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Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

BackgroundIn the context of the SARS-CoV-2 pandemic, reuse of personal protective equipment, specifically that of medical face coverings, has been recommended. The reuse of these typically single-use only items necessitates procedures to inactivate contaminating human respiratory and gastrointestinal pathogens. We previously demonstrated decontamination of surgical masks and respirators contaminated with infectious SARS-CoV-2 and various animal coronaviruses via low concentration- and short exposure methylene blue photochemical treatment (10 µM methylene blue, 30 minutes of 12,500-lux red light or 50,000 lux white light exposure).MethodsHere, we describe the adaptation of this protocol to the decontamination of a more resistant, non-enveloped gastrointestinal virus and demonstrate efficient photodynamic inactivation of murine norovirus, a human norovirus surrogate.ResultsMethylene blue photochemical treatment (100 µM methylene blue, 30 minutes of 12,500-lux red light exposure) of murine norovirus-contaminated masks reduced infectious viral titres by over four orders of magnitude on surgical mask surfaces.Discussion and ConclusionsInactivation of a norovirus, the most difficult to inactivate of the respiratory and gastrointestinal human viruses, can predict the inactivation of any less resistant viral mask contaminant. The protocol developed here thus solidifies the position of methylene blue photochemical decontamination as an important tool in the package of practical pandemic preparedness.

BackgroundOptical coherence tomography (OCT) is an ultra-high resolution real-time intravascular imaging method that is gaining interest in cerebrovascular applications.ObjectiveTo compare, in a rabbit elastase aneurysm model, digital subtraction angiography (DSA) and OCT as diagnostic tools for the assessment of aneurysmal remnants and baseline characteristics of aneurysms after flow diverter (FD) implantation.MethodsWith Institutional Animal Care and Use Committee approval, saccular aneurysms were created in 28 rabbits and treated with Derivo FDs. DSA was performed before, and immediately after, stent implantation. As a follow-up, DSA and OCT were performed 28 days after device implantation.ResultsDSA and OCT were successfully performed in 23 cases. OCT could not be achieved in 5 cases owing to navigational difficulties in the stent lumen with the OCT catheter. Residual aneurysms were significantly more often visible with OCT (18/23 (78%) than with DSA 12/23 (52%), p = 0.031).ConclusionOCT was more sensitive than conventional angiography for the assessment of residual aneurysms at 28 days after FD implantation in an animal model.

Summary Background Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries. Methods In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov , NCT03646227 , and is complete. Findings Between June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2–6] vs 2 [0–4] vs 2 [0–4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2–5] vs 1 [0–3] vs 1 [0–2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42–65) for China versus South America, 50% (41–61) for the USA versus China, and 53% (41–66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8–16; 29 of 246) than in the USA (23%, 16–30; 30 of 130) and South America (28%, 20–37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22–10·50) and the USA (aOR 3·34, 1·50–7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70–2·96). Interpretation Global CRKP epidemics have important regional differences in patients’ baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions. Funding The National Institutes of Health.

Background Many patients with Coronavirus disease-2019 (Covid-19) present with radiological evidence of pneumonia. Because it is difficult to determine co-existence of bacterial pneumonia, many of these patients are initially treated with antibiotics. We compared the rates of bacterial infections and mortality in Covid-19 patients with pulmonary infiltrates versus patients diagnosed with ‘pneumonia’ the year previously. Methods We conducted a medical record review of patients admitted with Covid-19 and a pulmonary infiltrate and compared them with patients diagnosed with pneumonia admitted in the prior year before the pandemic. Data abstracted included baseline demographics, comorbidities, signs and symptoms, laboratory and microbiological results, and imaging findings. Outcomes were bacterial infections and mortality. Patients presenting with and without Covid-19 were compared using univariable and multivariable analyses. Results There were 1398 and 1001 patients admitted through the emergency department (ED) with and without Covid-19 respectively. Compared with non-Covid-19 patients, those with Covid-19 were younger (61±18 vs. 65±25 years, P

The recently discovered first hyperbolic objects passing through the Solar System, 1I/’Oumuamua and 2I/Borisov, have raised the question about near term missions to Interstellar Objects. In situ spacecraft exploration of these objects will allow the direct determination of both their structure and their chemical and isotopic composition, enabling an entirely new way of studying small bodies from outside our solar system. In this paper, we map various Interstellar Object classes to mission types, demonstrating that missions to a range of Interstellar Object classes are feasible, using existing or near-term technology. We describe flyby, rendezvous and sample return missions to interstellar objects, showing various ways to explore these bodies characterizing their surface, dynamics, structure and composition. Their direct exploration will constrain their formation and history, situating them within the dynamical and chemical evolution of the Galaxy. These mission types also provide the opportunity to explore solar system bodies and perform measurements in the far outer solar system.

Salvage lymph node dissection is a rescue treatment for patients with nodal recurrence after radical prostatectomy. Very limited data are available on robotic salvage lymph node dissection. Our purpose was to investigate perioperative and oncological outcomes of robotic salvage lymph node dissection in a large monocentric series.Perioperative data, complications within 30 days after surgery and oncological outcomes as assessed by histology, prostate specific antigen changes, prostate specific antigen nadir after salvage lymph node dissection, and time to further therapy were analyzed. To identify predictive factors for oncological outcome, Kaplan-Meier and Cox-regression analyses were performed. For cases with a mismatch between preoperative positron emission tomography/computed tomography and the number of histologically positive lymph nodes, prostate specific membrane antigen immunohistochemistry was performed on removed lymph nodes.A total of 68 patients underwent robotic salvage lymph node dissection with a median operation time of 126 minutes, a blood loss of 50 ml, and a length of stay of 4 days. No major complications (Clavien 3) occurred. Median followup was 12.1 months. Median time to further therapy was 12.4 months, 37% of patients experienced complete biochemical response (prostate specific antigen0.2 ng/ml) and 11% reached an undetectable prostate specific antigen, which was maintained for1 year in 3 cases. Lower preoperative prostate specific antigen, longer time between radical prostatectomy and salvage lymph node dissection, preoperative prostate specific membrane antigen positron emission tomography/computed tomography and complete biochemical response after salvage lymph node dissection were significant predictors of longer therapy-free survival (all p0.005). Prostate specific membrane antigen immunohistochemistry revealed that prostate specific membrane antigen positron emission tomography/computed tomography tends to miss small lymph node metastases5 mm.Robotic salvage lymph node dissection is a feasible approach with low perioperative morbidity and delays further systemic therapy in most patients. Prostate specific membrane antigen positron emission tomography/computed tomography detection is mostly limited to tumor foci5 mm.

SummaryBackgroundWidely varying mortality rates of critically ill Coronavirus disease 19 (COVID-19) patients in the world highlighted the need for local surveillance of baseline characteristics, treatment strategies and outcome. We compared two periods of the COVID-19 pandemic to identify important differences in characteristics and therapeutic measures and their influence on the outcome of critically ill COVID-19 patients.MethodsThis multicenter prospective register study included all patients with a SARS-CoV‑2 infection confirmed by polymerase chain reaction, who were treated in 1 of the 12 intensive care units (ICU) from 8 hospitals in Tyrol, Austria during 2 defined periods (1 February 2020 until 17 July: first wave and 18 July 2020 until 22 February 2021: second wave) of the COVID-19 pandemic.ResultsOverall, 508 patients were analyzed. The majority (n = 401) presented during the second wave, where the median age was significantly higher (64 years, IQR 54–74 years vs. 72 years, IQR 62–78 years,p p = 0.003), as was the use of vasopressors (50.3% vs. 69.2%,p = 0.001) and renal replacement therapy (12.0% vs. 19.6%,p = 0.061), which resulted in shorter ICU length of stay (10 days, IQR 5–18 days vs. 18 days, IQR 5–31 days,p p = 0.159) and hospital mortality even increased (22.4% vs. 33.4%,p = 0.039) in the second period. Age, frailty and the number of comorbidities were significant predictors of hospital mortality in a multivariate logistic regression analysis of the overall cohort.ConclusionAdvanced treatment strategies and learning effects over time resulted in reduced rates of mechanical ventilation and vasopressor use in the second wave associated with shorter ICU length of stay. Despite these improvements, age appears to be a dominant factor for hospital mortality in critically ill COVID-19 patients.

Graphical abstract, Highlights • Myxomas are rare tumors in dogs, in contrast to humans. • Myxomas may cause left ventricular outflow tract obstructions. • Primary cardiac tumors should be considered even in young dogs. • Myxomas may be cavitated and dynamic.

Student dropout is a multi-causal process. Different theoretical models on student dropout consider dysfunctional study behavior (e.g., academic procrastination) and low study satisfaction as possible determinants of students’ dropout intentions during their university studies. However, these models neglect contemporary conceptualizations that assume reverse relationships between dropout intentions and other determinants of the dropout process. Until now, empirical evidence on these assumptions is scant. The present three-wave longitudinal study explored the reciprocal relationships between academic procrastination, study satisfaction, and dropout intentions over one semester. To this end, we used data of N = 326 undergraduate students enrolled in mathematics and law. Our latent cross-lagged panel model replicated existing empirical cross-sectional findings between the variables (i.e., academic procrastination, study satisfaction, and dropout intentions). Regarding the longitudinal relations, as expected, the cross-lagged effects showed that higher dropout intentions significantly related to subsequent higher academic procrastination and lower study satisfaction. Unexpectedly, academic procrastination did not significantly relate to subsequent dropout intentions. Additionally, higher study satisfaction significantly associated with subsequent higher dropout intentions—possibly due to unfulfilled expectations. Further, higher study satisfaction significantly related to subsequent higher procrastination—possibly due to more confidence among satisfied students. Our results broaden the view on dropout intentions as part of the dynamic interplay of student dropout determinants and the need to refine dropout models’ assumptions accordingly. Practically, realistic expectations seem important to reduce dropout intentions. Further, student counselors should have a closer look at the reasons for academic procrastination to develop individual solutions for this dysfunctional behavior.

The paper presents a method for measuring and recording the forces involved in the coal cutting process. Moreover, a method for visualization of all forces involved in the cutting process was described. In the following part, the construction and principle of operation of a device for determination of forces involved in the cutting process (coal mining), referred to by the author as POU-BW/01-WAP, are presented. Resistance extensometry was used to measure the forces. This is the only device in the world that determines two of three force components that take part in the cutting process. For this purpose, two independent measuring blocks were used, which are strain gauges of force: cutting (Fs) and knife pressure (Fd). In order to register these forces, a real mining knife used in longwall shearer drums was applied – i.e. tangential-rotary. The equipment has the ATEX certificate allowing for operation in real conditions as a device intended for use in potentially explosive atmospheres – in accordance with the directive 94/9/EC. It has received many awards at world fairs for inventions and innovative solutions.

The pleural lobes are the origin of different pathologies, including malignant tumors, e.g., pleural mesothelioma. In some cases, clinical and macroscopic presentation point strongly to the diagnosis but often enough the patient has another underlying disease; malignant neoplasms of the lung as well as other organs (skin, pancreas, prostate or kidney) can mimic pleural mesothelioma and if so, are defined as ‘pseudo-mesothelioma’. We present eight cases that are clinically and macroscopically highly suspicious for pleural mesothelioma. All patients were autopsied due to medico-legal issues and work-related diseases. Six out of eight patients underwent autopsy to exclude possibility of asbestos-related malignancy and two out of eight due to exclusion of silicosis. From the eight cases, only three were real pleural mesotheliomas. Another three were adenocarcinomas of the lung mimicking pleural mesotheliomas. One had squamous cell carcinoma of the lung. Lastly, one patient had an extraordinary case of papillary renal cell carcinoma metastasizing universally in both pleura lobes. Due to striking morphological similarities, the exact final diagnosis was only possible after extended immunohistochemical analysis of the tissues. In summary, not only is it difficult to distinguish between real or pseudo pleural mesothelioma in patients having had contact with asbestos. Even patients with no evidence of asbestos contact can have clinical and pathological events strongly suggesting asbestosis and mesothelioma, without having it.

Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.

We present an endovascular approach for anatomic reconstruction of the iliac bifurcation in life-threatening arterioureteral fistula without sacrificing the pelvic arterial vascular supply. Five consecutive patients suffering from acute onset of significant gross hematuria caused by iliac-ureteral fistula resulting from previous oncologic surgery and radiation therapy were treated by transfemoral stent graft implantation in a double-barrel technique. Iliac-ureteral pseudoaneurysm coverage succeeded in an iliac neobifurcation with preservation of pelvic perfusion. Follow-up ranging from 9 to 37 months confirmed cessation of hematuria. One patient experienced stent graft thrombosis of the external iliac artery as a result of large cervical cancer invasion treated by crossover bypass. In all other patients, stent grafts were patent.

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

Background The mechanisms underlying the association between obesity and coronavirus disease 2019 (COVID-19) severity remain unclear. After verifying that obesity was a correlate of severe COVID-19 in US Military Health System (MHS) beneficiaries, we compared immunological and virological phenotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in both obese and nonobese participants. Methods COVID-19–infected MHS beneficiaries were enrolled, and anthropometric, clinical, and demographic data were collected. We compared the SARS-CoV-2 peak IgG humoral response and reverse-transcription polymerase chain reaction viral load in obese and nonobese patients, stratified by hospitalization, utilizing logistic regression models. Results Data from 511 COVID-19 patients were analyzed, among whom 24% were obese and 14% severely obese. Obesity was independently associated with hospitalization (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.15–3.18) and need for oxygen therapy (aOR, 3.39; 95% CI, 1.61–7.11). In outpatients, severely obese had a log10 (1.89) higher nucleocapsid (N1) genome equivalents (GE)/reaction and log10 (2.62) higher N2 GE/reaction than nonobese (P = 0.03 and P < .001, respectively). We noted a correlation between body mass index and peak anti-spike protein IgG in inpatients and outpatients (coefficient = 5.48, P < .001). Conclusions Obesity is a strong correlate of COVID-19 severity in MHS beneficiaries. These findings offer new pathophysiological insights into the relationship between obesity and COVID-19 severity.

Theophylline is used in canine medicine for the management of chronic bronchitis and bradyarrhythmias, yet no species-validated commercial products are available. This study reports the single-dose and multidose pharmacokinetics and safety of a modified, compounded theophylline (MCT) product readily available from a well-established, USP-compliant compounding pharmacy, which may be a suitable and reliable source for theophylline for dogs. Eleven dogs underwent serial plasma theophylline measurement following 10 mg/kg MCT PO. After a 7 days washout, dogs received 10 mg/kg MCT PO q12h and serial plasma theophylline quantification was repeated after the ninth dose. Dogs were monitored for potential adverse effects. For the nine dogs that completed the study, plasma theophylline concentrations were between 5 and 30 μg/ml for 91 +/- 15% of the dosing interval. There was no significant difference in half-life between single-dose and multidose administration. The most common adverse effects reported were mild and included agitation, excitement, and increased activity. The results of this study support the use of 10 mg/kg MCT administered twice daily as a starting dosage in dogs. This regimen appears safe, achieves appropriate plasma drug concentrations in most dogs, and does not cause significant changes in pharmacokinetic properties at steady state. Because compounded drugs do not undergo consistent testing for identity, quality, strength, purity, and stability, results of research described in reports using compounded products may not be reproducible.

This is the first report of a segmental mediolysis occurring in arterioles, affecting the neck/tonsillar region and leading to a fatal hemorrhage after a tonsillectomy in a 20-year-old woman. Arteriolar mediolysis could be observed in tissue layers about 2 cm distant from the tonsillectomy region. Reparative changes were observed in the carotid and small neck arteries as well as in only one intramyocardial arteriole; however, no other vascular regions typically reported in segmental mediolysis arteriopathy were affected and aneurysm formation was not observed. No family history of vascular disease or hypertension was known. Pathophysiologically, previously reported reasons for post-tonsillectomy bleeding could be excluded. Segmental mediolysis may represent a wider spectrum of affected arteriolar vessels besides the reported small and medium sized arteries leading to aneurysms, which impedes radiographic diagnosis.

Little is known about severe acute respiratory syndrome coronavirus 2 “vaccine-breakthrough” infections (VBIs). Here we characterize 24 VBIs in predominantly young healthy persons. While none required hospitalization, a proportion endorsed severe symptoms and shed live virus as high as 4.13 × 103 plaque-forming units/mL. Infecting genotypes included both variant-of-concern (VOC) and non-VOC strains.

Malignant central nervous system (CNS) tumors in young children have a poor prognosis and pose a therapeutic challenge. We describe 11 patients with high-risk CNS tumors (6 atypical teratoid/rhabdoid tumor, 4 nonmedulloblastoma CNS embryonal tumors, and 1 glioblastoma multiforme) who received 32 consolidation cycles of myeloablative carboplatin/thiotepa followed by autologous peripheral blood stem cell rescue. All patients underwent successful stem cell harvest without significant complications. Mean time to absolute neutrophil count ≥0.5×103/µL was 10.2±1.3 days and the mean length of hospital stay was 15.7±3.0 days. There were no regimen-related deaths. Five-year event-free survival and overall survival were 45.5±15.0% and 58.4±16.3%, respectively. Tandem carboplatin/thiotepa consolidation with autologous stem cell rescue is well-tolerated in young children with nonmedulloblastoma CNS tumors.

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission. METHODS: In this phase 2a-b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)-negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection. RESULTS: Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, -0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups. CONCLUSIONS: The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.).

BackgroundRecently, liquid embolic agents have emerged for the endovascular treatment of cerebral aneurysms. Here we describe the in vivo performance of a novel liquid embolization agent (GPX Embolic Device).MethodsElastase-induced aneurysms were embolized with a GPX prototype under balloon assistance. Digital subtraction angiography was performed pre-deployment and immediately after, and at 5, 10, and 30 min post-deployment in 10 rabbits and at 1 month in 8 rabbits. The early post-deployment intra-aneurysmal flow was graded as unchanged, moderately diminished, or completely absent. At 1 month the status of aneurysm occlusion was evaluated. Adhesion to catheter material and migration of GPX was assessed.ResultsThe mean aneurysm neck diameter, width, and height were 3.6±1.0 mm, 3.0±0.8 mm, and 7.4±1.4 mm, respectively. The mean dome-to-neck ratio was 0.9±0.2. Complete stagnation of intra-aneurysmal flow was observed in 9 of 10 aneurysms (90%) within 30 min of device deployment. One aneurysm showed moderately diminished intra-aneurysmal flow at 30 min. At 1 month, 8 aneurysms were completely occluded. There was no evidence of GPX adhesion to the catheter material. Histologically, a leukocyte and foreign body reaction to GPX was detectable 28 days after embolization.ConclusionsThis is the first preclinical study reporting the performance of a protype version of the GPX Embolic Device in a wide-neck aneurysm model. GPX showed promising results by achieving and maintaining high rates of complete angiographic occlusion, but may induce an inflammatory reaction.

Die pachychorioidalen Erkrankungen sind alle durch eine Verdickung der Aderhaut gekennzeichnet. Die Gruppe umfasst die folgenden Krankheitsgruppen: pachychorioidale Pigmentepitheliopathie (PPE), Chorioretinopathia centralis serosa (CCS), pachychorioidale Neovaskulopathie (PNV), polypoidale chorioidale Vaskulopathie (PCV)/aneurysmatische chorioidale Neovaskularisation Typ 1 (ACNV‑1), fokale chorioidale Exkavation (FCE) und peripapillares pachychorioidales Syndrom (PPS). Wenn bei verdickter Aderhaut zusatzlich eine Veranderung des retinalen Pigmentepithels vorliegt, lautet die Diagnose PPE; wenn die verdickte Aderhaut von subretinaler Flussigkeit begleitet ist, lautet die Diagnose CCS; wenn eine chorioidale Neovaskularisation vorliegt, lautet die Diagnose PNV; wenn sie von Aneurysmen begleitet ist, lautet die Diagnose ACNV‑1. PPE, CCS, PNV und ACNV‑1 wurden als unabhangige Krankheitsentitaten angesehen, lassen sich aber als 4 Formen einer einzigen Krankheitsfamilie, der „pachychorioidalen Makulaerkrankung“, klassifizieren.

Background For peripheral artery disease (PAD), MR angiography (MRA) is a well-established diagnostic modality providing morphologic and dynamic information comparable to digital subtraction angiography (DSA). However, relatively large amounts of contrast agents are necessary to achieve this. Purpose To evaluate the diagnostic accuracy of time-resolved 4D MR-angiography with interleaved stochastic trajectories (TWIST-MRA) by using maximum intensity projections (MIPs) of dynamic images acquired with reduced doses of contrast agent. Study type Retrospective. Population Forty adult PAD patients yielding 1088 artery segments. Field strength/sequence A 3.0 T, time-resolved 4D MR-angiography with TWIST-MRA and MIP of dynamic images. Assessment DSA was available in 14 patients (256 artery segments) and used as reference standard. Three-segmental MIP reconstructions of TWIST-images after administration of 3 mL of gadolinium-based contrast agent (Gadoteridol/Prohance®, 0.5 M) per anatomical level (pelvis, thighs, and lower legs) yielded 256 artery segments for correlation between MRA and DSA. Three independent observers rated image quality (scale: 1 [nondiagnostic] to 4 [excellent]) and the degree of venous overlay (scale: 0 [none] to 2 [significant]) for all segments. Diagnostic accuracy for the detection of >50% stenosis and artery occlusion was calculated for all observers. Statistical tests Binary classification test (sensitivity, specificity, positive/negative predictive values, diagnostic accuracy). Intraclass correlation coefficients (ICCs), logistic regression analysis with comparison of areas under the receiver-operating-characteristics (ROC) curves (AUCs) with the DeLong method. Bland-Altman-comparison. Results High diagnostic performance was achieved for the detection of >50% stenosis (sensitivity 92.9% [84.3-99.9% (95%-CI)] and specificity 98.5% [95.7-99.8% (95%-CI)]) and artery occlusion (sensitivity 93.1% [77.2-99.2% (95%-CI)] and specificity 99.1% [96.9-99.9% (95%-CI)]). Inter-reader agreement was excellent with ICC values ranging from 0.95 to 1.0 for >50% artery stenosis and occlusion. Image quality was good to excellent for both readers (3.41 ± 0.72, 3.33 ± 0.65, and 3.38 ± 0.61 [mean ± SD]) with good correlation between observer ratings (ICC 0.71-0.81). No significant venous overlay was observed (0.06 ± 0.24, 0.23 ± 0.43 and 0.11 ± 0.45 [mean ± SD]). Data conclusion MIPs of dynamic TWIST-MRA offer a promising diagnostic alternative necessitating only reduced amounts (50%) of gadolinium-based contrast agents for the entire runoff vasculature. Evidence level 3 TECHNICAL EFFICACY: Stage 2.

In the electronic health record, using clinical notes to identify entities such as disorders and their temporality (e.g. the order of an event relative to a time index) can inform many important analyses. However, creating training data for clinical entity tasks is time consuming and sharing labeled data is challenging due to privacy concerns. The information needs of the COVID-19 pandemic highlight the need for agile methods of training machine learning models for clinical notes. We present Trove, a framework for weakly supervised entity classification using medical ontologies and expert-generated rules. Our approach, unlike hand-labeled notes, is easy to share and modify, while offering performance comparable to learning from manually labeled training data. In this work, we validate our framework on six benchmark tasks and demonstrate Trove’s ability to analyze the records of patients visiting the emergency department at Stanford Health Care for COVID-19 presenting symptoms and risk factors., In the electronic health record, using clinical notes to identify entities such as disorders and their temporality can inform many important analyses. Here, the authors present a framework for weakly supervised entity classification using medical ontologies and expert-generated rules.

Abstract. Background: Higher education is a challenging context in which students – particularly those endowed with a small array of resources – are susceptible to suffer from burnout. To screen, identify, and support students that are at risk of burnout, psychometrically robust instruments are essential. To this end, we extended the validation of the German short version of the Maslach Burnout Inventory – Student Survey (MBI-SS-KV) that allows measuring burnout among German-speaking university students. Method: We conducted a longitudinal study and analyzed the factorial validity, reliability, measurement invariance, and convergent as well as discriminant validity of the MBI-SS-KV in a sample of German university students ( N = 1,435). Results: Our results replicated the original three-factor structure of the MBI-SS-KV. Yet, a bi-factor structure of the MBI-SS-KV – composed of a general factor (i.e., student burnout) and three domain-specific factors (i.e., emotional exhaustion, cynicism, and reduced professional efficacy) – revealed a comparable fit and was used for further analyses due to theoretical and methodological advantages. Based on the bi-factor structure of the MBI-SS-KV, nested models with increasing invariance constraints provided support for measurement invariance of this instrument across female and male university students and across time. Besides, the average variance extracted estimates and the comparisons of these estimates with shared variances demonstrated convergent and discriminant validity of the factors emotional exhaustion and cynicism, but not for the factor reduced professional efficacy. Conclusion: To sum up, we found that the MBI-SS-KV is a reliable and for the most part valid instrument for the assessment of student burnout in German higher education.

Background Cardiac magnetic resonance imaging (CMR) allows for detection of fibrosis in hypertrophic cardiomyopathy (HCM) by quantification of the extracellular volume fraction (ECV). Hypothesis/Objectives To quantify native T1 mapping and ECV in cats. We hypothesize that native T1 mapping and ECV will be significantly increased in HCM cats compared with healthy cats. Animals Seventeen healthy and 12 preclinical HCM, age‐matched, client‐owned cats. Methods Prospective observational study. Tests performed included indirect blood pressure, CBC, biochemical analysis including total thyroid, urinalysis, transthoracic echocardiogram, and CMR. Cats were considered healthy if all tests were within normal limits and a diagnosis of HCM was determined by the presence of left ventricular concentric hypertrophy ≥6 mm on echocardiography. Results There were statistically significant differences in LV mass (healthy = 5.87 g, HCM = 10.3 g, P

Background: Social marketing successes are relatively well-documented, but mistakes and failures in the field are not. When mistakes and failures are reported, they are usually on an ad hoc basis, as opposed to a systematic gathering of evidence. This paper is the second half of a two-part research study that aims to understand the perceptions of social marketing professionals with regard to mistakes and failures in the field. Focus: This article is related to research and evaluation of the social marketing field. Research Question: What are the perceptions of the social marketing community regarding mistakes and failures in the field? Importance to the field: A greater understanding of mistakes and failures in the social marketing field will assist practitioners to assess their own shortcomings, address causes of mistakes and failures, and improve program outcomes. Method: This research is qualitative and exploratory, with a constructivist, grounded theory methodology. Surveys were completed by 100 social marketing community members. Survey data was analyzed and coded using SPSS software and Microsoft Excel. Results: According to the analyzed survey data, the social marketing community believes that inadequate research, poor strategy development, and mismanagement of stakeholders are the most common mistakes made by social marketers. Further, weak evaluation and monitoring is considered to be the “least well-managed” program element. Poor strategy development, external influences, and poorly designed program and behavioral objectives are considered to be the primary reasons for social marketing program failure. Recommendations for research or practice: Future research may explore the extent to which external influences lead to social marketing program success or failure, particularly in comparison to mistakes made by social marketers. Additionally, practitioners should be aware of and develop strategies to mitigate common mistakes and failures in order to improve program outcomes. Limitations: The 100 social marketing professionals who responded to the survey are not representative of the global social marketing community. Further, responses were based on self-report rather than direct observation, which may make them more susceptible to bias.

Die Fortschritte der kardialen Bildgebung und bei den 3‑D-Mappingverfahren haben in der letzten Dekade zu einem signifikanten Erkenntnisgewinn hinsichtlich der Korrelation ventrikularer Extrasystolen (VES) mit anatomischen Strukturen gefuhrt. Bei allem technischen Fortschritt bleibt die Interpretation des 12-Kanal-EKGs Grundlage fur die klinische Praxis. So lasst sich mit fundiertem Grundwissen uber die kardiale Anatomie und Erregungsausbreitung – unter Berucksichtigung der Limitationen der Methode – die Herkunft ventrikularer Ektopien mit hinreichender Genauigkeit bestimmen. Zur groben Eingrenzung reichen bereits wenige Anhaltspunkte. Anhand des Lagetyps kann zwischen einem diaphragmalen Ursprung mit superiorer Achse und einem weiter superior gelegenen Ursprung mit einem nach inferior gerichteten Summationsvektor unterschieden werden. In den Brustwandableitungen kann mit hoher Wahrscheinlichkeit von einem linksventrikularen Ursprung einer Ektopie ausgegangen werden, wenn diese eine Rechtsschenkelblock-Morphologie oder positive Konkordanz zeigt. Eine Linksschenkelblock-Morphologie kann neben dem rechten Ventrikel als Ursprungsort auch das interventrikulare Septum miteinschliesen. Je spater die R/S-Transition der Brustwandableitungen erfolgt, desto weiter anterior ist der Ursprung der VES. Die sich kreuzenden Ausflusstrakte der Ventrikel erschweren eine Lokalisation von VES aus diesem Bereich. Hier gibt v. a. die Form und Hohe der R‑Zacke in V1–V3 einen Aufschluss uber den moglichen Ursprungsort. Unscharfen in der EKG-Lokalisation bestehen insbesondere bei semimobilen Strukturen wie den Papillarmuskeln und dem Moderatorband, mit variablem Verlauf innerhalb der Ventrikel. Auf Basis der so gewonnenen Informationen kann in der Folge eine fundierte Einschatzung uber die Prognose und den zu erwartenden Erfolg einer medikamentosen oder invasiven Therapie getroffen werden.

Background and Aim Ustekinumab is approved in Europe for the treatment of moderate to severe Crohn's disease (CD). Italian real‐life data are scarce, so the aim of this study was to assess the effectiveness and safety of ustekinumab in an Italian cohort of CD patients. Methods Data of patients with CD who started using ustekinumab were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. Primary end‐points were steroid‐free clinical remission at 8, 24, and 52 weeks of therapy and reduction of C‐reactive protein. Secondary end‐points were treatment response, treatment persistence at 12 months, and safety. Results A total of 131 patients (males 56%; mean age 46 years ±15) were included. All patients were biologics experienced except for one. At 24 and 52 weeks, 40% and 43% of patients achieved steroid‐free clinical remission, and 64% and 62% had clinical response, respectively. At the end of follow‐up, there was a significant reduction of steroid use (P = 0.012) and of the Harvey‐Bradshaw Index (P = 0.001). The probability of persistence in therapy with ustekinumab after 12 months of treatment was 89%. The only factor associated with discontinuation was older age. Conclusions Data from our real‐life cohort of treatment‐refractory CD patients suggest the satisfactory effectiveness and safety profile of ustekinumab., We assessed one‐year effectiveness and safety of ustekinumab in an real‐life cohort of treatment‐refractory CD patients. At 52 weeks 43% of patients achieved steroid‐free clinical remission and 62% had clinical response with a persistence in therapy of 98% and a significant reduction of steroid use (p = 0.012) and of HBI (p = 0.001). Data from our cohort suggest satisfactory effectiveness and safety profile of ustekinumab.

To evaluate the clinical and radiological outcome, sum of acetabular and femoral cartilage thickness, and rate of failure in the midterm after arthroscopic treatment of femoroacetabular impingement (FAI) syndrome with femoral osteoplasty, labral repair, and rim trimming without labral detachment.This retrospective case series included patients with FAI syndrome who had undergone hip arthroscopy from January 2009 to December 2010 by a single surgeon, with a minimum follow-up of 55 months. Data from patients who had undergone arthroscopic hip procedures with labral repair, rim trimming, and femoral osteoplasty were analyzed pre- and postoperatively. Clinical outcome (nonarthritic hip score [NAHS], Short Form 36 [SF-36]), range of motion, progression of osteoarthritis (Tönnis grade), radiological parameters (α angle, lateral center-edge angle [LCEA], Tönnis angle), femoral and acetabular cartilage thickness (using magnetic resonance imaging [MRI]), and intraoperative findings were evaluated.Of 148 hip arthroscopies performed, 97 included rim trimming, labral refixation, and femoral osteoplasty. Ten cases were lost to follow-up, leaving 87 hips. Arthroscopic revision was performed on 4 hips and total hip replacement on 4 hips, and 1 hip underwent both arthroscopic revision and total hip replacement. Excluding these 9 cases of revision, for which follow-up was not possible (retrospective study), the remaining 78 hips were followed up for a minimum of 55 months (77 ± 11.4, mean ± SD; range 55 to 124). Mean NAHS (65 to 88, P.001), SF-36 physical subscale (65 to 85, P.001), and the numerical pain rating scale (NRS) (5 to 1, P.001) improved significantly. Outcome scores of minimal clinical importance (NAHS) were achieved in 67.6% of the patients. Mean range of movement improved significantly in flexion (109 to 122, P .001) and internal rotation (10 to 22.7, P.001). NAHS was positively associated with flexion of the hip postoperatively (r = 0.307, P = .011). In 16 cases, microfracture was performed (15 acetabular and 1 femoral). Preoperative α angles (anteroposterior and modified Dunn) were significantly higher in this cohort (P.001, 95% confidence interval 8.9 to 25.2, P = .001). Twenty hips (28 %) progressed to worse Tönnis grades. Initial Tönnis grades were grade 0, 38; grade 1, 48; grade 2, 8. Pre- or postoperative Tönnis grades did not show any correlation with pre- or postoperative NAHS and NRS. MRI measurements at the latest follow-up (69 patients) of the femoral and acetabular cartilage thickness did not reveal any significant reduction at the 12 o'clock position.Arthroscopic cam resection, rim trimming, and labral repair without detachment of the labrum provides good or excellent outcome in 77.1% of hips based on NAHS in the midterm. Higher range of motion in flexion is associated with higher NAHS postoperatively. Arthroscopic cam resection, rim trimming and labral repair without detachment of the labrum is a successful method for the treatment of FAI syndrome in the midterm.IV, retrospective case series.

Accurate gain control of PET detectors is a prerequisite for quantitative accuracy. A shift in the 511 keV peak position can lead to errors in scatter correction, degrading quantitation. The PET detectors in a PET/MR scanner are subject to thermal transients due to eddy currents induced during gradient-intensive MRI sequences. Since the gain of silicon photomultiplier-based detectors changes with temperature, good gain control is particularly challenging. In this paper we describe a method that utilizes information from the entire singles spectrum to create a real-time gain control method that maintains gain of PET detectors stable within approximately ±0.5% (±2.5 keV) with varying levels of scatter and in the presence of significant thermal transients. We describe the methods used to combine information about multiple peaks and how this algorithm is implemented in a way that permits real-time processing on a field-programmable gate array. Simulations demonstrate rapid response time and stability. A method (“virtual scatter filter”) is also described that extracts unscattered photopeak events from phantom data and demonstrates the accuracy of the photopeak for various radionuclides that emit energies in addition to the pure 511 keV annihilation peak. Radionuclides 52 Mn, 55 Co, 64 Cu, 89 Zr, 90 Y, and 124 I are included in the study for their various forms of spectral contamination.

Introduction The coronavirus disease 2019 (COVID-19) pandemic is a global public health emergency causing a disparate burden of death and disability around the world. The viral genetic variants associated with outcome severity are still being discovered. Methods We downloaded 155 958 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from GISAID. Of these genomes, 3637 samples included useable metadata on patient outcomes. Using this subset, we evaluated whether SARS-CoV-2 viral genomic variants improved prediction of reported severity beyond age and region. First, we established whether including genomic variants as model features meaningfully increased the predictive power of our model. Next, we evaluated specific variants in order to determine the magnitude of association with severity and the frequency of these variants among SARS-CoV-2 genomes. Results Logistic regression models that included viral genomic variants outperformed other models (area under the curve = 0.91 as compared with 0.68 for age and gender alone; P Conclusion Numerous SARS-CoV-2 variants have 2-fold or greater association with odds of mild or severe outcome and collectively, these variants are common. In addition to comprehensive mitigation efforts, public health measures should be prioritized to control the more severe manifestations of COVID-19 and the transmission chains linked to these severe cases. Lay summary: This study explores which, if any, SARS-CoV-2 viral genomic variants are associated with mild or severe COVID-19 patient outcomes. Our results suggest that there are common genomic variants in SARS-CoV-2 that are more often associated with negative patient outcomes, which may impact downstream public health measures.

Background: Untreated perinatal depression is a significant public health issue that disproportionately affects low-income black women and may lead to higher maternal mortality rates and disparate birth outcomes. Despite the growing literature documenting prevalence and risk for perinatal depression among black women, our knowledge of patient preferences of mental health interventions in obstetrical (OB) settings among this population is limited. This study explored mental health treatment preferences among black pregnant and postpartum women in an urban OB practice, serving predominantly black women with public insurance. Subjects and Method: The study sample consisted of 14 perinatal women at an urban obstetrics practice in Washington, DC. Semi-structured interviews were conducted to gain insight into their emotional experiences during pregnancy and postpartum, and to obtain patient recommendations for mental health interventions within an obstetrics setting. Patient interviews were audio-recorded, transcribed, and analyzed by two coders using inductive thematic analysis and consensus procedures. Results: Participants reported several general content themes: provider- patient relationship and intervention topic feedback. Within the overall content theme of provider-patient relationship, black women noted differences in their overall levels of comfort in discussing stress and mental health issues. Subthemes of authentic connection and perceived stigma emerged. Relevant subthemes on intervention topic preferences discussed content, modality, and logistics. Conclusion: Our findings support the importance of offering integrative, culturally competent, and accessible mental health interventions in order to prevent and treat perinatal depression among low-income black women in OB settings. Keywords: pregnancy, perinatal, depression, black women Correspondence: Courtney Glickman. Dept of Counseling and Human Development, The George Washington University2134 G St NW, Washington, DC 20052. Email: Cglickman22@gmail.com. Mobile: 727-324-3606. Journal of Maternal and Child Health (2020), 5(4): 352-362 https://doi.org/10.26911/thejmch.2020.05.04.02

OBJECTIVE To compare measurements of left ventricular volume and function derived from 2-D transthoracic echocardiography (2DE), transesophageal echocardiography (TEE), and the ultrasound velocity dilution cardiac output method (UDCO) with those derived from cardiac MRI (cMRI) in healthy neonatal foals. ANIMALS 6 healthy 1-week-old Standardbred foals. PROCEDURES Foals were anesthetized and underwent 2DE, TEE, and cMRI; UDCO was performed simultaneously with 2DE. Images acquired by 2DE included the right parasternal 4-chamber (R4CH), left apical 4- and 2-chamber (biplane), and right parasternal short-axis M-mode (M-mode) views. The longitudinal 4-chamber view was obtained by TEE. Measurements assessed included left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), ejection fraction, stroke volume (LVSV), cardiac output (CO), and cardiac index (CI). Bland-Altman analyses were used to compare measurements derived from biplane, R4CH, and M-mode images and UDCO with cMRI-derived measurements. Repeatability of measurements calculated by 3 independent reviewers was assessed by the intraclass correlation coefficient. RESULTS Compared with cMRI, all 2DE and TEE modalities underestimated LVEDV and LVESV and overestimated ejection fraction, CO, and CI. The LVSV was underestimated by the biplane, R4CH, and TEE modalities and overestimated by UDCO and M-mode methods. However, the R4CH-derived LVSV, CO, and CI were clinically comparable to cMRI-derived measures. Repeatability was good to excellent for measures derived from the biplane, R4CH, M-mode, UDCO, and cMRI methods and poor for TEE-derived measures. CONCLUSIONS AND CLINICAL RELEVANCE All assessed modalities yielded clinically acceptable measurements of LVEDV, LVESV, and function, but those measurements should not be used interchangeably when monitoring patient progress.

Background: Community-based social marketing (CBSM) offers a pragmatic five-step approach to developing a program that fosters sustainable behaviour. However, how the CBSM theoretical framework has been implemented into practice remains largely under-evaluated. To help address this gap, Lynes et al. developed 21 benchmarks to assess CBSM programs. This research builds upon these benchmarks by using both the benchmarks and additional assessment criteria to assess five Canadian programs that have used CBSM principles. Focus: This paper is related to research and evaluation of community-based social marketing. Research Question: How has the CBSM theoretical framework been implemented in practice at the community level? Importance to the Social Marketing Field: By exploring how five Canadian programs have implemented CBSM, this paper enables practitioners to align their programs with CBSM principles more closely. It also contributes to the literature on CBSM effectiveness. Methods: Five qualitative case studies were assessed, each featuring a Canadian community program seeking to influence residential water efficiency behaviour. In order to systematically assess each program’s adherence to the CBSM theoretical framework, a CBSM benchmark assessment tool that proposes additional assessment criteria to Lynes et al.’s 21 benchmarks was developed. The assessment tool allowed for replicable benchmark assessments across multiple programs. Triangulation of data from both primary (survey and interview) and secondary (peer-reviewed literature, gray literature, and online reporting) data sources informed the assessment of each case study. Results: On average, over the five case studies, just over half of the 21 benchmark criteria were fully integrated into the programs, whereas just under a third were partially integrated, and approximately one fifth were not integrated at all. Recommendations for Research or Practice: While the benchmarks were fairly well integrated overall, this paper outlines several recommendations that programs may consider to improve alignment with the CBSM theoretical framework and benchmarks. Recommendations for future research to explore CBSM effectiveness are also made. Limitations: Lack of generalizability due to small sample size, unable to make assessments of programmatic success, and inherent limitations of the benchmark assessment tool.

Background There has been growing scientific evidence in recent years that bipolar disorder (BD) is associated with alterations in the kynurenine (KYN) pathway. However, many of these studies have been limited by their focus on adults. Thus, this preliminary study investigated differences in the peripheral levels of KYN metabolites in children and adolescents with BD, unaffected offspring of parents with BD, and healthy controls (HCs). Methods Plasma samples were collected from 49 youths with BD, 19 bipolar offspring, and 31 HCs. Tryptophan (TRP), KYN, and kynurenic acid (KYNA) were separated using electrospray ionization. Results One-Way ANCOVA after controlling for age, gender, race, BMI-for-age, and smoking status showed that BD had lower levels of KYN, while unaffected high-risk offspring subjects had lower levels of TRP, KYN, and KYNA when compared to HCs. Moreover, we found that KYN, KYN/TRP, and KYNA/KYN levels predicted the severity of depressive symptoms, while the YMRS score was not associated with any metabolite. Conclusions In summary, this preliminary study has shown that KYN metabolites are decreased in both affected and unaffected subjects, strengthening the idea that the KYN pathway might underlie the familial risk of BD shown by high-risk offspring individuals. However, longitudinal studies are needed to examine whether the alterations observed in this study represent early markers of risk for later developing BD.

Summary Introduction On February 25, 2020, the first 2 patients were tested positive for severe acute respiratory syndrome coronavirus‑2 (SARS-CoV-2) in Tyrol, Austria. Rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease-2019 (COVID-19) patients. Methods This cohort study included all COVID-19 patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the State of Tyrol, Austria. Patients were recorded in the Tyrolean COVID-19 intensive care registry. Date of final follow-up was July 17, 2020. Results A total of 106 critically ill patients with COVID-19 were admitted to 1 of 13 ICUs in Tyrol from March 9 to July 17, 2020. Median age was 64 years (interquartile range, IQR 54–74 years) and the majority of patients were male (76 patients, 71.7%). Median simplified acute physiology score III (SAPS III) was 56 points (IQR 49–64 points). The median duration from appearance of first symptoms to ICU admission was 8 days (IQR 5–11 days). Invasive mechanical ventilation was required in 72 patients (67.9%) and 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 days (IQR 5–31 days), median hospital LOS was 27 days (IQR 13–49 days). The ICU mortality was 21.7% (23 patients), hospital mortality was 22.6%. There was no significant difference in ICU mortality in patients receiving invasive mechanical ventilation and in those not receiving it (18.1% vs. 29.4%, p = 0.284). As of July 17th, 2020, two patients are still hospitalized, one in an ICU, one on a general ward. Conclusion Critically ill COVID-19 patients in Tyrol showed high severity of disease often requiring complex treatment with increased lengths of ICU and hospital stay. Nevertheless, the mortality was found to be remarkably low, which may be attributed to our adaptive surge response providing sufficient ICU resources.

BACKGROUND Trauma-induced coagulopathy (TIC) substantially contributes to mortality in bleeding trauma patients. OBJECTIVE The aim of the study was to administer fibrinogen concentrate in the prehospital setting to improve blood clot stability in trauma patients bleeding or presumed to bleed. DESIGN A prospective, randomised, placebo-controlled, double-blinded, international clinical trial. SETTING This emergency care trial was conducted in 12 Helicopter Emergency Medical Services (HEMS) and Emergency Doctors' vehicles (NEF or NAW) and four trauma centres in Austria, Germany and Czech Republic between 2011 and 2015. PATIENTS A total of 53 evaluable trauma patients aged at least 18 years with major bleeding and in need of volume therapy were included, of whom 28 received fibrinogen concentrate and 25 received placebo. INTERVENTIONS Patients were allocated to receive either fibrinogen concentrate or placebo prehospital at the scene or during transportation to the study centre. MAIN OUTCOME MEASURES Primary outcome was the assessment of clot stability as reflected by maximum clot firmness in the FIBTEM assay (FIBTEM MCF) before and after administration of the study drug. RESULTS Median FIBTEM MCF decreased in the placebo group between baseline (before administration of study treatment) and admission to the Emergency Department, from a median of 12.5 [IQR 10.5 to 14] mm to 11 [9.5 to 13] mm (P = 0.0226), but increased in the FC Group from 13 [11 to 15] mm to 15 [13.5 to 17] mm (P = 0.0062). The median between-group difference in the change in FIBTEM MCF was 5 [3 to 7] mm (P