Prevalence of multimodal treatment in children and adolescents with ADHD in Germany: a nationwide study based on health insurance data

Background Attention-deficit hyperactivity disorder (ADHD) ranks top among neurodevelopmental disorders in children and adolescents. Due to a large number of unfavorable outcomes including psychiatric comorbidities, school problems, and lower socioeconomic status, early and effective treatment of ADHD is essential. Multimodal treatment has become the gold standard in ADHD management, comprising pharmacotherapy and psychosocial interventions, e.g., psychotherapy. Yet, little is known about the prevalence of multimodal treatment in routine care. Methods Based on German health claims data for the years 2009–2017, we identified children and adolescents aged 3–17 years diagnosed with ADHD and characterized them cross-sectionally (per calendar year) in terms of treatment status and psychiatric comorbidities. The detection of pharmacotherapy was based on dispensations of drugs to treat ADHD (e.g., methylphenidate); psychotherapeutic treatment was based on corresponding billing codes. Multimodal treatment was assumed if ADHD medication and psychotherapeutic treatment were coded within the same calendar year. Psychiatric comorbidities were based on outpatient and inpatient diagnoses. Prevalences of ADHD and proportions of different treatment options were calculated and standardized by age and sex. Results In 2017, 91,118 children met the study criteria for ADHD (prevalence: 42.8/1000). Of these, 25.2% had no psychiatric comorbidity, 28.8% had one, 21.6% had two, and 24.5% had three or more. Regarding overall treatment status, 36.2% were treated only pharmacologically, 6.5% received multimodal treatment, and 6.8% were treated with psychotherapy only (neither treatment: 50.2%). With increasing numbers of psychiatric comorbidities, the proportions of patients with multimodal treatment increased from 2.2% (no psychiatric comorbidities) to 11.1% (three or more psychiatric comorbidities) while the proportions of untreated (from 56.8% to 42.7%) or only pharmacologically treated patients (38.4% to 35.0%) decreased. From 2009 to 2017, prevalences were stable and the proportion of patients with only pharmacotherapy decreased from 48% to 36.5%. Concurrently, the proportion of patients with neither pharmacotherapy nor psychotherapy increased from 40.5% to 50.2%. The fraction of patients with multimodal treatment ranged between 6.5% (2017) and 7.4% (2013). Conclusions Multimodal treatment, although recommended as the standard of treatment, is rather the exception than the rule. It is, however, increasingly common in ADHD patients with psychiatric comorbidities.

The Blood Lead Levels of Children and the Loss of Ca2+ from Neurons Owing to Lead

In order to understand current blood lead levels (BLLs), we investigated the BLLs of children in Sichuan Province from 2011 to 2020. We then monitored the treatment effects of calcium in children with high BLLs to assess their treatment status. Finally, we explored the effects of lead on Ca2+ through in-situ experiments. Whole blood samples were used for BLL tests. The BLLs of 76,362 children aged 0–7 years were measured using atomic absorption spectrometry. The median BLL was 35 μg/L (interquartile range: 28–47). The BLLs were significantly higher in boys than in girls (p < 0.001). The BLLs generally decreased annually and increased with age. The overall prevalence of BLLs ≥ 100 μg/L was 1.20%. The children with high BLLs received subsequent check-ups, and the median time required for effective treatment was 18 months. We observed that lead exposure led to a gradual and persistent loss of Ca2+ levels in neurons of mice brain slices, and the effect did not subside immediately even after the lead was removed. China has made rapid progress in pediatric healthcare, but the treatment status remains unsatisfactory. Because lead causes an irreversible loss of Ca2+, there is an urgent need to develop new standardized treatments to reduce the treatment duration.

Long-Term Survival Benefit of Eculizumab Treatment in Patients with Paroxysmal Nocturnal Hemoglobinuria: Data from the International PNH Registry

Background Eculizumab, the first C5 inhibitor approved for paroxysmal nocturnal hemoglobinuria (PNH), transformed PNH treatment by improving survival to that of an age- and sex- matched general population. Previous analyses demonstrating the survival benefit of eculizumab in patients with PNH leveraged historical data and were limited by small patient numbers and short follow-up durations; few evaluated survival of patients receiving eculizumab compared with untreated patients. The objective of the current analysis was to describe the baseline characteristics and overall survival of a large international cohort of eculizumab-treated patients compared with a contemporaneous untreated cohort using data from the prospective, observational International PNH Registry (NCT01374360). Methods Data from patients enrolled in the Registry after March 16, 2007 with complete information for birth date, sex, enrollment date, and treatment status were included (database cut-off, April 12, 2021). Ever-treated patients were those who received eculizumab for a minimum treatment period of 35 days while enrolled in the Registry; never-treated patients did not receive eculizumab at any time before or during Registry participation. Univariate and multivariate analyses were performed using a Cox proportional hazards that incorporated the following parameters at baseline as covariates: treatment status, presence of high disease activity (HDA), age, sex, history of bone marrow failure (BMF), history of thrombotic events (TE), transfusion dependence, and estimated glomerular filtration rate ≤60 mL/min/1.73 m 2. HDA was defined as lactate dehydrogenase (LDH) ratio ≥1.5 × upper limit of normal (ULN) and ≥1 of the following: history of major adverse vascular events (including TE); anemia (hemoglobin &lt;10 g/dL), or physician-documented abdominal pain, dyspnea, dysphagia, fatigue, hemoglobinuria, or erectile dysfunction at any time before and including baseline. Baseline was defined as the date of eculizumab treatment initiation (ever-treated patients) or date of Registry enrollment (never-treated patients). Survival time was analyzed using a left-truncation approach that mapped time in patients' survival based on disease start date, defined as the earliest date of first-reported PNH diagnosis, PNH symptom, or first consistent flow cytometry result. Results Baseline characteristics of the 4627 patients included in the analysis (mean [SD] age at disease start, 40.2 [18.71] years; 53% female; 75% white) were comparable between the ever-treated and never-treated groups (n=1892 and n=2735, respectively). Compared with never-treated patients, more ever-treated patients had LDH ≥1.5 × ULN (90% vs 35%), and fewer had &lt;10% PNH granulocytes (3% vs 57%) or history of BMF (45% vs 76%). The univariate Cox proportional hazard ratio (HR) for mortality in ever-treated vs never-treated patients was 0.48 (95% CI, 0.39-0.60; P&lt;0.0001), indicating a 52% increase in survival in the treated group (Table). Among ever-treated patients, those with HDA at baseline experienced the largest reduction in mortality risk (HR [95% CI], 0.46 [0.33-0.64]; n=174); however, decreased mortality was also evident in ever-treated patients without HDA (HR, 0.65 [0.39-1.10]; n=212) or with unknown HDA status (HR, 0.50 [0.32-0.76; n=120) at baseline. Overall survival probability by treatment status was consistently greater in ever-treated vs never-treated patients through 20 years of follow-up; survival probability at 20 years was 82% (ever-treated) vs 69% (never-treated). Although long-term survival probability was greatest throughout follow-up in ever-treated patients with HDA at baseline, increased survival among ever-treated patients was evident in all 3 HDA status groups (Figure). Conclusion In this analysis of Registry data, treatment with the C5 inhibitor eculizumab improved patient survival compared with a never-treated cohort at a comparable time point in their disease course. Covariates were assessed at baseline only and competing risks and time on treatment were not controlled for, which are potential limitations. Survival benefits conferred by eculizumab treatment were observed regardless of HDA status at baseline, were more pronounced in treated patients with HDA vs those without HDA, and were maintained through 2 decades of real-world follow-up. Figure 1 Figure 1. Disclosures Terriou: Alexion, AstraZeneca Rare Disease: Consultancy, Membership on an entity's Board of Directors or advisory committees. Patriquin: Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Speakers Bureau; Biocryst: Honoraria; Apellis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria. Griffin: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees; BioCryst Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis: Other: Educational grant support. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees. Gustovic: Alexion, AstraZeneca Rare Disease: Current Employment. Patel: Alexion, AstraZeneca Rare Disease: Current Employment. Szer: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Prevail Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Outcomes of Patients with Hematologic Malignancies and COVID-19: Perspective of a Large Hematology Center in Greece

The emergence of SARS-CoV-2, as of July 2021 has affected 469,042 individuals and accounted for 12,851 deaths nationally in Greece, according to WHO database. Mortality rate is higher in elderly patients (pts) and in pts with comorbidities, including malignancies. However, there is a growing interest on COVID-19 outcomes in pts with hematologic diseases. The aim of this study was to perform a systematic registration and analysis of the outcomes of pts with hematologic disease and COVID-19 in our center. The study is a single-center, retrospective study, conducted at a Hematology Department and HCT unit of a tertiary Hospital after approval from local Ethics Committee. We included pts with a hematologic disease and RT-PCR confirmed COVID-19 infection between October 2020 and July 2021. We reviewed hematological medical records to extract demographic and clinical data of COVID-19 infections. Most of the data have already been intergraded in ASH Research Collaborative Data Hub. Hematologic diseases were categorized to: Acute Myeloblastic Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Non-Hodgkin Lymphomas (NHL), Chronic Lymphocytic Leukemia (CLL), Hodgkin Lymphoma (HL), Multiple Myeloma (MM), Myelodysplastic Syndromes (MDS), Chronic Myeloid Leukemia (CML), Myeloproliferative Neoplasms (MPN, including all Philadelphia-negative MPN) and other hematologic conditions. We evaluated a total of 89 pts, 54% were male and 46% female, with a median age of 64.5 (20-86) and 59.5 (21-85) years respectively. 83% of pts were ≥40 years and 27% ≥70 years old. Most of them (92%) acquired infection outside a hospital setting. 13% of pts were asymptomatic and diagnosis was confirmed only with positive RT-PCR test. The most common represented malignancies were NHL 26%, CLL 20% and acute leukemias 13.5%, while 15% of pts underwent transplantation (HCT). Pts presented with moderate/severe COVID-19 were 55%, while 43% of hospitalized pts required Intensive Care Unit (ICU) admission. Overall, the death rate was 24%, while remarkably almost all pts required ICU support did not survive (mortality 94%). Higher mortality observed in patients with MDS (50%), MM (43%), CLL (39%), ALL (33%) and NHL (30%). Further analysis showed a positive correlation between mortality and male gender with 16 deaths out of 21 (p = .0245), as well as mortality and ICU admission (p &lt; .001). A chi-square test of independence was performed to examine the relation between age and COVID-19 severity, without any statistically significant result [x 2 (2, N = 87) = 3.475, p = .176]. Whereas the only significant correlation between age and mortality was among age groups 18-39 and &gt;70 years (p = .0146). Regarding treatment, pts were divided into two subgroups, 78% of them received anticancer therapy at least once in their lives, while 22% of them have never been on treatment, mainly pts with CLL and indolent NHL. 62% of the first subgroup manifested moderate/severe COVID-19 infection requiring hospitalization with 28% death rate, while the same rates in the 2 nd subgroup were 30% and 10% respectively. Although there was a significant correlation between the treatment status and the severity of COVID-19 infection (p = .020), the above was not translated in statistically higher death rate in the first subgroup (p = .14). There was also a correlation between HCT and COVID-19 severity in general (p = .005), with autologous HCT having statistically higher mortality than the allogeneic subgroup (p = .032). Α similar analysis in CLL and NHL groups showed no relation among treatment status, COVID-19 severity, and mortality (p values .638 and .115/ .34 and .62 respectively). As anticipated in hematological pts, the immunocompromised nature of the underlying disease makes them extremely vulnerable to COVID-19 infection regardless of their treatment status, a fact that is also reflected in mortality despite ICU admission and support. In general, the severity of infection is correlated to anticancer therapy, while mortality to male sex, ICU admission and autologous HCT. Larger number of pts are necessary for further studies to better understand the parameters that impact the outcome of COVID-19 in hematological pts. Hematology departments should remain COVID-19 free zones, dedicated only to hematologic treatment and pts should strictly comply with social distancing. It remains to see if vaccines can play a key role to protect this special group of pts. Figure 1 Figure 1. Disclosures Anagnostopoulos: Abbvie: Other: clinical trials; Sanofi: Other: clinical trials ; Ocopeptides: Other: clinical trials ; GSK: Other: clinical trials; Incyte: Other: clinical trials ; Takeda: Other: clinical trials ; Amgen: Other: clinical trials ; Janssen: Other: clinical trials; novartis: Other: clinical trials; Celgene: Other: clinical trials; Roche: Other: clinical trials; Astellas: Other: clinical trials .

330. Evaluating the Relationship Between Comorbidity Treatment Status and In-hospital Mortality Among COVID-19 Patients

Background Chronic comorbidities increase the risk of poor outcomes in patients with COVID-19. However, there are insufficient data to determine whether control of chronic comorbidities influences outcomes. The purpose of this study was to determine whether pharmacologic treatment for common comorbidities influences in-hospital mortality. Methods This multicenter, retrospective study included adult patients with diabetes, hypertension, and/or dyslipidemia who were hospitalized with COVID-19 in Southwest GA, U.S. Patients were divided into two groups based on treatment status, where treated was defined as documentation in the electronic medical record of outpatient pharmacologic therapy indicated for that specific comorbidity while untreated was defined as no record of pharmacologic therapy for one or more comorbidity. The primary outcome was to compare in-hospital mortality between treated and untreated COVID-19 patients. Secondary outcomes included comparing length of hospital stay, development of thrombotic events, requirement for vasopressors, mechanical ventilation, and transfer to the ICU between groups. Results A total of 360 patients were included with a median age of 66 years (IQR 56-75). The majority were African American (83%) and female (61%) with a median Charlson Comorbidity Index of 4 (IQR 2-6). Hypertension, diabetes, and dyslipidemia were present in 91%, 55%, and 45% of patients, respectively, of which 76% (n=274) were treated. Mortality was similar between treated and untreated patients (25% vs 20%, p=0.304). Average length of stay was 9.5 days (SD 8.7) in treated patients compared to 10.6 days (SD 9.1) in untreated patients (p=0.302). No differences were observed in the rates of thrombosis (3% vs 4%, p=0.765), receipt of vasopressors (23% vs 21%, p=0.741), mechanical ventilation (31% vs 27%, p=0.450), or transfer to the ICU (27% vs 14%, p=0.112). Conclusion Hospitalized COVID-19 patients being treated for hypertension, diabetes, and/or dyslipidemia have similar rates of complications and mortality compared to untreated patients. Further research is needed to determine whether degree of control of chronic comorbidities impacts COVID-19 outcomes. Disclosures All Authors: No reported disclosures

Association of Phthalate Exposure with Thyroid Function and Thyroid Homeostasis Parameters in Type 2 Diabetes

Aims. Phthalates, which are recognized environmental endocrine-disrupting chemicals, are associated with thyroid hormone disruption. We aimed to evaluate the relationship of phthalate metabolites with thyroid function and thyroid homeostasis parameters in type 2 diabetes and to explore whether thyroid autoimmunity status and metformin, the most common antidiabetic drug, may influence such associations. Methods. Concurrent urine and blood samples were collected from 639 participants with type 2 diabetes in the METAL (Environmental Pollutant Exposure and Metabolic Diseases in Shanghai) study. We measured urinary concentrations of thirteen phthalate metabolites along with serum levels of thyroid-stimulating hormone (TSH), total T4 and T3, free T4 (FT4) and T3 (FT3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). Four parameters of thyroid homeostasis, including the sum activity of step-up deiodinases (SPINA-GD), thyroid secretory capacity (SPINA-GT), Jostel’s TSH index (TSHI), and thyrotroph thyroid hormone resistance index (TTSI), were also calculated. Results. Among all participants, after full adjustment, multivariable regression analysis showed that some urine phthalate metabolites were negatively associated with TSH, TSHI, and TTSI levels and positively associated with FT3, T3, SPINA-GD, and SPINA-GT levels. None of the urine phthalate metabolites exhibited a significant association with thyroid autoimmunity. The associations of phthalate metabolites with thyroid function and thyroid homeostasis parameters differed based on thyroid autoantibody and metformin treatment status. Conclusions. Urinary phthalate metabolites may be associated with thyroid function and thyroid homeostasis parameters among participants with type 2 diabetes. Furthermore, our present study suggested that thyroid autoantibody status and metformin treatment status are potential mediators of such associations.

Epidemiological and Clinical Features, Treatment Status, and Economic Burden of Traumatic Spinal Cord Injury in China

Background <br />China has the largest population of traumatic spinal cord injury (TSCI), but has not yet performed a national-level study on its epidemiological and clinical features, treatment status, and economic burden. <br />Methods A total of 14 754 patients were recruited between January 2013 and December 2018 from 37 hospitals in 11 provinces and municipalities, which represented all geographical divisions of China. The percentage of TSCI in hospitalized patients and the percentage of TSCI in hospitalized patients through the orthopaedic departments were calculated. The treatment status, total and daily costs were collected. <br />Results The percentage of TSCI in hospitalized patients and the percentage of TSCI in hospitalized patients through the orthopaedic departments did not change significantly overall (APC= -0.5%, 95% CI: -3.0 to 2.1 and -1.6%, -4.9 to 1.8, respectively). A total of 10 918 (74.0%) patients received surgery after TSCI. However, only 3.0% of patients underwent surgery received surgery less than 24 hours after injury. A total of 2 084 (14.1%) patients were treated with methylprednisolone sodium succinate/methylprednisolone (MPSS/MP) at a high dose (?500 mg) and 641 (4.3%) patients receiving it within 8 hours. The total costs for acute TSCI decreased (-4.8%, -6.2 to -3.4), while the daily costs did not change significantly (0.5%, -1.2 to 2.2). <br />Conclusions This study revealed epidemiological and clinical features, treatment status, and economic burden of TSCI that occurred in China from 2013 to 2018.<br />Funding National Key Research and Development Project of Stem Cell and Transformation Research (2019YFA0112100).