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1.
Lancet ; 398(10303): 843-855, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-1599473

ABSTRACT

BACKGROUND: A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. METHODS: PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 µg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. FINDINGS: The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). INTERPRETATION: Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. FUNDING: National Institute of Health Research and United Kingdom Research Innovation.


Subject(s)
Budesonide/administration & dosage , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Administration, Inhalation , Aged , Bayes Theorem , COVID-19/mortality , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
2.
Preprint | EuropePMC | ID: ppcovidwho-296746

ABSTRACT

Introduction: Determining the long-term impact of telemedicine in care across the diagnostic and age spectrum of child neurology during the COVID-19 pandemic and with the re-opening of outpatient clinics. Methods An observational cohort study of 34,837 in-person visits and 14,820 telemedicine outpatient pediatric neurology visits between October 1, 2019 and April 9, 2021. We assessed differences in care across visit types, time-period observed, time between follow-ups, patient portal activation rates and demographic factors. Results 26,399 patients were observed in this study (median age 11.4 years [interquartile range, 5.5-15.9];13,209 male). We observed a higher proportion of telemedicine for epilepsy (ICD10 G40: OR 1.4, 95% CI 1.3-1.5) and a lower proportion for movement disorders (ICD10 G25: OR 0.7, 95% CI 0.6-0.8;ICD10 R25: OR 0.7, 95% CI 0.6-0.9). Infants were more likely to be seen in-person after re-opening clinics than by telemedicine (OR 1.6, 95% CI 1.5-1.8) as were individuals with neuromuscular disorders (OR 0.6, 95% CI 0.6-0.7). Racial and ethnic minority populations and those with highest social vulnerability had lower rates of telemedicine participation throughout the pandemic (OR 0.8, 95% CI 0.8-0.8;OR 0.7, 95% CI 0.7-0.8). Discussion Telemedicine implementation was followed by continued use even once in-person clinics were available. Pediatric epilepsy care can often be performed using telemedicine while young children and patients with neuromuscular disorders often require in-person assessment. Prominent barriers for socially vulnerable families and racial and ethnic minorities persist.

3.
Emerg Med J ; 2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1574442

ABSTRACT

OBJECTIVE: This study explored the perspectives and behaviours of emergency physicians (EPs), regularly involved in resuscitation, to identify the sources and effects of any stress experienced during a resuscitation as well as the strategies employed to deal with these stressors. METHODS: This was a two-centre sequential exploratory mixed-methods study of EPs consisting of a focus group, exploring the human factors related to resuscitation, and an anonymous survey. Between April and June 2020, the online survey was distributed to all EPs working at Australia's largest two major trauma centres, both in Melbourne, and investigated sources of stress during resuscitation, impact of stress on performance, mitigation strategies used, impact of the COVID-19 pandemic on stress and stress management training received. Associations with gender and years of clinical practice were also examined. RESULTS: 7 EPs took part in the focus group and 82 responses to the online survey were received (81% response rate). The most common sources of stress reported were resuscitation of an 'unwell young paediatric patient' (81%, 95% CI 70.6 to 87.6) or 'unwell pregnant patient' (71%, 95% CI 60.1 to 79.5) and 'conflict with a team member' (71%, 95% CI 60.1 to 79.5). The most frequently reported strategies to mitigate stress were 'verbalising a plan to the team' (84%, 95% CI 74.7 to 90.5), 'implementing a standardised/structured approach' (73%, 95% CI 62.7 to 81.6) and 'asking for help' (57%, 95% CI 46.5 to 67.5). 79% (95% CI 69.3 to 86.6) of EPs reported that they would like additional training on stress management. Junior EPs more frequently reported the use of 'mental rehearsal' to mitigate stress during a resuscitation (62% vs 22%; p<0.01) while female EPs reported 'asking for help' as a mitigator of stress more frequently than male EPs (79% vs 47%; p=0.01). CONCLUSIONS: Stress is commonly experienced by EPs during resuscitation and can impact decision-making and procedural performance. This study identifies the most common sources of stress during a resuscitation as well as the strategies that EPs use to mitigate the effects of stress on their performance. These findings may contribute to the development of tailored stress management training for critical care clinicians.

4.
JAMA ; 326(17): 1690-1702, 2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1525402

ABSTRACT

Importance: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. Objective: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. Interventions: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). Main Outcomes and Measures: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. Results: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11 secondary outcomes. Serious adverse events were reported in 3.0% (32/1075) of participants in the convalescent plasma group and in 1.3% (12/905) of participants in the no convalescent plasma group. Conclusions and Relevance: Among critically ill adults with confirmed COVID-19, treatment with 2 units of high-titer, ABO-compatible convalescent plasma had a low likelihood of providing improvement in the number of organ support-free days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
COVID-19/therapy , ABO Blood-Group System , Adult , Aged , Critical Illness/therapy , Female , Hospital Mortality , Humans , Immunization, Passive , Length of Stay , Logistic Models , Male , Middle Aged , Respiration, Artificial/statistics & numerical data , Treatment Failure , Vasoconstrictor Agents/therapeutic use
5.
Lancet Respir Med ; 9(9): 1010-1020, 2021 09.
Article in English | MEDLINE | ID: covidwho-1331331

ABSTRACT

BACKGROUND: Doxycycline is often used for treating COVID-19 respiratory symptoms in the community despite an absence of evidence from clinical trials to support its use. We aimed to assess the efficacy of doxycycline to treat suspected COVID-19 in the community among people at high risk of adverse outcomes. METHODS: We did a national, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in older people (PRINCIPLE) across primary care centres in the UK. We included people aged 65 years or older, or 50 years or older with comorbidities (weakened immune system, heart disease, hypertension, asthma or lung disease, diabetes, mild hepatic impairment, stroke or neurological problem, and self-reported obesity or body-mass index of 35 kg/m2 or greater), who had been unwell (for ≤14 days) with suspected COVID-19 or a positive PCR test for SARS-CoV-2 infection in the community. Participants were randomly assigned using response adaptive randomisation to usual care only, usual care plus oral doxycycline (200 mg on day 1, then 100 mg once daily for the following 6 days), or usual care plus other interventions. The interventions reported in this manuscript are usual care plus doxycycline and usual care only; evaluations of other interventions in this platform trial are ongoing. The coprimary endpoints were time to first self-reported recovery, and hospitalisation or death related to COVID-19, both measured over 28 days from randomisation and analysed by intention to treat. This trial is ongoing and is registered with ISRCTN, 86534580. FINDINGS: The trial opened on April 2, 2020. Randomisation to doxycycline began on July 24, 2020, and was stopped on Dec 14, 2020, because the prespecified futility criterion was met; 2689 participants were enrolled and randomised between these dates. Of these, 2508 (93·3%) participants contributed follow-up data and were included in the primary analysis: 780 (31·1%) in the usual care plus doxycycline group, 948 in the usual care only group (37·8%), and 780 (31·1%) in the usual care plus other interventions group. Among the 1792 participants randomly assigned to the usual care plus doxycycline and usual care only groups, the mean age was 61·1 years (SD 7·9); 999 (55·7%) participants were female and 790 (44·1%) were male. In the primary analysis model, there was little evidence of difference in median time to first self-reported recovery between the usual care plus doxycycline group and the usual care only group (9·6 [95% Bayesian Credible Interval [BCI] 8·3 to 11·0] days vs 10·1 [8·7 to 11·7] days, hazard ratio 1·04 [95% BCI 0·93 to 1·17]). The estimated benefit in median time to first self-reported recovery was 0·5 days [95% BCI -0·99 to 2·04] and the probability of a clinically meaningful benefit (defined as ≥1·5 days) was 0·10. Hospitalisation or death related to COVID-19 occurred in 41 (crude percentage 5·3%) participants in the usual care plus doxycycline group and 43 (4·5%) in the usual care only group (estimated absolute percentage difference -0·5% [95% BCI -2·6 to 1·4]); there were five deaths (0·6%) in the usual care plus doxycycline group and two (0·2%) in the usual care only group. INTERPRETATION: In patients with suspected COVID-19 in the community in the UK, who were at high risk of adverse outcomes, treatment with doxycycline was not associated with clinically meaningful reductions in time to recovery or hospital admissions or deaths related to COVID-19, and should not be used as a routine treatment for COVID-19. FUNDING: UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research.


Subject(s)
Anti-Bacterial Agents/administration & dosage , COVID-19/drug therapy , Doxycycline/administration & dosage , Age Factors , Aged , Aged, 80 and over , Anti-Bacterial Agents/adverse effects , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Doxycycline/adverse effects , Female , Hospitalization/statistics & numerical data , Humans , Intention to Treat Analysis , Male , Middle Aged , Minimal Clinically Important Difference , Risk Factors , SARS-CoV-2/isolation & purification , Self Report/statistics & numerical data , Treatment Outcome , United Kingdom/epidemiology
6.
Intensive Care Med ; 47(8): 867-886, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1305144

ABSTRACT

PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.


Subject(s)
COVID-19 , Ritonavir , Adult , Antiviral Agents/therapeutic use , Bayes Theorem , COVID-19/drug therapy , Critical Illness , Drug Combinations , Humans , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2
7.
Epilepsia ; 62(7): 1617-1628, 2021 07.
Article in English | MEDLINE | ID: covidwho-1262319

ABSTRACT

OBJECTIVE: Improvement in epilepsy care requires standardized methods to assess disease severity. We report the results of implementing common data elements (CDEs) to document epilepsy history data in the electronic medical record (EMR) after 12 months of clinical use in outpatient encounters. METHODS: Data regarding seizure frequency were collected during routine clinical encounters using a CDE-based form within our EMR. We extracted CDE data from the EMR and developed measurements for seizure severity and seizure improvement scores. Seizure burden and improvement was evaluated by patient demographic and encounter variables for in-person and telemedicine encounters. RESULTS: We assessed a total of 1696 encounters in 1038 individuals with childhood epilepsies between September 6, 2019 and September 11, 2020 contributed by 32 distinct providers. Childhood absence epilepsy (n = 121), Lennox-Gastaut syndrome (n = 86), and Dravet syndrome (n = 42) were the most common epilepsy syndromes. Overall, 43% (737/1696) of individuals had at least monthly seizures, 17% (296/1696) had a least daily seizures, and 18% (311/1696) were seizure-free for >12 months. Quantification of absolute seizure burden and changes in seizure burden over time differed between epilepsy syndromes, including high and persistent seizure burden in patients with Lennox-Gastaut syndrome. Individuals seen via telemedicine or in-person encounters had comparable seizure frequencies. Individuals identifying as Hispanic/Latino, particularly from postal codes with lower median household incomes, were more likely to have ongoing seizures that worsened over time. SIGNIFICANCE: Standardized documentation of clinical data in childhood epilepsies through CDE can be implemented in routine clinical care at scale and enables assessment of disease burden, including characterization of seizure burden over time. Our data provide insights into heterogeneous patterns of seizure control in common pediatric epilepsy syndromes and will inform future initiatives focusing on patient-centered outcomes in childhood epilepsies, including the impact of telemedicine and health care disparities.


Subject(s)
Cost of Illness , Electronic Health Records , Epilepsy/economics , Adolescent , Anticonvulsants/therapeutic use , Child , Child, Preschool , Common Data Elements , Epilepsies, Myoclonic/epidemiology , Epilepsy, Absence/epidemiology , Female , Humans , Lennox Gastaut Syndrome/epidemiology , Male , Seizures/epidemiology , Socioeconomic Factors , Telemedicine , Treatment Outcome
8.
Emerg Med Australas ; 33(4): 728-733, 2021 08.
Article in English | MEDLINE | ID: covidwho-1255059

ABSTRACT

OBJECTIVE: In response to COVID-19, we introduced and examined the effect of a raft of modifications to standard practice on adverse events and first-attempt success (FAS) associated with ED intubation. METHODS: An analysis of prospectively collected registry data of all ED intubations over a 3-year period at an Australian Major Trauma Centre. During the first 6 months of the COVID-19 pandemic in Australia, we introduced modifications to standard practice to reduce the risk to staff including: aerosolisation reduction, comprehensive personal protective equipment for all intubations, regular low fidelity simulation with 'sign-off' for all medical and nursing staff, senior clinician laryngoscopist and the introduction of pre-drawn medications. RESULTS: There were 783 patients, 136 in the COVID-19 era and 647 in the pre-COVID-19 comparator group. The rate of hypoxia was higher during the COVID-19 era compared to pre-COVID-19 (18.4% vs 9.6%, P < 0.005). This occurred despite the FAS rate remaining very high (95.6% vs 93.8%, P = 0.42) and intubation being undertaken by more senior laryngoscopists (consultant 55.9% during COVID-19 vs 22.6% pre-COVID-19, P < 0.001). Other adverse events were similar before and during COVID-19 (hypotension 12.5% vs 7.9%, P = 0.082; bradycardia 1.5% vs 0.5%, P = 0.21). Video laryngoscopy was more likely to be used during COVID-19 (95.6% vs 82.5%, P < 0.001) and induction of anaesthesia more often used ketamine (66.9% vs 42.3%, P < 0.001) and rocuronium (86.8% vs 52.1%, P < 0.001). CONCLUSIONS: This raft of modifications to ED intubation was associated with significant increase in hypoxia despite a very high FAS rate and more senior first laryngoscopist.


Subject(s)
Airway Management/methods , COVID-19/therapy , Emergency Service, Hospital/statistics & numerical data , Intubation, Intratracheal/methods , Intubation, Intratracheal/standards , Adult , Aged , Airway Management/standards , Airway Management/statistics & numerical data , Australia , COVID-19/epidemiology , Female , Humans , Intubation, Intratracheal/adverse effects , Laryngoscopy/adverse effects , Laryngoscopy/methods , Male , Middle Aged , Pandemics , Prospective Studies , Quality Improvement , SARS-CoV-2
9.
N Engl J Med ; 384(16): 1491-1502, 2021 04 22.
Article in English | MEDLINE | ID: covidwho-1101727

ABSTRACT

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Receptors, Interleukin-6/antagonists & inhibitors , Adult , Aged , Antibodies, Monoclonal, Humanized/adverse effects , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Critical Illness , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Odds Ratio , Respiration, Artificial
12.
JAMA ; 324(13): 1317-1329, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-739603

ABSTRACT

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Coronavirus Infections/drug therapy , Hydrocortisone/administration & dosage , Pneumonia, Viral/drug therapy , Respiration, Artificial/statistics & numerical data , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Inflammatory Agents/adverse effects , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Early Termination of Clinical Trials , Female , Humans , Hydrocortisone/adverse effects , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , SARS-CoV-2 , Shock/drug therapy , Shock/etiology , Treatment Outcome
13.
Neurology ; 95(9): e1257-e1266, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-592503

ABSTRACT

OBJECTIVE: To assess the rapid implementation of child neurology telehealth outpatient care with the onset of the coronavirus disease 2019 (COVID-19) pandemic in March 2020. METHODS: This was a cohort study with retrospective comparison of 14,780 in-person encounters and 2,589 telehealth encounters, including 2,093 audio-video telemedicine and 496 scheduled telephone encounters, between October 1, 2019 and April 24, 2020. We compared in-person and telehealth encounters for patient demographics and diagnoses. For audio-video telemedicine encounters, we analyzed questionnaire responses addressing provider experience, follow-up plans, technical quality, need for in-person assessment, and parent/caregiver satisfaction. We performed manual reviews of encounters flagged as concerning by providers. RESULTS: There were no differences in patient age and major ICD-10 codes before and after transition. Clinicians considered telemedicine satisfactory in 93% (1,200 of 1,286) of encounters and suggested telemedicine as a component for follow-up care in 89% (1,144 of 1,286) of encounters. Technical challenges were reported in 40% (519 of 1,314) of encounters. In-person assessment was considered warranted after 5% (65 of 1,285) of encounters. Patients/caregivers indicated interest in telemedicine for future care in 86% (187 of 217) of encounters. Participation in telemedicine encounters compared to telephone encounters was less frequent among patients in racial or ethnic minority groups. CONCLUSIONS: We effectively converted most of our outpatient care to telehealth encounters, including mostly audio-video telemedicine encounters. Providers rated the vast majority of telemedicine encounters to be satisfactory, and only a small proportion of encounters required short-term in-person follow-up. These findings suggest that telemedicine is feasible and effective for a large proportion of child neurology care. Additional strategies are needed to ensure equitable telemedicine use.


Subject(s)
Coronavirus Infections/therapy , Neurology/statistics & numerical data , Pediatrics/statistics & numerical data , Pneumonia, Viral/therapy , Telemedicine/statistics & numerical data , Adolescent , COVID-19 , Caregivers/statistics & numerical data , Child , Child, Preschool , Cohort Studies , Female , Humans , Job Satisfaction , Male , Minority Groups/statistics & numerical data , Pandemics/statistics & numerical data , Patient Satisfaction , Retrospective Studies , Surveys and Questionnaires
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