Search

Background: Under a master protocol, open platform trials allow new experimental treatments to enter an existing clinical trial. Whether late-entry experimental treatments should be compared to all available or concurrently randomized controls is not well established. Using all available data can increase power and precision; however, drift in population parameters can yield biased estimates and impact type I error rate., Methods: We explored the application of methods developed to incorporate historical controls in two-arm trials to the analysis of a late-entry arm in a simulated open platform trial under varying scenarios of parameter drift. Methods explored include test-then-pool, fixed power prior, dynamic power prior, and multi-source exchangeability model approaches., Results/conclusions: Simulated trial results confirm that in the presence of no drift, naively pooling all controls increases power and produces more precise, unbiased estimates when compared to using concurrent controls only. However, under drift, pooling can result in type I error rate inflation or deflation and biased estimates. In the presence of parameter drift, methods that partially borrow non-concurrent data, either through a static weighting mechanism or through methods that allow the heterogeneity between non-concurrent and concurrent data to determine the degree of borrowing, are superior to naively pooling the data. However, compared to using concurrent controls only, these approaches cannot guarantee type I error control or unbiased estimates. Thus, concurrent controls should be used as comparators in confirmatory studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: High-volume and fellowship-trained surgeons have superior outcomes. However, in gynecology, a large proportion of cases are performed by low-volume surgeons. Simulation has been shown to be useful in assessing surgical skill and may be a useful tool in hospital credentialing and maintenance of privileges., Objective: To determine the correlation between a surgical case volume and fellowship training with performance on simulated procedural tasks., Study Design: A total of 108 obstetricians and gynecologists with laparoscopic privileges at 2 academic institutions completed a pre-test survey and performed 3 tasks on the LapSim laparoscopic virtual reality simulator. The pre-test survey inquired about the monthly laparoscopic case volume and prior training. Simulations included a basic skills task (peg transfer) followed by a procedural task (salpingectomy) of 2 difficulty levels (low and moderate). Spearman correlation and Wilcoxon tests were used to determine correlations between the survey responses and performance metrics., Results: Participants included 67 generalists (62%) and 41 fellowship-trained specialists (38%). There was an observed weak correlation among surgical volume (more than 6 cases per month), time to completion, and the amount of blood loss when performing the low-difficulty level salpingectomy (r=-0.32, P=.0007 and r=-0.29, P=.002, respectively). The economy of movement (instrument path length) was correlated to high surgical volume (r=-0.35, P=.0002). Compared with generalists, surgeons with fellowship training performed tasks faster (410.8 seconds [interquartile range, 309.7-595.2]) vs 530.2 seconds (interquartile range, 406.2-605.0; P=.0009), more efficiently at 6.1 m (interquartile range, 4.8-7.3) vs 8.1 m (interquartile range, 5.8-10.7; P=.0003), and with less blood loss at 21.7 mL (interquartile range, 11.8-37.7) vs 42.9 mL (interquartile range, 18.1-70.6; P=.002). Regarding the case volume and fellowship background, there was no difference in ovarian diathermy damage. In addition, there was no difference among most performance parameters for the peg transfer task and the moderate-difficulty salpingectomy procedure., Conclusion: Surgical experience obtained through higher case volume and fellowship training correlate with higher performance scores during simulated procedural tasks. In a previous study, we found a similar correlation with simulated basic skills tasks. The current study is a continuation of an ongoing quality initiative to establish a summative assessment of laparoscopic surgical skills using virtual reality simulator for the maintenance of credentials among obstetrical and gynecologic surgeons. Future studies will compare the performance metrics from laparoscopic procedures performed on virtual reality simulator with the performance in the operating room and clinical outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Chest radiography (CXR) often is performed in the acute setting to help understand the extent of respiratory disease in patients with COVID-19, but a clearly defined role for negative chest radiograph results in assessing patients has not been described., Research Question: Is portable CXR an effective exclusionary test for future adverse clinical outcomes in patients suspected of having COVID-19?, Study Design and Methods: Charts of consecutive patients suspected of having COVID-19 at five EDs in New York City between March 19, 2020, and April 23, 2020, were reviewed. Patients were categorized based on absence of findings on initial CXR. The primary outcomes were hospital admission, mechanical ventilation, ARDS, and mortality., Results: Three thousand two hundred forty-five adult patients, 474 (14.6%) with negative initial CXR results, were reviewed. Among all patients, negative initial CXR results were associated with a low probability of future adverse clinical outcomes, with negative likelihood ratios of 0.27 (95% CI, 0.23-0.31) for hospital admission, 0.24 (95% CI, 0.16-0.37) for mechanical ventilation, 0.19 (95% CI, 0.09-0.40) for ARDS, and 0.38 (95% CI, 0.29-0.51) for mortality. Among the subset of 955 patients younger than 65 years and with a duration of symptoms of at least 5 days, no patients with negative CXR results died, and the negative likelihood ratios were 0.17 (95% CI, 0.12-0.25) for hospital admission, 0.09 (95% CI, 0.02-0.36) for mechanical ventilation, and 0.09 (95% CI, 0.01-0.64) for ARDS., Interpretation: Initial CXR in adult patients suspected of having COVID-19 is a strong exclusionary test for hospital admission, mechanical ventilation, ARDS, and mortality. The value of CXR as an exclusionary test for adverse clinical outcomes is highest among young adults, patients with few comorbidities, and those with a prolonged duration of symptoms., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: In March 2020, as community spread of severe acute respiratory syndrome coronavirus 2 became increasingly prevalent, pregnant women seemed to be equally susceptible to developing coronavirus disease 2019. Although the disease course usually appears mild, severe and critical cases of coronavirus disease 2019 seem to lead to substantial morbidity, including intensive care unit admission with prolonged hospital stay, intubation, mechanical ventilation, and even death. Although there are recent reports regarding the impact of coronavirus disease 2019 on pregnancy, there is a lack of information regarding the severity of coronavirus disease 2019 in pregnant vs nonpregnant women., Objective: We aimed to describe the outcomes of severe and critical cases of coronavirus disease 2019 in pregnant vs nonpregnant, reproductive-aged women., Study Design: This is a multicenter, retrospective, case-control study of women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection hospitalized with severe or critical coronavirus disease 2019 in 4 academic medical centers in New York City and 1 in Philadelphia between March 12, 2020, and May 5, 2020. The cases consisted of pregnant women admitted specifically for severe or critical coronavirus disease 2019 and not for obstetrical indications. The controls consisted of reproductive-aged, nonpregnant women admitted for severe or critical coronavirus disease 2019. The primary outcome was a composite morbidity that includes the following: death, a need for intubation, extracorporeal membrane oxygenation, noninvasive positive pressure ventilation, or a need for high-flow nasal cannula O 2 supplementation. The secondary outcomes included intensive care unit admission, length of stay, a need for discharge to long-term acute care facilities, and discharge with a home O 2 requirement., Results: A total of 38 pregnant women with severe acute respiratory syndrome coronavirus 2 polymerase chain reaction-confirmed infections were admitted to 5 institutions specifically for coronavirus disease 2019, 29 (76.3%) meeting the criteria for severe disease status and 9 (23.7%) meeting the criteria for critical disease status. The mean age and body mass index were markedly higher in the nonpregnant control group. The nonpregnant cohort also had an increased frequency of preexisting medical comorbidities, including diabetes, hypertension, and coronary artery disease. The pregnant women were more likely to experience the primary outcome when compared with the nonpregnant control group (34.2% vs 14.9%; P=.03; adjusted odds ratio, 4.6; 95% confidence interval, 1.2-18.2). The pregnant patients experienced higher rates of intensive care unit admission (39.5% vs 17.0%; P<.01; adjusted odds ratio, 5.2; 95% confidence interval, 1.5-17.5). Among the pregnant women who underwent delivery, 72.7% occurred through cesarean delivery and the mean gestational age at delivery was 33.8±5.5 weeks in patients with severe disease status and 35±3.5 weeks in patients with critical coronavirus disease 2019 status., Conclusion: Pregnant women with severe and critical coronavirus disease 2019 are at an increased risk for certain morbidities when compared with nonpregnant controls. Despite the higher comorbidities of diabetes and hypertension in the nonpregnant controls, the pregnant cases were at an increased risk for composite morbidity, intubation, mechanical ventilation, and intensive care unit admission. These findings suggest that pregnancy may be associated with a worse outcome in women with severe and critical cases of coronavirus disease 2019. Our study suggests that similar to other viral infections such as severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, pregnant women may be at risk for greater morbidity and disease severity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The primary objective was to measure IUD-fundus and IUD-myometrium distances by ultrasound of IUDs placed during cesarean section over the first year of use. The secondary objective was to determine if these distances are associated with risk of expulsion or removal for side effects., Study Design: In this prospective observational study, we performed ultrasounds at six - ten weeks, three months and one year postpartum to measure the distance from the top of the device to the fundal serosa (IUD-fundus) and upper margin of the endometrial cavity (IUD-myometrium). We also assessed IUD expulsion or discontinuation for side effects at each visit., Results: We enrolled 93 women who had copper (n = 77) or levonorgestrel (n = 16) IUDs placed at time of cesarean section. Two patients had complete expulsion, six had partial expulsion and nine requested removal for symptoms. Overall, median IUD-fundus measurements were 2.13 cm (IQR 1.87-2.55) at 6-10 weeks, 1.87 cm (IQR 1.53-2.23) at 3-months and 2.02 cm (IQR 1.67-2.40) at 1-year. Among copper IUD users, distances at six weeks and three months were similar in women who did or did not have expulsion or removal at one year however small numbers limit our ability to assess this relationship., Conclusion: We describe the location on ultrasound of IUDs placed at the time of Cesarean section over the first year. We found similar IUD locations at six weeks and three months for participants who did or did not experience expulsion or removal by one year., Implications: Position of intrauterine devices placed during cesarean section was similar for those who did or did not have expulsion or removal for symptoms in the first year after placement. These data may help in the design of future studies to determine if ultrasound measurement of IUDs predicts IUD complications., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Acute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains., Methods: Baseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored., Results: PROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores., Conclusion: Pain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response.

Background: Epiaortic ultrasound detects and localizes ascending aortic atherosclerosis. In this analysis we investigated the association between epiaortic ultrasound-based atheroma grade during surgical aortic valve replacement (SAVR) and perioperative adverse outcomes., Methods: SAVR patients in a randomized trial of 2 embolic protection devices underwent a protocol-defined 5-view epiaortic ultrasound read at a core laboratory. Aortic atherosclerosis was quantified with the Katz atheroma grade, and patients were categorized as mild (grade I-II) or moderate/severe (grade III-V). Multivariable logistic regression was used to estimate associations between atheroma grade and adverse outcomes, including death, clinically apparent stroke, cerebral infarction on diffusion-weighted magnetic resonance imaging, delirium, and acute kidney injury (AKI) by 7 and 30 days., Results: Precannulation epiaortic ultrasound data were available for 326 of 383 randomized patients (85.1%). Of these, 106 (32.5%) had moderate/severe Katz atheroma grade at any segment of the ascending aorta. Although differences in the composite of death, stroke, or cerebral infarction on diffusion-weighted magnetic resonance imaging by 7 days were not statistically significant, moderate/severe atheroma grade was associated with a greater risk of AKI by 7 days (adjusted odds ratio, 2.63; 95% confidence interval, 1.24-5.58; P = .01). At 30 days, patients with moderate/severe atheroma grade had a greater risk of death, stroke, or AKI (adjusted odds ratio, 1.97; 95% confidence interval, 1.04-3.71; P = .04)., Conclusions: Moderate/severe aortic atherosclerosis was associated with an increased risk of adverse events after SAVR. Epiaortic ultrasound may serve as a useful adjunct for identifying patients who may benefit from strategies to reduce atheroembolic complications during SAVR., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigated sex-based differences in outcomes after mitral valve (MV) surgery for severe ischemic mitral regurgitation (SIMR)., Background: Whether differences in outcomes exist between men and women after surgery for SIMR remains unknown., Methods: Patients enrolled in a randomized trial comparing MV replacement versus MV repair for SIMR were included and followed for 2 years. Endpoints for this analysis included all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE) (defined as the composite of death, stroke, hospitalization for heart failure, worsening New York Heart Association functional class or MV re-operation), quality of life (QOL), functional status, and percentage of change in left ventricular end-systolic volume index (LVESVI) from baseline through 2 years., Results: Of 251 patients enrolled in the trial, 96 (38.2%) were women. Compared with men, women had smaller LV volumes and effective regurgitant orifice areas (EROA) but greater EROA/left ventricular (LV) end-diastolic volume ratios. At 2 years, women had higher rates of all-cause mortality (27.1% vs. 17.4%, respectively; adjusted hazard ratio [adjHR]: 1.85; 95% confidence interval [CI]: 1.05 to 3.26; p = 0.03) and of MACCE (49.0% vs. 38.1%, respectively; adjHR: 1.58; 95% CI: 1.06 to 2.37; p = 0.02). Women also reported worse QOL and functional status at 2 years. There were no significant differences in the percentage of change over 2 years in LVESVI between women and men (adjβ: -10.4; 95% CI: -23.4 to 2.6; p = 0.12)., Conclusions: Women with SIMR displayed different echocardiographic features and experienced higher mortality and worse QOL after MV surgery than men. There were no significant differences in the degree of reverse LV remodeling between sexes. (Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation [Severe Ischemic Mitral Regurgitation]; NCT00807040)., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Research Question: Does the composite morphology score or a particular developmental component (expansion stage, inner cell mass [ICM] or trophectoderm [TE]) of euploid blastocysts undergoing single frozen embryo transfer (FET) impact ongoing pregnancy/live birth (OP/LB) rates?, Design: Retrospective cohort study including a total of 2236 embryos from 1629 patients who underwent single euploid FET between 2012 and 2017., Results: Embryos with an ICM grade of A compared with C had a higher OP/LB rate (55.6% versus 32.3%, P < 0.001). Blastocysts with a TE grade of A or B compared with C had a higher likelihood of OP/LB (A versus C: odds ratio [OR] 1.6, 99% confidence interval [CI] 1.1-2.3, B versus C: OR 1.5, 99% CI 1.1-2.1), and blastocysts with a developmental stage of 4 or 5 compared with 6 had higher odds of OP/LB (4 versus 6: OR 1.6, 99% CI 1.2-2.2, 5 versus 6: OR 1.6, 99% CI 1.2-2.3)., Conclusions: Among euploid embryos, ICM morphology is the best predictor of sustained implantation; however, a composite score may provide additional guidance. While there is a known benefit in genomic screening prior to embryo selection, morphology provides individualized, prognostic information about implantation potential., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

In this study, women at risk for BRCA were surveyed to understand their choice of prophylactic surgery and associated risk of uterine cancers. The study was conducted as an anonymous online web-based survey that assessed personal and family histories and choice of prophylactic surgery. Respondents were targeted through social media groups that bring awareness to hereditary breast and ovarian cancer. The study cohort included an international group of 601 respondents. The majority were female (99.3%), in their 40s (34.2%), and had completed college or graduate school (68.8%). 87% of respondents carry BRCA gene mutation. Of 339 respondents who underwent risk-reducing salpingo-oophorectomy (RRSO), 55.8% had a hysterectomy at time of RRSO. Most common reasons for hysterectomy at time of RRSO included: 39% provider recommendation, 27.6% personal desire, 9.7% benign indications, 1.6% cancer in uterus, 1.1% precancerous uterine lesion, and 21.1% other (N = 185). In this cohort, nine were diagnosed with uterine cancer. Three were diagnosed after risk-reducing surgery. Both patients with uterine serous carcinoma were BRCA1 carriers. Two thirds of BRCA carriers surveyed had undergone RRSO. Of these, more than half had hysterectomy at time of RRSO. One third chose to have hysterectomy based on surgeon recommendation. <1% (2 out of 258) of BRCA1 gene mutation carriers reported being diagnosed with uterine serous carcinomas. While this incidence is low, it may be an underestimate based on the limitations of this study. Additional studies are needed to select which patients will benefit from concurrent hysterectomy and RRSO.

Purpose: The overall published experience with pediatric type 1 Gaucher disease (GD1) has been based on ascertainment through clinical presentation of the disease. We describe the longitudinal follow-up in a presymptomatic pediatric cohort., Methods: The cohort includes children diagnosed with GD1, either prenatally or postnatally by molecular genetic testing, and followed for clinical care at our center from 1998 to 2016. All patients' parents were GBA mutation carriers identified through carrier screening programs. Longitudinal clinical, laboratory, and imaging data were obtained through chart review., Results: Thirty-eight patients aged 1-18 years (mean at last visit 6.9 ± 4.1 years) were followed, including 32 p.N409S homozygotes and 6 p.N409S/p.R535H compound heterozygotes. At the last evaluation, a minority had hematological (5%), bone (15%), or linear growth (19%) issues. Only 12% had splenomegaly and 74% had moderate hepatomegaly. Chitotriosidase activity varied widely (6-5,640 nmol/hour/ml) and generally increased with age. Pediatric Gaucher severity scores (GSS) remained stable and within the mild-disease range for most (95%). Treatment for progressive disease during this period was recommended for four children., Conclusion: Most children with the p.N409S/p.N409S and p.N409S/p.R535H GD1 genotypes have minimal disease manifestations and progression during childhood and can be monitored using limited assessments. Those with other mutations may require additional monitoring. These data are valuable for newborn screening and counseling.Genet Med advance online publication 13 October 2016.

Background: Chronic injury in kidney transplants remains a major cause of allograft loss. The aim of this study was to identify a gene set capable of predicting renal allografts at risk of progressive injury due to fibrosis., Methods: This Genomics of Chronic Allograft Rejection (GoCAR) study is a prospective, multicentre study. We prospectively collected biopsies from renal allograft recipients (n=204) with stable renal function 3 months after transplantation. We used microarray analysis to investigate gene expression in 159 of these tissue samples. We aimed to identify genes that correlated with the Chronic Allograft Damage Index (CADI) score at 12 months, but not fibrosis at the time of the biopsy. We applied a penalised regression model in combination with permutation-based approach to derive an optimal gene set to predict allograft fibrosis. The GoCAR study is registered with ClinicalTrials.gov, number NCT00611702., Findings: We identified a set of 13 genes that was independently predictive for the development of fibrosis at 1 year (ie, CADI-12 ≥2). The gene set had high predictive capacity (area under the curve [AUC] 0·967), which was superior to that of baseline clinical variables (AUC 0·706) and clinical and pathological variables (AUC 0·806). Furthermore routine pathological variables were unable to identify which histologically normal allografts would progress to fibrosis (AUC 0·754), whereas the predictive gene set accurately discriminated between transplants at high and low risk of progression (AUC 0·916). The 13 genes also accurately predicted early allograft loss (AUC 0·842 at 2 years and 0·844 at 3 years). We validated the predictive value of this gene set in an independent cohort from the GoCAR study (n=45, AUC 0·866) and two independent, publically available expression datasets (n=282, AUC 0·831 and n=24, AUC 0·972)., Interpretation: Our results suggest that this set of 13 genes could be used to identify kidney transplant recipients at risk of allograft loss before the development of irreversible damage, thus allowing therapy to be modified to prevent progression to fibrosis., Funding: National Institutes of Health., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

IRAK-4 and MyD88 deficiencies impair interleukin 1 receptor and Toll-like receptor (TLR) signaling and lead to heightened susceptibility to invasive bacterial infections. Individuals with these primary immunodeficiencies have fewer immunoglobulin M (IgM)(+)IgD(+)CD27(+) B cells, a population that resembles murine splenic marginal zone B cells that mount T-independent antibody responses against bacterial antigens. However, the significance of this B-cell subset in humans is poorly understood. Using both a 610 carbohydrate array and enzyme-linked immunosorbent assay, we found that patients with IRAK-4 and MyD88 deficiencies have reduced serum IgM, but not IgG antibody, recognizing T-independent bacterial antigens. Moreover, the quantity of specific IgM correlated with IgM(+)IgD(+)CD27(+) B-cell frequencies. As with mouse marginal zone B cells, human IgM(+)CD27(+) B cells activated by TLR7 or TLR9 agonists produced phosphorylcholine-specific IgM. Further linking splenic IgM(+)IgD(+)CD27(+) B cells with production of T-independent IgM, serum from splenectomized subjects, who also have few IgM(+)IgD(+)CD27(+) B cells, had reduced antibacterial IgM. IRAK-4 and MyD88 deficiencies impaired TLR-induced proliferation of this B-cell subset, suggesting a means by which loss of this activation pathway leads to reduced cell numbers. Thus, by bolstering the IgM(+)IgD(+)CD27(+) B-cell subset, IRAK-4 and MyD88 promote optimal T-independent IgM antibody responses against bacteria in humans., (© 2014 by The American Society of Hematology.)

Background: The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy., Methods: Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181., Findings: Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months [SD 19·7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14-0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management., Interpretation: The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up., Funding: National Institutes of Health, National Institute of Neurological Disorders and Stroke., (Copyright © 2014 Elsevier Ltd. All rights reserved.)