Immunomodulatory therapy in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS, MIS-C; RECOVERY): a randomised, controlled, open-label, platform trial

The Lancet Child & Adolescent Health · 2024 · 34 citations

• Medicine
• Internal medicine
• Virology

BACKGROUND: Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS), also known as multisystem inflammatory syndrome in children (MIS-C) emerged in April, 2020. The paediatric comparisons within the RECOVERY trial aimed to assess the effect of intravenous immunoglobulin or corticosteroids compared with usual care on duration of hospital stay for children with PIMS-TS and to compare tocilizumab (anti-IL-6 receptor monoclonal antibody) or anakinra (anti-IL-1 receptor antagonist) with usual care for those with inflammation refractory to initial treatment. METHODS: We did this randomised, controlled, open-label, platform trial in 51 hospitals in the UK. Eligible patients were younger than 18 years and had been admitted to hospital for PIMS-TS. In the first randomisation, patients were randomly assigned (1:1:1) to usual care (no additional treatments), usual care plus methylprednisolone (10mg/kg per day for 3 consecutive days), or usual care plus intravenous immunoglobulin (a single dose of 2 g/kg). If further anti-inflammatory treatment was considered necessary, children aged at least 1 year could be considered for a second randomisation, in which patients were randomly assigned (1:2:2) to usual care, intravenous tocilizumab (12 mg/kg in patients <30 kg; 8mg/kg in patients ≥30 kg, up to a maximum dose of 800 mg), or subcutaneous anakinra (2 mg/kg once per day in patients ≥10 kg). Randomisation was by use of a web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was duration of hospital stay. Analysis was by intention to treat. For treatments assessed in each randomisation, a single Bayesian framework assuming uninformative priors for treatment was used to jointly assess the efficacy of each intervention compared with usual care. The trial was registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between May 18, 2020, and Jan 20, 2022, 237 children with PIMS-TS were enrolled and included in the intention-to-treat analysis. Of the 214 patients who entered the first randomisation, 73 were assigned to receive intravenous immunoglobulin, 61 methylprednisolone, and 80 usual care. Of the 70 children who entered the second randomisation (including 23 who did not enter the first randomisation), 28 were assigned to receive tocilizumab, 14 anakinra, and 28 usual care. Mean age was 9·5 years (SD 3·8) in the randomisation and 9·6 years (3·6) in the second randomisation. 118 (55%) of 214 patients in the first randomisation and 39 (56%) of 70 patients in the second randomisation were male. 130 (55%) of 237 patients were Black, Asian, or minority ethnic, and 105 (44%) were White. Mean duration of hospital stay was 7·4 days (SD 0·4) in children assigned to intravenous immunoglobulin and 7·6 days (0·4) in children assigned to usual care (difference -0·1 days, 95% credible interval [CrI] -1·3 to 1·0; posterior probability 59%). Mean duration of hospital stay was 6·9 days (SD 0·5) in children assigned to methylprednisolone (difference from usual care -0·7 days, 95% CrI -1·9 to 0·6; posterior probability 87%). Mean duration of hospital stay was 6·6 days (SD 0·7) in children assigned to second-line tocilizumab and 9·9 days (0·9) in children assigned to usual care (difference -3·3 days, 95% CrI -5·6 to -1·0; posterior probability >99%). Mean duration of hospital stay was 8·5 days (SD 1·2) in children assigned to anakinra (difference from usual care -1·4 days, 95% CrI -4·3 to 1·8; posterior probability 84%). Two persistent coronary artery aneurysms were reported among patients assigned to usual care in the first randomisation. There were few cardiac arrythmias, bleeding, or thrombotic events in any group. Two children died; neither was considered related to study treatment. INTERPRETATION: Moderate evidence suggests that, compared with usual care, first-line intravenous methylprednisolone reduces duration of hospital stay for children with PIMS-TS. Good evidence suggests that second-line tocilizumab reduces duration of hospital stay for children with inflammation refractory to initial treatment. Neither intravenous immunoglobulin nor anakinra had any effect on duration of hospital stay compared with usual care. FUNDING: Medical Research Council and National Institute of Health Research.

Empagliflozin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

The Lancet Diabetes & Endocrinology · 2023 · 38 citations

• Medicine
• Emergency medicine
• Internal medicine

BACKGROUND: Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19. METHODS: In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge (whichever came first) using web-based simple (unstratified) randomisation with allocation concealment. The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. On March 3, 2023 the independent data monitoring committee recommended that the investigators review the data and recruitment was consequently stopped on March 7, 2023. The ongoing RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between July 28, 2021 and March 6, 2023, 4271 patients were randomly allocated to receive either empagliflozin (2113 patients) or usual care alone (2158 patients). Primary and secondary outcome data were known for greater than 99% of randomly assigned patients. Overall, 289 (14%) of 2113 patients allocated to empagliflozin and 307 (14%) of 2158 patients allocated to usual care died within 28 days (rate ratio 0·96 [95% CI 0·82-1·13]; p=0·64). There was no evidence of significant differences in duration of hospitalisation (median 8 days for both groups) or the proportion of patients discharged from hospital alive within 28 days (1678 [79%] in the empagliflozin group vs 1677 [78%] in the usual care group; rate ratio 1·03 [95% CI 0·96-1·10]; p=0·44). Among those not on invasive mechanical ventilation at baseline, there was no evidence of a significant difference in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (338 [16%] of 2084 vs 371 [17%] of 2143; risk ratio 0·95 [95% CI 0·84-1·08]; p=0·44). Two serious adverse events believed to be related to empagliflozin were reported: both were ketosis without acidosis. INTERPRETATION: In adults hospitalised with COVID-19, empagliflozin was not associated with reductions in 28-day mortality, duration of hospital stay, or risk of progressing to invasive mechanical ventilation or death so is not indicated for the treatment of such patients unless there is an established indication due to a different condition such as diabetes. FUNDING: UK Research and Innovation (Medical Research Council) and National Institute of Health Research (MC_PC_19056), and Wellcome Trust (222406/Z/20/Z). TRANSLATIONS: For the Nepali, Hindi, Indonesian (Bahasa) and Vietnamese translations of the abstract see Supplementary Materials section.

Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

Intensive Care Medicine · 2021 · 98 citations

• Medicine
• Internal medicine
• Virology

LEVO-TRANSPOSITION OF THE GREAT ARTERIES WITHOUT ASSOCIATED STRUCTURAL ABNORMALITIES

Journal of the American College of Cardiology · 2019-03-01

Randomized Trial of Clitoral Vacuum Suction Versus Vibratory Stimulation in Neurogenic Female Orgasmic Dysfunction

Archives of Physical Medicine and Rehabilitation · 2017-09-09 · 35 citations

7 Adults with left-to-right cardiac shunts and with shunts treated in childhood

2011-09-14

Adults with left-to-right cardiac shunts and with shunts treated in childhood

International Journal on Disability and Human Development · 2010-11-01

Pediatric cardiac care has advanced over the past decade and many children born with heart defects have been operated and managed resulting in improvement of outcome and life expectancy. This review focuses on patients born with left-to-right shunts that survive into adulthood and we believe it is important for the adult primary care physician to realize that more and more patients with congenital heart defects will enter into their practice over the next several decades as improvements in childhood cardiac care continue to be made. Although the field of adult congenital heart disease continues to grow and advance, the number of cardiologists specifically trained in this area are not yet adequate to deal with the growing amount of patients with these conditions. This requires a concerted effort from cardiologists of both adult and pediatric specialties, but perhaps more importantly from the multitude of primary care physicians that will most probably be the only physicians many of these patients will ever see. Many adult patients born with left-to-right heart lesions underwent treatment and repair early in childhood and might not have felt it necessary to continue follow-up with a cardiologist. Many other patients with these defects might have survived to adulthood without diagnosis and could present to the primary care provider with new symptoms that finally developed. Primary care physicians will most certainly be at the frontlines of caring for these congenital heart defects.

Recommendations for Discussing Sexuality After Spinal Cord Injury/Dysfunction in Children, Adolescents, and Adults

Journal of Spinal Cord Medicine · 2007-01-01 · 30 citations

BACKGROUND/OBJECTIVE: To review the literature and provide a framework for sex education for the child, adolescent, or adult with a spinal cord injury (SCI) or disorder. METHODS: Discussion and review of the literature. RESULTS: There is a paucity of research available regarding the impact of SCIs and disorders on sexuality in children and adolescents; however, there is a significant body of literature on this topic in adults. Recommendations based on these findings are presented. Guidelines regarding sexuality in children and adolescents with general disabilities may be adapted for the education of children and adolescents with SCIs and disorders. CONCLUSIONS: Parents, partners, and persons with SCIs and disorders should be provided with age-appropriate information about sexuality that includes specific information with respect to SCIs and disorders. Although there has been a significant increase in information that is available about the impact of sexuality in adults after SCI, more information is needed about the effects of SCIs and disorders on the healthy sexual development of children and adolescents.

Effects of level and degree of spinal cord injury on male orgasm

Spinal Cord · 2006-06-27 · 88 citations

The Effects of Spinal Cord Injury on Psychogenic Sexual Arousal in Males

The Journal of Urology · 2006-12-10 · 47 citations

PURPOSE: We determined if the degree of preservation of sensory function in the T11-L2 dermatomes could be used to determine the potential for psychogenic erectile responses in men with spinal cord injury. MATERIALS AND METHODS: Subjects included 45 men with spinal cord injury and 16 able-bodied control subjects. A 78-minute laboratory based analysis was done of subject subjective arousal, penile circumference, blood pressure, and heart rate responses to audiovisual erotic and audiovisual erotic combined with manual penile stimulation. RESULTS: Able-bodied subjects generally had significantly greater penile circumferences than spinal cord injured subjects during the stimulation periods. The degree of preservation of combined pinprick and light touch sensation in the T11-L2 dermatomes distinguished those who did and did not have a significant increase in penile circumference with audiovisual stimulation. Blood pressure and heart rate readings were generally higher in able-bodied than spinal cord injured subjects throughout the experimental protocol. However, all readings were within normal limits. CONCLUSIONS: Results support the hypothesis that psychogenic erection depends on the sympathetic nervous system. Findings underscore a possible parallel in neurological control of sexual responses between the sexes.