Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Vitamin B12 and Folate Status in Cognitively Healthy Older Adults and Associations with Cognitive Performance.

OBJECTIVES: To determine prevalence of vitamin B12 and folate deficiency and associations with cognitive performance in participants recruited for the Cognitive Health in Ageing Register: Investigational, Observational, and Trial Studies in Dementia Research: Prospective Readiness cOhort Study (CHARIOTPRO) SubStudy (CPRO-SS). DESIGN: Cross-sectional analysis of data collected in the screening phase for the CPRO-SS. SETTING: Participants were recruited from the Chariot Register at Imperial College London comprising approximately 39,000 community dwelling volunteers. PARTICIPANTS: Community dwelling individuals aged 60-85 years with B vitamin biomarker measures available were included (n=1946). After medical history and other exclusions, 1347 cognitively healthy participants were included for analysis of cognitive data. MEASUREMENTS: Cognitive status was assessed with the Repeatable Battery for Neuropsychological Status (RBANS). Assays included vitamin B12 and folate, followed by serum methylmalonic acid and homocysteine levels for those with low vitamin B12. Gender-specific linear regression analysis was performed for associations between cognition and biomarkers. Non-gender specific regression for groups graded by B vitamin deficiency severity were also performed. RESULTS: Vitamin B12 deficiency (<148pmol/L) was found in 17.2% of individuals and folate deficiency (<10nmol/L) in 1% of our participants. Low vitamin B12 was associated with poorer memory (p<0.03) in men. A high BMI predicted poorer attention and visuospatial indices (p<0.05). A regression analysis by B12 level revealed associations with poorer attention (ß -6.46; p=0.004) for the deficient group and with immediate memory (ß -2.99; p=0.019) for those categorised as severely deficient. CONCLUSION: Older men and women are prone to vitamin B12 deficiency with associated subtle and different domain-specific disruptive effects in measures of memory and attention. Elevated homocysteine and methylmalonic acid contributed to poorer cognitive performance. Novel groups at particular risk of cognitive deficit were identified for future interventional studies in this field.

COVID-19 in critically ill patients in North Brabant, the Netherlands: Patient characteristics and outcomes.

PURPOSE: Since the SARS-CoV-2 pandemic, countries are overwhelmed by critically ill Coronavirus disease 2019 (COVID-19) patients. As ICU capacity becomes limited we characterized critically ill COVID-19 patients in the Netherlands. METHODS: In this case series, COVID-19 patients admitted to the ICU of the Jeroen Bosch Hospital were included from March 9 to April 7, 2020. COVID-19 was confirmed by a positive result by a RT-PCR of a specimen collected by nasopharyngeal swab. Clinical data were extracted from medical records. RESULTS: The mean age of the 50 consecutively included critically ill COVID-19 patients was 65 ± 10 years, the mean BMI was 29 ± 4.7 and 66% were men. Seventy-eight percent of patients had ≥1 comorbidity, 34% had hypertension. Ninety-six percent of patients required mechanical ventilation and 80% were ventilated in prone position. Venous thromboembolism was recognized in 36% of patients. Seventy-four percent of patients survived and were successfully discharged from the ICU, the remaining 26% died (median follow up 86 days). The length of invasive ventilation in survivors was 15 days (IQR 12-31). CONCLUSIONS: The survival rate of COVID-19 critically ill patients in our population is considerably better than previously reported. Thrombotic complications are commonly found and merit clinical attention. TRIAL REGISTRATION NUMBER: NL2020.07.04.01.

Rationale and design of the PRAETORIAN-COVID trial: A double-blind, placebo-controlled randomized clinical trial with valsartan for PRevention of Acute rEspiraTORy dIstress syndrome in hospitAlized patieNts with SARS-COV-2 Infection Disease.

There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-infected patients. Although it has been suggested that ARBs might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking. METHODS: The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2-infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020). SUMMARY: The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2-infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally.

A glimpse of gluons through deeply virtual compton scattering on the proton.

The internal structure of nucleons (protons and neutrons) remains one of the greatest outstanding problems in modern nuclear physics. By scattering high-energy electrons off a proton we are able to resolve its fundamental constituents and probe their momenta and positions. Here we investigate the dynamics of quarks and gluons inside nucleons using deeply virtual Compton scattering (DVCS)-a highly virtual photon scatters off the proton, which subsequently radiates a photon. DVCS interferes with the Bethe-Heitler (BH) process, where the photon is emitted by the electron rather than the proton. We report herein the full determination of the BH-DVCS interference by exploiting the distinct energy dependences of the DVCS and BH amplitudes. In the regime where the scattering is expected to occur off a single quark, measurements show an intriguing sensitivity to gluons, the carriers of the strong interaction.

Rosenbluth Separation of the π

We report the first longitudinal-transverse separation of the deeply virtual exclusive π^{0} electroproduction cross section off the neutron and coherent deuteron. The corresponding four structure functions dσ_{L}/dt, dσ_{T}/dt, dσ_{LT}/dt, and dσ_{TT}/dt are extracted as a function of the momentum transfer to the recoil system at Q^{2}=1.75 GeV^{2} and x_{B}=0.36. The ed→edπ^{0} cross sections are found compatible with the small values expected from theoretical models. The en→enπ^{0} cross sections show a dominance from the response to transversely polarized photons, and are in good agreement with calculations based on the transversity generalized parton distributions of the nucleon. By combining these results with previous measurements of π^{0} electroproduction off the proton, we present a flavor decomposition of the u and d quark contributions to the cross section.

Rosenbluth Separation of the π

We present deeply virtual π^{0} electroproduction cross-section measurements at x_{B}=0.36 and three different Q^{2} values ranging from 1.5 to 2 GeV^{2}, obtained from Jefferson Lab Hall A experiment E07-007. The Rosenbluth technique is used to separate the longitudinal and transverse responses. Results demonstrate that the cross section is dominated by its transverse component and, thus, is far from the asymptotic limit predicted by perturbative quantum chromodynamics. Nonetheless, an indication of a nonzero longitudinal contribution is provided by the measured interference term σ_{LT}. Results are compared with several models based on the leading-twist approach of generalized parton distributions (GPDs). In particular, a fair agreement is obtained with models in which the scattering amplitude includes convolution terms of chiral-odd (transversity) GPDs of the nucleon with the twist-3 pion distribution amplitude. This experiment, together with previous extensive unseparated measurements, provides strong support to the exciting idea that transversity GPDs can be accessed via neutral pion electroproduction in the high-Q^{2} regime.

Are too many compression ultrasounds being performed for acute lower limb deep venous thrombosis in tertiary inpatients?

BACKGROUND: Venous thromboembolism (VTE) is a complex and serious condition, with high morbidity and mortality, especially in hospitalised patients. Yet its diagnosis remains challenging because of its unspecific clinical presentation. The objective of this study was to apply an algorithmic combination approach to diagnosing VTE by the addition of a D-dimer assay and Wells' criteria for our hospital's internal referral forms requesting compression ultrasound (CUS), to determine the effect on the number of referrals for CUS and the incidence of deep vein thrombosis (DVT) diagnoses. METHOD: Inpatients who had been referred to the hospital's vascular laboratory and who had undergone a CUS to exclude an acute lower limb DVT were retrospectively analysed between January 2009 and December 2013, and compared to prospectively collected data for the full year (2014) after the introduction of the new referral form. Comparisons included the mean annual number of referrals for CUS and the incidence of DVT diagnoses. RESULTS: The hospital incidence of diagnosed DVTs for 2009-2013 was 0.17%, compared to 0.16% for 2014 (ρ = 0.930). In contrast, the total number of referrals for CUS as a percentage of all hospital admissions dropped from 0.84% in 2009-2013 to 0.63% in 2014 (ρ = 0.009, odds ratio 0.76, 95% confidence interval: 0.62-0.93). CONCLUSION: The implementation of Wells' criteria and D-dimer to the new request form for CUS significantly decreased referrals to the hospital's vascular laboratory without impacting on the number of DVT cases diagnosed. This is a positive change which simplifies care and reduces the expense of ultrasonography investigations.

Polarization Transfer in Wide-Angle Compton Scattering and Single-Pion Photoproduction from the Proton.

Wide-angle exclusive Compton scattering and single-pion photoproduction from the proton have been investigated via measurement of the polarization transfer from a circularly polarized photon beam to the recoil proton. The wide-angle Compton scattering polarization transfer was analyzed at an incident photon energy of 3.7 GeV at a proton scattering angle of θ_{cm}^{p}=70°. The longitudinal transfer K_{LL}, measured to be 0.645±0.059±0.048, where the first error is statistical and the second is systematic, has the same sign as predicted for the reaction mechanism in which the photon interacts with a single quark carrying the spin of the proton. However, the observed value is ~3 times larger than predicted by the generalized-parton-distribution-based calculations, which indicates a significant unknown contribution to the scattering amplitude.

Measurement of the Target-Normal Single-Spin Asymmetry in Quasielastic Scattering from the Reaction (3)He(↑)(e,e').

We report the first measurement of the target single-spin asymmetry, A(y), in quasielastic scattering from the inclusive reaction (3)He(↑)(e,e') on a (3)He gas target polarized normal to the lepton scattering plane. Assuming time-reversal invariance, this asymmetry is strictly zero for one-photon exchange. A nonzero A(y) can arise from the interference between the one- and two-photon exchange processes which is sensitive to the details of the substructure of the nucleon. An experiment recently completed at Jefferson Lab yielded asymmetries with high statistical precision at Q(2)=0.13, 0.46, and 0.97 GeV(2). These measurements demonstrate, for the first time, that the (3)He asymmetry is clearly nonzero and negative at the 4σ-9σ level. Using measured proton-to-(3)He cross-section ratios and the effective polarization approximation, neutron asymmetries of -(1-3)% were obtained. The neutron asymmetry at high Q(2) is related to moments of the generalized parton distributions (GPDs). Our measured neutron asymmetry at Q(2)=0.97 GeV(2) agrees well with a prediction based on two-photon exchange using a GPD model and thus provides a new, independent constraint on these distributions.

Precision Measurement of the p(e,e

New results are reported from a measurement of π^{0} electroproduction near threshold using the p(e,e^{'}p)π^{0} reaction. The experiment was designed to determine precisely the energy dependence of s- and p-wave electromagnetic multipoles as a stringent test of the predictions of chiral perturbation theory (ChPT). The data were taken with an electron beam energy of 1192 MeV using a two-spectrometer setup in Hall A at Jefferson Lab. For the first time, complete coverage of the ϕ_{π}^{*} and θ_{π}^{*} angles in the pπ^{0} center of mass was obtained for invariant energies above threshold from 0.5 up to 15 MeV. The 4-momentum transfer Q^{2} coverage ranges from 0.05 to 0.155 (GeV/c)^{2} in fine steps. A simple phenomenological analysis of our data shows strong disagreement with p-wave predictions from ChPT for Q^{2}>0.07 (GeV/c)^{2}, while the s-wave predictions are in reasonable agreement.

Measurement of double-polarization asymmetries in the quasielastic (3)He[→](e[→],e(')d) process.

We present a precise measurement of double-polarization asymmetries in the ^{3}He[over →](e[over →],e^{'}d) reaction. This particular process is a uniquely sensitive probe of hadron dynamics in ^{3}He and the structure of the underlying electromagnetic currents. The measurements have been performed in and around quasielastic kinematics at Q^{2}=0.25(GeV/c)^{2} for missing momenta up to 270 MeV/c. The asymmetries are in fair agreement with the state-of-the-art calculations in terms of their functional dependencies on p_{m} and ω, but are systematically offset. Beyond the region of the quasielastic peak, the discrepancies become even more pronounced. Thus, our measurements have been able to reveal deficiencies in the most sophisticated calculations of the three-body nuclear system, and indicate that further refinement in the treatment of their two-and/or three-body dynamics is required.

Initially unrecognised group A streptococcal pelvic inflammatory disease in a postmenopausal woman.

Invasive group A streptococcal infection is a severe disease with high mortality. Invasive group A streptococcal infection may arise after pelvic inflammatory disease. Pelvic inflammatory disease in postmenopausal women is rare. Here, we report a unique case of a postmenopausal woman with fatal invasive group A streptococcal infection due to pelvic inflammatory disease and an extraordinary course of diagnosis.

Precision measurement of the neutron twist-3 matrix element d(2)(n): probing color forces.

Double-spin asymmetries and absolute cross sections were measured at large Bjorken x (0.25≤x≤0.90), in both the deep-inelastic and resonance regions, by scattering longitudinally polarized electrons at beam energies of 4.7 and 5.9 GeV from a transversely and longitudinally polarized (3)He target. In this dedicated experiment, the spin structure function g(2)((3)He) was determined with precision at large x, and the neutron twist-3 matrix element d(2)(n) was measured at ⟨Q(2)⟩ of 3.21 and 4.32 GeV(2)/c(2), with an absolute precision of about 10(-5). Our results are found to be in agreement with lattice QCD calculations and resolve the disagreement found with previous data at ⟨Q(2)⟩=5 GeV(2)/c(2). Combining d(2)(n) and a newly extracted twist-4 matrix element f(2)(n), the average neutron color electric and magnetic forces were extracted and found to be of opposite sign and about 30 MeV/fm in magnitude.

Probing the repulsive core of the nucleon-nucleon interaction via the (4)He(e,e'pN) triple-coincidence reaction.

We studied simultaneously the (4)He(e,e'p), (4)He(e,e'pp), and (4)He(e,e'pn) reactions at Q(2)=2(GeV/c)(2) and x(B)>1, for an (e,e'p) missing-momentum range of 400 to 830 MeV/c. The knocked-out proton was detected in coincidence with a proton or neutron recoiling almost back to back to the missing momentum, leaving the residual A=2 system at low excitation energy. These data were used to identify two-nucleon short-range correlated pairs and to deduce their isospin structure as a function of missing momentum, in a region where the nucleon-nucleon (NN) force is expected to change from predominantly tensor to repulsive. The abundance of neutron-proton pairs is reduced as the nucleon momentum increases beyond ∼500 MeV/c. The extracted fraction of proton-proton pairs is small and almost independent of the missing momentum. Our data are compared with calculations of two-nucleon momentum distributions in (4)He and discussed in the context of probing the elusive repulsive component of the NN force.

Measurement of the target-normal single-spin asymmetry in deep-inelastic scattering from the reaction (3)He(↑)(e,e')X.

We report the first measurement of the target-normal single-spin asymmetry in deep-inelastic scattering from the inclusive reaction 3)He(↑)(e,e')X on a polarized (3)He gas target. Assuming time-reversal invariance, this asymmetry is strictly zero in the Born approximation but can be nonzero if two-photon-exchange contributions are included. The experiment, conducted at Jefferson Lab using a 5.89 GeV electron beam, covers a range of 1.72 GeV, which is nonzero at the 2.89σ level. Our measured asymmetry agrees both in sign and magnitude with a two-photon-exchange model prediction that uses input from the Sivers transverse momentum distribution obtained from semi-inclusive deep-inelastic scattering.

The aetiology of community-acquired pneumonia and implications for patient management.

PURPOSE: Understanding which pathogens are associated with clinical manifestation of community-acquired pneumonia (CAP) is important to optimise treatment. We performed a study on the aetiology of CAP and assessed possible implications for patient management in the Netherlands. METHODS: Patients with CAP attending the emergency department of a general hospital were invited to participate in the study. We used an extensive combination of microbiological techniques to determine recent infection with respiratory pathogens. Furthermore, we collected data on clinical parameters and potential risk factors. RESULTS: From November 2007 through January 2010, 339 patients were included. Single bacterial infection was found in 39% of these patients, single viral infection in 12%, and mixed bacterial-viral infection in 11%. Streptococcus pneumoniae was the most frequently identified pathogen (22%; n=74). Infection with atypical bacteria was detected in 69 (20%) of the patients. CONCLUSION: Initial empirical antibiotics should be effective against S. pneumoniae, the most common pathogen identified in CAP patients. The large proportion of patients with infection with atypical bacteria points to the need for improved diagnostic algorithms including atypical bacteria, especially since these atypical bacteria are not covered by the first-choice antibiotic treatment according to the recently revised Dutch guidelines on the management of CAP.

Measurements of parity-violating asymmetries in electron-deuteron scattering in the nucleon resonance region.

We report on parity-violating asymmetries in the nucleon resonance region measured using inclusive inelastic scattering of 5-6 GeV longitudinally polarized electrons off an unpolarized deuterium target. These results are the first parity-violating asymmetry data in the resonance region beyond the Δ(1232). They provide a verification of quark-hadron duality-the equivalence of the quark- and hadron-based pictures of the nucleon-at the (10-15)% level in this electroweak observable, which is dominated by contributions from the nucleon electroweak γZ interference structure functions. In addition, the results provide constraints on nucleon resonance models relevant for calculating background corrections to elastic parity-violating electron scattering measurements.

Bilothorax: a bitter complication of liver surgery.

Bilothorax is a rare condition, mostly associated with surgery involving the biliary system or trauma. In this article a case of bilothorax secondary to liver surgery is reported, which recovered by pleural and abdominal drainage. Bilothorax should be considered as a cause of respiratory detoriation in patients with recent biliary or hepatic surgery.