Transcranial Doppler Ultrasonographic Evaluation of Cerebrovascular Abnormalities in Children With Acute Bacterial Meningitis

Introduction: Bacterial meningitis (BM) is a global public health concern that results in significant morbidity and mortality. Cerebral arterial narrowing contributes to stroke in BM and may be amenable to intervention. However, it is difficult to diagnose in resource-limited settings where the disease is common.Methods: This was a prospective observational study from September 2015 to December 2019 in sub-Saharan Africa. Children 1 month−18 years of age with neutrophilic pleocytosis or a bacterial pathogen identified in the cerebrospinal fluid were enrolled. Transcranial Doppler ultrasound (TCD) of the middle cerebral arteries was performed daily with the aim to identify flow abnormalities consistent with vascular narrowing.Results: Forty-seven patients were analyzed. The majority had Streptococcus pneumoniae (36%) or Neisseria meningitides (36%) meningitis. Admission TCD was normal in 10 (21%). High flow with a normal pulsatility index (PI) was seen in 20 (43%) and high flow with a low PI was identified in 7 (15%). Ten (21%) had low flow. All children with a normal TCD had a good outcome. Patients with a high-risk TCD flow pattern (high flow/low PI or low flow) were more likely to have a poor outcome (82 vs. 38%, p = 0.001).Conclusions: Abnormal TCD flow patterns were common in children with BM and identified those at high risk of poor neurological outcome.</jats:p

PubChem3D: a new resource for scientists

<p>Abstract</p> <p>Background</p> <p>PubChem is an open repository for small molecules and their experimental biological activity. PubChem integrates and provides search, retrieval, visualization, analysis, and programmatic access tools in an effort to maximize the utility of contributed information. There are many diverse chemical structures with similar biological efficacies against targets available in PubChem that are difficult to interrelate using traditional 2-D similarity methods. A new layer called PubChem3D is added to PubChem to assist in this analysis.</p> <p>Description</p> <p>PubChem generates a 3-D conformer model description for 92.3% of all records in the PubChem Compound database (when considering the parent compound of salts). Each of these conformer models is sampled to remove redundancy, guaranteeing a minimum (non-hydrogen atom pair-wise) RMSD between conformers. A diverse conformer ordering gives a maximal description of the conformational diversity of a molecule when only a subset of available conformers is used. A pre-computed search per compound record gives immediate access to a set of 3-D similar compounds (called "Similar Conformers") in PubChem and their respective superpositions. Systematic augmentation of PubChem resources to include a 3-D layer provides users with new capabilities to search, subset, visualize, analyze, and download data.</p> <p>A series of retrospective studies help to demonstrate important connections between chemical structures and their biological function that are not obvious using 2-D similarity but are readily apparent by 3-D similarity.</p> <p>Conclusions</p> <p>The addition of PubChem3D to the existing contents of PubChem is a considerable achievement, given the scope, scale, and the fact that the resource is publicly accessible and free. With the ability to uncover latent structure-activity relationships of chemical structures, while complementing 2-D similarity analysis approaches, PubChem3D represents a new resource for scientists to exploit when exploring the biological annotations in PubChem.</p

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Exploring the consequences of reducing survey effort for detecting individual and temporal variability in survival

1. Long-term monitoring programmes often involve substantial input of skilled staff time. In mark–recapture studies, considerable effort is usually devoted to both marking and recapturing/resighting individuals. Given increasing budgetary constraints, it is essential to streamline field protocols to minimize data redundancy while still achieving targets such as detecting trends or ecological effects. 2. We evaluated different levels of field effort investment in marking and resighting individuals by resampling existing mark–recapture–recovery data to construct plausible scenarios of changes in field protocols. We demonstrate the method with 26 years data from a common guillemot Uria aalge monitoring programme at a major North Sea colony. We also assess the impact of stopping the ringing of chicks on our ability to study population demography using integrated population models (IPM) fitted to data including information on breeding adults. Different data sets were removed artificially to explore the ability to compensate for missing data. 3. Current ringing effort at this colony appears adequate but resighting effort could be halved while still maintaining the capacity to monitor first-year survival and detect the effect of hatch date on survival prospects. 4. The IPM appears robust for estimating survival, productivity or abundance of the breeding population, but has limited capacity to recover year-specific first-year survival when chick data are omitted. If productivity were not monitored, the inclusion of chick data would be essential to estimate it, albeit imprecisely. 5. Synthesis and applications: Post-study evaluation can help streamline existing long-term environmental monitoring programmes. To our knowledge, this study is the first use of data thinning of existing mark–recapture–recovery data to identify potential field effort reductions. We also highlight how alternative monitoring scenarios can be evaluated with integrated population models when data are collected on different aspects of demography and abundance. When effort reduction is necessary, both approaches provide decision-support tools for adjusting field protocols to collect demographic data. The framework has broad applicability to other taxa and demographic parameters, provided suitable long-term data are available, and we discuss its use in different context

Short- and long-term adverse events in patients on temporary circulatory support before durable ventricular assist device: An IMACS registry analysis

BACKGROUND: Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival rates after implantation of durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival rates in patients requiring pre-operative TCS. METHOD: We analyzed 13,511 adults (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] Profiles 1-3) with continuous-flow dVADs in International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (2013-2017) according to the need for pre-operative TCS (n = 5,632) vs no TCS (n = 7,879). Of these, 726 (5.4%) had biventricular assist devices (BiVAD). Furthermore, we compared prevalent rates (events/100 patient-months) of bleeding, device-related infection, hemorrhagic and ischemic cerebrovascular accidents (hemorrhagic cerebral vascular accident [hCVA], and ischemic cerebral vascular accident [iCVA]) in early (<3 months) and late (≥3 months) post-operative periods. RESULTS: TCS included extracorporeal membrane oxygenation (ECMO) (n = 1,138), intra-aortic balloon pump (IABP) (n = 3,901), and other TCS (n = 593). Within 3 post-operative months, there were more major bleeding and cerebrovascular accidents (CVAs) in patients with pre-operative ECMO (events/100 patient-months rates: bleeding = 19, hCVA = 1.6, iCVA = 2.8) or IABP (bleeding = 17.3, hCVA = 1.5, iCVA = 1.5) vs no TCS (bleeding = 13.2, hCVA = 1.1, iCVA = 1.2, all p < 0.05). After 3 months, adverse events were lower and similar in all groups. Patients with ECMO had the worst short- and long-term survival rates. Patients with BiVAD had the worst survival rate regardless of need for pre-operative TCS. CVA and multiorgan failures were the common causes of death for patients with TCS and patients without TCS. CONCLUSIONS: Patients requiring TCS before dVAD had a sicker phenotype and higher rates of early post-operative adverse events than patients without TCS. ECMO was associated with very high early ischemic stroke, bleeding, and mortality. The extreme CS phenotype needing ECMO warrants a higher-level profile status, such as INTERMACS "0."status: publishe

Longitudinal impact of temporary mechanical circulatory support on durable ventricular assist device outcomes: An IMACS registry propensity matched analysis

BACKGROUND: Patients with advanced heart failure and cardiogenic shock (CS) often require temporary circulatory support (TCS) as a bridge to durable ventricular assist devices (dVADs). We aim to characterize longitudinal outcomes of patients with and without CS. METHODS: Between 2013 and 2017, 13,813 adult patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 1 to 3 with continuous flow left ventricular assist devices or biventricular assist devices were registered into the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support. Patients were sub-grouped according to support type (extracorporeal membrane oxygenation [ECMO], intra-aortic balloon pump [IABP], and other TCS). Other TCS included all other surgical and percutaneous TCS devices. Estimated survival was compared based on need for pre-operative TCS and by profile. RESULTS: Pre-operative TCS was used in 5,632 (41%) cases. Of these, ECMO was used in 1,138 (20%) cases, IABP in 3,901 (69%) cases, and other TCS in 595 (11%) cases. Patients requiring ECMO had greater needs for biventricular support after dVAD (22% ECMO, 5% IABP, and 7% other TCS; p < 0.001) with longer post-implant intensive care stays (ECMO 24 days, IABP 14 days, and other TCS 12 days; p < 0.001). INTERMACS Profile 1 to 3 patients with pre-implant ECMO had the lowest longitudinal survival (82% at 1 month and 44% at 48 months) compared with IABP (93% at 1 month and 51% at 48 months), other TCS (92% at 1 month and 52% at 48 months), and non-TCS (95% at 1 months and 55 % at 48 months) (p < 0.0001). Propensity score matching analysis of the pre-implant ECMO INTERMACS Profile 1 group when compared with alternative pre-implant TCS strategies had an associated higher hazard impacting early phase survival vs other TCS (hazard ratio, 1.80; p < 0.01) and IABP (hazard ratio, 1.65; p < 0.01). CONCLUSIONS: In advanced heart failure with patients with CS, the use of ECMO before dVAD was associated with lower longitudinal survival and increased utilization of biventricular support compared with alternative TCS strategies. Research focused on longitudinal profiling in CS and pre-implant TCS is warranted to further understand these differences.status: publishe

Short- and long-term adverse events in patients on temporary circulatory support before durable ventricular assist device: An IMACS registry analysis

BACKGROUND: Patients with cardiogenic shock (CS) needing temporary circulatory support (TCS) have poor survival rates after implantation of durable ventricular assist device (dVAD). We aimed to characterize post-dVAD adverse event burden and survival rates in patients requiring pre-operative TCS. METHOD: We analyzed 13,511 adults (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] Profiles 1-3) with continuous-flow dVADs in International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support (2013-2017) according to the need for pre-operative TCS (n = 5,632) vs no TCS (n = 7,879). Of these, 726 (5.4%) had biventricular assist devices (BiVAD). Furthermore, we compared prevalent rates (events/100 patient-months) of bleeding, device-related infection, hemorrhagic and ischemic cerebrovascular accidents (hemorrhagic cerebral vascular accident [hCVA], and ischemic cerebral vascular accident [iCVA]) in early (\u3c3 \u3emonths) and late (≥3 months) post-operative periods. RESULTS: TCS included extracorporeal membrane oxygenation (ECMO) (n = 1,138), intra-aortic balloon pump (IABP) (n = 3,901), and other TCS (n = 593). Within 3 post-operative months, there were more major bleeding and cerebrovascular accidents (CVAs) in patients with pre-operative ECMO (events/100 patient-months rates: bleeding = 19, hCVA = 1.6, iCVA = 2.8) or IABP (bleeding = 17.3, hCVA = 1.5, iCVA = 1.5) vs no TCS (bleeding = 13.2, hCVA = 1.1, iCVA = 1.2, all p \u3c 0.05). After 3 months, adverse events were lower and similar in all groups. Patients with ECMO had the worst short- and long-term survival rates. Patients with BiVAD had the worst survival rate regardless of need for pre-operative TCS. CVA and multiorgan failures were the common causes of death for patients with TCS and patients without TCS. CONCLUSIONS: Patients requiring TCS before dVAD had a sicker phenotype and higher rates of early post-operative adverse events than patients without TCS. ECMO was associated with very high early ischemic stroke, bleeding, and mortality. The extreme CS phenotype needing ECMO warrants a higher-level profile status, such as INTERMACS 0