Intra-individual Dose Escalation of Abiraterone According to Its Plasma Exposure in Patients with Progressive Metastatic Castration-Resistant Prostate Cancer: Results of the OPTIMABI Trial.

BACKGROUND AND OBJECTIVE: Trough abiraterone concentration (ABI Cmin) of 8.4 ng/mL has been identified as an appropriate efficacy threshold in patients treated for metastatic castration-resistant prostate cancer (mCRPC). The aim of the phase II OPTIMABI study was to evaluate the efficacy of pharmacokinetics (PK)-guided dose escalation of abiraterone acetate (AA) in underexposed patients with mCRPC with early tumour progression. METHODS: This multicentre, non-randomised study consisted of two sequential steps. In step 1, all patients started treatment with 1000 mg of AA once daily. Abiraterone Cmin was measured 22-26 h after the last dose intake each month during the first 12 weeks of treatment. In step 2, underexposed patients (Cmin < 8.4 ng/mL) with tumour progression within the first 6 months of treatment were enrolled and received AA 1000 mg twice daily. The primary endpoint was the rate of non-progression at 12 weeks after the dose doubling. During step 1, adherence to ABI treatment was assessed using the Girerd self-reported questionnaire. A post-hoc analysis of pharmacokinetic (PK) data was conducted using Bayesian estimation of Cmin from samples collected outside the sampling guidelines (22-26 h). RESULTS: In the intention-to-treat analysis (ITT), 81 patients were included in step 1. In all, 21 (26%) patients were underexposed in step 1, and 8 of them (38%) experienced tumour progression within the first 6 months. A total of 71 patients (88%) completed the Girerd self-reported questionnaire. Of the patients, 62% had a score of 0, and 38% had a score of 1 or 2 (minimal compliance failure), without a significant difference in mean ABI Cmin in the two groups. Four patients were enrolled in step 2, and all reached the exposure target (Cmin > 8.4 ng/mL) after doubling the dose, but none met the primary endpoint. In the post-hoc analysis of PK data, 32 patients (39%) were underexposed, and ABI Cmin was independently associated with worse progression-free survival [hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.07-5.81; p = 0.03], in contrast to the ITT analysis. CONCLUSION: The ITT and per-protocol analyses showed no statistical association between ABI underexposure and an increased risk of early tumour progression in patients with mCRPC, while the Bayesian estimator showed an association. However, other strategies than dose escalation at the time of progression need to be evaluated. Treatment adherence appeared to be uniformly good in the present study. Finally, the use of a Bayesian approach to recover samples collected outside the predefined blood collection time window could benefit the conduct of clinical trials based on drug monitoring. OPTIMABI trial is registered as National Clinical Trial number NCT03458247, with the EudraCT number 2017-000560-15).

The experience of diagnosis announcement in rare endocrine diseases: A survey of the French FIRENDO network.

CONTEXT: Diagnosis announcement of a chronic disease is a crucial moment for patients as well as for their families and an important step in the management of severe conditions such as rare endocrine diseases. Little is known of how diagnosis is communicated to patients and families. The FIRENDO network was created by the third French Plan for Rare Diseases, to promote autonomy, care and research on rare endocrine diseases. OBJECTIVES: The aim of this study was to characterize, for the first time, the experience and needs of patients and/or their parents around the announcement of diagnosis to ensure optimal quality of care. METHODS: A quantitative self-administered survey on diagnosis announcement procedures in rare endocrine diseases was launched in April 2017 by the ad hoc FIRENDO thematic working group in collaboration with its 11 partnering patient associations and support groups. The questionnaire was designed and revised by patient support group representatives, adult and pediatric endocrinologists, psychologists and biologists, all expert in rare endocrine diseases. It was made available on the FIRENDO network website and distributed mainly by email with electronic links on their respective websites to members of all affiliated patient support groups. RESULTS: Questionnaires were filled out by 391 patients and 223 parents (median age of patients: 39 years). The following conditions were associated with at least 30 answers: Addison's disease, classical forms of congenital adrenal hyperplasia (CAH), Russell-Silver syndrome, Cushing's syndrome, acromegaly and craniopharyngioma. Overall, some announcement modalities were judged favorably by patients: physician's empathy, availability and use of clear terms, and presence of family at the time of announcement. However, a lack of psychological care and information documents was reported, as well as some inadequate procedures such as postal mail announcements. CONCLUSION: This work suggests that better knowledge of the patient's experience is useful for improving the diagnosis announcement of rare endocrine disorders. The main recommendations derived from the survey were the need for several announcement visits, information on patient support groups and reference centers, imperatively avoiding impersonal announcement, and the usefulness of a written accompanying document.

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.

Efficacy and safety of oral corticosteroids to treat outpatients with acute exacerbations of COPD in primary care: a multicentre pragmatic randomised controlled study.

Aim: To compare prednisone and placebo for the treatment of outpatients treated for acute exacerbations of chronic obstructive pulmonary disease (COPD) in a primary care setting. Methods: A multicentre, parallel, double-blind, pragmatic randomised controlled trial was performed in France. A total of 66 general practitioners included patients aged ≥40 years with cumulative smoking of ≥10 pack-years and a diagnosis of certain or likely acute exacerbation of COPD. Oral prednisone (40 mg) or placebo were administered daily for 5 days. The main outcome was treatment failure at 8 weeks, defined as a composite criterion based on the occurrence of at least one of the following: unplanned visit to an emergency department or to a practitioner in the ambulatory setting, hospital admission or death. The planned sample size was 202 patients per group. Results: 175 patients were included from February 2015 to May 2017 (43% of the planned sample). All-cause 8-week treatment failure rate was 42.0% in the prednisone group and 34.5% in the placebo group (relative risk 1.22, 95% CI 0.87-1.69, p=0.25). Respiratory-related 8-week treatment failure rate was 27.6% in the prednisone group and 13.6% in the placebo group (relative risk 2.00, 95% CI 1.15-3.57, p=0.015). Conclusion: Although the planned sample size was not achieved, the study does not suggest that oral corticosteroids are more effective than placebo for the treatment of an acute exacerbation of COPD in a primary care setting.

Differences in Disability Perception in Systemic Sclerosis: A Mirror Survey of Patients and Health Care Providers.

Differences in disability perception between patients and care providers may impact outcomes. We aimed to explore differences in disability perception between patients and care providers in systemic sclerosis (SSc). We conducted a cross-sectional internet-based mirror survey. SSc patients participating in the online SPIN Cohort and care providers affiliated with 15 scientific societies were surveyed using the Cochin Scleroderma International Classification of Functioning, Disability and Health (ICF)-65 questionnaire, including 65 items (from 0 to 10), representing 9 domains of disability. Mean differences between patients and care providers were calculated. Care providers' characteristics associated with a mean difference ≥ 2 of 10 points were assessed in multivariate analysis. Answers were analyzed for 109 patients and 105 care providers. The mean age of patients was 55.9 (14.7) years and the disease duration was 10.1 (7.5) years. For all domains of the ICF-65, care providers' rates were higher than those of patients. The mean difference was 2.4 (1.0) of 10 points. Care providers' characteristics associated with this difference were organ-based specialty (OR = 7.0 [2.3-21.2]), younger age (OR = 2.7 [1.0-7.1]) and following patients with disease duration ≥5 years (OR = 3.0 [1.1-8.7]). We found systematic differences in disability perception between patients and care providers in SSc.

Plasma amyloid beta predicts conversion to dementia in subjects with mild cognitive impairment: The BALTAZAR study.

INTRODUCTION: Blood-based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis. METHODS: Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, a large-scale longitudinal multicenter cohort, were followed-up for 3 years. A total of 165 of them converted to dementia (95% AD). Associations of conversion and plasma amyloid beta (Aß)1-42 , Aß1-40 , Aß1-42 /Aß1-40 ratio were analyzed with logistic and Cox models. RESULTS: Converters to dementia had lower level of plasma Aß1-42 (37.1 pg/mL [12.5] vs. 39.2 [11.1] , P value = .03) and lower Aß1-42 /Aß1-40 ratio than non-converters (0.148 [0.125] vs. 0.154 [0.076], P value = .02). MCI participants in the highest quartile of Aß1-42 /Aß1-40 ratio (>0.169) had a significant lower risk of conversion (hazard ratio adjusted for age, sex, education, apolipoprotein E ε4, hippocampus atrophy = 0.52 (95% confidence interval [0.31-0.86], P value = .01). DISCUSSION: In this large cohort of MCI subjects we identified a threshold for plasma Aß1-42 /Aß1-40 ratio that may detect patients with a low risk of conversion to dementia within 3 years.

Prevention of SARS-CoV-2 transmission during a large, live, indoor gathering (SPRING): a non-inferiority, randomised, controlled trial.

BACKGROUND: Mass indoor gatherings were banned in early 2020 to prevent the spread of SARS-CoV-2. We aimed to assess, under controlled conditions, whether infection rates among attendees at a large, indoor gathering event would be similar to those in non-attendees, given implementation of a comprehensive prevention strategy including antigen-screening within 3 days, medical mask wearing, and optimised ventilation. METHODS: The non-inferiority, prospective, open-label, randomised, controlled SPRING trial was done on attendees at a live indoor concert held in the Accor Arena on May 29, 2021 in Paris, France. Participants, aged 18-45 years, recruited via a dedicated website, had no comorbidities, COVID-19 symptoms, or recent case contact, and had had a negative rapid antigen diagnostic test within 3 days before the concert. Participants were randomly allocated in a 2:1 ratio to the experimental group (attendees) or to the control group (non-attendees). The allocation sequence was computer-generated by means of permuted blocks of sizes three, six, or nine, with no stratification. The primary outcome measure was the number of patients who were SARS-CoV-2-positive by RT-PCR test on self-collected saliva 7 days post-gathering in the per-protocol population (non-inferiority margin <0·35%). This trial is registered with ClinicalTrials.gov, NCT04872075. FINDINGS: Between May 11 and 25, 2021, 18 845 individuals registered on the dedicated website, and 10 953 were randomly selected for a pre-enrolment on-site visit. Among 6968 who kept the appointment and were screened, 6678 participants were randomly assigned (4451 were assigned to be attendees and 2227 to be non-attendees; median age 28 years; 59% women); 88% (3917) of attendees and 87% (1947) of non-attendees complied with follow-up requirements. The day 7 RT-PCR was positive for eight of the 3917 attendees (observed incidence, 0·20%; 95% CI 0·09-0·40) and three of the 1947 non-attendees (0·15%; 0·03-0·45; absolute difference, 95% CI -0·26% to 0·28%), findings that met the non-inferiority criterion for the primary endpoint. INTERPRETATION: Participation in a large, indoor, live gathering without physical distancing was not associated with increased SARS-CoV-2-transmission risk, provided a comprehensive preventive intervention was implemented. FUNDING: French Ministry of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Patient acceptable symptom state for patient-reported outcomes in people with non-specific chronic low back pain.

BACKGROUND: The patient acceptable symptom state (PASS) is a treatment-response criterion developed to determine the clinical relevance of a treatment effect. Its estimates for some patient-reported outcomes (PROs) in non-specific chronic low back pain (cLBP) are lacking and the stability of PRO estimates between independent cLBP populations is unknown. We hypothesized that these PRO estimates will be stable. OBJECTIVES: To estimate and compare the PASS for PROs between 2 independent cLBP populations. METHODS: We conducted a secondary analysis of a randomized controlled trial (PREDID) and a cohort of outpatients with non-specific cLBP. Using an anchoring question, participants who self-rated their health as "excellent", "very good" or "good" at 1 month were considered to have an acceptable symptom state. PASS estimates for 5 PROs were calculated by using the 75th percentile method. Estimates were compared between the 2 populations with bootstrap resampling. RESULTS: A total of 256 participants with non-specific cLBP were included: 135 patients with cLBP and active discopathy from the PREDID trial and 121 outpatients with cLBP without active discopathy followed up in an independent cohort. Overall, 137/256 (54%) participants had an acceptable symptom state at 1 month. PASS estimates were 47.5 (95% confidence interval [CI] 40.0 to 50.0)/100 for lumbar pain (0, no pain and 100, maximal pain), 30.5 (30.0 to 40.0)/100 for radicular pain, 39.3 (33.6 to 45.3)/100 for Quebec Back Pain Disability score (0, no disability and 100, maximal disability), 10.0 (9.2 to 10.0)/21 for the Hospital Anxiety Depression anxiety subscale (0, no anxiety, and 21, maximal anxiety) and 6.7 (6.0 to 8.0)/21 for the depression subscale (0, no depression, and 21, maximal depression). PASS estimates did not differ between the 2 populations. CONCLUSIONS: Our study provides PASS estimates for 5 PROs commonly used in cLBP. Our estimates were stable between 2 independent populations of people with cLBP. The stability of our PASS estimates suggests that they are relevant for interpreting PRO values in clinical trials and practice. ClinicalTrials.gov no. (PREDID trial) NCT00804531.

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.

Lung CAncer SCreening in French women using low-dose CT and Artificial intelligence for DEtection: the CASCADE study protocol.

INTRODUCTION: Lung cancer screening (LCS) using low-dose CT has been demonstrated to reduce lung cancer-related mortality in large randomised controlled trials. Moving from trials to practice requires answering practical questions about the level of expertise of CT readers, the need for double reading as in trials and the potential role of artificial intelligence (AI). In addition, most LCS studies have predominantly included male participants with women being under-represented, even though the benefit of screening is greater for them. Thus, this study aims to compare the performance of a single CT reading by general radiologists trained in LCS using AI as a second reader to that of a double reading by expert thoracic radiologists, in a campaign for low-dose CT screening in high-risk women. METHODS AND ANALYSIS: This observational cohort study will recruit 2400 asymptomatic women aged between 50 and 74 years, current or former smokers with at least a 20 pack-year smoking history, in 4 different French district areas. Assistance with smoking cessation will be offered to current smokers. An initial low-dose CT scan will be performed, with subsequent follow-ups at 1 year and 2 years. The primary objective is to compare CT scan readings by a single LCS-trained, AI-assisted radiologist to that of an expert double reading. The secondary objectives are: to evaluate the performance of AI as a stand-alone reader; the adherence to screening of female participants; the influence on smoking cessation; the psychological consequences of screening; the detection of chronic obstructive pulmonary disease (COPD), coronary artery disease and osteoporosis on low-dose CT scans and the costs incurred by screening. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Comité de Protection des Personnes Sud-Est 1 (ethics approval number: 2021-A02265-36 with an amendment on 15 July 2022). Trial results will be disseminated at conferences, through relevant patient groups and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05195385.

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.

Circulating bile acids concentration is predictive of coronary artery disease in human.

Synthetized by the liver and metabolized by the gut microbiota, BA are involved in metabolic liver diseases that are associated with cardiovascular disorders. Animal models of atheroma documented a powerful anti-atherosclerotic effect of bile acids (BA). This prospective study examined whether variations in circulating BA are predictive of coronary artery disease (CAD) in human. Consecutive patients undergoing coronary angiography were enrolled. Circulating and fecal BA were measured by high pressure liquid chromatography and tandem mass spectrometry. Of 406 screened patients, 80 were prospectively included and divided in two groups with (n = 45) and without (n = 35) CAD. The mean serum concentration of total BA was twice lower in patients with, versus without CAD (P = 0.005). Adjusted for gender and age, this decrease was an independent predictor of CAD. In a subgroup of 17 patients, statin therapy doubled the serum BA concentration. Decreased serum concentrations of BA were predictors of CAD in humans. A subgroup analysis showed a possible correction by statins. With respect to the anti-atherosclerotic effect of BA in animal models, and their role in human lipid metabolism, this study describe a new metabolic disturbance associated to CAD in human.

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.

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.

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.

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.

Prevalence of Silent Atherosclerosis and Other Comorbidities in an Outpatient Cohort of Adults Living with HIV: Associations with HIV Parameters and Biomarkers.

People living with HIV (PLWH) are at risk of noninfectious comorbidities. It is important to individualize those at higher risk. In a single-center cohort of PLWH, we performed a cross-sectional analysis of comorbidities, diagnosed according to standard procedures. The primary endpoint was the prevalence of subclinical carotid/coronary atherosclerosis. Secondary endpoints were its association with selected inflammatory/immune activation biomarkers and with other comorbidities. Associations were examined by using Chi-square or Fisher's exact test for categorical variables and Student or Wilcoxon tests for quantitative variables, and a stepwise multivariate logistical model was performed for further exploration. Among 790 participants [median age: 49.8 years (interquartile range, IQR: 44.5-55.6), 77.1% males, median CD4: 536/mm3 (IQR: 390-754), 83.6% with undetectable viral load], asymptomatic atherosclerosis was found in 26% and was associated in multivariate analysis with older age, longer known duration of infection, higher sCD14, and lower adiponectin levels. Hypertension was found in 33.5% of participants, diabetes in 19.4%, renal impairment in 14.6%, elevated low-density lipoprotein-cholesterol in 13.3%, elevated triglyceride/high-density lipoprotein (HDL)-cholesterol ratio in 6.6%, and osteoporosis in 7.9%. The presence of two or more comorbidities was found in 42.1% of participants and was associated in multivariate analysis with older age and longer exposure to antiretrovirals. Comorbidities were diversely associated with biomarkers: osteoporosis with higher IL-6, renal impairment with higher sCD14, hypertension with higher D-dimer, diabetes and elevated triglyceride/HDL-cholesterol ratio both with lower adiponectin and lower 25-hydroxyvitamin D. Asymptomatic atherosclerosis and multimorbidity were frequent in a cohort of middle-aged, well-controlled, PLWH and were associated with traditional and HIV-specific factors. Associations between morbidities and inflammatory/immune activation biomarkers were diverse.

Ophthalmic Insert versus Eye Drops for Mydriasis in Neonates: A Randomized Clinical Trial.

BACKGROUND: Eye drop treatment routinely used to obtain mydriasis prior to fundoscopy in neonates requires repeated instillations of mydriatic agents that can lead to systemic side effects. OBJECTIVES: The aim of this study was to compare the mydriatic efficacy and tolerance of administration of phenylephrine and tropicamide via the ophthalmic insert Mydriasert® versus standard eye drop treatment in neonates. METHODS: In this prospective, single-blinded, noninferiority study, 80 hospitalized neonates (age < 18 months) requiring bilateral fundus examination were randomized to receive eye drops (repeated instillations of 2.5% phenylephrine and 0.5% tropicamide) or the insert. The primary outcome was mydriasis suitable for fundoscopy 75 min after mydriatic agent introduction (T75). RESULTS: Mydriasis was successfully achieved in both eyes at T75 in 97.5% (n = 39/40) of the insert group patients versus 90% (n = 36/40) receiving eye drops (between-group difference 7.5%, demonstrating noninferiority). Mydriasis remained stable in 60.0% of patients (n = 24/40) in the insert group versus 15% (n = 6/40) in the eye drop group (p < 0.0001). The insert group required fewer nursing interventions than the eye drop group (p = 0.0001). Mean blood pressure were significantly higher in the insert versus the eye drop group (p < 0.0001 and p = 0.0003, respectively); mean heart rate was not significantly different between the groups (p = 0.37). In the insert group, 2 patients reported an adverse event (bradycardia, n = 1, and gastroesophageal reflux, n = 1; both appeared to be related to neonate pathology). CONCLUSIONS: The degree of mydriasis achieved with Mydriasert® was noninferior to that obtained with eye drops. The insert appears to be safe to use in neonates without a history of increased vagal tone or gastrointestinal reflux.