Background In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov ( NCT04381936 ). Findings Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding UK Research and Innovation (Medical Research Council) and National Institute of Health Research.

Summary Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus. Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894. Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus. Funding National Institute for Health Research Health Technology Assessment programme.

Contracts in the for-hire trucking industry are unusual in that, although they establish prices for different services, there is typically no legally binding obligation or penalty for either party to offer or accept a load. When a load is rejected by all contract carriers, shippers must turn to the spot market, which can significantly increase supply chain costs. Because these transactions occur between private parties, data on load acceptances/rejections and contract/spot prices have not been available to academic researchers, leaving the freight rejection problem largely unexplored. We are able to examine this problem using a detailed transactional data set of a large national shipper. We estimate that spot prices for truckload services average about 62% higher than contract rates. We find key operational and economic factors to be drivers of freight rejection and the shipper-carrier relationship to be a deterrent to freight rejection. We also find that primary and secondary carriers respond differently to these operational and economic factors. We discuss how these insights could be used by a shipper to get better performance and lower cost from their carrier base.

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An individual's temptation to violate regulations for personal gain increases with the economic payoff to do so. Firms, however, adopt strategies to reduce undesirable behavior from their employees. This article examines how individuals change their propensity to violate regulations as the price for their services varies. We posit that individuals will commit more intentional, but not unintentional, violations as the payoff to do so increases, and that this effect will be moderated by the size of the firm for whom he or she works and whether the firm or the individual owns the assets used for production. To test our hypotheses, we link data from millions of inspections of truck driver logbooks with spot market prices observed over the same 4‐year period. We find that drivers who operate independently intentionally violate restrictions on their work hours more frequently when prices increase—violating 34% more frequently when prices are at their highest versus lowest—but larger firms and the firm's ownership of the assets reduce a driver's responsiveness to price changes. At the extreme, drivers for large asset‐owning firms are completely unresponsive to prices. Asset‐owning drivers are responsive to market prices, even for the largest firms.

W hen a shipper urgently needs truckload service, they often utilize the spot market. But despite its importance, little is known about this market. I analyze a longitudinal data set of auctions for spot truckload service where I observe invitations for carriers to bid, whether a bid is placed, and the bid price if one is placed, and augment this with information about the bidding carriers. Drawing upon auction theory, I suggest that a carrier's a priori characteristics (size, market specialization) explain the two primary decisions made in the auctions-whether to bid and how much to bid. I find that brokers, who act as intermediaries between shippers and asset-based carriers, bid much more frequently and higher than asset-based carriers. Price indexes show that broker bid prices follow similar patterns, but asset-based carrier prices do not. The results suggest that an online marketplace linking shippers directly with the thousands of asset-based carriers could add considerable value to the for-hire trucking industry, a development which appears to be happening.

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Research shows that electronic monitoring technologies can reduce illicit agent (e.g., frontline worker) behavior along monitored dimensions such that principals (e.g., firms) benefit. Drawing on theory from criminology regarding the concept of offense displacement, we explain why the benefits from increased monitoring may be mitigated if agents subsequently increase other types of illicit acts not subject to greater monitoring. We investigate this possibility by examining how a mandate requiring millions of truck drivers to adopt electronic logging devices to record their working hours affected different safety behaviors and outcomes. Using data from millions of driver inspections and crash counts before and after the mandate and a differences‐in‐differences identification strategy, we find greater monitoring due to the mandate achieved its first‐order effect of reducing the frequency that drivers were in non‐compliance with work hour rules (the monitored dimension). However, drivers for small firms that were most affected by the mandate also appear to have increased their frequency of unsafe driving (e.g., speeding). We also find that crash counts for small firms did not fall relative to large firms, and may have increased. These results call into question whether increased electronic monitoring has improved safety in this industry.