What level of D-dimers can safely exclude pulmonary embolism in COVID-19 patients presenting to the emergency department?

OBJECTIVES: To identify which level of D-dimer would allow the safe exclusion of pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: This retrospective study was conducted on the COVID database of Assistance Publique - Hôpitaux de Paris (AP-HP). COVID-19 patients who presented at the ED of AP-HP hospitals between March 1 and May 15, 2020, and had CTPA following D-dimer dosage within 48h of presentation were included. The D-dimer sensitivity, specificity, and positive and negative predictive values were calculated for different D-dimer thresholds, as well as the false-negative and failure rates, and the number of CTPAs potentially avoided. RESULTS: A total of 781 patients (mean age 62.0 years, 53.8% men) with positive RT-PCR for SARS-Cov-2 were included and 60 of them (7.7%) had CTPA-confirmed PE. Their median D-dimer level was significantly higher than that of patients without PE (4,013 vs 1,198 ng·mL-1, p < 0.001). Using 500 ng·mL-1, or an age-adjusted cut-off for patients > 50 years, the sensitivity and the NPV were above 90%. With these thresholds, 17.1% and 31.5% of CTPAs could have been avoided, respectively. Four of the 178 patients who had a D-dimer below the age-adjusted cutoff had PE, leading to an acceptable failure rate of 2.2%. Using higher D-dimer cut-offs could have avoided more CTPAs, but would have lowered the sensitivity and increased the failure rate. CONCLUSION: The same D-Dimer thresholds as those validated in non-COVID outpatients should be used to safely rule out PE. KEY POINTS: • The median D-dimer level was significantly higher in COVID-19 patients with PE as compared to those without PE (4,013 ng·mL-1 vs 1,198 ng·mL-1 respectively, p < 0.001). • Using 500 ng·mL-1, or an age-adjusted D-dimer cut-off to exclude pulmonary embolism, the sensitivity and negative predictive value were above 90%. • Higher cut-offs would lead to a reduction in the sensitivity below 85% and an increase in the failure rate, especially for patients under 50 years.

Endoscopic radiofrequency ablation or surveillance in patients with Barrett's oesophagus with confirmed low-grade dysplasia: a multicentre randomised trial.

OBJECTIVE: Due to an annual progression rate of Barrett's oesophagus (BO) with low-grade dysplasia (LGD) between 9% and 13% per year endoscopic ablation therapy is preferred to surveillance. Since this recommendation is based on only one randomised trial, we aimed at checking these results by another multicentre randomised trial with a similar design. DESIGN: A prospective randomised study was performed in 14 centres comparing radiofrequency ablation (RFA) (maximum of 4 sessions) to annual endoscopic surveillance, including patients with a confirmed diagnosis of BO with LGD. Primary outcome was the prevalence of LGD at 3 years. Secondary outcomes were the prevalence of LGD at 1 year, the complete eradication of intestinal metaplasia (CE-IM) at 3 years, the rate of neoplastic progression at 3 years and the treatment-related morbidity. RESULTS: 125 patients were initially included, of whom 82 with confirmed LGD (76 men, mean age 62.3 years) were finally randomised, 40 patients in the RFA and 42 in the surveillance group. At 3 years, CE-IM rates were 35% vs 0% in the RFA and surveillance groups, respectively (p<0.001). At the same time, the prevalence LGD was 34.3% (95% CI 18.6 to 50.0) in the RFA group vs 58.1% (95% CI 40.7 to 75.4) in the surveillance group (OR=0.38 (95% CI 0.14 to 1.02), p=0.05). Neoplastic progression was found in 12.5% (RFA) vs 26.2% (surveillance; p=0.15). The complication rate was maximal after the first RFA treatment (16.9%). CONCLUSION: RFA modestly reduced the prevalence of LGD as well as progression risk at 3 years. The risk-benefit balance of endoscopic ablation therapy should therefore be carefully weighted against surveillance in patients with BO with confirmed LGD. TRIAL REGISTRATION NUMBER: NCT01360541.

Study of Thoracic CT in COVID-19: The STOIC Project.

Background There are conflicting data regarding the diagnostic performance of chest CT for COVID-19 pneumonia. Disease extent at CT has been reported to influence prognosis. Purpose To create a large publicly available data set and assess the diagnostic and prognostic value of CT in COVID-19 pneumonia. Materials and Methods This multicenter, observational, retrospective cohort study involved 20 French university hospitals. Eligible patients presented at the emergency departments of the hospitals involved between March 1 and April 30th, 2020, and underwent both thoracic CT and reverse transcription-polymerase chain reaction (RT-PCR) testing for suspected COVID-19 pneumonia. CT images were read blinded to initial reports, RT-PCR, demographic characteristics, clinical symptoms, and outcome. Readers classified CT scans as either positive or negative for COVID-19 based on criteria published by the French Society of Radiology. Multivariable logistic regression was used to develop a model predicting severe outcome (intubation or death) at 1-month follow-up in patients positive for both RT-PCR and CT, using clinical and radiologic features. Results Among 10 930 patients screened for eligibility, 10 735 (median age, 65 years; interquartile range, 51-77 years; 6147 men) were included and 6448 (60%) had a positive RT-PCR result. With RT-PCR as reference, the sensitivity and specificity of CT were 80.2% (95% CI: 79.3, 81.2) and 79.7% (95% CI: 78.5, 80.9), respectively, with strong agreement between junior and senior radiologists (Gwet AC1 coefficient, 0.79). Of all the variables analyzed, the extent of pneumonia at CT (odds ratio, 3.25; 95% CI: 2.71, 3.89) was the best predictor of severe outcome at 1 month. A score based solely on clinical variables predicted a severe outcome with an area under the curve of 0.64 (95% CI: 0.62, 0.66), improving to 0.69 (95% CI: 0.6, 0.71) when it also included the extent of pneumonia and coronary calcium score at CT. Conclusion Using predefined criteria, CT reading is not influenced by reader's experience and helps predict the outcome at 1 month. ClinicalTrials.gov identifier: NCT04355507 Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Rubin in this issue.

Impact of a handpiece with a built-in fluidics pressure sensor on phacoemulsification: a multicentre prospective comparative study.

OBJECTIVE: We assessed whether the immediate pressure adjustments provided by a phacoemulsification handpiece with a built-in pressure sensor (Active Sentry, AS) could decrease the amount of energy delivered in the eye during cataract surgery. METHODS AND ANALYSIS: The Study of Active Sentry in Cataract Surgery was a multicentre prospective clinical trial. The Centurion system (Alcon Labs) was used and we compared phacoemulsifications performed with the AS handpiece with procedures using a sensor placed in the phacoemulsifier (non-AS). The primary outcome measure was the cumulative dissipated energy (CDE) used during the procedures. The secondary outcome measures were the total, longitudinal and torsional ultrasound (US) times, the duration of the surgery and the amount of fluid used during the surgeries. RESULTS: The study analysed 1432 (800 AS and 632 non-AS) procedures. The mean patient age was 72.4±10.0 years. The median CDE was respectively 6.3 (IQR 3.5-9.9) and 6.7 (IQR 4.5-11.5) with and without AS (p=0.0001). The median US time was, respectively, 48.0 s (IQR 34.0-68.0) and 55.0 s (IQR 38.0-80.0) with and without AS (p<0.0001). Torsional and longitudinal US times were reduced with AS. The median duration of the procedure was, respectively, 9.0 min (IQR 7.0-12.0) and 10.0 min (IQR 7.0-13.0) (p=0.0002) with and without AS. The median balanced salt solution volume used was 52.0 cm3 (IQR 41.0-72.0) and 57.0 cm3 (IQR 42.0-81.0) with and without AS (p=0.0018). CONCLUSION: The phacoemulsifications performed with a pressure sensor built in the handpiece delivered less energy in the eye and were shorter. TRIAL REGISTRATION NUMBER: NCT04732351.

Prospective analysis over time of semen parameters in spinal cord-injured patients: Results of a pilot study.

BACKGROUND: Spinal cord injury often results in erectile dysfunction and an ejaculation along with impaired semen parameters. Fertility is a major concern in spinal cord injury adult males and some fear that the delay post-spinal cord injury may negatively affect sperm quality. OBJECTIVES: We aimed to (i) assess semen parameters over time in SCI patients according to age at spinal cord injury, time post-spinal cord injury, and the spinal cord injury level and completeness and (ii) measure markers in semen for inflammation and marker of oxidative stress to investigate their impact on sperm parameters. MATERIALS AND METHODS: The study is a prospective, longitudinal, pilot study over 18 months. Thirty-five men with spinal cord injury from 18 to 60 years of age were enrolled. Their mean age was 29.4 ± 6.4 years. Semen retrieval was scheduled every 6 months, allowing analysis of four ejaculates, in association with measurement of granulocyte and seminal plasma elastase concentrations to assess markers in semen for inflammation and spermatozoa DNA fragmentation to assess oxidative stress. RESULTS: Based on reference limits, a normal total sperm number, decreased motility and vitality of the spermatozoa, and increased morphological abnormalities were found. Mean round cell and granulocyte concentrations were elevated in the semen. Markers in semen for inflammation and marker of oxidative stress were elevated in several semen samples, compared to reference limits. However, neither the presence of markers in semen for inflammation or oxidative stress, the completeness or the level of the spinal cord lesion, the age or the time post-spinal cord injury had a negative impact on the semen quality over time. DISCUSSION: There was no significant decline in semen quality in spinal cord injury patients over time within the limitations of this pilot study. Moreover, a chronic genital inflammatory status was not associated with impairment of semen quality. CONCLUSION: The present findings are reassuring for men with spinal cord injury and could guide the management of their reproductive ability. According to these preliminary data, not all spinal cord injury patients who are able to ejaculate require systematic freezing of their spermatozoa.

Intra-articular botulinum toxin A injection for painful base-of-thumb osteoarthritis: a double-blind, randomised, controlled, phase 3 trial (RHIBOT).

BACKGROUND: Intra-articular botulinum toxin A injection might have analgesic effects in patients with joint diseases. We aimed to compare the effects of intra-articular botulinum toxin A injection with those of intra-articular saline injection for patients with painful base-of-thumb osteoarthritis. METHODS: RHIBOT was a double-blind, randomised, controlled, phase 3 trial conducted at Cochin Hospital, Paris, France. We recruited adult patients with x-ray evidence of trapeziometacarpal osteoarthritis who fulfilled the 1990 American College of Rheumatology criteria for hand osteoarthritis and reported a pain intensity score of at least 30 on an 11-point numeric rating scale (0: no pain to 100: maximal pain). Participants were randomly assigned (1:1), using a computer-generated randomisation list with permuted blocks of variable size (4 or 6), to receive an ultrasound-guided injection of either botulinum toxin A (50 Allergan units) in 1 mL of saline (experimental group) or 1 mL of saline alone (control group) in the trapeziometacarpal joint, in addition to custom-made rigid splinting. The primary outcome was the mean change from baseline in base-of-thumb pain in the previous 48 h on a numeric rating scale at 3 months after injection, analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT03187626. FINDINGS: Between Nov 2, 2018, and Nov 3, 2020, we assessed 370 individuals for eligibility and recruited 60 (16%) participants (mean age 64·9 years [SD 9·4], 47 [78%] women and 13 [22%] men), of whom 30 (50%) participants were randomly assigned to the experimental group and 30 (50%) to the control group. At baseline, base-of-thumb pain score was 60·0 of 100·0 (SD 15·9). At 3 months, the mean reduction in base-of-thumb pain was -25·7 (95% CI -35·5 to -15·8) in the experimental group and -9·7 (-17·1 to -2·2) in the control group (absolute difference -16·0 [-28·1 to -3·9]; p=0·043). Overall, 51 adverse events were reported in both groups: 27 (53%) in the experimental group and 24 (47%) in the control group. During follow-up, 14 (47%) participants in the experimental group and two (7%) participants in the control group reported mild transient motor deficit of the thenar muscle. No serious adverse events were reported. INTERPRETATION: Botulinum toxin A could be considered as a fast-acting, intra-articular therapy targeting chronic pain in individuals with base-of-thumb osteoarthritis. Future studies are needed to investigate the potential mechanism of the effects observed in this trial, to replicate our findings, and to assess the effects of repeated injections over time and their clinical effectiveness, including an analysis of cost-effectiveness. FUNDING: Assistance Publique-Hôpitaux de Paris.

Efficacy of a Web App-Based Music Intervention During Cataract Surgery: A Randomized Clinical Trial.

IMPORTANCE: Hypertensive events during cataract surgery may induce complications. Information and communication technologies applied to health are popular, but clinical evidence of its usefulness is rare and limited to treating anxiety without specific analysis. Recent publications have described the potential effects of personalized music choices as mobile-based intervention on pain but not on anxiety. OBJECTIVE: To demonstrate the effects of a web app-based music intervention on the incidence of hypertension in participants during cataract surgery performed under local anesthesia. DESIGN, SETTING, AND PARTICIPANTS: This randomized, single masked, controlled clinical trial was composed of 2 arms and took place at a single center at Cochin Hospital in Paris, France. A total of 313 participants were screened between February 2017 and July 2018. Among these, 311 participants undergoing a phacoemulsification procedure for elective surgery for their first eye cataract under local anesthesia were enrolled. Analysis was intention to treat and began in September 2018 and ended November 2018. INTERVENTIONS: Participants requiring cataract surgery were assigned randomly to either the experimental arm (web app-based music listening intervention delivered via headphones) or control arm (noise-canceling headphones without music) for 20 minutes before surgery. MAIN OUTCOMES AND MEASURES: The occurrence of at least 1 hypertensive event during surgery. RESULTS: A total of 310 participants were randomized in the study (155 to each arm) and 309 were analyzed (1 participant in the music arm had already undergone cataract surgery to the other eye). The mean (SD) age of the participants was 68.9 (10.8) years, and there were 176 female individuals (57%). On the primary end point, the incidence of hypertension was significantly lower in the music arm (21 [13.6%]) than in the control arm (82 [52.9%]), with a difference between the 2 arms of 39.3% (95% CI, 21.4%-48.9%; P < .001). Regarding the secondary end points, the mean (SD) visual measure of anxiety was lower in the music arm (1.4 [2.0]) than in the control arm (3.1 [2.4]), with a difference of 1.5 (95% CI, 1.0-2.1; P = .005). The mean (SD) number of sedative drug injections required during surgery was 0.04 (0.24) vs 0.54 (0.74) in the music vs control arms, respectively, with a difference of 0.50 (95% CI, 0.43-0.57; P < .001). CONCLUSIONS AND RELEVANCE: For participants similar to those enrolled in this study, the trial suggests that a web app-based personalized music intervention before cataract surgery may be considered to lower anxiety levels and hypertension or reduce the need for sedative medication. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02892825.

Identification and comparison of France to other countries of the teaching of research to nursing students: Results of an international survey of nursing educator.

PURPOSE: Registered nurses must have a level of scientific literacy to be able to interpret research data and access Scientific's knowledge. Several studies have been conducted to explore barriers and levers to the dissemination of nurse's knowledge; however, the scientific literacy that nursing students acquire has not been studied. OBJECTIVE: The aim was to examine and compare the way that research is taught to undergraduate nursing students in France and other countries. DESIGN: Cross-sectional, Internet survey. SETTINGS: Universities providing undergraduate nursing programs around the world. PARTICIPANTS: Nurses educators. METHODS: Schools of nursing and universities were contacted by mail, through social networks and with the help of national or international nursing organizations. Respondents provided demographic data on schools and faculties of nursing, the teaching of scientific databases, Reading Critical Analysis and the teaching of scientific English. Information on the transmission of articles and access to scientific knowledge by students through the institution were also requested. FINDINGS: A total of 245 nursing schools/universities participated. Most respondents were educational research referees (52.2%), worked in a public institution (85.7%) and were in the nursing program leading to a bachelor's degree (74.3%). Databases were taught at 56.8%, Critical Reading of Articles at 70.1%, scientific English at 60.6% of nursing schools or universities. Articles were provided to students at 89.6% of institution and students had access to data through the institution in 66.1% of nursing schools or universities. Several significant differences were found between French schools of nursing and nursing schools/universities in other countries. CONCLUSIONS: Our results show that most schools or universities of nursing teach the three majors' components to promote, provide articles to students and give access to scientific knowledge. However, there is wide heterogeneity between countries. There is a need to standardize research education for nursing students worldwide to promote the development of scientific literacy skills.

Feasibility and safety of targeted focal microwave ablation of the index tumor in patients with low to intermediate risk prostate cancer: Results of the FOSTINE trial.

OBJECTIVE: To assess the feasibility, safety and precision of organ-based tracking (OBT)-fusion targeted focal microwave ablation (FMA), in patients with low to intermediate risk prostate cancer. PATIENTS AND METHOD: Ten patients with a visible index tumor of Gleason score ≤3+4, largest diameter <20mm were included. Transrectal OBT-fusion targeted FMA was performed using an 18G needle. Primary endpoint was the evidence of complete overlap of the index tumor by ablation zone necrosis on MRI 7 days after ablation. Urinary and sexual function were assessed with IPSS, IIEF5 and MSHQ-EjD-SF. Oncological outcomes were assessed with PSA at 2 and 6 months, and re-biopsy at 6 months. RESULTS: Median [IQR] age was 64.5 [61-72] years and baseline PSA was 5 [4.3-8.1] ng/mL. Seven (70%) and 3 (30%) patients had a low and intermediate risk cancer, respectively. Median largest tumor axis was of 11 [9.0-15.0] mm. Median duration of procedure was of 82 [44-170] min. No patient reported any pain or rectal bleeding, and all 10 patients were discharged the next day. Seven days after ablation, total necrosis of the index tumor on MRI was obtained in eight (80% [95%CI 55%-100%]) patients. One patient was treated with radical prostatectomy. Re-biopsy at 6 months in the other 9 did not show evidence of cancer in 4 patients. IPSS, IIEF-5 and MSHQ-EjD-SF were not statistically different between baseline and 6 months follow up. CONCLUSIONS: OBT-fusion targeted FMA was feasible, precise, and safe in patients with low to intermediate risk localized prostate cancer.

COVID-19 pneumonia: Diagnostic and prognostic role of CT based on a retrospective analysis of 214 consecutive patients from Paris, France.

OBJECTIVES: To evaluate the diagnostic and prognostic performance of CT in patients referred for COVID19 suspicion to a French university hospital, depending on symptoms and date of onset. METHODS: From March 1st to March 28th, 214 patients having both chest CT scan and reverse transcriptase polymerase chain reaction (RT- PCT) within 24 h were retrospectively evaluated. Sensitivity, specificity, negative and positive predictive values of first and expert readings were calculated together with inter reader agreement, with results of RT-PCR as standard of reference and according to symptoms and onset date. Patient characteristics and disease extent on CT were correlated to short-term outcome (death or intubation at 3 weeks follow-up). RESULTS: Of the 214 patients (119 men, mean age 59 ±â€¯19 years), 129 had at least one positive RT-PCR result. Sensitivity, specificity, negative and positive predictive values were 79 % (95 % CI: 71-86 %), 84 %(74-91 %), 72 %(63-81 %) and 88 % (81-93 %) for initial CT reading and 81 %(74-88 %), 91 % (82-96 %), 76 % (67-84 %) and 93 % (87-97 %), for expert reading, with strong inter-reader agreement (kappa index: 0.89). Considering the 123 patients with symptoms for more than 5 days, the corresponding figures were 90 %, 78 %, 80 % and 89 % for initial reading and 93 %, 88 %, 86 % and 94 % for the expert. Disease extent exceeded 25 % for 68 % and 26 % of severe and non-severe patients, respectively (p < 0.001). CONCLUSION: CT sensitivity increased after 5 days of symptoms. A disease extent > 25 % was associated with poorer outcome.