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Background Infection with the novel severe acute respiratory syndrome coronavirus 2 has been associated with a hypercoagulable state. Emerging data from China and Europe have consistently shown an increased incidence of venous thromboembolism (VTE). We aimed to identify the VTE incidence and early predictors of VTE at our high-volume tertiary care center. Methods We performed a retrospective cohort study of 147 patients who had been admitted to Temple University Hospital with coronavirus disease 2019 (COVID-19) from April 1, 2020 to April 27, 2020. We first identified the VTE (pulmonary embolism [PE] and deep vein thrombosis [DVT]) incidence in our cohort. The VTE and no-VTE groups were compared by univariable analysis for demographics, comorbidities, laboratory data, and treatment outcomes. Subsequently, multivariable logistic regression analysis was performed to identify the early predictors of VTE. Results The 147 patients (20.9% of all admissions) admitted to a designated COVID-19 unit at Temple University Hospital with a high clinical suspicion of acute VTE had undergone testing for VTE using computed tomography pulmonary angiography and/or extremity venous duplex ultrasonography. The overall incidence of VTE was 17% (25 of 147). Of the 25 patients, 16 had had acute PE, 14 had had acute DVT, and 5 had had both PE and DVT. The need for invasive mechanical ventilation (adjusted odds ratio, 3.19; 95% confidence interval, 1.07-9.55) and the admission D-dimer level ≥1500 ng/mL (adjusted odds ratio, 3.55; 95% confidence interval, 1.29-9.78) were independent markers associated with VTE. The all-cause mortality in the VTE group was greater than that in the non-VTE group (48% vs 22%; P = .007). Conclusions Our study represents one of the earliest reported from the United States on the incidence rate of VTE in patients with COVID-19. Patients with a high clinical suspicion and the identified risk factors (invasive mechanical ventilation, admission D-dimer level ≥1500 ng/mL) should be considered for early VTE testing. We did not screen all patients admitted for VTE; therefore, the true incidence of VTE could have been underestimated. Our findings require confirmation in future prospective studies.

Phosphoinositide-3-kinase δ (PI3Kδ) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3Kδ over the closely related isoforms. Interrogation through the Free-Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3Kδ and provides a predictive model for the activity against the PI3K isoforms.

To assess the safety and efficacy of tocilizumab (TCZ) in elderly (≥65 years) rheumatoid arthritis (RA) patients treated in daily practice.We conducted a retrospective study of TCZ use in RA patients in five French university hospitals between 2009 and 2012. We considered two age groups, under 65 years (65) and over 65 years (≥65). TCZ efficacy was evaluated at 24 weeks by the European League Against Rheumatism (EULAR) response and remission score. We also evaluated drug maintenance and safety, relative to adverse events discontinuation. A multivariate cumulative logit model for ordinal categories was performed to assess the relationship between age class and EULAR response (none, moderate and good) adjusted on possible confounders. TCZ retention (drug survival) over time was estimated with the Kaplan-Meier method. Treatment retention curves were compared according to age group with the log-rank test.Among 222 RA patients treated with TCZ, 61 (27.5%) were≥65 years at the initiation of treatment. After 6 months, this elderly patient group less often reached remission (27.8% versus 45.6%; P=0.02) or good EULAR response (40.7% versus 61.0%; P0.01) compared to the younger patient group (65). Multivariate analysis adjusted on baseline C-reactive protein and disease duration confirmed that elderly patients were more likely to have a lower EULAR response (none vs moderate-good or none-moderate vs good) (OR: 3.63; 95% CI [1.86-7.06], P0.001) compared to younger patients. Drug maintenance for TCZ and adverse events discontinuation rates were similar between the two age groups.In daily practice, TCZ seems to be well tolerated in RA patients but is less efficient in elderly patients. A broader field of analysis to include an international register will be required to confirm these results.

SUMMARYWe performed a spatial-temporal analysis to assess household risk factors for Ebola virus disease (Ebola) in a remote, severely-affected village. We defined a household as a family's shared living space and a case-household as a household with at least one resident who became a suspect, probable, or confirmed Ebola case from 1 August 2014 to 10 October 2014. We used Geographic Information System (GIS) software to calculate inter-household distances, performed space-time cluster analyses, and developed Generalized Estimating Equations (GEE). Village X consisted of 64 households; 42% of households became case-households over the observation period. Two significant space-time clusters occurred among households in the village; temporal effects outweighed spatial effects. GEE demonstrated that the odds of becoming a case-household increased by 4·0% for each additional person per household (P< 0·02) and 2·6% per day (P< 0·07). An increasing number of persons per household, and to a lesser extent, the passage of time after onset of the outbreak were risk factors for household Ebola acquisition, emphasizing the importance of prompt public health interventions that prioritize the most populated households. Using GIS with GEE can reveal complex spatial-temporal risk factors, which can inform prioritization of response activities in future outbreaks.

International audience; Objective. The aim of this study was to evaluate the impact of introducing tocilizumab (TCZ) as co-therapy with CS in patients with RA.Methods. This study was an open, observational, retrospective multicentre study. RA patients treated with oral CS for >3 months who started treatment with TCZ between December 2009 and June 2011 in five centres were included. Variables included demographic data, disease history, co-treatments, disease activity and dose of CS at inclusion and at weeks 4, 8, 12 and 24. The evolution of disease activity and of the dose of CS (analysis of variance with repeated measures) were analysed, searching for factors correlated with changes in the dose of CS.Results. Inclusion of 130 patients [women 80.8%, mean age 56.7 years (S.D. 14.0), RA duration 16.3 years (S.D. 10.4), mean baseline 28-joint DAS (DAS28) 5.1 (S.D. 1.4), mean baseline dose of CS 10.0 mg/day (S.D. 8.2) prednisone equivalent. Decreases in the mean daily dose of CS and in the DAS28 were observed during follow-up [respectively 6.5mg (S.D. 4.8) at week 24 (P < 0.0001) and 3.0mg (S.D. 1.4) at week 24 (P < 0.0001)]. The only variable that correlated with the decrease in the dose of CS was the initial dose of the drug (r = 0.82, P < 0.001).Conclusion. The introduction of TCZ led to rapid and long-lasting CS sparing that did not correlate with the reduction in disease activity. It is possible that in patients treated with high-dose CS, the main objective of the clinician is to reduce dosage of CS rather than RA activity.

Objective.To assess the relationship between the body mass index (BMI) and the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA).Methods.We conducted a retrospective study in 222 patients with RA followed by 5 centers. The European League Against Rheumatism response was evaluated at 6 months. Univariate and multivariate logistic regressions were performed.Results.No significant association between the BMI and the response to TCZ at 6 months was found after adjustment for potential confounding factors (adjusted OR 0.45, 95% CI 0.16–1.24, p = 0.13 and OR 1.19, 95% CI 0.31–4.48, p = 0.78 for BMI 25–30 kg/m2 and BMI > 30 kg/m2, respectively, compared to BMI < 25 kg/m2).Conclusion.Response to TCZ in patients with RA is not influenced by the baseline BMI, in contrast to anti-tumor necrosis factor drugs.

Supplementary data are available at Rheumatology Online.; International audience; Objective: The objective of this study was to identify predictors of response and remission to tocilizumab (TCZ) in RA patients seen in daily routine clinical practice.Methods: The efficacy of TCZ was evaluated after 12 and 24 weeks of treatment by the European League Against Rheumatism (EULAR) response criteria. Regression analysis was performed to study the association between remission or EULAR response and the following characteristics: gender, age, current smokers, prior cardiovascular disease (CVD), 28-joint disease activity score (DAS28), CRP, RF or ACPA positivity, combination therapy with DMARDs and TCZ as the first biological therapy or after failure of at least one biological therapy.Results: In total, 204 patients were included with a mean DAS28 score of 5.14. EULAR response and remission were obtained in 86.1% and 40% of patients, respectively, at week 24. In multiple regression analysis, a high baseline CRP level [odds ratio (OR) 4.454 (95% CI 1.446, 13.726)] was significantly associated with EULAR response at week 24 and, inversely, age >55 years [OR 0.285 (95% CI 0.086, 0.950)] and prior CVD [OR 0.305 (95% CI 0.113, 0.825)] were significantly associated with lower EULAR response at week 24. Older age was also associated with less remission at week 24 [OR 0.948 (95% CI 0.920, 0.978)]. No additional effectiveness was found when TCZ was used in combination with a DMARD or when patients were naive to biological agents.Conclusion: In daily practice we identified three predictors of a better response for TCZ therapy in RA: a younger age, a high baseline CRP level and no history of CVD.

Ofloxacin 0.3% ophthalmic solution or ointment was administered preoperatively to 13 patients undergoing cataract surgery. Mean drug concentrations in conjunctival biopsies were 2.62 and 6.55 micrograms/gm and in aqueous humor samples were 0.36 micrograms/mL and 0.43 micrograms/mL, for ointment and solution respectively. Mean conjunctival concentrations of ofloxacin achieved MIC90 values for 419 gram-positive and gram-negative organisms previously analyzed.

In eighty-eight cases of myocardial infarction, clinically identified, of which the electrocardiographic features were pathognomonic in the standard limb leads, the unipolar limb leads and the six Wilson's unipolar precordial leads, the evolution of two-thirds of which was followed, additional thoracic and abdominal unipolar leads have been studied. These may be divided into three groups: (1) Lead V E from the ensiform cartilage; (2) two leads on the median abdominal line, one at the level of the umbilicus (V O ), the other at the center of a line joining V E and V O , which may be called V EO ; and (3) the lateroposterior leads V 7 , V 8 , and V 9 . Every lead has been recorded in thirty-three normal subjects. The cases of infarction studied may be divided according to their location into: anterior less or more extensive, 20; anteroseptal, 7; anterolateral, 12; plain posterior, 33; posterolateral, 7; posteroseptal, 3; that is, 39 infarctions of the anterior group and 43 of the posterior group; lastly, 4 infarcts both anterior and posterior and 2 subendocardial infarcts. From this survey, the following conclusions may be drawn: 1.1. Lead V E shows direct infarction patterns in nearly all anterior infarcts studied, whatever their location and extension, and in the anteroseptal and posteroseptal infarcts studied. This lead is, on the contrary, silent in the case of anterolateral and posterior infarcts. However, it may show direct patterns when the infarcts are or become posterolateral. 2.2. The high abdominal Leads V EO and V O usually show direct patterns of infarction, not only in the plain posterior infarcts, Lead V E remaining silent, but also in cases of infarcts which are or become posterolateral. In the latter, the features in V EO and V O are more characteristic and complete than in V E . Leads V EO and V O are often silent in the cases of anterior, anteroseptal, or anterolateral infarction. 3.3. Lead V 7 may be useful for measuring the extent of a large anterior infarct, the features of which may spread exceptionally to V 8 . The same conditions are true in the case of anterolateral infarcts that may show infarction patterns up to V 9 . Leads V 7 , V 8 , and V 9 often show direct infarction patterns in the cases of plain posterior infarction and of posterolateral infarction. By leading from V E , V EO and V O , it is possible to know whether a posterior infarct involves chiefly the inferior wall of the heart (V EO and V O ) or spreads to its anterior wall (V E ) and, reciprocally, it would be possible to know if an anterior infarct (V E ) spreads over the inferior wall (V EO and V O ). The unipolar dorsal Leads V 7 , V 8 , and V 9 give information on the lateral and posterior location and extension of the infarcts. Lead V E seems to belong to the group of leads that explore the anterior wall of the left ventricle and the septum. Usually, it does not furnish information about the lesions of the posterior or inferior wall which give rise to characteristic changes at lower lead points at the level of the abdominal wall. Leads V 7 , V 8 , and V 9 are useful for exploring the posterior wall, and more especially the posterolateral wall, of the left ventricle.