Changes in Hematologic Lab Measures Observed in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with C5 Inhibitors, Ravulizumab and Eculizumab: Real-World Evidence from a US Based EMR Network.

Paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired hematologic disorder, can be treated with C5 inhibitors (C5i) such as eculizumab or ravulizumab. This retrospective study is the first to describe real-world treatment patterns and changes in hematologic PNH-monitoring laboratory tests among C5i-treated US patients. Data were extracted from TriNetX Dataworks Network and included patients with a PNH diagnosis between 1 January 2010, and 20 August 2021. Patients were stratified into three cohorts based on their C5i usage: eculizumab, ravulizumab (prior eculizumab), and ravulizumab (eculizumab naïve). Hematological markers (hemoglobin [Hb], lactate dehydrogenase [LDH], and absolute reticulocyte count [ARC]) and relevant clinical events (e.g., breakthrough hemolysis [BTH], complement-amplifying conditions [CAC], thrombosis, infection, and all-cause mortality) were captured any time within 12 months post-index treatment. Of the 143 (eculizumab), 43 (ravulizumab, prior eculizumab), and 33 (ravulizumab, eculizumab naïve) patients, mean age across cohorts was 42-51 years, 55-61% were female, 63-73% were White, and 33-40% had aplastic anemia. Among all cohorts 12 months post-C5i treatment, 50-82% remained anemic, 8-32% required ≥1 transfusion, and 13-59% had BTH, of which 33%-54% had CACs. Additionally, thrombosis was seen in 7-15% of patients, infection in 20-25%, and mortality in 1-7%. These findings suggest many C5i-treated patients experience suboptimal disease control.

Incidence of Uncommon Clinical Events in USA Patients with Dialysis-Dependent and Nondialysis-Dependent Chronic Kidney Disease: Analysis of Electronic Health Records from TriNetX.

INTRODUCTION: Further understanding of adverse clinical events in patients with chronic kidney disease (CKD) is needed. This study aimed to describe characteristics of patients with nondialysis-dependent (NDD) and dialysis-dependent (DD) CKD and to assess incidence rates of uncommon adverse clinical events of interest in these patients. METHODS: This retrospective study used electronic medical record data from USA CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 between January 1, 2010, and December 31, 2018, obtained from the USA-based TriNetX database. NDD-CKD and DD-CKD were diagnosed and staged from ≥2 consecutive eGFR readings, recorded ≥90 days apart. Dialysis was identified using procedure codes for renal replacement therapy. Outcomes assessed were select uncommon adverse clinical events, defined by International Classification of Disease, 9th and 10th Revision codes. RESULTS: Incidence rates of adverse clinical events per 100 person-years (95% confidence interval) were generally higher in patients with DD-CKD versus NDD-CKD. Differences were particularly pronounced for hyperkalemia (26.9 [26.2-27.6] vs. 4.5 [4.5-4.6]), acidosis (15.1 [14.7-15.6] vs. 3.4 [3.4-3.4]), and sepsis (14.6 [14.2-15.1] vs. 3.3 [3.3-3.4]). Among DD-CKD patients, incidence rates of adverse events were particularly high during the first 3 months following dialysis initiation. Incidence of adverse clinical events generally increased with decreasing eGFR among patients with NDD-CKD and with hemoglobin <10 g/dL in both NDD- and DD-CKD patients. CONCLUSIONS: Our results help establish baseline rates of uncommon adverse clinical events and provide additional evidence of increased morbidity for patients with DD-CKD versus NDD-CKD.

A retrospective cohort study of 12,306 pediatric COVID-19 patients in the United States.

Children and adolescents account for ~ 13% of total COVID-19 cases in the United States. However, little is known about the nature of the illness in children. The reopening of schools underlines the importance of understanding the epidemiology of pediatric COVID-19 infections. We sought to assess the clinical characteristics and outcomes in pediatric COVID-19 patients. We conducted a retrospective cross-sectional analysis of pediatric patients diagnosed with COVID-19 from healthcare organizations in the United States. The study outcomes (hospitalization, mechanical ventilation, critical care) were assessed using logistic regression. The subgroups of sex and race were compared after propensity score matching. Among 12,306 children with lab-confirmed COVID-19, 16.5% presented with respiratory symptoms (cough, dyspnea), 13.9% had gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain), 8.1% had dermatological symptoms (rash), 4.8% had neurological (headache), and 18.8% had other non-specific symptoms (fever, malaise, myalgia, arthralgia and disturbances of smell or taste). In the study cohort, the hospitalization frequency was 5.3%, with 17.6% needing critical care services and 4.1% requiring mechanical ventilation. Following propensity score matching, the risk of all outcomes was similar between males and females. Following propensity score matching, the risk of hospitalization was greater in non-Hispanic Black (RR 1.97 [95% CI 1.49-2.61]) and Hispanic children (RR 1.31 [95% CI 1.03-1.78]) compared with non-Hispanic Whites. In the pediatric population infected with COVID-19, a substantial proportion were hospitalized due to the illness and developed adverse clinical outcomes.

Coronary artery bypass graft surgery outcomes in the United States: Impact of the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: There has been a substantial decline in patients presenting for emergent and routine cardiovascular care in the United States after the onset of the coronavirus disease 2019 (COVID-19) pandemic. We sought to assess the risk of adverse clinical outcomes among patients undergoing coronary artery bypass graft (CABG) surgery during the 2020 COVID-19 pandemic period and compare the risks with those undergoing CABG before the pandemic in the year 2019. METHODS: A retrospective cross-sectional analysis of the TriNetX Research Network database was performed. Patients undergoing CABG between January 20, 2019, and September 15, 2019, contributed to the 2019 cohort, and those undergoing CABG between January 20, 2020, and September 15, 2020, contributed to the 2020 cohort. Propensity-score matching was performed, and the odds of mortality, acute kidney injury, stroke, acute respiratory distress syndrome, and mechanical ventilation occurring by 30 days were evaluated. RESULTS: The number of patients undergoing CABG in 2020 declined by 35.5% from 5534 patients in 2019 to 3569 patients in 2020. After propensity-score matching, 3569 patient pairs were identified in the 2019 and the 2020 cohorts. Compared with those undergoing CABG in 2019, the odds of mortality by 30 days were 0.96 (95% confidence interval [CI], 0.69-1.33; P = .80) in those undergoing CABG in 2020. The odds for stroke (odds ratio [OR], 1.201; 95% CI, 0.96-1.39), acute kidney injury (OR, 0.76; 95% CI, 0.59-1.08), acute respiratory distress syndrome (OR, 1.01; 95% CI, 0.60-2.42), and mechanical ventilation (OR, 1.11; 95% CI, 0.94-1.30) were similar between the 2 cohorts. CONCLUSIONS: The number of patients undergoing CABG in 2020 has substantially declined compared with 2019. Similar odds of adverse clinical outcomes were seen among patients undergoing CABG in the setting of COVID-19 compared with those in 2019.

COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients.

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

Age of Onset, Current Use of Alcohol, Tobacco or Marijuana and Current Polysubstance Use Among Male and Female Mexican Students.

AIMS: This study aimed to examine alcohol, tobacco or marijuana use onset and associations between age of onset and current use, and between age of onset and current polysubstance use among a sample of Mexican young people aged 17-20 years. METHODS: Alcohol, tobacco, marijuana and other substance use were identified in a 2012 cross-sectional survey of male and female students entering first year university in Mexico City. Chi-square tests and logistic regression models examined associations between gender, age of onset, order of onset, family substance use and current polysubstance use among 22,224 students. RESULTS: The largest proportions of males and females initiated alcohol at age 15, tobacco at ages 15-16 and marijuana at ages 16-17. Earlier alcohol and tobacco initiation was associated with past 30-day use of the same substance. Gender differences in alcohol and tobacco use were small but males were significantly more likely than females to use marijuana and be polysubstance users. Family substance use was associated with earlier onset. There was a significant association between the earliest age of any of the three substances and current polysubstance use. CONCLUSIONS: A number of contextual and cultural factors in Mexico may be contributing to early onset, continued use and polysubstance use and deserve attention in research and by prevention programs.

Parental monitoring and family relations: associations with drinking patterns among male and female Mexican students.

INTRODUCTION: Parental monitoring and family relations are recognized as protective factors for youth alcohol use. The purpose of this study was to investigate perceived parental monitoring and family relations among subgroups of Mexican youths with different patterns of drinking behaviors and consequences. METHODS: A latent profile analysis (LPA) identified profiles of drinking behavior in a cross-sectional survey of entering first year university students. Multinomial regression examined associations between parental monitoring, family relations and drinking profiles among 22,224 students. RESULTS: Both lower perceived parental monitoring and weaker perceived family relations were associated with heavier drinking profiles among males and females, but more strongly associated with female than male heavier drinking profiles. Being older, having parents with lower education, and not living with parents were also associated with lower parental monitoring and weaker family relations. There was a general trend of lower parental monitoring and weaker family relations as the profiles increased from Non/Infrequent-No Consequences to Excessive-Many Consequences Drinkers. Lower perceived parental monitoring and weaker perceived family relations were more strongly associated with drinking profiles among females than among males. Both the parental monitoring and family relations scales had similar associations with drinking profiles. CONCLUSIONS: Findings suggest that drinking norms and values may contribute to any protective influences of parental monitoring and family relations on Mexican youths' drinking. Research about changes in drinking norms, contextual factors, and youth-parent trust would inform the utility of parental monitoring or family relations as protective strategies against alcohol misuse among Mexican and Mexican American youths and also youths from other backgrounds.

Natural mentors and youth drinking: a qualitative study of Mexican youths.

Parental influences on youth drinking are well documented but not the influence of extended family members. This article explores extended family influences on alcohol use among Mexican youths and whether extended family members can be considered natural mentors. We conducted a qualitative study using ethnographic open ended interviews with 117 first year university students in Mexico City. The ethnographic interviews revealed six drinking groups: excessive, heavy, regular, occasional, abstainers and non drinkers. Youths reported close relationships with extended family members who provided counsel and acted as representatives of familial norms and values. The alcohol beliefs and behaviors of these family members, including their alcohol misuse, had a positive influence on youths' alcohol attitudes. The naturally occurring mentoring relationships of Mexican extended family members can positively influence moderate youth drinking. Natural mentoring relationships should be encouraged and facilitated in prevention efforts for Mexican youths, Mexican-American youths and potentially other Hispanic/Latino youths.

Alcohol Use among Mexican Youths: Is Familismo Protective for Moderate Drinking?

The construct of familismo has been identified as a potential protective cultural value in Hispanic cultures. This paper considers familismo and alcohol use among young people in Mexico. We conducted a qualitative study using ethnographic open ended interviews with 117 first year students at a large free public university in Mexico City between April-May 2011. The findings indicate that dimensions of familismo can act as protective factors against misuse of alcohol among Mexican youths and may be protective for moderate drinking. Future research should explore the relationship of familismo to gender roles and other cultural values during adolescence. Given the enduring influence of Mexican cultural values among Mexican Americans the research has implications for prevention programs for both Mexican and Mexican American youths.

Drinking patterns and victimization among male and female students in Mexico.

AIMS: The purpose of this study is to estimate the prevalence of alcohol use and alcohol-related consequences, identify drinking profiles using latent profile analysis (LPA), and investigate associations between profiles and violent victimization among young people in Mexico. METHODS: LPA identified profiles of drinking behavior in a survey of entering first year university students. Multinomial and logistic regression examined associations between drinking patterns, socio-demographic variables and violent victimization. RESULTS: The LPA identified five profiles of behaviors and consequences among the 22,224 current, former and never drinkers: Non/Infrequent-No Consequences, Occasional-Few Consequences, Regular-Some Consequences, Heavy-Many Consequences and Excessive-Many Consequences drinkers. The Occasional-Few Consequences profile comprised the largest, and the Excessive-Many Consequences profile the smallest, group of drinkers. Multinomial regression showed males and older students more likely to be Heavy or Excessive-Many Consequences drinkers. Living alone was associated with higher odds, and higher maternal education with lower odds, of being a Non/Infrequent-No Consequences drinker. Heavier drinking profiles were more likely to experience violent victimization adverse consequences. Logistic regression showed male and female Heavy and Excessive-Many Consequences drinkers had the highest odds, and Non/Infrequent drinkers the lowest odds, of experiencing any victimization. CONCLUSION: Findings suggest changes in male and female drinking behavior and a continuation of the established pattern of infrequent but high consumption among Mexican youths. Both male and female Heavy and Excessive-Many Consequences drinkers were at elevated risk for experiencing victimization. Identifying cultural gender norms about drinking including drinker expectations and drinking context that contribute to these patterns can inform prevention efforts.

Changes in alcohol use among first year university students in Mexico.

BACKGROUND: Alcohol use and misuse is widespread among university students in many countries. Specific cultural factors may impact alcohol use after entering university. OBJECTIVE: This paper considers changes in alcohol use among first year university students in Mexico. METHODS: A qualitative study using ethnographic interviews with 57 female and 60 male student drinkers in Mexico City from March to June 2011. Each interview was evaluated by a set of thematic codes developed inductively from the interviews. Findings from excessive, heavy, regular, occasional drinkers, abstainers, and non-drinkers were analyzed to explore whether or not linkages existed between and/or among particular themes. RESULTS: Students reported factors associated with changes in role and status, friendships, and increased autonomy as reasons for increasing or decreasing their alcohol use after entering university. CONCLUSIONS/IMPORTANCE: Understanding the influence of Mexican cultural norms on alcohol use among Mexican and Mexican Americans can be helpful in informing studies and preventive efforts among both Mexican and Mexican American young people.

Problematic substance use in urban adolescents: role of intrauterine exposures to cocaine and marijuana and post-natal environment.

BACKGROUND: Linkages between intrauterine exposures to cocaine and marijuana and adolescents' problematic substance use have not been fully delineated. METHODS: Prospective longitudinal study with assessors unaware of intrauterine exposure history followed 157 urban participants from birth until late adolescence. Level of intrauterine exposures was identified by mother's report and infant's meconium. Problematic substance use, identified by the Voice Diagnostic Interview Schedule for Children (V-DISC) or the Audio Computer Assisted Self-Interview (ACASI) and urine assay, was a composite encompassing DSM-IV indication of tolerance, abuse, and dependence on alcohol, marijuana, and tobacco and any use of cocaine, glue, or opiates. RESULTS: Twenty percent (32/157) of the sample experienced problematic substance use by age 18 years, of whom the majority (22/157) acknowledged abuse, tolerance or dependence on marijuana with or without other substances. Structural equation models examining direct and indirect pathways linking a Cox survival model for early substance initiation to a logistic regression models found effects of post-natal factors including childhood exposure to violence and household substance use, early youth substance initiation, and ongoing youth violence exposure contributing to adolescent problematic substance use. CONCLUSION: We did not identify direct relationships between intrauterine cocaine or marijuana exposure and problematic substance use, but did find potentially modifiable post-natal risk factors also noted to be associated with problematic substance use in the general population including earlier substance initiation, exposure to violence and to household substance use.

Parental monitoring and alcohol use among Mexican students.

Parental monitoring has been described as a protective factor and useful strategy to prevent substance misuse among youths. The aim of this study was to examine whether perceived parental monitoring influences frequency of alcohol use, age of drinking onset and risky drinking among entering public high school and university students in Mexico City. The study is a cross-sectional survey of entering first year students in the high school and university school system of a large public university in Mexico City conducted during registration at the beginning of the school year. In 2008, of 34,840 students accepted to the affiliated high schools, 28,996 students (51.8% female) completed the alcohol survey and of 37,683 students accepted into university 30,084 students (51.5% female) completed the alcohol survey. The findings suggest that compared to students with higher perceived parental monitoring those reporting lower perceived parental monitoring were more likely to report risky behavior. They were more likely to be ever drinkers, frequent drinkers, have earlier age of onset and high AUDIT scores. Overall, higher parental monitoring was strongly associated with being female and lower parental monitoring with being male. Our findings suggest that more research on parental monitoring as a protective strategy against alcohol misuse is needed. Research focusing on cultural factors including gender and age-related norms and familismo would increase knowledge of the association of parental monitoring and alcohol use among Mexican youths, Mexican American youths and potentially youths from other Hispanic backgrounds.