Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).

Sepsis accounts for 30% to 50% of all in-hospital deaths in the United States. Other than antibiotics and source control, management strategies are largely supportive with fluid resuscitation and respiratory, renal, and circulatory support. Intravenous vitamin C in conjunction with thiamine and hydrocortisone has recently been suggested to improve outcomes in patients with sepsis in a single-center before-and-after study. However, before this therapeutic strategy is adopted, a rigorous assessment of its efficacy is needed. The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial. It will enroll patients with sepsis causing respiratory or circulatory compromise or both. Patients will be randomly assigned (1:1) to receive intravenous vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) every 6 h or matching placebos until a total of 16 administrations have been completed or intensive care unit discharge occurs (whichever is first). Patients randomly assigned to the comparator group are permitted to receive open-label stress-dose steroids at the discretion of the treating clinical team. The primary outcome is consecutive days free of ventilator and vasopressor support (VVFDs) in the 30 days following randomization. The key secondary outcome is mortality at 30 days. Sample size will be determined adaptively by using interim analyses with pre-stated stopping rules to allow the early recognition of a large mortality benefit if one exists and to refocus on the more sensitive outcome of VVFDs if an early large mortality benefit is not observed. VICTAS is a large, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled trial that will test the efficacy of vitamin C, thiamine, and hydrocortisone as a combined therapy in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. Because the components of this therapy are inexpensive and readily available and have very favorable risk profiles, demonstrated efficacy would have immediate implications for the management of sepsis worldwide. ClinicalTrials.gov Identifier: NCT03509350 . First registered on April 26, 2018, and last verified on December 20, 2018. Protocol version: 1.4, January 9, 2019

Frontline health care workers (HCWs) are at high risk of acquiring respiratory viral infections, including influenza and SARS-CoV-2 infections.^1,2 During the COVID-19 pandemic, HCWs used personal protective equipment (PPE), such as an N95 filtering facepiece respirator (hereafter, N95), to reduce their risk of becoming infected.^3,4 N95s are tight-fitting, disposable respirators designed to prevent aerosolized transmission of viral particles and reduce the likelihood of HCWs acquiring a respiratory viral infection, thus mitigating risk for an essential workforce.^4-7 Under nonpandemic circumstances, standard practice is to discard an N95 after close contact with a patient (ie, single use). Prior infectious disease outbreaks and pandemics necessitating N95 conservation prompted the Centers for Disease Control and Prevention to revise its recommendation to include guidelines for both extended use (wearing the same N95 for multiple patient encounters without donning and doffing) and limited reuse (storing an N95 between donnings for no more than 5 donnings), albeit with limited evidence.^8,9 Frontline HCWs (including those in emergency departments [EDs]) generally followed these guidelines to conserve PPE during the COVID-19 pandemic, practicing a combination of reuse and extended use of N95s, which we collectively term reuse.¹⁰ In practice, patterns of use varied across EDs based on a number of factors, including supply chain and local hospital guidance.

Background: Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock. Methods and design: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000. This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study. Trial registration: ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018.

Background: Children who experience a mild Traumatic Brain Injury (mTBI) may encounter cognitive and behavioral changes that often negatively impact school performance. Communication linkages between the various healthcare systems and school systems are rarely well-coordinated, placing children with an mTBI at risk for prolonged recovery, adverse impact on learning, and mTBI re-exposure. The objective of this study is to rigorously appraise the pediatric Mild Traumatic Brain Injury Evaluation and Management (TEaM) Intervention that was designed to enhance diagnosis and management of pediatric mTBI through enhanced patient discharge instructions and communication linkages between school and primary care providers.Methods: This is a combined randomized and 2 × 2 quasi-experimental study design with educational and technology interventions occurring at the clinician level with patient and school outcomes as key endpoints. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework will be utilized as a mix methods approach to appraise a multi-disciplinary, multi-setting intervention with the intent of improving outcomes for children who have experienced mTBI.Discussion: Utilization of the RE-AIM framework complemented with qualitative inquiry is suitable for evaluating effectiveness of the TEaM Intervention with the aim of emphasizing priorities regarding pediatric mTBI. This program evaluation has the potential to support the knowledge needed to critically appraise the impact of mTBI recovery interventions across multiple settings, enabling uptake of the best-available evidence within clinical practice.