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Orientation: The retail industry is the largest contributor to employment and the gross domestic product (GDP) in the Western Cape, South Africa. The management of human resources in this very competitive industry is a high priority for all retailers. The successful implementation, maintenance and use of human resource information systems (HRISs) are an integral part of many retailers. Research purpose: Human resource information systems are difficult to implement and maintain, and as a result, organisations cannot effectively utilise these systems to their benefit. The purpose of this paper is to explore the factors affecting the implementation, maintenance and use of HRISs in two retail organisations in the Western Cape. Motivation of study: Many retailers find it difficult to apply and utilise HRISs to their benefit and to the systems’ full potential. This study explores the challenges retailers are facing when implementing, maintaining and using HRISs. Research design, approach and method: Multiple case studies were used to conduct the research. Data were collected through a semi-structured questionnaire using interviews. Twenty-one interviews were conducted in the two retail companies to gain an understanding of the use of HRISs within these organisations. The data were analysed using a thematic method of analysis. The units of analysis were the Human Resources and the Information Technology departments of both companies. The units of observation were (21) purposively selected employees in the two mentioned departments of both retail organisations. Main findings: This research shows an under-utilisation of the HRIS in both companies as a result of poor data quality, lack of adequate training and the high cost of implementing and maintaining the system. There is a gap in terms of data analytics and report generation. This gap leads to the under-utilisation of the HRISs preventing the retailers to optimise the benefits of the HRIS. Practical and managerial implications: For organisations to reap benefits from HRISs, a change management strategy and a rigorous training programme are needed that will focus on the implemented maintenance and improved usage of these systems. Contribution: The contribution of the study includes proposed guidelines for the effective and efficient use of HRISs. The study further contributes to the body of knowledge in shedding light on the implementation, maintenance and use of HRISs in the retail industry in the Western Cape, South Africa.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease worldwide, affecting more than four million people. Typically, it affects individuals above 45, when they are still productive, compromising both aging and quality of life. Therefore, the cost of the disease must be identified, so that the use of resources can be rational and efficient. Additionally, in Brazil, there is a lack of research on the costs of neurodegenerative diseases, such as PD, a gap addressed in this study. This systematic review critically addresses the various methodologies used in original research around the world in the last decade on the subject, showing that costs are hardly comparable. Nonetheless, the economic and social impacts are implicit, and important information for public health agents is provided.

BackgroundClinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined.MethodsWe evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots.ResultsUS ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets.ConclusionsAlthough surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

We believe in many different ways. One very common one is by supporting ideas we like. We label them correct and we act to dismiss doubts about them. We take sides about ideas and theories as if that was the right thing to do. And yet, from a rational point of view, this type of support and belief is not justifiable. The best we can hope when describing the real world, as far as we know today, is to have probabilistic knowledge. In practice, estimating a real probability can be too hard to achieve but that just means we have more uncertainty, not less. There are ideas we defend that define, in our minds, our own identity. And recent experiments have been showing that we stop being able to analyze competently those propositions we hold so dearly. In this paper, I gather the evidence we have about taking sides and present the obvious but unseen conclusion that these facts combined mean that we should actually never believe in anything about the real world, except in a probabilistic way. We must actually never take sides since taking sides compromise our abilities to seek for the most correct description of the world. That means we need to start reformulating the way we debate ideas, from our teaching to our political debates. Here, I will show the logical and experimental basis of this conclusion. I will also show, by presenting new models for the evolution of opinions, that our desire to have something to believe is probably behind the emergence of extremism in debates. And we will see how this problem can even have an impact in the reliability of whole scientific fields. The crisis around $p$-values is discussed and much better understood under the light of this paper results. Finally, I will debate possible consequences and ideas on how to deal with this problem.

OBJECTIVE: It was to analyze clinical aspects of patients with blepharospasm, including outcomes of botulinum toxin treatment. Additionally, clinical characteristics of isolated blepharospasm were compared to those of blepharospasm plus other movement disorders. METHODS: Clinical data recorded during 17 years were reviewed. The variables included age, gender, age of onset, past medical history, head trauma, smoking history, family history of dystonia, severity, duration of botulinum toxin relief and adverse effects. RESULTS: A total of 125 patients were included and 75.2% were female. The mean age of onset was 54.3 years; 89.6% of the individuals started with contractions in eye region, and 39.2% of them spread to lower face or neck. Isolated blepharospasm group was compared with blepharospasm-plus group for demographic and clinical features, and therapeutic outcomes, without significant differences. Botulinum toxin treatment improved the severity of contractions (p=0.01) with low rate of side effects (14%). CONCLUSIONS: Both groups - isolated blepharospasm and blepharospasm-plus - shared similar results concerning epidemiology, clinical features and therapeutic response to botulinum toxin.

Small nonequilibrium systems in contact with a heat bath can be analyzed with the framework of stochastic thermodynamics. In such systems, fluctuations, which are not negligible, follow universal relations such as the fluctuation theorem. More recently, it has been found that, for nonequilibrium stationary states, the full spectrum of fluctuations of any thermodynamic current is bounded by the average rate of entropy production and the average current. However, this bound does not apply to periodically driven systems, such as heat engines driven by periodic variation of the temperature and artificial molecular pumps driven by an external protocol. We obtain a universal bound on current fluctuations for periodically driven systems. This bound is a generalization of the known bound for stationary states. In general, the average rate that bounds fluctuations in periodically driven systems is different from the rate of entropy production. We also obtain a local bound on fluctuations that leads to a trade-off relation between speed and precision in periodically driven systems, which constitutes a generalization to periodically driven systems of the so called thermodynamic uncertainty relation. From a technical perspective, our results are obtained with the use of a recently developed theory for 2.5 large deviations for Markov jump processes with time-periodic transition rates.

We performed a secondary analysis of the National Institutes of Health-sponsored Adaptive COVID-19 Treatment Trial (ACTT-2) randomized controlled trial and found that baricitinib was associated with a 50% reduction in secondary infections after controlling for baseline and postrandomization patient characteristics. This finding provides a novel mechanism of benefit for baricitinib and supports the safety profile of this immunomodulator for the treatment of coronavirus disease 2019.

The origin of amyotrophic lateral sclerosis (ALS) remains unknown, although it seems to be multifactorial. The role of environmental factors has been frequently investigated and suspicion of its influence can be obtained when clusters of a rare disease are described. OBJECTIVE: To describe conjugal cases of ALS in Brazil. METHOD: We describe 2 couples in which both spouses were affected by ALS. Both couples had lived in southeast Brazil and were married for at least 20 years. RESULTS: There was a great variability in clinical presentation of ALS in our patients. In both couples the interval between disease onsets was short. No precise environmental factors could be identified at the origin of these conjugal cases. CONCLUSION: The occurrence of ALS in couples living in the same area may be epidemiologically important, but we cannot exclude that cases may be due to a chance association.A origem da esclerose lateral amiotrófica (ELA) permanece desconhecida. O papel de fatores ambientais tem sido freqüentemente investigado e a suspeição de sua influência pode ser obtida quando são descritas salvas de casos de uma doença rara. OBJETIVO: Descrever casos de ELA em casais no Brasil. MÉTODO: Apresentamos dois casais em que ambos os cônjuges forma acometidos pela ELA. Ambos os casais residiram na região sudeste do Brasil e estiveram casados por pelo menos 20 anos. RESULTADOS: Houve grande variabilidade na apresentação clínica da ELA em nossos pacientes. Em ambos os casais, o intervalo de início da doença foi curto. Nenhum fator ambiental foi identificado na etiologia destes casos conjugais. CONCLUSÃO: A ocorrência de ELA em casais que habitam a mesma região pode ser epidemiologicamente importante, mas não podemos excluir que estes casos tenham sido mera associação.

Pituitary tumor apoplexy is a medical emergency due to acute infarction or hemorrhage in the pituitary gland. In this review, the authors discuss the sellar anatomy, the pituitary gland and adenomas' vascularization and the general aspects of the syndrome such as its ethiopatogenesis, predisposing factors, clinical features, treatment and prognosis.A apoplexia em tumor hipofisário é uma emergência médica decorrente do infarto agudo ou hemorrágico na glândula hipófise. Nesta revisão os autores discutem a anatomia da região selar, a vascularização da hipófise e adenomas hipofisários, e demais aspectos da síndrome como etiopatogenia, fatores predisponentes, quadro clínico, tratamento e prognóstico.

OBJECTIVE: To describe clinical and neuroimaging (SPECT) characteristics of Brazilian patients with Parkinson's disease (PD) and mutations in PARK2 or PARK8 genes. METHOD: A total of 119 patients meeting clinical criteria for PD were evaluated. RESULTS: Of all patients studied, 13 had mutations in either PARK2 (n=9) or PARK8 genes (n=4). No statistically significant differences in clinical characteristics in both groups were seen. SPECT with [99mTc] TRODAT-1 showed significant differences between patient and control and the most remarkable difference was between PARK2 and control. CONCLUSION: The study found a frequency of mutation of 10.1% and it was most commonly seen in women. These patients had long disease course and high rates of dyskinesia after L-DOPA use. PARK8 patients did not have a relevant family history of PD.OBJETIVO: Descrever as características clínicas e de neuroimagem (SPECT) de pacientes brasileiros com doença de Parkinson e mutações PARK2 e PARK8. MÉTODO: Foram avaliados 119 pacientes com critérios clínicos para a doença de Parkinson. RESULTADO: Entre os pacientes avaliados foram encontrados 13 pacientes com mutação nos genes PARK2 (n=9) ou PARK8 (n=4). Não houve diferença significativa na avaliação das características clínicas entre os dois grupos. Os resultados de SPECT mostraram diferenças significativas quanto ao potencial de ligação do [99mTc] TRODAT-1 SPECT entre pacientes vs. controle, sendo a diferença mais pronunciada entre PARK2 e controle. CONCLUSÃO: A freqüência de mutação encontrada foi 10,1%, sendo mais comum em mulheres. Estes pacientes apresentavam longo tempo de doença e alta prevalência de discinesias associadas ao uso da levodopa. Nossos pacientes com PARK8 não apresentaram uma história familiar relevante de doença de Parkinson.

OBJECTIVE: The association of cervical dystonia (CD) with other movement disorders have been already described, but data on clinical outcome regarding these patients are scant. The aim of this paper was to investigate whether patients with CD and head tremor (HT) would have a different outcome regarding to botulinum toxin type-A (BTX-A) treatment response and clinical and demographic parameters. METHOD: We retrospectively evaluated 118 medical charts of patients with CD and divided them into two groups: with (HT+) and without (HT-) head tremor. We compared the following clinical and demographic parameters: age at onset, disease duration, progression of symptoms, etiology, familial history, presence of hand tremor. We also analyzed the response to BTX-A according to Tsui score in both groups. RESULTS: The occurrence of head tremor in our sample was of 38.2%. The occurrence of postural hand tremor in the patients from the HT+ group was higher than in the HT- one (p=0.015) and if we compare BTX-A response in each group, we observe that patients with HT present a better outcome in a setting of longer follow-up. In HT+ group, Tsui score pre treatment was 10 (6-12.5) and after follow-up was 8 (5.5-10.5); pOBJETIVO: A associação de distonia cervical (DC) com outros transtornos do movimento já foi descrita, mas há poucos dados quanto à evolução clínica destes pacientes. Avaliamos se os pacientes com DC e tremor cefálico (TC) apresentam características clínicas e demográficas, assim como a resposta ao tratamento com toxina botulínica tipo A, diferentes. MÉTODOS: Analisamos retrospectivamente 118 prontuários de pacientes com DC e os dividimos em dois grupos: com (TC+) e sem (TC-) tremor cefálico. Comparamos os seguintes parâmetros clínicos e demográficos entre os grupos: idade de início, duração da doença, progressão de sintomas, etiologia, história familiar, presença de tremor em mãos. Também analisamos a resposta ao tratamento com toxina botulínica de acordo com escore Tsui em ambos os grupos. RESULTADOS: A ocorrência de tremor cefálico em nosso grupo de pacientes foi 38,2%. A ocorrência de tremor postural nas mãos em pacientes TC+ foi maior (p=0,015) e se compararmos a resposta ao tratamento com toxina botulínica em cada grupo, observamos que os pacientes com TC têm melhor evolução em uma situação de seguimento mais prolongado. No grupo TC+, o escore Tsui pré-tratamento foi 10 (6-12,5) e após o período de "follow-up" foi 8 (5,5-10,5); p

BACKGROUND: The association between Dystonia and Parkinson's disease (PD) has been well described especially for foot and hand dystonia. There is however few data on dystonic postures in patients with atypical parkinsonism. OBJECTIVE: To evaluate the frequency and pattern of dystonia in a group of patients with atypical parkinsonism (multiple system atrophy - MSA, progressive supranuclear palsy - PSP, and corticobasal degeneration - CBD) and to investigate whether dystonia could be the first presenting symptom at disease onset in those patients. METHOD: A total of 38 medical charts were reviewed (n=23/MSA group; n=7/CBD group; n=8/PSP group) and data values were described as means/standard deviations. The variables evaluated were sex, age at onset, disease duration, first symptom, clinical features of dystonia and other neurological signs, response to levodopatherapy, Hoehn&Yahr scale >3 after three years of disease, and magnetic resonance imaging findings. RESULTS: The overall frequency of dystonia in our sample was 50% with 30.4% (n=7) in the MSA group, 62.5% (n=5) in the PSP group, and 100% (n=8) in the CBD group. In none of these patients, dystonia was the first complaint. Several types of dystonia were found: camptocormia, retrocollis, anterocollis, blepharoespasm, oromandibular, and foot/hand dystonia. CONCLUSION: In our series, dystonia was a common feature in atypical parkinsonism (overall frequency of 50%) and it was part of the natural history although not the first symptom at disease onset. Neuroimaging abnormalities are not necessarily related to focal dystonia, and levodopa therapy did not influence the pattern of dystonia in our group of patients.INTRODUÇÃO: A associação de distonia e doença de Parkinson (DP) já foi bem estabelecida, principalmente para distonia focal em pé ou mão. Entretanto, há poucos dados quanto a distonia em pacientes com parkinsonismo atípico. OBJETIVO: Avaliar a freqüência e o padrão da distonia em um grupo de pacientes com parkisnonismo atípico (atrofia de múltiplos sistemas - AMS; paralisia supranuclear progressiva - PSP; degeneração corticobasal - DCB) e investigar se a distonia pode ser a manifestação inicial neste grupo. MÉTODO: Um total de 38 prontuários médicos foi revisado (n=23/grupo AMS; n=8/grupo PSP; n=7/grupo PSP) e os dados foram apresentados em médias/desvios padrões. As variaveis avaliadas foram: sexo, idade de início, duração da doença, primeiro sintoma, características clínicas da distonia e outros sinais neurológicos, resposta ao tratamento com levodopa, escala de Hoehn & Yahr >3 em 3 anos de doença, e achados de ressonância magnética. RESULTADOS: A frequência total de distonia em nosso grupo foi 50%, sendo 30,4% (n=7) no grupo AMS, 62.5% (n=5) no grupo PSP e 100% (n=8) no grupo DCB. Em nenhum dos pacientes, distonia foi o primeiro sintoma. Várias apresentações de distonia foram observadas: camptocormia, anterocólis, retrocólis, distonia oromandibular, em pé e mão. CONCLUSÃO: Em nossa série, distonia foi uma característica comum em pacientes com parkinsonismo atípico (freqüência de 50%) e fez parte da história natural em todos os grupos, embora não tenha sido o sintoma inicial em nenhum deles. Anormalidades no exame de neuroimagem não necessariamente estão relacionadas a distonia focal, e o tratamento com levodopa não influenciou o padrão da distonia em nosso grupo de pacientes.

The two most significant impediments to renal allograft survival are rejection and the direct nephrotoxicity of the immunosuppressant drugs required to prevent it. Calcineurin inhibitors (CNI), a mainstay of most immunosuppression regimens, are particularly nephrotoxic. Until less toxic antirejection agents become available, the only option is to optimize our use of those at hand.To determine whether intensive rabbit anti-thymocyte globulin (rATG) induction followed by CNI withdrawal would individually or combined improve graft function and reduce graft chronic histopathology-surrogates for graft and, therefore, patient survival. As previously reported, a single large rATG dose over 24 hours was well-tolerated and associated with better renal function, fewer infections, and improved patient survival. Here we report testing whether complete CNI discontinuation would improve renal function and decrease graft pathology.Between April 20, 2004 and 4-14-2009 we conducted a prospective, randomized, non-blinded renal transplantation trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment = 180). Subsequent maintenance immunosuppression consisted of tacrolimus, a CNI, and sirolimus, a mammalian target of rapamycin inhibitor. We report here the outcome of converting patients after six months either to minimized tacrolimus/sirolimus or mycophenolate mofetil/sirolimus. Primary endpoints were graft function and chronic histopathology from protocol kidney biopsies at 12 and 24 months.CNI withdrawal (on-treatment analysis) associated with better graft function (p

PurposeTo evaluate efficacy and safety of venetoclax + azacitidine in treatment-naïve patients with acute myeloid leukemia harboring poor-risk cytogenetics and TP53mut or TP53wt.Patients and methodsWe analyzed data from a phase III study (NCT02993523) comparing venetoclax (400 mg orally days 1-28) + azacitidine (75 mg/m2 days 1-7) or placebo + azacitidine, and from a phase Ib study (NCT02203773) of venetoclax + azacitidine. Patients were ineligible for intensive therapy. TP53 status was analyzed centrally; cytogenetic studies were performed locally.ResultsPatients (n = 127) with poor-risk cytogenetics receiving venetoclax + azacitidine (TP53wt = 50; TP53mut = 54) were compared with patients with poor-risk cytogenetics (n = 56) receiving azacitidine alone (TP53wt = 22; TP53mut = 18).For poor-risk cytogenetics + TP53wt patients, venetoclax + azacitidine versus azacitidine alone resulted in composite remission rates (CRc) of 70% versus 23%, median duration of remission (DoR) of 18.4 versus 8.5 months, and median overall survival (OS) of 23.4 versus 11.3 months, respectively. Outcomes with venetoclax + azacitidine were comparable with similarly treated patients with intermediate-risk cytogenetics and TP53wt.For poor-risk cytogenetics + TP53mut patients, venetoclax + azacitidine versus azacitidine alone resulted in CRc of 41% versus 17%, median DoR of 6.5 versus 6.7 months, and median OS of 5.2 versus 4.9 months, respectively.For poor-risk cytogenetics + TP53mut patients, predominant grade ≥3 adverse events (AE) for venetoclax + azacitidine versus azacitidine were febrile neutropenia (55%/39%), thrombocytopenia (28%/28%), neutropenia (26%/17%), anemia (13%/6%), and pneumonia (28%/33%). AEs were comparable between TP53mut and TP53wt patients.ConclusionsIn poor-risk cytogenetics + TP53mut patients, venetoclax + azacitidine improved remission rates but not DoR or OS compared with azacitidine alone. However, in poor-risk cytogenetics + TP53wt patients, venetoclax + azacitidine resulted in higher remission rates and longer DoR and OS than azacitidine alone, with outcomes comparable with similarly treated patients with intermediate-risk cytogenetics. Toxicities were similar in TP53mut and TP53wt patients. See related commentary by Green and Zeidner, p. 5235.

Artificial molecular machines are often driven by the periodic variation of an external parameter. This external control exerts work on the system of which a part can be extracted as output if the system runs against an applied load. Usually, the thermodynamic cost of the process that generates the external control is ignored. Here, we derive a refined second law for such small machines that include this cost, which is, for example, generated by free energy consumption of a chemical reaction that modifies the energy landscape for such a machine. In the limit of irreversible control, this refined second law becomes the standard one. Beyond this ideal limiting case, our analysis shows that due to a new entropic term unexpected regimes can occur: the control work can be smaller than the extracted work and the work required to generate the control can be smaller than this control work. Our general inequalities are illustrated by a paradigmatic three-state system.

To estimate conduction velocities from activation times in myocardial tissue, the average vector method computes all the local activation directions and velocities from local activation times and estimates the fastest and slowest propagation speed from these local values. The single vector method uses areas of apparent uniform elliptical spread of activation and chooses a single vector for the estimated longitudinal velocity and one for the transversal. A simulation study was performed to estimate the influence of grid size, anisotropy, and vector angle bin size. The results indicate that the average vector method can best be used if the grid- or bin-size is large, although systematic errors occur. The single vector method performs better, but requires human intervention for the definition of fiber direction. The average vector method can be automated.

Brownian clocks are biomolecular networks that can count time. A paradigmatic example are proteins that go through a cycle, thus regulating some oscillatory behavior in a living system. Typically, such a cycle requires free energy often provided by ATP hydrolysis. We investigate the relation between the precision of such a clock and its thermodynamic costs. For clocks driven by a constant thermodynamic force, a given precision requires a minimal cost that diverges as the uncertainty of the clock vanishes. In marked contrast, we show that a clock driven by a periodic variation of an external protocol can achieve arbitrary precision at arbitrarily low cost. This result constitutes a fundamental difference between processes driven by a fixed thermodynamic force and those driven periodically. As a main technical tool, we map a periodically driven system with a deterministic protocol to one subject to an external protocol that changes in stochastic time intervals, which simplifies calculations significantly. In the nonequilibrium steady state of the resulting bipartite Markov process, the uncertainty of the clock can be deduced from the calculable dispersion of a corresponding current.

BackgroundBaricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.MethodsIn this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.FindingsBetween Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).InterpretationIn hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.FundingNational Institute of Allergy and Infectious Diseases.