-up assessment of exchange sex typology.

Characterizing the risk and impacts of tropical cyclones on banana production in the Philippines

The Philippines is one of the world’s largest producers of banana. The Philippines is also vulnerable to climate change and tropical cyclones (TCs), which caused over 236 billion Philippine Pesos worth of losses and damages to agriculture between 1990-2013. TCs can have impacts on banana, which is sensitive to strong winds and flooding. However, banana remains under-studied in the context of food security, climate change, and variability. Here, the physical risk of banana production to TCs by characterizing the hazard, exposure, and physical sensitivity of suitable cropland to TCs. Data on TCs, banana production and prices, and the costs of damages from TCs were also analyzed to provide a picture of TC impacts. The analysis shows that there are different levels of risk to cropland from TCs, and it is higher in Luzon and Eastern Visayas which are exposed to more, and more intense TCs. Mindanao currently has a low calculated physical risk to TCs, although because of the concentration of banana production in Central and Southeastern Mindanao, there may be more exposed, and thus vulnerable, cropland. Linear statistical relationships are poor between banana production and TCs, although recent experience from Typhoons Pablo and Odette (TC Bopha and Rai, 2012 and 2021) give evidence to the significant losses and damages from TC on banana production in Mindanao. Because TCs are projected to potentially become more intense, with more variability and uncertainty from climate change, more research is needed, given the banana’s importance in the Philippines.

Assessing a Polygenic Risk Score for Lung Cancer Susceptibility in Non-Hispanic White and Black Populations.

Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black populations in model development. We used a previously published lung cancer PRS on the basis of 80 SNPs associated with lung cancer risk in the OncoArray cohort and validated in UK Biobank. The PRS was evaluated for association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of chronic obstructive pulmonary disease, and the top five principal components for genetic ancestry. Among the 80 PRS SNPs included in the score, 14 were significantly associated with lung cancer risk (P < 0.05) in INHALE White participants, while there were no significant SNPs among INHALE Black participants. After adjusting for covariates, the PRS was significantly associated with risk in Whites (continuous score P = 0.007), but not in Blacks (continuous score P = 0.88). The PRS remained a statistically significant predictor of lung cancer risk in Whites ineligible for lung cancer screening under current U.S. Preventive Services Task Force guidelines (P = 0.02). Using a previously validated PRS, we did find some predictive ability for lung cancer in INHALE White participants beyond traditional risk factors. However, this effect was not observed in Black participants, indicating the need to develop and validate ancestry-specific lung cancer risk models. While a previously published lung cancer PRS was able to stratify White participants into different levels of risk, the model was not predictive in Blacks. Our findings highlight the need to develop and validate ancestry-specific lung cancer risk models.

Exploring Caregiver Interest in and Preferences for Interventions for Children With Risk of Asthma Exacerbation: Web-Based Survey.

Maintaining control of asthma symptoms is the cornerstone of asthma treatment guidelines in the United States. However, suboptimal asthma control and asthma exacerbations among young people are common and are associated with many negative outcomes. Interventions to improve asthma control are needed. For such interventions to be successful, it is necessary to understand the types of interventions that are appealing to caregivers of children with different levels of risk of exacerbation. This study aimed to evaluate whether caregivers of children with high (vs low) risk of asthma exacerbation show different levels of interest in and preferences for potential intervention programs and delivery methods. We contracted with Ipsos to administer a web-based survey to caregivers of children with asthma who were residing in the United States. Caregivers (N=394) reported their interest (1=not at all; 3=a lot) in 9 possible intervention programs and 8 possible intervention delivery methods. Caregivers also indicated their preferences by selecting the 3 intervention programs and 3 delivery methods that "most" interested them. Finally, caregivers completed 2 open-ended questions asking what other resources might be useful for managing their children's asthma. We classified children as having a high risk of exacerbation if they had an exacerbation in the past 3 months (n=116) and a low risk of exacerbation if otherwise (n=278). Caregivers reported higher levels of interest in all intervention programs and delivery methods if they cared for a child with a high risk rather than a low risk of exacerbation. However, regardless of the child's risk status, caregivers expressed the highest levels of interest in programs to increase their child's self-management skills, to help pay for asthma care, and to work with the school to manage asthma. Caregivers expressed the highest levels of interest in delivery methods that maintained personal control over accessing information (websites, videos, printed materials, and smartphone apps). Caregivers' preferences were consistent with their interests; programs and delivery methods that were rated as high in interest were also selected as one of the 3 that "most" interested them. Although most caregivers did not provide additional suggestions for the open-ended questions, a few caregivers suggested intervention programs and delivery methods that we had not included (eg, education about avoiding triggers and medication reminders). Similar interests and preferences among caregivers of children with high and low risk of exacerbation suggest a broad need for support in managing childhood asthma. Providers could help caregivers by directing them toward resources that make asthma care more affordable and by helping their children with asthma self-management. Interventions that accommodate caregivers' concerns about having personal control over access to asthma information are likely to be more successful than interventions that do not.

Nomogram for predicting survival of patients with gastric cancer and multiple primary malignancies: a real-world retrospective analysis using the Surveillance, Epidemiology and End Results database.

Gastric cancer combined with multiple primary malignancies (GCM) is increasingly common. This study investigated GCM clinical features and survival time. Patients with GCM and GC only (GCO) were selected from the Surveillance, Epidemiology and End Results (SEER) database. Survival was compared between GCM and GCO groups using propensity score matching. Then, the GCM group was divided into a training cohort and a validation cohort. These cohorts were used to establish a nomogram for survival prediction in patients with GCM. Survival time was significantly longer in the GCM group than in the GCO group. All-subsets regression was used to identify four variables for nomogram establishment: age, gastric cancer sequence, N stage, and surgery. The concordance index and time-dependent receiver operating characteristic curve indicated that the nomogram had favorable discriminative ability. Calibration plots of predicted and actual probabilities showed good consistency in both the training and validation cohorts. Decision curve analysis and risk stratification showed that the nomogram was clinically useful; it had favorable discriminative ability to recognize patients with different levels of risk. Compared with GCO, GCM is a relatively indolent malignancy. The nomogram developed in this study can help clinicians to assess GCM prognosis.

Economic policy uncertainty and stock market in G7 Countries: A panel threshold effect perspective.

Based on the literature, it is commonly understood that stock prices (SP) are influenced by economic policy uncertainty (PU), with a rise in PU typically having a negative impact on SP. However, the relationship between PU and SP may not always be linear due to the varying risk preferences of individuals. Risk preference theory posits that individuals respond differently to different levels of risk. Therefore, this study aims to investigate whether PU determines SP asymmetrically (i.e., in a non-linear manner) by considering risk preferences and addressing a gap in the literature. To answer this question, the study employs a panel threshold approach to examine the effect of PU on SP in the Group of Seven (G7) countries, namely Canada, France, Germany, Italy, Japan, UK, and the US. In contrast to previous research, this study finds evidence of an asymmetric effect of PU on SP in the G7 countries. Specifically, the panel threshold results reveal that the impact of increased PU on SP is positive up to a certain level (Threshold1), beyond which it becomes negative (Threshold2). These findings are in line with information asymmetry hypothesis, prospect theory, behavioural finance hypothesis, and market liquidity hypothesis and shed light on the asymmetric behaviour of SP in response to varying levels of PU. The implications of these findings are significant for understanding how to manage risks effectively in the financial markets.

Portfolio Selection Strategies in Bursa Malaysia Based on Quadratic Programming

The study aims to select the efficient portfolio on stock listed in Bursa Malaysia by using the quadratic programming method. It can help the investors to gain expected returns from the diversification portfolio. However, there are some problems that should be considered such as the measurement of inputs for Mean-Variance Models (MVM), use of portfolio models through time and consistency with management objectives in the portfolio. These problems will affect the performance of selected portfolio and cause the loss problem. Therefore, this study implements a quadratic programming approach to select an efficient portfolio on stocks listed in Bursa Malaysia. The study will choose 15 potential companies which have the best performance in the Bursa Malaysia. Quadratic programming (QP) model can solve any type of mathematical optimisation problem in the study. Therefore, investors can optimise the investment portfolio returns by using QP methods. However, we can observe the efficient frontier which is a graph that representing a list of portfolios that optimising expected return for a different level of portfolio risk so can help the investors make a good decision. The findings of this study will give important inputs, especially to the investors to maximise their portfolio return at different level of risks.

Disease-modifying anti-rheumatic drugs associated with different diabetes risks in patients with rheumatoid arthritis

ObjectivesPatients with rheumatoid arthritis are prone to developing diabetes, which may lead to various sequelae and even cardiovascular diseases, the most common cause of death in such patients. Previous research...

Polygenic risk scores in assessing lung cancer susceptibility in non-Hispanic White and Black populations.

10548 Background: Polygenic risk scores (PRS) have become an increasingly popular approach to evaluate cancer susceptibility, but have not adequately represented Black patients in model development. We used previously identified single nucleotide polymorphisms (SNPs) and annotated SNPs in associated gene regions to develop PRS in non-Hispanic Whites and Blacks using the INHALE dataset. Methods: Using the Multi-Ethnic Genotype Array, 1,204 SNPs for non-Hispanic Whites and 1,515 SNPs for Blacks were evaluated for their association with lung cancer risk adjusting for age, sex, total pack-years, family history of lung cancer, history of COPD and the top five PCs for genetic ancestry. Gene region-specific significant SNPs (p &lt; 0.05) were used to develop race-specific PRS. Results: The race-specific PRS included different sets of significant SNPs and were highly associated with lung cancer risk in both non-Hispanic Whites (OR = 1.07, 95% CI: 1.05-1.09, p = 3.44x10-9) and Blacks (OR = 1.12, 95% CI: 1.08-1.17, p = 9.14x10-8). These models remained significant for both Whites (OR = 1.05, 95% CI: 1.03-1.09, p = 0.0004) and Blacks (OR = 1.08, 95% CI: 1.01-1.15, p = 0.01) who currently do not meet USPSTF screening guidelines. AUC analysis demonstrated the Black-specific model (AUC = 0.68) outperformed the White-specific model (AUC = 0.57) (p = 0.03) when examined exclusively in the Black cohort. Conclusions: Using previously validated SNPs and gene regions, we developed race-specific PRS in non-Hispanic White and Black INHALE participants. Further validation of PRS could enable the incorporation of genetic risk modeling into lung cancer screening to identify patients who do not have traditional risk factors for lung cancer, as well as stratify patients into different levels of risk based on their genetic profile. Through the development of a reliable genetic risk factor prediction model, clinicians will have another method by which to evaluate lung cancer susceptibility, potentially leading to earlier diagnoses that portend more favorable treatment outcomes.

SA27 Utility Maximization Vs Regret Minimization: Choice Behavior Under Uncertainty

To examine whether random utility maximization (RUM) or Random Regret Minimization (RRM) better describes how people make decisions when facing with different levels of risks and survivals.

Failure mode and Effect Analysis of personal fall arrest system under the intuitionistic fuzzy environment

Background and aimsIntuitionistic fuzzy sets (IFS) theory is more powerful than classic fuzzy sets theory in handling uncertainty. A new approach for Failure Mode and Effect Analysis (FMEA) was developed based on IFS and group decision-making (known as IF-FMEA) for investigating Personal Fall Arrest System (PFAS). MethodFMEA parameters, including occurrence, consequence, and detection, were re-defined based on a seven-point linguistic scale. Each linguistic term was associated with an intuitionistic triangular fuzzy set. Opinions on the parameters were gathered from a panel of experts, integrated using the similarity aggregation method, and defuzzified utilizing the center of gravity approach. ResultsNine failure modes were identified and analyzed using both FMEA and IF-FMEA. The risk priority numbers (RPNs) and prioritization obtained from the two approaches were different, highlighting the importance of using IFS. The highest RPN was associated with the lanyard web failure, while the failure of the anchor D-ring had the least RPN. Detection score was higher for metal parts of the PFAS, suggesting that failures in these parts are harder to detect. ConclusionIn addition to being economical in terms of calculations, the proposed method was efficient in handling uncertainty. Different parts of a PFAS create different levels of risk.

Letter: Commentary: The Anatomy of Disvalued Codes: The 63047 and the 22633.

Letter: Commentary: The Anatomy of Disvalued Codes: The 63047 and the 22633.

Balancing the beautiful and the good in pursuit of biomarkers for depression.

Balancing the beautiful and the good in pursuit of biomarkers for depression.

HAART induced inflammation, toxicity and its determinants among HIV positive children in Addis Ababa, Ethiopia

BackgroundHighly Active Antiretroviral therapy (HAART) plays significant role in reduction of mortality among children infected with HIV. Despite the inevitable impact of HAART on inflammation and toxicity, there is limited evidence on its impact among children in Ethiopia. Moreover, evidence on contributing factors to toxicity has been poorly described. Hence, we evaluated HAART induced inflammation and toxicity among children taking HAART in Ethiopia. MethodThis cross-sectional study was conducted among children (<15 years old) taking HAART in Ethiopia. Stored plasma samples and secondary data from a previous study on HIV-1 treatment failure were used for this analysis. By 2018, a total of 554 children were recruited from randomly selected 43 health facilities in Ethiopia. The different levels of liver (SGPT), renal (Creatinine) and hematologic toxicity (Hemoglobin) toxicity were assessed using established cut-off value. Inflammatory biomarkers (CRP and vitamin-D) were also determined. Laboratory tests were done at the national clinical chemistry laboratory. Clinical and baseline laboratory data were retrieved from the participant's medical record. Questionnaire was also administered to study guardians to assess individual factors to inflammation and toxicity. Descriptive statistics was used to summarize the characteristics of the study participants. Multivariable analysis was conducted and considered significant at P < 0.05. ResultOverall 363 (65.6%) and 199 (36%) of children taking HAART in Ethiopia developed some level of inflammation and vitamin-D in-sufficiency, respectively. A quarter of the children 140 (25.3%) were at Grade-4 liver toxicity while renal toxicity were 16 (2.9%). A third 275 (29.6%) of the children also developed anemia. Children who were on TDF+3 TC + EFV, those who were not virally suppressed and children with liver toxicity were at 17.84 (95%CI = 16.98, 18.82), 2.2 (95%CI = 1.67, 2.88) and 1.20 (95%CI = 1.14, 1.93) times risk of inflammation, respectively. Children on TDF+3 TC + EFV, those with CD4 count of <200 cells/mm3 and with renal toxicity were at 4.10 (95%CI = 1.64, 6.89), 2.16(95%CI = 1.31, 4.26) and 5.94 (95%CI = 1.18, 29.89) times risk of vitamin-D in-sufficiency, respectively. Predictors of liver toxicity were history of HAART substitution (AOR = 4.66; 95%CI = 1.84, 6.04) and being bedridden (AOR = 3.56; 95%CI = 2.01, 4.71). Children from HIV positive mother were at 4.07 (95%CI = 2.30, 6.09) times risk of renal toxicity while the different type of HAARTs had different level of risk for renal toxicity AZT+3 TC + EFV (AOR = 17.63; 95%CI = 18.25, 27.54); AZT+3 TC + NVP (AOR = 22.48; 95%CI = 13.93, 29.31); d4t+3 TC + EFV (AOR = 4.34; 95%CI = 2.51, 6.80) and d4t+3 TC + NVP (AOR = 18.91; 95%CI = 4.87, 27.74) compared to those who were on TDF+3 TC + NVP. Similarly, children who were on AZT+3 TC + EFV were at 4.92 (95%CI = 1.86, 12.70) times risk of anemia compared to those who were on TDF+ 3 TC + EFZ. ConclusionThe high level of HAART induced inflammation and liver toxicity among children calls for the program to consider safer regimens for pediatric patients. Moreover, the high proportion of vitamin-D in-sufficiency requires program level supplement. The impact of TDF+3 TC + EFV on inflammation and vitamin-D deficiency calls for the program to revise this regimen.