Presence Of Complex Chronic Condition Research Articles

Epidemiology, Outcomes, and Trend Analysis of Hospitalized Infants With Respiratory Syncytial Virus (RSV) Bronchiolitis From 1997 to 2019.

Background Most children with respiratory syncytial virus (RSV) infection have a self-limiting course that can be managed with supportive care, and hospitalization is uncommon. The objectives of this study were to evaluate the epidemiology, outcomes, associated comorbidities, and temporal trends in the prevalence of infants one to 24 months of age who required hospitalization for RSV infection in the United States of America from 1997 to 2019. Methods In this retrospective cross-sectional study, we utilized the Kids' Inpatient Database (KID) to investigate the prevalence and outcomes of RSV bronchiolitis within a large cohort of discharged patients from 1997 to 2019. We included children one to 24 months of age admitted with a diagnosis of RSV bronchiolitis. Neonates were excluded from the analysis. A chi-square for linear trend was used to analyze trends in the prevalence of RSV bronchiolitis hospitalization, the presence of complex chronic conditions (CCC), congenital heart disease (CHD), the use of non-invasive and invasive mechanical ventilation (NIV and IMV), and hospital mortality. Results There were a total of 566,786 infants aged one to 24 months hospitalized with RSV infection out of a total of 9,309,597 discharges during the eight-year cohort, with a hospital prevalence of 60.9 per 1000 discharges and a hospital mortality rate of 0.09% (95% confidence interval (CI): 0.08%-0.1%). There was no trend in hospitalization rates of RSV infections per 100,000 U.S. population during the study period, with a decrease in hospital mortality trend. Children with RSV bronchiolitis were more likely to have government insurance and reside in zip codes with the lowest income quartile. There was a significant seasonal and regional variation in RSV-related hospitalizations. The presence of CCC was identified in 2.4% of the RSV group compared to 5.1% of non-RSV discharges (odds ratio (OR): 0.46, 95% CI: 0.45-0.47; p<0.001). The prevalence of RSV among all discharges has significantly increased over the study period, rising from 51.6 cases per 1000 discharges in 1997 to 180.1 cases per 1000 discharges in 2019 (p<0.001). The prevalence of CCC and CHD among RSV patients has also shown an upward trend, with CCC cases increasing from 1,411 in 1997 to 2,795 in 2019 and CHD cases rising from 1,795 to 3,622 during the same period. The use of invasive mechanical ventilation, non-invasive ventilation, and extracorporeal membrane oxygenation has consistently increased over time. Additionally, complications such as the need for cardiopulmonary resuscitation have demonstrated a similar increasing trend, although they have remained overall low. However, population-based hospitalization rates showed no significant trend. Conclusions The hospitalization rates at a population level in the United States for RSV infection in children aged one to 24 months remained steady from 1997 to 2019, while hospital mortality rates showed a declining trend. There is an increased proportion of comorbid conditions and increased resource utilization in children with RSV. These findings are important for monitoring the effectiveness of preventive strategies for severe RSV infections.

Prevalence of and Risks for Bacterial Infections in Hospitalized Children With Bronchiolitis.

Viral bronchiolitis is a common pediatric illness. Treatment is supportive; however, some children have concurrent serious bacterial infections (cSBIs) requiring antibiotics. Identifying children with cSBI is challenging and may lead to unnecessary treatment. Improved understanding of the prevalence of and risk factors for cSBI are needed to guide treatment. We sought to determine the prevalence of cSBI and identify factors associated with cSBI in children hospitalized with bronchiolitis. We performed a retrospective cohort study of children <2 years old hospitalized with bronchiolitis at a free-standing children's hospital from 2012 to 2019 identified by International Classification of Diseases codes. cSBI was defined as bacteremia, urinary tract infection, meningitis, or pneumonia. Risk factors for cSBI were identified using logistic regression. We identified 7871 admissions for bronchiolitis. At least 1 cSBI occurred in 4.2% of these admissions; with 3.5% meeting our bacterial pneumonia definition, 0.4% bacteremia, 0.3% urinary tract infection, and 0.02% meningitis. cSBI were more likely to occur in children with invasive mechanical ventilation (odds ratio [OR] 2.53, 95% confidence interval [CI] 1.78-3.63), a C-reactive protein ≥4 mg/dL (OR 2.20, 95% CI 1.47-3.32), a concurrent complex chronic condition (OR 1.67, 95% CI 1.22-2.25) or admission to the PICU (OR 1.46, 95% CI 1.02-2.07). cSBI is uncommon among children hospitalized with bronchiolitis, with pneumonia being the most common cSBI. Invasive mechanical ventilation, elevated C-reactive protein, presence of complex chronic conditions, and PICU admission were associated with an increased risk of cSBI.

Epidemiology of Adenovirus Infection in Hospitalized Children in the United States From 1997 to 2019.

The study aimed to explore the prevalence, clinical features, resource utilization, temporal trends and outcomes associated with adenoviral infections in hospitalized children. A retrospective analysis using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997 to 2019 was performed. Children 29 days to 17 years of age with adenoviral infection were selected. Chi-square, Kruskal-Wallis tests, linear trend analysis and multivariable analysis were used for data analysis. A total of 40,135 children under 18 years of age with adenoviral infection were discharged in the United States with an overall prevalence of 18.9 per 10,000 discharges and 6.9 children per 100,000 population. By linear trend analysis, the hospitalization rate has significantly increased with the highest prevalence in 2019. Adenoviral infection was more prevalent in Black children, in winter months, in the Midwest region, in children with government insurance and in the lowest income quartile. The majority (85%) of adenovirus-related hospitalizations occurred under 6 years of age. Mechanical ventilation, extracorporeal membrane oxygenation support, acute kidney injury and liver failure were documented in 11.9%, 0.4%, 2.7% and 0.4%, respectively. The overall case fatality rate was 1.4%, which decreased from 1997 to 2019 ( P < 0.05). By regression analysis, an increased mortality rate was associated with the need for mechanical ventilation, the presence of complex chronic conditions, immune deficiency, central nervous system infection and pneumonia/bronchiolitis. Most human adenovirus infections occur in children under 6 years of age and cause mild illness. Human adenovirus can lead to serious illness in children with complex chronic conditions and immune deficiency conditions.

Racial Inequities in Palliative Referral for Children with High-Intensity Neurologic Impairment

ObjectiveTo evaluate whether racial and socioeconomic inequities in pediatric palliative care utilization extend to children with high-intensity neurologic impairment (HI-NI), which is a chronic neurological diagnosis resulting in substantial functional morbidity and mortality. Study designWe conducted a retrospective study of patients with HI-NI who received primary care services at a tertiary care center from 2014 through 2019. HI-NI diagnoses that warranted a palliative care referral were identified by consensus of a multidisciplinary team. The outcome was referral to palliative care. The primary exposure was race, categorized as Black or non-Black to represent the impact of anti-Black racism. Additional exposures included ethnicity (Hispanic/non-Hispanic) and insurance status (Medicaid/non-Medicaid). Descriptive statistics, bivariate analyses, and multivariable logistic regression models were performed to assess associations between exposures and palliative care referral. ResultsA total of 801 patients with HI-NI were included; 7.5% received a palliative referral. There were no differences in gestational age, sex, or ethnicity between patients who received a referral and those who did not. In multivariable analysis, adjusting for ethnicity, sex, gestational age, and presence of complex chronic conditions, Black children (aOR 0.47, 95% CI 0.26, 0.84) and children with Medicaid insurance (aOR 0.40, 95% CI 0.23, 0.70) each had significantly lower odds of palliative referral compared with their non-Black and non-Medicaid-insured peers, respectively. ConclusionsWe identified inequities in pediatric palliative care referral among children with HI-NI by race and insurance status. Future work is needed to develop interventions, with families, aimed at promoting more equitable, antiracist systems of palliative care.

Nutritional risk and functionality of children and adolescents hospitalized with COVID-19.

Retrospective cross-sectional study with patients under 19years old, positive for SARS-COV-2 by RT-PCR test, from February 2020 to May 2022. The STRONGKids screening (Screening Tool Risk On Nutritional Status and Growth) was used to assess nutritional risk on hospital admission and the Functional Status Scale (FSS-Brazil) to determine the functionality of patients on admission and discharge. Data was collected from hospital medical records. Poisson regressions with crude robust variance were used to test the association between nutritional risk and functional status at admission, with adjustments for the age, length of stay, and presence of complex chronic conditions. Of the 217 patients, 55.7% (n = 121) were boys with a median age of 6years (IQ 0-12), 58.5% (n = 127) had at least one complex chronic condition, 64% (n = 139) had medium/high nutritional risk, and 23.9% (n = 52) had some degree of dysfunctionality upon admission and 14.6% (n = 31) upon discharge. By associating STRONGKids and the FSS-Brasil of hospital admission, it was observed that children with low nutritional risk had a mean global FSS lower (6.4 ± 0.7) than children with medium/high nutritional risk (7. 7 ± 2.8; p < 0.001). Children with low nutritional risk on admission also had a lower mean (6.1 ± 0.59) on the FSS at hospital discharge than children with medium/high nutritional risk (7.1 ± 2.5; p < 0.001). After adjustments, it was identified that the addition of one STRONGKids point increases by 36% (PR 1.36; 95%CI 1.15-1.62) the probability of the patient presenting some degree of functional impairment on admission. Conclusion: The study found a positive association between nutritional risk and functional impairment in hospitalized children and adolescents with COVID-19 on admission, even after adjusting for age, length of stay, and complex chronic conditions. Furthermore, patients with medium/high nutritional risk at admission also had worse functionality, both on admission and at discharge. • Children and adolescents infected with COVID-19 tend to exhibit milder symptoms and lower hospitalization rates compared to adults, although severe cases and complications can occur. • A paucity of targeted investigations exists regarding the correlation between nutritional risk and functionality in children and adolescents with COVID-19. • Children and adolescents with COVID-19 who presented with medium to high nutritional risk upon hospital admission demonstrated functional impairments, both at admission and hospital discharge.

Epidemiology and outcomes of septic shock in children with complex chronic conditions in a developing country PICU

ObjectiveTo investigate the role of Complex Chronic Conditions (CCCs) on the outcomes of pediatric patients with refractory septic shock, as well as the accuracy of PELOD-2 and Vasoactive Inotropic Score (VIS) to predict mortality in this specific population. MethodsThis is a single-center, retrospective cohort study. All patients diagnosed with septic shock requiring vasoactive drugs admitted to a 13-bed PICU in southern Brazil, between January 2016 and July 2018, were included. Clinical and demographic characteristics, presence of CCCs and VIS, and PELOD-2 scores were accessed by reviewing electronic medical records. The main outcome was considered PICU mortality. Results218 patients with septic shock requiring vasoactive drugs were identified in the 30-month period and 72% of them had at least one CCC. Overall mortality was 22%. Comparing to patients without previous comorbidities, those with CCCs had a higher mortality (26.7% vs 9.8%; OR = 3.4 [1.3–8.4]) and longer hospital length of stay (29.3 vs 14.8; OR 2.39 [1.1- 5.3]). Among the subgroups of CCCs, “Malignancy” was particularly associated with mortality (OR = 2.3 [1.0–5.1]). VIS and PELOD-2 scores in 24 and 48 hours were associated with mortality and a PELOD-2 in 48 hours > 8 had the best performance in predicting mortality in patients with CCC (AUROC = 0.89). ConclusionPatients with CCCs accounted for the majority of those admitted to the PICU with septic shock and related to poor outcomes. The high prevalence of hospitalizations, use of resources, and significant mortality determine that patients with CCCs should be considered a priority in the healthcare system.

Association of Sugammadex or Neostigmine With Major Postoperative Pulmonary Complications in Children.

Recent data in adult patients indicate that the use of sugammadex compared to neostigmine for reversal of neuromuscular block (NMB) was associated with a significant reduction in the risk of composite postoperative pulmonary complications. Despite the clinical significance of pulmonary complications in children, studies exploring the role of NMB reversal in the risk of these complications are currently unavailable. We performed a propensity score-matched retrospective study using the Pediatric Health Information System (PHIS) dataset spanning the years 2016 and 2020. We studied children <18 years who underwent elective, inpatient, noncardiac surgical procedures and received either neostigmine or sugammadex for reversal of NMB. Our primary outcome was major postoperative pulmonary complication, which we defined as the occurrence of either postoperative pneumonia or respiratory failure. Our study included a study population of 33,819 children, of whom 23,312 (68.9%) received neostigmine and 10,507 (31.1%) received sugammadex. After propensity score matching (10,361 matched from each group), we found no evidence of a statistically significant association between the NMB reversal agent and the incidence of pulmonary complications (3.1% vs 3.1%; odds ratio [OR], 0.90; 95% confidence interval [CI], 0.78-1.05; P = .19). The components of pulmonary complications, including respiratory failure and pneumonia, were not statistically associated with the choice of NMB reversal agent. Choice of NMB reversal agent does not appear to impact the incidence of major postoperative pulmonary complications. Further research is needed to determine whether our results carry forth across subpopulations defined by surgical specialty, the presence of complex chronic conditions, and anesthesia technique.

Characteristics and Outcomes of Pediatric Rapid Response With a Respiratory Trigger.

Authors of adult rapid response (RRT) studies have established that RRT triggers play an important role in outcomes, but this association is not studied in pediatrics. In this study, we explore the characteristics and outcomes of pediatric rapid response with a respiratory trigger (Resp-RRT). We hypothesize that outcomes differ on the basis of patients' primary diagnoses at the time of Resp-RRT. We conducted a 2-year retrospective observational study at an academic tertiary care pediatric hospital. Among the 1287 Resp-RRTs in 1060 patients, those with a respiratory diagnosis (N = 686) were younger, less likely to have complex chronic conditions, and less likely to have concurrent triggers (P < .01) than those with a nonrespiratory diagnosis (N = 601). Patients with a respiratory diagnosis were more likely to receive noninvasive ventilation, less likely to receive vasoactive support, and had lower 30-day mortality (P < .01). Among those with a respiratory diagnosis, the 541 patients with acute illness were younger, less likely to have complex chronic conditions, and less likely to receive vasoactive support than those with acute on chronic illness (N = 100) (P < .01). Among pediatric respiratory-triggered RRT events, patients with a respiratory diagnosis were more likely to receive acute respiratory support in ICU but have better long-term outcomes. Presence of complex chronic conditions increases risk of acute respiratory support and mortality. The interplay of primary diagnosis with RRT trigger can potentially inform resource needs and outcomes for pediatric Resp-RRTs.

P0086 / #419: EPIDEMIOLOGY OF RED BLOOD CELL TRANSFUSIONS IN A PEDIATRIC INTENSIVE CARE UNIT

Aims & Objectives: to determine the prevalence of red blood cell (RBC) transfusions in a PICU. To describe the profile and evolution of the transfused population in comparison with those not transfused during their PICU stay. Methods: retrospective, observational study. We included all patients aged 1 -216 month, admitted to the medical/surgical PICU of a Public University Hospital between 4-1-2017 and 3-31-2018. We performed descriptive statistics; simple and multivariate logistic and linear regression models for the statistical analysis. Results: 294 admissions were registered during the study period. The prevalence of RBC transfusion was 42.8% (95% CI 37-48%). The RBC transfusion was associated with younger age [(21 months (IQR 7-84) in children transfused vs 69.5 (66-113) in those no transfused, p: 0.03;] higher mortality risk predicted by PIM2 [9.3 (SD 13.9) vs 5.64 (SD 12.5), p <0.001] and admission diagnosis of leukemia or sepsis [OR 3 (95% CI 1.14-9.25) and 4.8 (2.53-9.4) respectively]. The mean pretransfusional hemoglobin value (PHb) was 7.75 gr / dl (SD 1.2). There was no statistically significant difference in its value according to admission diagnosis, presence of complex chronic condition, solid tumors or leukemia. The RBC transfusion was associated with higher PICU mortality (OR 11.87; 95% CI 3.8-37.5), length of stay in PICU and length of mechanical ventilation, adjusted by confounding factors. Conclusions: The prevalence of RBC transfusion and the value of PHb is higher than suggested by international guidelines. It is necessary to optimize the resource use in the PICU.

Iatrogenic events contributing to paediatric intensive care unit admission.

To identify the incidence of iatrogenic events leading to paediatric intensive care unit (PICU) admission and to analyse these patients regarding demographic, illness severity and outcome parameters. This was a retrospective case series. The computerised charts of all patients admitted to the multidisciplinary, tertiary, 18-bed PICU in 2014 were analysed. Iatrogenic events leading to PICU admission were identified and their preventability assessed. Underlying diseases, causes of iatrogenic events, illness severity at PICU admission, presence of complex chronic conditions, patient origin, length of stay on the PICU and outcome were analysed. There were 138 admissions associated with iatrogenic events out of 1102 admissions (12.5%). Ninety iatrogenic events led to unplanned admissions and 48 cases concerned scheduled admissions, where the iatrogenic event would have led to PICU admission by itself or caused a second, planned PICU admission for re-operation. Iatrogenic complications during surgery (31% of all iatrogenic events), wrong management decisions / delayed diagnoses (20%) and nosocomial infections (14%) were the categories most often involved. Regarding origin of the patients, the greatest difference between iatrogenic event admissions and non-iatrogenic event admissions was found for the ward (21% vs 11%). The patients admitted for iatrogenic events had a higher mean expected mortality (8.4 vs 4.7%, p = 0.02) and a higher observed PICU mortality (5.8 vs 3.3%, p = 0.15). Of all iatrogenic events, 60.1% were judged to be preventable. The highest preventability rate was found in the categories &ldquo;nosocomial infections&rdquo; (100%) and &ldquo;management decisions / delayed diagnoses&rdquo; (92.9%). In our setting, the number of PICU admissions associated with iatrogenic events is significant and comparable to adult data on admission to ICU caused by iatrogenic events. The categories with most potential for improvement are nosocomial infections and the wrong management decisions / delayed diagnoses. Focused measures on these iatrogenic events may have a major impact on patient outcome, availability of PICU resources and healthcare costs.

906. Surgical Site Infections in Children with Beta-Lactam Allergy: A Matched Cohort Study

BackgroundSurgical site infections (SSIs) are a significant cause of morbidity and mortality. The administration of appropriate pre-operative antimicrobial prophylaxis (AMP) reduces SSI risk and beta-lactam antibiotics are considered the most effective agents. Studies in adult patients found increased SSI risk in patients with documented beta-lactam allergy (BLA) due to use of second line AMP agents. The SSI risk in BLA pediatric patients is not well-described.MethodsWe conducted a retrospective matched cohort study of patients (1-19 years-old) who underwent a surgical procedure at a quaternary pediatric hospital during 2010-2017. Patients with documented BLA at the time of surgery were matched 1:1 to patients with no BLA by age at surgery, National Surgical Quality Improvement Program (NSQIP) category, surgical calendar year, and presence of complex chronic conditions (CCC). AMP by BLA status was considered appropriate if recommended by the 2013 American Society of Health-System Pharmacists (ASHP) guidelines, antibiotic class appropriate, or recommended by an infectious disease physician. McNemar’s test was used to assess differences in SSI rates and antibiotic regimen appropriate for BLA status between BLA and no BLA groups.ResultsOf the 11878 surgical procedures among 9781 patients during the study period, 1021(9%) of patients had a reported BLA and we matched 972. SSI was rare in both groups and there was no significant difference in rates (18 (1.9%) in no BLA, 17 (1.8%) in BLA, p=1.0). BLA were more likely to receive an antibiotic regimen considered inappropriate for BLA status (22%) compared to no BLA (3%) with 89% receiving a beta-lactam-containing AMP regimen (p< 0.01).ConclusionBLA was not associated with increased SSI risk in the pediatric patients studied. Interestingly, a significant proportion of children with a documented allergy received a beta-lactam for AMP. This suggests some providers recognize that allergy labels are inaccurate and may be comfortable administering beta-lactam AMP regardless of allergy status.Disclosures All Authors: No reported disclosures

Disparities Associated with Sepsis Mortality in Critically Ill Children.

Disparities in health care related to socioeconomic status and race/ethnicity are well documented in adult and neonatal sepsis, but they are less characterized in the critically ill pediatric population. This study investigated whether socioeconomic status and/or race/ethnicity is associated with mortality among children treated for sepsis in the pediatric intensive care unit (PICU). A retrospective cohort study was conducted using information from 48 children's hospitals included in the Pediatric Health Information System database. We included visits by children ≤ 21 years with All Patients Refined Diagnosis-Related Groups (APR-DRG) diagnosis codes of septicemia and disseminated infections that resulted in PICU admission from 2010 to 2016. Multivariable logistic regression was used to measure the effect of race/ethnicity and socioeconomic status (insurance status and median household income for zip code) on mortality after adjustment for age, gender, illness severity, and presence of complex chronic condition. Among the 14,276 patients with sepsis, the mortality rate was 6.8%. In multivariable analysis, socioeconomic status, but not race/ethnicity, was associated with mortality. In comparison to privately insured children, nonprivately insured children had increased odds of mortality (public: adjusted odds ratio [aOR]: 1.2 [1.0, 1.5]; uninsured: aOR: 2.1 [1.2, 3.7]). Similarly, children living in zip codes with the lowest quartile of annual household income had higher odds of mortality than those in the highest quartile (aOR: 1.5 [1.0, 2.2]). These data suggest the presence of socioeconomic, but not racial/ethnic, disparities in mortality among children treated for sepsis. Further research is warranted to understand why such differences exist and how they may be addressed.

Undernutrition at PICU Admission Is Predictor of 60-Day Mortality and PICU Length of Stay in Critically Ill Children

BackgroundThere are few studies that assess the role of different nutritional assessment variables at pediatric intensive care unit (PICU) admission in predicting clinical outcomes. ObjectiveTo identify nutritional variables in the first 4 days of PICU stay that predict 60-day mortality and time to discharge alive from the PICU. DesignSingle-center prospective study in Southern Brazil, conducted between July 2013 and February 2016. At PICU admission, children with z scores <−2 for body mass index (BMI)-for-age, mid-upper arm circumference (MUAC)-for-age, and triceps skinfold thickness (TSF)-for-age were considered as undernourished. Participants/settingThere were 199 patients, aged <15 years, with PICU stay >48 hours. Main outcome measuresSixty-day mortality and time to discharge alive from the PICU. Statistical analysis performedCox regression model was applied to determine predictors of 60-day mortality and time to discharge alive from the PICU. ResultsMedian age was 23.1 months (interquartile range=3.9 to 89.1), and 63% were male, with 18% prevalence of undernutrition at admission by BMI-for-age. Median PICU stay was 7 days (interquartile range=4 to 12), and 60-day mortality was 12%. After adjusting for sex, age, Pediatric Index of Mortality 2, and presence of complex chronic conditions, undernutrition based on BMI-for-age (hazard ratio [HR]=3.75; 95% CI=1.41 to 9.95; P=0.008), MUAC-for-age (HR=7.62; 95% CI=2.42 to 23.97; P=0.001), and TSF-for-age (HR=4.01; 95% CI=1.14 to 14.15; P=0.031) was associated with higher risk of 60-day mortality. Based on MUAC-for-age with the same adjustment model, undernourished children had longer time to discharge alive from the PICU (HR=0.45; 95% CI=0.21 to 0.98; P=0.045). ConclusionsUndernutrition at PICU admission based on different anthropometric variables was predictive of 60-day mortality and longer time to discharge alive from the PICU.

Epidemiology of Polypharmacy and Potential Drug-Drug Interactions Among Pediatric Patients in ICUs of U.S. Children's Hospitals.

Polypharmacy is common in hospitalized children in the United States and has been identified as a major risk factor for exposure to potential drug-drug interactions. Little is known about the characteristics and prevalence of exposure of pediatric patients to polypharmacy and potential drug-drug interactions in PICUs. Retrospective cohort study using the Pediatric Health Information System database. Forty-two freestanding children's hospitals throughout the United States. A total of 54,549 patients less than 18 years old cared for in PICUs in 2011. Patients in neonatal ICUs were not included. PICU patients were on average exposed to 10 distinct drugs each hospital day and to 20 drugs cumulatively during their hospitalization. Seventy-five percent of patients were exposed to greater than or equal to one potential drug-drug interaction regardless of severity level, 6% to greater than or equal to one contraindicated potential drug-drug interaction, 69% to greater than or equal to one major potential drug-drug interaction, 57% to greater than or equal to one moderate potential drug-drug interaction, 19% to greater than or equal to one minor potential drug-drug interaction. Potential drug-drug interaction exposures were significantly associated with specific diagnoses (p < 0.001), presence of complex chronic conditions (p < 0.001), increasing number of total distinct drugs used (p < 0.001), increasing length of stay in PICU (p < 0.001), and white race (p < 0.001). Many PICU patients are exposed to substantial polypharmacy and potential drug-drug interactions. Future research should identify the risk of adverse drug events following specific potential drug-drug interaction exposures, especially the risk of adverse drug events due to multiple potential drug-drug interaction exposures, and determine the probability and magnitude of the actual harm (if any) for each specific potential drug-drug interaction, especially for multiple potential drug-drug interaction exposures.