Current Recommendations Research Articles

Reproducible Radiomics Features from Multi-MRI-Scanner Test-Retest-Study: Influence on Performance and Generalizability of Models.

Radiomics models trained on data from one center typically show a decline of performance when applied to data from external centers, hindering their introduction into large-scale clinical practice. Current expert recommendations suggest to use only reproducible radiomics features isolated by multiscanner test-retest experiments, which might help to overcome the problem of limited generalizability to external data. To evaluate the influence of using only a subset of robust radiomics features, defined in a prior in vivo multi-MRI-scanner test-retest-study, on the performance and generalizability of radiomics models. Retrospective. Patients with monoclonal plasma cell disorders. Training set (117 MRIs from center 1); internal test set (42 MRIs from center 1); external test set (143 MRIs from center 2-8). 1.5T and 3.0T; T1-weighted turbo spin echo. The task for the radiomics models was to predict plasma cell infiltration, determined by bone marrow biopsy, noninvasively from MRI. Radiomics machine learning models, including linear regressor, support vector regressor (SVR), and random forest regressor (RFR), were trained on data from center 1, using either all radiomics features, or using only reproducible radiomics features. Models were tested on an internal (center 1) and a multicentric external data set (center 2-8). Pearson correlation coefficient r and mean absolute error (MAE) between predicted and actual plasma cell infiltration. Fisher's z-transformation, Wilcoxon signed-rank test, Wilcoxon rank-sum test; significance level P < 0.05. When using only reproducible features compared with all features, the performance of the SVR on the external test set significantly improved (r = 0.43 vs. r = 0.18 and MAE = 22.6 vs. MAE = 28.2). For the RFR, the performance on the external test set deteriorated when using only reproducible instead of all radiomics features (r = 0.33 vs. r = 0.44, P = 0.29 and MAE = 21.9 vs. MAE = 20.5, P = 0.10). Using only reproducible radiomics features improves the external performance of some, but not all machine learning models, and did not automatically lead to an improvement of the external performance of the overall best radiomics model. Stage 2.

Size Dimension Chart for Reference Cuff Validation and Limitations in Current Recommendations.

International standards used for device validation protocols require that the reference cuff conform to a width and length that is 37 to 50% and 75 to 100% of the arm circumference, respectively. However, there is no published chart of appropriate width and length dimensions across the range of arm circumferences. Our objective was to create a chart that could be used to guide reference cuff selection and compare recommended dimensions with two common cuff systems. Arm circumferences, ranging from 22 to 52cm were used to create a reference table for width and length requirements. Arm circumferences were grouped following the American Heart Association recommendation for cuff sizes. Cuff dimension data was extracted from the website of a cuff system commonly used for validations (the Baum Corporation) and compared both the American Heart Association recommendations and Baum sizes with the recommended reference dimensions. There were discrepancies in size naming conventions between the Baum Corporation and the American Heart Association cuff systems. Moreover, there were gaps in both systems where the cuff would not be recommended for validation (31-32cm for Baum and 30-31cm for the American Heart Association). Neither system had cuffs that could be used for the largest arm circumferences. Our chart highlights the need for more than one cuff system in validation studies and the critical need for cuffs that could be used for validation among larger arm circumferences.

Zinc about it – zinc and calf immunity

Micronutrients, such as vitamins and trace minerals, are critical for supporting growth, performance, health and maintaining redox balance. Zinc (Zn), an essential micronutrient, aids the functioning of innate and adaptive immune cells. This scoping review aims to assemble and evaluate the evidence available for the role of Zn within calf immunity. Relevant literature was identified within Web of Science, PubMed, and CABI using search terms specific to the major innate and adaptive immune cell populations. There was no evidence that Zn supplementation altered neutrophil, natural killer cell, or T-cell functions. However, there was limited evidence to support Zn supplementation with reduced monocyte numbers, but there was no evidence to associate the monocytopenia with improvements in monocyte function. There is moderate evidence to suggest that Zn supplementation was beneficial for maintaining epithelial barriers of integumental and mucosal surfaces. The evidence supports supplementation above the current industry recommendations for improving immunoglobulin (Ig) production, with the strongest results being observed for IgG and IgM. Moreover, Zn supplementation was associated with reduced proinflammatory cytokine production, which may reduce inflammation-associated hypophagia and warrants further investigation. Furthermore, Zn reduced the duration of clinical signs in animals facing respiratory disease and diarrhea. However, consensus is needed about the optimal dose, route, and Zn formulation most appropriate for supporting immunity. In conclusion, while the literature supports that Zn could enhance calf immunity, there is insufficient evidence to adequately determine the extent to which Zn impacts innate immune cell and T-cell functions. Determination of the immune cell functions susceptible to modification by Zn supplementation is an important knowledge gap for enhancing the understanding of Zn and calf immunity.

Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.

Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations areassociated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.

Deworming and micronutrient status by community open defecation prevalence: An observational study using nationally representative data from India, 2016-2018.

Micronutrient deficiencies are widespread in India. Soil-transmitted helminth (STH) infections are acquired by interaction with soil and water contaminated by human feces and lead to blood loss and poor micronutrient absorption. The current recommendation for control of STH-related morbidity is targeted deworming, yet little is known about the effectiveness of deworming on micronutrient status in varying sanitation contexts. Ranging between 1% and 40% prevalence across Indian states, open defecation (OD) remains high despite India's investments at elimination by promoting community-wide sanitation. This variation provides an opportunity to study the relationship between deworming, micronutrient status, and OD at-scale. Cross-sectional datasets that were representative for India were obtained the Comprehensive National Nutrition Survey in 2016 to 2018 (n = 105,060 individuals aged 1 to 19 years). Consumption of deworming medication was described by age and community OD level. Logistic regression models were used to examine the relationship between deworming, cluster OD, and their interactions, with anemia and micronutrient deficiencies (iron, zinc, vitamin A, folate, and vitamin B12), controlling for age, sex, wealth, diet, and seasonality. These regression models further allowed us to identify a minimum OD rate after which deworming becomes ineffective. In sensitivity analyses, the association between deworming and deficiencies were tested in subsamples of communities classified into 3 OD levels based on statistical tertiles: OD free (0% of households in the community practicing OD), moderate OD (>0% and <30%), or high OD (at least 30%). Average deworming coverage and OD prevalence in the sample were 43.4% [IQR 26.0, 59.0] and 19.1% [IQR 0, 28.5], respectively. Controlling for other determinants of nutritional status, adolescents living in communities with higher OD levels had lower coverage of deworming and higher prevalence of anemia, zinc, vitamin A, and B12 deficiencies. Compared to those who were not dewormed, dewormed children and adolescents had lower odds of anemia (adjusted odds ratio 0.72, (95% CI [0.67, 0.78], p < 0.001) and deficiencies of iron 0.78, (95% CI [0.74, 0.82], p < 0.001) and folate 0.69, (95% CI [0.64,0.74], p<0.001)) in OD free communities. These protective effects remained significant for anemia but diminished for other micronutrient deficiencies in communities with moderate or high OD. Analysis of community OD indicated a threshold range of 30% to 60%, above which targeted deworming was no longer significantly associated with lower anemia, iron, and folate deficiency. The primary limitations of the study included potential for omitted variables bias and inability to capture longitudinal effects. Moderate to high rates of OD significantly modify the association between deworming and micronutrient status in India. Public health policy could involve sequencing interventions, with focus on improving deworming coverage in communities that have achieved minimum thresholds of OD and re- triggering sanitation interventions in high OD communities prior to deworming days, ensuring high coverage for both. The efficacy of micronutrient supplementation as a complementary strategy to improve nutritional outcomes alongside deworming and OD elimination in this age group needs further study.

Potential factors-embedding group recommendation for online education

Online education platform urgently needs recommendation methods to service learning groups. The existing group recommendation methods rely on member preference aggregation. However, potential factors such as teachers and schools have an important impact on the decision-making of learning groups. Due to the different ways in which potential factors operate, it is very challenging to model the impact these potential factors have on groups. In this paper, we propose a group recommendation method for online education (GEMst) that innovatively designs two modules to capture different types of potential factor embedding. In the subjective guidance module, we construct a heterogeneous information network based on the relationship between guiders (teacher, leader, etc.) and groups, analyze the influence of the guider on the group, and obtain the group representation from this perspective. In the objective environment hypergraph module, we consider the influence mode of the environment (school, platform, etc.) on the group, and propose the objective relationship hypergraph convolution. Compared with hypergraph convolution, it directly learns the influence between groups in the same environment. We provide information fusion strategies that GEMst can collaboratively consider group members’ opinions and the impact of potential factors. In addition, to enhance the learning effect of the model, we design a pre-training strategy based on the user grouping relationship that obtains more accurate user embedding representations. We test GEMst on two real-world datasets, and the results show that GEMst outperforms the current baseline group recommendation method.

Management of respiratory issues in patients with Rett syndrome: Italian experts' consensus using a delphi approach

AbstractBackgroundDespite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems.ObjectiveIdentification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients.Materials and MethodsUsing a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1–5 scale. The cut‐off level for consensus was 75%, obtained through multiple rounds.ResultsThe panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome, and in selected cases with other RS types. Noninvasive ventilation should be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP‐mask, AMBU bag, or cough machine), more appropriate and tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomy in patients at increased risk of ab ingestis pneumonia.ConclusionsThis consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.

Is there a role for intra-aortic balloon pump in patients with cardiogenic shock? predictors of success

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Hospital Clínico San Carlos Madrid. Background Cardiogenic shock (CS) remains a clinical challenge associated with unacceptable high mortality rates. Early revascularization is the cornerstone for CS management. However, CS patients usually requires further advanced therapies such as vasopressors and mechanical circulatory support devices. Intra-aortic balloon pump (IABP) is not routinely used in patients with CS according to the current recommendations. However, this device could be associated with potential benefit in selected patients and we believe it is underutilized. Our aim was to assess for potential predictors of success after IABP implantation in patients with CS. Methods From 2013 to 2023, 136 consecutive patients diagnosed with CS and admitted to an Acute Cardiac Care Unit in a tertiary care hospital were recruited. Demographic, clinical, and analytical variables were retrospectively collected. SCAI classification was used to define shock state. Patient were followed-up to November-2023 and clinical events were also recorded. For purposes of analysis, patients were classified in two groups: IABP success (N=70) and IABP failure (N=66). Success, in terms of IABP use, was defined as patient’s survival to the index event. Failure of IABP was defined as in-hospital death. A multivariate logistic regression analysis was performed to identify potential predictors of success. Results Mean age was 67.2±12.2 years and 64.7% were females. There were no significant differences in cardiovascular risk factors and comorbidities between groups: hypertension (56.6% vs 43.5%, p 0.132), diabetes (40.9% vs 59.1%, p 0.088), chronic kidney disease (50% vs 50%, p 0.800), previous stroke (53.9% vs 41.2%, p 0.857) in "Success-group" vs "Failure-group" respectively. STEMI was the most frequent cause of CS requiring an IABP (65.9%). Non-ST elevation myocardial infarction was more common in the "Success-group", whereas cardiac arrest was more common in the "Failure-group" (Table 1). Regarding the CS classification, patients with IABP failure were more frequently in SCAI D and E categories (Table 1). In addition, patients in the failure-group had worse hemodynamic and analytic parameters (Table 1) and the IABP failed to significantly improve them. There were no significant differences in coronary artery disease burden and treatment. Complete revascularization was accomplished in a similar proportion of patients in both groups (Table 1). The multivariate analysis showed that SCAI B&amp;C states were independently associated with success after IABP implantation, whereas lactate level prior to IABP implantation was associated with failure (Table 2). Conclusion Selecting the appropriate timing for IABP implantation is critical for the prognosis, as success rates are higher in less advanced stages of cardiogenic shock. Preimplantation lactate levels are also associated with success rates.

Reporting on Health Care and Social Service Provider Approaches to Promoting Alcohol Abstinence During Pregnancy

ABSTRACT Despite the known detrimental health effects of alcohol use during pregnancy, there are still health care (HCP) and social service providers (SSP) who do not promote complete abstinence. The purpose of this study was to explore the current practices of HCPs and SSPs when discussing alcohol use during pregnancy, and to understand their rationale for their specific recommendations. An online survey was completed by 1123 HCPs (n = 588) and SSPs (n = 535) that asked them to identify their approach to discussing alcohol and pregnancy. Participants had the option to further explain their current recommendations regarding alcohol use during pregnancy in an open-ended format. Open-ended responses were analyzed using a content analysis approach (n = 156). The majority of respondents recommend abstinence (83.9% of HCPs, n = 493; 78.4% of SSPs, n = 419), while 9.8% of HCPs (n = 57) and 2.2% of SSPs (n = 12) responded that low levels of consumption may be acceptable. HCPs may recommend low levels of consumption based on other international guidelines, limited evidence to suggest that one unit of alcohol is harmful, and as a harm reduction strategy. SSPs stated that they refer clients to HCPs for recommendations related to alcohol consumption, and that they prefer to provide information based on public health guidelines. This exploratory work may inform the development of resources to support HCPs and SSPs to recommend abstinence from alcohol throughout gestation.

Impact and timing of pulmonary rehabilitation in patients undergoing bronchoscopic lung volume reduction with endobronchial valves: A multicentre randomized controlled trial in patients with severe emphysema.

Both bronchoscopic lung volume reduction with endobronchial valves (BLVR-EBV) and pulmonary rehabilitation (PR) are effective treatments for improving exercise capacity and patient-reported outcomes in patients with severe Chronic Obstructive Pulmonary Disease (COPD). According to current recommendations, all BLVR-EBV patients should have undergone PR first. Our aim was to study the effects of PR both before and after BLVR-EBV compared to BLVR-EBV alone. We included patients with severe COPD who were eligible for BLVR-EBV and PR. Participants were randomized into three groups: PR before BLVR-EBV, PR after BLVR-EBV or BLVR-EBV without PR. The primary outcome was change in constant work rate cycle test (CWRT) endurance time at 6-month follow-up of the PR groups compared to BLVR-EBV alone. Secondary endpoints included changes in 6-minute walking test, daily step count, dyspnoea and health-related quality of life. Ninety-seven participants were included. At 6-month follow-up, there was no difference in change in CWRT endurance time between the PR before BLVR-EBV and BLVR-EBV alone groups (median: 421 [IQR: 44; 1304] vs. 787 [123; 1024] seconds, p = 0.82) or in any of the secondary endpoints, but the PR after BLVR-EBV group exhibited a smaller improvement in CWRT endurance time (median: 107 [IQR: 2; 573], p = 0.04) and health-related quality of life compared to BLVR-EBV alone. The addition of PR to BLVR-EBV did not result in increased exercise capacity, daily step count or improved patient-reported outcomes compared to BLVR-EBV alone, neither when PR was administered before BLVR-EBV nor when PR was administered after BLVR-EBV.

In situ and Operando Characterisation in the Preferential Oxidation of Carbon Monoxide over Base Metal Oxide Catalysts: A Review

Polymer electrolyte membrane fuel cells (PEMFCs) are the core technology of the steadily growing hydrogen (H2) economy as they can convert chemical energy, in the form of H2, to electrical energy. If the H2 is derived from (green) hydrocarbons, via steam reforming and the water‐gas‐shift reaction, then it would contain small amounts of carbon monoxide (CO, 0.5 – 2%), among other gases. CO poisons the platinum‐based anode catalyst in the PEMFC, and the current recommendation is to decrease its concentration to below 0.01% (or 100 ppm) in the H2‐rich PEMFC feed. The preferential oxidation of CO (CO‐PrOx) is a promising strategy for decreasing the CO concentration, and base metal oxide catalysts have shown great potential in this regard. However, such catalysts tend to undergo physicochemical changes that cause undesirable catalytic activity and selectivity changes. This review discusses the different base metal oxide catalysts that have been evaluated in CO‐PrOx, while paying special attention to the various in situ and operando techniques that have been used to monitor the physicochemical changes of such catalysts during operation. We conclude the review by highlighting the recent and possible future attempts of circumventing the undesired physicochemical changes of base metal oxides during CO‐PrOx.

“It Takes a Village”- A Conversation with the Interprofessional Diabetes Clinic at the ECU Health Family Medicine Center

Interprofessional collaboration and shared understanding positively impact both patients and providers. Current recommendations from the CDC and experts agree that collaboration between diverse professions is necessary to improve patient outcomes and empower patients to selfmanage their chronic conditions.

Survival, but not the severity of hypoxic–ischemic encephalopathy, is associated with higher mean arterial blood pressure after cardiac arrest: a retrospective cohort study

BackgroundThis study investigates the association between the mean arterial blood pressure (MAP), vasopressor requirement, and severity of hypoxic–ischemic encephalopathy (HIE) after cardiac arrest (CA).MethodsBetween 2008 and 2017, we retrospectively analyzed the MAP 200 h after CA and quantified the vasopressor requirements using the cumulative vasopressor index (CVI). Through a postmortem brain autopsy in non-survivors, the severity of the HIE was histopathologically dichotomized into no/mild and severe HIE. In survivors, we dichotomized the severity of HIE into no/mild cerebral performance category (CPC) 1 and severe HIE (CPC 4). We investigated the regain of consciousness, causes of death, and 5-day survival as hemodynamic confounders.ResultsAmong the 350 non-survivors, 117 had histopathologically severe HIE while 233 had no/mild HIE, without differences observed in the MAP (73.1 vs. 72.0 mmHg, pgroup = 0.639). Compared to the non-survivors, 211 patients with CPC 1 and 57 patients with CPC 4 had higher MAP values that showed significant, but clinically non-relevant, MAP differences (81.2 vs. 82.3 mmHg, pgroup &amp;lt; 0.001). The no/mild HIE non-survivors (n = 54), who regained consciousness before death, had higher MAP values compared to those with no/mild HIE (n = 179), who remained persistently comatose (74.7 vs. 69.3 mmHg, pgroup &amp;lt; 0.001). The no/mild HIE non-survivors, who regained consciousness, required fewer vasopressors (CVI 2.1 vs. 3.6, pgroup &amp;lt; 0.001). Independent of the severity of HIE, the survivors were weaned faster from vasopressors (CVI 1.0).ConclusionsAlthough a higher MAP was associated with survival in CA patients treated with a vasopressor-supported MAP target above 65 mmHg, the severity of HIE was not. Awakening from coma was associated with less vasopressor requirements. Our results provide no evidence for a MAP target above the current guideline recommendations that can decrease the severity of HIE.

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

Two Cases of Malpositioning of Internal Jugular Central Venous Catheters: A Review of Literature and Current Treatment Recommendations

Two Cases of Malpositioning of Internal Jugular Central Venous Catheters: A Review of Literature and Current Treatment Recommendations

Tenecteplase Versus Alteplase in Acute Ischemic Stroke in Chinese Patients: Protocol for the ORIGINAL Study

BACKGROUND Tenecteplase, a bioengineered variant of alteplase, is a new alternative thrombolytic agent. The ORIGINAL study aims to evaluate the efficacy and safety of tenecteplase versus standard care in Chinese patients with acute ischemic stroke within 4.5 hours of symptom onset. METHODS This is a multicenter phase III study that employs a randomized (1:1), active‐controlled, parallel‐group, prospective, open‐label, blinded–end point design. Adult participants (aged ≥18 years) with acute ischemic stroke who are eligible for intravenous thrombolysis within 4.5 hours of symptom onset according to current guideline recommendations are recruited from ≈55 neurology clinics/stroke centers throughout China. RESULTS The primary objective of the ORIGINAL study is to demonstrate the noninferiority of tenecteplase (0.25 mg/kg) to alteplase (0.9 mg/kg) on the basis of the proportion of patients who achieve a modified Rankin Scale score of 0 or 1 on day 90, that is, a favorable functional outcome. The prespecified noninferiority risk ratio margin is 0.937. Secondary end points include other functional outcomes and the following safety end points: adjudicated symptomatic intracerebral hemorrhage (up to 36 hours after the end of study drug administration) based on the European Cooperative Acute Stroke Study III definition; all‐cause death within 90 days; and the proportion of patients with a modified Rankin Scale score of 5 or 6 on day 90. CONCLUSIONS It is anticipated that the results of this study will contribute to the growing body of evidence for the noninferiority of tenecteplase to alteplase given within 4.5 hours of acute ischemic stroke symptom onset and support a new indication for tenecteplase in China. Clinical Trial Registration Information NCT04915729 ( https://clinicaltrials.gov/study/NCT04915729 )

Paediatric antibiotic prescribing in a nationwide direct-to-consumer telemedicine platform in France, 2018-2021.

Recent regulatory and reimbursement changes facilitated the development of teleconsultation within primary care. French guidance advises against antibiotic prescribing in children in teleconsultation. We assessed paediatric antibiotic prescribing on a French teleconsultation platform. This cross-sectional observational study analysed paediatric (0-14 years) visits on a national direct-to-consumer teleconsultation platform between January 2018 and December 2021. Teleconsultations with complete information regarding diagnosis (ICD-10 coding) and prescriptions were included. We assessed antibiotic prescription rates per 100 visits across diagnoses and used logistic regression to identify factors associated with antibiotic prescribing. In the 37 587 included paediatric teleconsultations (median age 3 years) performed by 713 general practitioners (GPs) and 89 paediatricians, antibiotics were prescribed for 12.1%. Respiratory tract infections (RTIs) accounted for 49.5% of antibiotic prescriptions. Antibiotic prescription rates per 100 visits were: sinusitis, 69.5%; urinary tract infections, 62.2%; pharyngitis, 59.0%; pneumonia, 45.5%; otitis, 46.6%; bronchitis, 19.6%; rhinitis, 11.6%; bronchiolitis 6.6%. Antibiotic prescription rates were higher in GPs than paediatricians [OR 2.21 (IC95% 2.07-2.35)], among physicians aged 45-54 and over 65 [OR 1.66 (1.48-1.85) and 1.48 (1.32-1.66), respectively], in female practitioners [OR 1.13 (1.05-1.21)], in children 3-6 years old [OR 1.41 (1.28-1.56)] and over 6 [OR 1.50 (1.35-1.66)], during winter [OR 1.28 (1.21-1.37)] and for RTIs [OR 1.99 (1.87-2.10)]. Antibiotic prescription rates were lower in doctors with extensive experience in teleconsultation [OR 0.92 (0.86-0.98)]. Despite current recommendations, paediatric patients were frequently prescribed antibiotics during acute care teleconsultations. Specific antibiotic stewardship campaigns should target paediatric teleconsultations.

A Simulation-Based Assessment of Levetiracetam Concentrations Following Fixed and Weight-Based Loading Doses: A Meta-Regression and Pharmacokinetic Modeling Analysis.

Current recommendations for refractory status epilepticus (SE) unresponsive to benzodiazepines suggest a loading dose of levetiracetam (LEV) of 60 mg/kg to a maximum of 4500 mg. LEV therapeutic drug monitoring can help guide therapy and is garnering increasing attention. The objective of this study is to simulate the probability of target attainment (PTA) of fixed dose and weight-based loading doses of LEV with respect to established therapeutic target concentrations. Meta-regression of the current literature was performed to evaluate the relationship between intravenous LEV loading dose and seizure cessation in refractory SE patients. A previously published pharmacokinetic model was used to simulate the PTA capacity of competing single intravenous dosing schemes (fixed vs weight-based dosing) to achieve maximum (Cpeak) and 12-h (C12h) plasma concentrations that exceed 12 mg/L. The meta-regression indicated that dosage was not a statistically significant modulator of seizure control at dosages between 20 and 60 mg/kg. Stochastic simulations showed all dosing schemes achieved plasma Cpeak >12 mg/L, but C12h levels were <12 mg/L in subjects over 60 kg with a fixed dose ≤2000 mg or in subjects <60 kg with a weight-based dose <30 mg/kg. Dosages of 40 and 60 mg/kg provided ≥90% PTAs across all weights. Using a weight-based loading dose of 40 mg/kg, up to a suggested maximum of 4500 mg, improves the likelihood of achieving a sustained therapeutic drug concentration after the initial LEV dose, whereas fixed <3000 mg may not achieve the desired concentration before maintenance dosing.

29 Effects of using different dietary standardized ileal digestible lysine plans on growth performance and carcass characteristics of PIC 337 or PIC 800 sired grow-finish pigs

Abstract The present study aimed to evaluate the impact of using different dietary standardized ileal digestible (SID) lysine (Lys) plans on growth performance of PIC 337 and PIC 800 sired grow-finish pigs. A total of 2,016 gilts and barrows were placed in 2 separate rooms with 48 single sex pens each (21 pigs/pen; 0.69 m2/pig). Pens were blocked by body weight (BW) and randomly allotted in a 2 × 2 × 2 factorial arrangement with genetic line (PIC 337 or 800), sex (barrows or gilts), and nutrition plan (current SID Lys curve recommendation for PIC 800 as % of PIC 337 SID Lys curve or alternative SID Lys curve) as factors. Pigs (27.4 ± 1.41 kg BW) were followed during the grower-finisher phase until slaughter. Pigs were fed either the current recommendation or an alternative SID Lys curve for PIC 800, in a 5 phase feeding program: phase 1 (23-40 kg; 97 vs 100%, respectively); phase 2 (40-60 kg; 97 vs 95%, respectively); phase 3 (60-80 kg; 97 vs 95%, respectively); phase 4 (80-105 kg; 97 vs 95%, respectively); and phase 5 (105-135 kg; 97 vs 90%, respectively). Pigs were fed isoenergetic diets. Performance and carcass traits, and removals and mortality were recorded. Data were analyzed using mixed models in R, and considering pen as the experimental unit for performance traits and individual carcasses for carcass traits. There was no evidence of interaction between genetic line and nutrition plan factors. Overall, PIC 337 vs 800 pigs did not differ on average daily gain (ADG; P &amp;gt; 0.05), but PIC 337 pigs consumed 150 g/d less and were 0.1 more feed efficient than PIC 800 pigs (P &amp;lt; 0.05; Table 1). Moreover, PIC 337 pigs had 1.9 kg less of hot carcass weight, but 2.1 mm more of loin depth compared with PIC 800 pigs (P &amp;lt; 0.05; Table 1). Regarding nutrition plan, no significant differences were observed for overall performance and carcass traits between pigs fed the current or alternative SID Lys curve (P &amp;gt; 0.05; Table 1). Additionally, no significant differences were observed for overall removals and mortality by genetic line or nutrition plan (P &amp;gt; 0.05; Table 1). In summary, different genetic sire line (PIC 337 and PIC 800) differed on performance and carcass traits. Further research is needed to continue studying the genetic evolution and nutrition plan for each genetic sire line in the grower-finisher period to understand their nutrient requirements.

30 Effects of using different dietary standardized ileal digestible lysine plans on growth performance and carcass characteristics of grow-finish pigs from high or low breeding value boars

Abstract The present study aimed to evaluate the impact of using different dietary standardized ileal digestible (SID) lysine (Lys) plans on growth performance and carcass characteristics of grow-finish pigs coming from high or low breeding value boars. A total of 2,080 pigs (PIC 800 × PIC Camborough) were housed in 20 mixed sex pens (26 pigs/pen), blocked by body weight (BW), and randomly allotted in a 2 × 2 factorial arrangement with boar breeding value (high or low) and nutrition Lys plan (current SID Lys curve recommendation for PIC 800 as % of PIC 337 SID Lys curve or alternative SID Lys curve). Pigs were weaned at 21 d of age (6.1 ± 0.05 kg BW) and followed during the wean-to-finish period until reach the market slaughter weight. Pigs were fed either the current recommendation or an alternative SID Lys curve for PIC 800, in a 6 phase feeding program: phase 1 (6-11 kg; 100 vs 100%, respectively); phase 2 (11-23 kg; 97 vs 100%, respectively); phase 3 (23-45 kg; 97 vs 100%, respectively); phase 4 (45-73 kg; 97 vs 95%, respectively); phase 5 (73-102 kg; 97 vs 95%, respectively); and phase 6 (102-132 kg; 97 vs 90%, respectively). Pigs were fed isoenergetic diets. Performance and carcass traits, and removals and mortality were recorded. Data were analyzed using mixed models in R, and considering pen as the experimental unit for performance traits and individual carcasses for carcass traits. There was no evidence of interaction between boar breeding value and nutrition plan factors. Overall, high breeding value pigs had greater average daily gain (ADG; 0.84 ± 0.005 g/d) compared with low breeding value pigs (0.82 ± 0.005 kg/d; P &amp;lt; 0.01), which was driven by increased average daily feed intake (ADFI; 1.92 ± 0.011 and 1.89 ± 0.011 kg/d, respectively; P &amp;lt; 0.05; Table 1). Moreover, high breeding value pigs had greater hot carcass weight (HCW; 97.8 ± 1.09 kg), carcass yield (74.1 ± 0.23%), backfat thickness (16.3 ± 0.29 mm) and lower lean meat % (57.0 ± 0.21%) compared with low breeding value pigs (96.0 ± 1.09 kg; 73.7 ± 0.23 %; 15.4 ± 0.28; 57.5 ± 0.21%, respectively; P &amp;lt; 0.05; Table 1). Regarding nutrition plan, no significant differences were observed for overall performance traits between pigs fed the current or alternative SID Lys curve (P &amp;gt; 0.05; Table 1). Nevertheless, pigs fed the alternative SID Lys curve had heavier HCW (97.3 ± 1.09 kg) compared with pigs fed the current SID Lys curve (96.6±1.09 kg; P &amp;lt; 0.05; Table 1). No significant differences were observed for overall removals and mortality by breeding value or nutrition Lys plan (P &amp;gt; 0.05). In summary, grow finish pigs from high breeding value boars have an improved productive performance. PIC 800 pigs may achieve the same productive performance with lower lysine levels at the end of the grow-finish period.