Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Heteroplasmic pathogenic m.12315G>A variant in MT-TL2 presenting with MELAS syndrome and depletion of nitric oxide donors.

The MT-TL2 m.12315G>A pathogenic variant has previously been reported in five individuals with mild clinical phenotypes. Herein we report the case of a 5-year-old child with heteroplasmy for this variant who developed neurological regression and stroke-like episodes similar to those observed in mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Biochemical evaluation revealed depletion of arginine on plasma amino acid analysis and low z-scores for citrulline on untargeted plasma metabolomics analysis. These findings suggested that decreased availability of nitric oxide may have contributed to the stroke-like episodes. The use of intravenous arginine during stroke-like episodes and daily enteral L-citrulline supplementation normalized her biochemical values of arginine and citrulline. Untargeted plasma metabolomics showed the absence of nicotinamide and 1-methylnicotinamide, and plasma total glutathione levels were low; thus, nicotinamide riboside and N-acetylcysteine therapies were initiated. This report expands the phenotype associated with the rare mitochondrial variant MT-TL2 m.12315G>A to include neurological regression and a MELAS-like phenotype. Individuals with this variant should undergo in-depth biochemical analysis to include untargeted plasma metabolomics, plasma amino acids, and glutathione levels to help guide a targeted approach to treatment.

Prognostics of multiple malaria episodes and nutritional status in children aged 6 to 59 months from 2013 to 2017 in Dangassa, Koulikoro region, Mali.

BACKGROUND: In Africa, the relationship between childhood nutritional status and malaria remains complex and difficult to interpret. Understanding it is important in the improvement of malaria control strategies. This study aimed to assess the influence of nutritional status on the occurrence of multiple malaria episodes in children aged 6 to 59 months between 2013 and 2017 living in the village of Dangassa, Mali. METHODS: A community-based longitudinal study was conducted using cross-sectional surveys (CSSs) at the beginning (June) and end (November) of the malaria transmission season associated with passive case detection (PCD) at the Dangassa Community Health Centre. Children with asymptomatic malaria infection during cross-sectional surveys were selected and their malaria episodes followed by PCD. Malaria indicators in person-months were estimated using an ordinal-logistic model repeated on subjects during follow-up periods. RESULTS: The incidence rate (IR) during the period of high transmission (June to October), for 1 episode and for 2 + episodes peaked in 2013 with 65 children (IR = 95.73 per 1000 person-months) and 24 cases (IR = 35.35 per 1000 person-months), respectively. As expected, the risk of multiple episodes occurring during the period of high transmission was 3.23 compared to the period of low transmission after adjusting for other model parameters (95% CI [2.45-4.26], p = 0.000). Children with anaemia were at high risk of having multiple episodes (OR = 1.6, 95% CI [1.12-2.30], p = 0.011). However, the risk of having 2 + episodes for anemic children was higher during the period of low transmission (RR = 1.67, 95% CI [1.15-2.42], p = 0.007) compared to the period of high transmission (RR = 1.58, 95% CI [1.09-2.29], p = 0.016). The trend indicated that anemic and underweight children were significantly associated with multiple malaria episodes during the period of low transmission (p < 0.001). CONCLUSION: Results show that multiple episodes of malaria are significantly related to the nutritional status (anaemia and underweight) of the child during the two transmission seasons and more pronounced during the dry season (period of low transmission). Further research including other malnutrition parameters will be needed to confirm these findings.

Costs in Colectomy Episodes of Care: Opportunities to Prevent Emergency Operations and Decrease Costs.

INTRODUCTION: Payment structured around Episodes of Care is a method for incentivizing decreased care utilization after major procedures. We examined Major Bowel Episodes of Care (MB-EoC)-the focus among general surgery procedures-within a large health system to determine the contribution of emergency bowel surgery to higher costs of care. METHODS: Adult MB-EoC cases from July 2018 to June 2021 were reviewed for 90-d costs, examining patient age, insurance, diagnosis, cost of care, and contributors to cost. For patients aged ≥45 y who had nonelective care for colon cancer, incidence of prior screening colonoscopy was examined. RESULTS: We identified 1292 colectomy cases. Mean age was 65 y. Of these patients, 90% had Medicare/commercial insurance. Colon cancer comprised 41% of primary diagnoses. Twenty-eight percent of cases were nonelective, more likely to have Medicaid/underinsured (21% versus 7%, P < 0.001), and had higher utilization of postdischarge cost-drivers. Ninety-day EoC per case cost was 66% higher for emergent versus elective cases. Of eligible emergency cancer cases, 43% (40/93) had undergone prior colonoscopy within 10 y. For patients with colon cancer, 90-d EoC per case was 39% higher for emergent versus elective cases. CONCLUSIONS: Emergency MB-EoC cases disproportionally contribute to higher 90-d care utilization and costs. Efforts to increase screening colonoscopy in appropriate populations may have a substantial impact on MB-EoC costs.

Intravenous fluid therapy and hospital outcomes for vaso-occlusive episodes in children, adolescents, and young adults with sickle cell disease.

BACKGROUND: While intravenous fluid (IVF) therapy in patients with sickle cell disease (SCD) admitted for a vaso-occlusive episode (VOE) can help reduce red blood cell sickling, clinical practice varies across institutions. We examined the relationship between IVF therapy and hospital length of stay (HLOS), as well as adverse events, such as acute chest syndrome (ACS), pediatric intensive care unit (PICU) transfer, and 28-day re-admission. METHODS: This is a single-center retrospective analysis of SCD VOE hospitalizations between January 2015 and April 2020. Patients with SCD, age 0-30, with consecutive hospitalizations for VOE were included. For the first 3 days of each admission, an "IVF ratio" was calculated by dividing actual IVF rate administered by weight-based maintenance IVF (mIVF) rate. RESULTS: A total of 617 hospitalizations for 161 patients were included. Mean HLOS was 5.7 days, (SD 3.9), and mean IVF volume over the first 3 days of admission was 139.6 mL/kg/day (SD 57.8). Multivariate analysis showed that for each additional 0.5 times the mIVF rate, HLOS increased by 0.53 day (p < .001; 95% confidence interval [CI]: 0.609-0.989), but there was no significant association between IVF therapy and adverse events. History of chronic pain was associated with increased odds of re-admission (OR 6.4; 95% CI: 3.93-10.52). CONCLUSIONS: Despite the theoretical potential for IVF therapy to slow down the sickling process, our findings suggest that increased IVF therapy was associated with prolonged HLOS, which places a burden on patients, families, and the health system.

Closed loop stimulation reduces the incidence of atrial high-rate episodes compared with conventional rate-adaptive pacing in patients with sinus node dysfunctions.

AIMS: Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing. METHODS AND RESULTS: Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72-0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71-0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms. CONCLUSION: Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing.

An imported malaria case with repeated episodes of neurological syndromes resulting from different Plasmodium species.

BACKGROUND: Imported cerebral malaria (CM) cases in non-endemic areas are often misdiagnosed, which delays treatment. Post-malaria neurological syndrome (PMNS) after recovery from severe malaria can also complicate diagnosis. CASE: We report an imported malaria case from West Africa with two sequential episodes with neurological syndromes within about a month. The first episode was diagnosed as CM with microscopy-positive Plasmodium falciparum infection. The second episode, occurring a month after the recovery from the first CM episode, was consistent with PMNS, since malaria parasites were not detected by microscopy in peripheral blood smears. However, this diagnosis was complicated by the detection of Plasmodium vivax in peripheral blood by PCR, suggesting a potential cause of the second episode by P. vivax. CONCLUSION: This study suggests that PMNS often occurs after severe falciparum malaria. Concurrent P. vivax infection with pathogenic biomass being predominantly extravascular further complicates accurate diagnosis.

Characterization and quantification of epilepsy patients with hospital episodes in Portugal: A multicenter retrospective study from Liga Portuguesa Contra a Epilepsia.

INTRODUCTION: Epilepsy affects around 50 million people worldwide and is associated with lower quality of life scores, an increased risk of premature death, and significant socio-economic implications. The lack of updated evidence on current epidemiology and patient characterization creates considerable uncertainty regarding the epilepsy burden in Portugal. The study aims to characterize and quantify the epilepsy patients who have been hospitalized, with medical or surgical procedures involved, and to analyze their associated comorbidities and mortality rates. METHODS: A multicenter retrospective study was conducted using hospital production data of epilepsy patients. The study included all patients diagnosed with epilepsy-related International Classification of Diseases-9/10 codes between 2015 and 2018 in 57 Portuguese National Health Service (NHS) hospitals (n = 57 institutions). Patient characterization and quantification were done for all patients with an epilepsy diagnosis, with specific analyses focusing on those whose primary diagnosis was epilepsy. Baseline, demographic, and clinical characteristics were analyzed using descriptive statistics. RESULTS: Between 2015 and 2018, a total of 80,494 hospital episodes (i.e., patient visit that generates hospitalization and procedures) were recorded, with 18 % to 19 % directly related to epilepsy. Among these epilepsy-related hospital episodes, 13.0 % led to short term hospitalizations (less than 24 h). Additionally, the average length of stay for all these epilepsy-related episodes was 8 days. A total of 49,481 patients were identified with epilepsy based on ICD-9/10 codes. The median age of patients was 64 years (min: 0; max: 104), with a distribution of 4.8 patients per 1,000 inhabitants. From the total of deaths (9,606) between 2015 and 2018, 14% were associated with patients whose primary diagnosis was epilepsy, with 545 of these being epilepsy-related deaths. Among patients with a primary diagnosis of epilepsy, the most common comorbidities were hypertension (24%) and psychiatric-related or similar comorbidities (15%), such as alcohol dependance, depressive and major depressive disorders, dementia and other convulsions. CONCLUSION: This study showed similar results to other European countries. However, due to methodological limitations, a prospective epidemiological study is needed to support this observation. Furthermore, the present study provides a comprehensive picture of hospitalized epilepsy patients in Portugal, their comorbidities, mortality, and hospital procedures.

Synthesized V7 QRS Amplitude and Oversensing Episodes in Patients With Subcutaneous Implantable Cardioverter-Defibrillators.

BACKGROUND: Patients with subcutaneous implantable cardioverter-defibrillators (S-ICDs) experience an oversensing episode (OS) more frequently than those with transvenous ICDs. However, no established electrocardiography (ECG) parameters can accurately detect an OS. This study aimed to evaluate the incidence of an OS in real-world clinical practice and the association of synthesized 18-lead ECG (syn18-ECG) parameters with an OS. METHODS: We retrospectively included 21 consecutive patients who underwent S-ICD implantation and collected syn18-ECG parameters. We placed the generator in a deep posterior position and defined an OS as an inappropriate charging episode caused by cardiac or noncardiac signals. A SMART pass filter and two tachyarrhythmia zones were programed. RESULTS: The most frequent underlying heart disease was Brugada/J wave syndrome (n = 7). During a median follow-up period of 1188 days, an OS was observed in six patients (28.6%). The QRS amplitude in synthesized V7 lead (synV7) was significantly lower in the OS group than in the non-OS group (0.59 ± 0.17 vs. 0.91 ± 0.35 mV, p = 0.019). The optimal cutoff value of synV7 QRS amplitude was 0.61 mV, with a sensitivity of 80.0% and a specificity of 83.7% for predicting an OS. Univariate logistic analysis showed that a synV7 QRS amplitude of <0.61 mV was only associated with an OS (odd ratio, 20.0; 95% confidence interval, 1.66-241.72; p = 0.018). CONCLUSIONS: In patients with S-ICDs, an OS was not a rare complication during long-term follow-up. A low synV7 QRS amplitude was associated with a high OS incidence.

Association Between P-Wave Duration, Dispersion, and Interatrial Block and Atrial High-Rate Episodes in CIED Patients.

INTRODUCTION: Atrial high-rate episodes (AHRE) have been linked to increased thromboembolic risk and all-cause mortality in patients with cardiac implantable electronic devices (CIEDs). Various predictors of AHRE development have been identified, emphasizing the need for close monitoring and the potential transition to clinical atrial fibrillation (AF). However, the predictive value of P wave characteristics on AHRE development remains conflicting. This meta-analysis aims to summarize existing data to investigate this association. METHOD: We examined studies from MEDLINE and EMBASE databases up to May 2024 to investigate the association of baseline P-wave duration (PWD), P-wave dispersion (PWDIS), and interatrial block (IAB) with the risk of developing AHRE. We extracted the mean and standard deviations of PWD and PWDIS to calculate the pooled mean difference (MD). Risk ratios (RR) and 95% confidence intervals (CIs) were used to assess the association between IAB and AHRE risk, using the generic inverse variance method for combination. RESULTS: The meta-analysis included nine studies. Patients with AHRE had longer PWD and PWDIS compared to those without AHRE, with a pooled MD for PWD of 9.17 ms (95% CI: 4.74-13.60; I2 = 47%, p < 0.001) and a pooled MD for PWDIS of 20.56 ms (95% CI: 11.57-29.56; I2 = 57%, p < 0.001). Additionally, patients with IAB had a higher risk of developing AHRE, with a pooled RR of 3.33 (95% CI: 2.53-4.38; I2 = 0%, p < 0.001), compared to those without IAB. CONCLUSIONS: Our meta-analysis found that patients with AHRE had higher PWD and PWDIS than those without AHRE. Additionally, IAB was associated with a higher risk of developing AHRE. These findings emphasize the importance of close monitoring and risk stratification, particularly for patients with P wave abnormalities.

Chemotherapy-induced febrile neutropenia (FN): healthcare resource utilization (HCRU) and costs in commercially insured patients in the US.

PURPOSE: Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data. METHODS: A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group. RESULTS: 7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851). CONCLUSIONS: FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.

Neurological function and drug-refractory epilepsy in Sturge-Weber syndrome children: a retrospective analysis.

Epilepsy in Sturge-Weber syndrome (SWS) is common, but drug-refractory epilepsy (DRE) in SWS has rarely been studied in children. We investigated the characteristics of epilepsy and risk factors for DRE in children with SWS. A retrospective study was conducted to analyze the clinical characteristics of children with SWS with epilepsy in our hospital from January 2013 to October 2022. Univariate and multivariate logistic analyses were performed to investigate the factors influencing DRE in children with SWS. A total of 35 SWS children with epilepsy were included (51% male; mean age of presentation 3.6 ± 0.5 years), 71% of children with SWS had their first seizure within the first year of life, and the most common type of seizure was focal seizure (77%). Eleven (31%) patients developed DRE. The median age of onset for the first seizure was 1.0 years and all these cases were of SWS type I. Multivariate logistic analysis revealed that stroke-like episodes and seizure clusters were risk factors for DRE in SWS children. A poor neurological function group was observed in twenty-five children with SWS. Status epilepticus was a risk factor that affected the neurological function of SWS children with epilepsy.  Conclusion: The study explored the epileptic features of children with SWS. The results revealed that stroke-like episodes and seizure clusters are risk factors for DRE in children with SWS. The occurrence of status epilepticus impacts the neurological function of SWS children with epilepsy. Thus, long-term follow-up is necessary to monitor outcomes. What is Known: • Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder, over 75% of children with SWS experience seizures, and 30-57% develop drug-refractory epilepsy (DRE), which leads to a poor outcome. • Drug-refractory epilepsy in SWS has been rarely studied in children, and the risk factors associated with DRE are unclear. What is New: • Clinical features of SWS children with drug-refractory epilepsy. • In SWS, stroke-like episodes and seizure clusters are risk factors of DRE, the occurrence of status epilepticus impacts the neurological function.

Hypotensive episodes at 24-h ambulatory blood pressure monitoring predict adverse outcomes in Parkinson's disease.

PURPOSE: Neurogenic orthostatic hypotension (nOH) is a frequent nonmotor feature of Parkinson's disease (PD), associated with adverse outcomes. Recently, 24-h ambulatory blood pressure monitoring (ABPM) showed good accuracy in diagnosing nOH. This study aims at evaluating the prognostic role of ABPM-hypotensive episodes in predicting PD disability milestones and mortality and comparing it to the well-defined prognostic role of bedside nOH. METHODS: Patients with PD who underwent ABPM from January 2012 to December 2014 were retrospectively enrolled and assessed for the development of falls, fractures, dementia, bed/wheelchair confinement, hospitalization, and mortality, during an up-to-10-year follow-up. Significant ABPM-hypotensive episodes were identified when greater than or equal to two episodes of systolic BP drop ≥ 15 mmHg (compared with the average 24 h) were recorded during the awakening-to-lunch period. RESULTS: A total of 99 patients (74% male, age 64.0 ± 10.1 years, and PD duration 6.4 ± 4.0 years) were enrolled. At baseline, 38.4% of patients had ABPM-hypotensive episodes and 46.5% had bedside nOH. On Kaplan-Meier analysis, patients with ABPM-hypotensive episodes showed earlier onset of falls (p = 0.001), fractures (p = 0.004), hospitalizations (p = 0.009), bed/wheelchair confinement (p = 0.032), dementia (p = 0.001), and shorter survival (8.0 versus 9.5 years; p = 0.009). At Cox regression analysis (adjusted for age, disease duration, Charlson Comorbidity Index, and Hoehn and Yahr stage) a significant association was confirmed between ABPM-hypotensive episodes and falls [odds ratio (OR) 3.626; p = 0.001), hospitalizations (OR 2.016; p = 0.038), and dementia (OR 2.926; p = 0.008), while bedside nOH was only associated with falls (OR 2.022; p = 0.039) and dementia (OR 1.908; p = 0.048). CONCLUSIONS: The presence of at least two ABPM-hypotensive episodes independently predicted the development of falls, dementia, and hospitalization, showing a stronger prognostic value than the simple bedside assessment.

Factors affecting the syncopal episodes in pediatric vasovagal syncope.

OBJECTIVE: To investigate factors that influence the syncopal episodes in pediatric vasovagal syncope (VVS). METHODS: A retrospective analysis was performed on the clinical data of 2908 children who were diagnosed with VVS for the first time between January 2001 and February 2023. The study examined the linear relationships among age, sex, height, weight, heart rate (HR), blood pressure, hemodynamic type, and head-up tilt test (HUTT) mode in relation to the onset of syncope. RESULTS: (1) Comparative analysis of intergroup differences revealed statistically significant variations in sex, age, height, weight, HR, systolic blood pressure, hemodynamic classification, and HUTT mode among syncopal episodes groups (P < 0.05); (2) Univariate analysis identified age, female, height, weight, VVS-cardioinhibited type (VVS-CI), VVS-mixed type (VVS-M) as potential risk factors for syncope episodes. Conversely, HR and sublingual nitroglycerin HUTT (SNHUT) emerged as potential protective factors against syncope episodes. (3) Multivariate analysis indicated that the frequency of syncope episodes increased by 0.27/0.02 for each unit increase in age/weight. When females compared to males and VVS-CI and VVS-M compared to VVS-vasoinhibited type (VVS-VI), the frequency of syncope episodes increased by 1.36, 0.53, and 0.66 respectively. Furthermore, SNHUT was associated with a reduction in the number of syncope episodes by 0.34 relative to basic HUTT. CONCLUSION: Female, age, weight, VVS-CI, and VVS-M were identified as independent risk factors for syncopal episodes, while SNHUT was recognized as an independent protective factor against syncopal episodes.

Direct oral anticoagulants for stroke prevention in patients with device-detected atrial fibrillation: assessing net clinical benefit.

Subclinical, device-detected atrial fibrillation (AF) is frequently recorded by pacemakers and other implanted cardiac rhythm devices. Patients with device-detected AF have an elevated risk of stroke, but a lower risk of stroke than similar patients with clinical AF captured with surface electrocardiogram. Two randomized clinical trials (NOAH-AFNET 6 and ARTESiA) have tested a direct oral anticoagulant (DOAC) against aspirin or placebo. A study-level meta-analysis of the two trials found that treatment with a DOAC resulted in a 32% reduction in ischaemic stroke and a 62% increase in major bleeding; the results of the two trials were consistent. The annualized rate of stroke in the control arms was ∼1%. Several factors point towards overall net benefit from DOAC treatment for patients with device-detected AF. Strokes in ARTESiA were frequently fatal or disabling and bleeds were rarely lethal. The higher absolute rates of major bleeding compared with ischaemic stroke while on treatment with a DOAC in the two trials are consistent with the ratio of bleeds to strokes seen in the pivotal DOAC vs. warfarin trials in patients with clinical AF. Prior research has concluded that patients place a higher emphasis on stroke prevention than on bleeding. Further research is needed to identify the characteristics that will help identify patients with device-detected AF who will receive the greatest benefit from DOAC treatment.

Model-based comparison of subcutaneous versus sublingual apomorphine administration in the treatment of motor fluctuations in Parkinson's disease.

The objective of this study was to compare the effectiveness of subcutaneous (SC) and sublingual (SL) formulations of apomorphine for the treatment of motor fluctuations in Parkinson's disease using a pharmacokinetics (PK)/pharmacodynamics (PD) modeling approach. The PK of SC and SL apomorphine are best described by a one-compartment model with first-order absorption and a two-compartment model with delayed absorption, respectively. The PK/PD model relating apomorphine plasma concentrations to the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores was described by a sigmoidal Emax model assuming effective concentration = drug concentration in an effect compartment. Apomorphine concentrations and UPDRS motor scores were simulated from the PK/PD models using 500 hypothetical subjects. UPDRS motor score change from baseline was evaluated using time to clinically relevant response, response duration, area under the curve, maximal response, and time to maximal response. Higher doses of each apomorphine formulation were associated with shorter time to response, longer response duration, and greater maximal response. Although the mean maximal responses to SC and SL apomorphine were comparable, the time to response was four times shorter (7 vs. 31 min) and time to maximal response was two times shorter (27 vs. 61 min) for 4 mg SC vs. 50 mg SL. Thus, faster onset of action was observed for the SC formulation compared to SL. These data may be useful for physicians when selecting "on demand" therapy for patients with Parkinson's disease experiencing motor fluctuations.

Trends in Bundled Outpatient Behavioral Health Services in VA-Direct Versus VA-Purchased Care.

The Veterans Health Administration (VA) increasingly purchases community-based care (CC) to improve healthcare access, including behavioral health. In 2018, VA introduced standardized episodes of care (SEOCs) to guide authorization and purchase of CC services for specific indications in a defined timeframe without bundling payment. In this retrospective cross-sectional study, we describe trends in VA and CC behavioral healthcare utilization using the VA Outpatient Psychiatry SEOC definition. Counts of Outpatient Psychiatry SEOC-allowable service and procedure codes during fiscal years 2016-2019 were organized according to four SEOC-defined service types (evaluation and management, laboratory services, psychiatry services, transitional care) and measured as percentages of all included codes. Trends comparing behavioral healthcare utilization between Veterans using any CC versus VA only were analyzed using a linear mixed effects model. We identified nearly 3 million Veterans who registered 60 million qualifying service and procedure codes, with overall utilization increasing 77.8% in CC versus 5.2% in VA. Veterans receiving any CC comprised 3.9% of the cohort and 4.7% of all utilization. When examining service type as a percent of all Outpatient Psychiatry SEOC-allowable care among Veterans using CC, psychiatry services increased 12.2%, while transitional care decreased 8.8%. In regression analysis, shifts in service type utilization reflected descriptive results but with attenuated effect sizes. In sum, Outpatient Psychiatry SEOC-allowable service utilization grew, and service type composition changed, significantly more in CC than in VA. The role of SEOCs and their incentives may be important when evaluating future behavioral healthcare quality and value in bundled services.

High ADMA Is Associated with Worse Health Profile in Heart Failure Patients Hospitalized for Episodes of Acute Decompensation.

Background and Objectives: episodes of acute decompensation in chronic heart failure (ADHF), a common health problem for the growing elderly population, pose a significant socio-economic burden on the public health systems. Limited knowledge is available on both the endothelial function in and the cardio-metabolic health profile of old adults hospitalized due to ADHF. This study aimed to investigate the connection between asymmetric dimethylarginine (ADMA)-a potent inhibitor of nitric oxide-and key health biomarkers in this category of high-risk patients. Materials and Methods: this pilot study included 83 individuals with a known ADHF history who were admitted to the ICU due to acute cardiac decompensation. Selected cardiovascular, metabolic, haemogram, renal, and liver parameters were measured at admission to the ICU. Key renal function indicators (serum creatinine, sodium, and potassium) were determined again at discharge. These parameters were compared between patients stratified by median ADMA (114 ng/mL). Results: high ADMA patients showed a significantly higher incidence of ischemic cardiomyopathy and longer length of hospital stay compared to those with low ADMA subjects. These individuals exhibited significantly higher urea at admission and creatinine at discharge, indicating poorer renal function. Moreover, their lipid profile was less favorable, with significantly elevated levels of total cholesterol and HDL. However, no significant inter-group differences were observed for the other parameters measured. Conclusions: the present findings disclose multidimensional, adverse ADMA-related changes in the health risk profile of patients with chronic heart failure hospitalized due to recurrent decompensation episodes.

Elaborations of the influencing factors on the formation of secondary inorganic aerosols in a heavily polluted urban area of China.

In this study, online water-soluble inorganic ions were detected to deduce the formation mechanism of secondary inorganic aerosol in Xianyang, China during wintertime. The dominant inorganic ions of sulfate (SO42-), nitrate (NO3-), and ammonium (NH4+) (the sum of those is abbreviated as SNA) accounted for 17%, 21%, and 12% of PM2.5 mass, respectively. While the air quality deteriorated from excellent to poor grades, the precursor gas sulfur dioxide (SO2) of SO42- increased and then decreased with a fluctuation, while nitrogen dioxide (NO2) and ammonia (NH3), precursors of NO3- and NH4+, and SNA show increasing trends. Meteorological factors including boundary layer height (BLH), temperature, and wind speed also show decline trends, except relative humidity (RH). Meanwhile, the secondary conversion ratio shows a remarkable increasing trend, indicating that there was a strong secondary transformation. From the perspective of chemical mechanisms, RH is positively correlated with sulfur oxidation ratios (SOR), nitrogen oxidation ratios (NOR), and ammonia conversion ratios, representing that the increase of humidity could promote the generation of SNA. Notably, SOR and NOR were also positively related to the ammonia. On the one hand, the low wind speed and BLH led to the accumulation of pollutants. On the other hand, the increases of RH and ammonia promoted more formations of SNA and PM2.5. The results advance our identification of the contributors to the haze episodes and assist to establish more efficient emission controls in Xianyang, in addition to other cities with similar emission and geographical characteristics.

Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management.

OBJECTIVES: Patients with PMM2-CDG develop acute events (stroke-like episodes (SLEs), thromboses, haemorrhages, seizures, migraines) associated with both clotting factors (factor XI) and coagulation inhibitors (antithrombin, protein C and protein S) deficiencies. The aim of the study was to correlate acute events to haemostasis and propose practical guidelines. METHODS: In this multicentric retrospective study, we evaluated clinical, radiological, haemostasis and electroencephalography data for PMM2-CDG patients hospitalized for acute events. Cerebral events were classified as thrombosis, haemorrhage, SLE, or "stroke mimic" (SM: normal brain imaging or evoking a migraine). RESULTS: Thirteen patients had a total of 31 acute episodes: 27 cerebral events with 7 SLEs, 4 venous thromboses, 4 haemorrhages (3 associated with thrombosis), 15 SMs at a mean age of 7.7 years; 4 non-cerebral thromboses, one of which included bleeding. A trigger was frequently involved (infection, head trauma). Although sometimes normal at baseline state, factor XI, antithrombin and protein C levels decreased during these episodes. No correlation between haemostasis anomalies and type of acute event was found. DISCUSSION: Acute events in PMM2-CDG are not negligible and are associated with haemostasis anomalies. An emergency protocol is proposed for their prevention and treatment (https://www.filiere-g2m.fr/urgences). For cerebral events, brain Magnetic Resonance Imaging with perfusion weight imaging and diffusion sequences, electroencephalogram and haemostasis protein levels guide the treatment: anticoagulation, antithrombin or fresh frozen plasma supplementation, antiepileptic therapy. Preventing bleeding and thrombosis is required in cases of surgery, prolonged immobilization, hormone replacement therapy. CONCLUSION: Acute events in PMM2-CDG are associated with abnormal haemostasis, requiring practical guidance.