Studies on concave Young-functions

We succeeded to isolate a special class of concave Young-functions enjoying the so-called \emph{density-level property}. In this class there is a proper subset whose members have each the so-called degree of contraction denoted by $c^{\ast}$, and map bijectively the interval $[ c^{\ast}, \infty)$ onto itself. We constructed the fixed point of each of these functions. Later we proved that every positive number $b$ is the fixed point of a concave Young-function having $b$ as degree of contraction. We showed that every concave Young-function is square integrable with respect to a specific Lebesgue measure. We also proved that the concave Young-functions possessing the density-level property constitute a dense set in the space of concave Young-functions with respect to the distance induced by the $L^{2}$-norm

Inferior vena cava injury: survival of a rare case

The inferior vena cava is the most commonly injured abdominal vessel and accounts for about 25% of abdominal vascular injuries. Despite improved preoperative care and operative techniques, the mortality rates for the inferior vena cava injuries are still high due to delayed presentation, inadequate or delayed fluid resuscitation, difficulty of diagnosis and technical problems in repair. A case of the inferior vena cava injury encountered after abdominal stabinjury with about 4cm vertical tear of infrarenal vena cava, survived due to immediate transportation, appropriate and successful perioperative fluid and blood resuscitation, prompt surgical management with a team approach and critical post-operative surgical management.Keywords: The inferior vena cava (IVC), stab wound, venorrhaphy, haemoperitoneu

Establishing and augmenting acceptability of the Fever trial: a mixed methods feasibility study

Introduction: Paediatric clinical trials in critical care settings are challenging to conduct. Establishing trial acceptability can help inform trial design and avoid research waste. This paper reports on how research with parents and staff established and augmented perspectives and the design of a trial investigating temperature thresholds in critically ill children with fever and infection (Fever trial). // Methods: We used a mixed methods approach to explore perspectives at three time points: 1) before, 2) during and 3) after a pilot trial. This included: 1) pre-trial focus groups with staff and interviews with parents; 2) questionnaires with parents of randomised children following trial recruitment; 3) post-trial interviews with parents and focus groups and a survey with staff. Data analysis drew on Sekhon et al (2017) theoretical framework of acceptability. // Results: 1) 25 parents were interviewed and 56 staff took part focus groups, 2) 60 parents of 57 randomised children took part in questionnaires, 3) 19 parents were interviewed and 50 staff took part in focus group and 48 in a survey. There was initial support for the trial, although both groups raised concerns regarding proposed thresholds and not using paracetamol for pain or discomfort. Pre-trial findings informed pilot trial protocol changes and training, which assisted practitioner ‘buy in’. However, concerns about children being in pain or discomfort when weaned from ventilation led to cases of withdrawal and protocol non-adherence. Nevertheless, 95% of parents provided consent and all supported the trial. Those trained by the Fever team found the trial more acceptable than those trained by colleagues. Trusting parent and staff relationships were linked to trial acceptability. // Conclusions: Pre-trial findings and pilot trial experience augmented perspectives, providing insight into how challenges may be overcome. The proposed trial was deemed feasible. We present an adapted theoretical framework of acceptability to inform the design of future trial feasibility studies

Establishing and augmenting views on the acceptability of a paediatric critical care randomised controlled trial (the FEVER trial): a mixed methods study

OBJECTIVE: To explore parent and staff views on the acceptability of a randomised controlled trial investigating temperature thresholds for antipyretic intervention in critically ill children with fever and infection (the FEVER trial) during a multi-phase pilot study. DESIGN: Mixed methods study with data collected at three time points: (1) before, (2) during and (3) after a pilot trial. SETTING: English, Paediatric Intensive Care Units (PICUs). PARTICIPANTS: (1) Pre-pilot trial focus groups with pilot site staff (n=56) and interviews with parents (n=25) whose child had been admitted to PICU in the last 3 years with a fever and suspected infection, (2) Questionnaires with parents of randomised children following pilot trial recruitment (n=48 from 47 families) and (3) post-pilot trial interviews with parents (n=19), focus groups (n=50) and a survey (n=48) with site staff. Analysis drew on Sekhon et al's theoretical framework of acceptability. RESULTS: There was initial support for the trial, yet some held concerns regarding the proposed temperature thresholds and not using paracetamol for pain or discomfort. Pre-trial findings informed protocol changes and training, which influenced views on trial acceptability. Staff trained by the FEVER team found the trial more acceptable than those trained by colleagues. Parents and staff found the trial acceptable. Some concerns about pain or discomfort during weaning from ventilation remained. CONCLUSIONS: Pre-trial findings and pilot trial experience influenced acceptability, providing insight into how challenges may be overcome. We present an adapted theoretical framework of acceptability to inform future trial feasibility studies. TRIAL REGISTRATION NUMBERS: ISRCTN16022198 and NCT03028818

Establishing and augmenting views on the acceptability of a paediatric critical care randomised controlled trial (the FEVER trial) : a mixed methods study

Objective: To explore parent and staff views on the acceptability of a randomised controlled trial investigating temperature thresholds for antipyretic intervention in critically ill children with fever and infection (the FEVER trial) during a multi-phase pilot study. Design: Mixed methods study with data collected at three time points: (1) before, (2) during and (3) after a pilot trial. Setting: English, Paediatric Intensive Care Units (PICUs). Participants: (1) Pre-pilot trial focus groups with pilot site staff (n=56) and interviews with parents (n=25) whose child had been admitted to PICU in the last 3 years with a fever and suspected infection, (2) Questionnaires with parents of randomised children following pilot trial recruitment (n=48 from 47 families) and (3) post-pilot trial interviews with parents (n=19), focus groups (n=50) and a survey (n=48) with site staff. Analysis drew on Sekhon et al’s theoretical framework of acceptability. Results: There was initial support for the trial, yet some held concerns regarding the proposed temperature thresholds and not using paracetamol for pain or discomfort. Pre-trial findings informed protocol changes and training, which influenced views on trial acceptability. Staff trained by the FEVER team found the trial more acceptable than those trained by colleagues. Parents and staff found the trial acceptable. Some concerns about pain or discomfort during weaning from ventilation remained. Conclusions: Pre-trial findings and pilot trial experience influenced acceptability, providing insight into how challenges may be overcome. We present an adapted theoretical framework of acceptability to inform future trial feasibility studies. Trial registration numbers: ISRCTN16022198 and NCT03028818

Parents' prioritised outcomes for trials investigating treatments for paediatric severe infection:A qualitative synthesis

Objective To identify parents' prioritised outcomes by combining qualitative findings from two trial feasibility studies of interventions for paediatric suspected severe infection. Design Qualitative synthesis combining parent interview data from the Fluids in Shock (FiSh) and Fever feasibility studies. Parents had experience of their child being admitted to a UK emergency department or intensive care unit with a suspected infection. Participants n=: 85 parents. FiSh study: n=41 parents, 37 mothers, 4 fathers, 7 were bereaved. Fever study: n=44 parents, 33 mothers, 11 fathers, 7 were bereaved. Results In addition to survival, parents prioritised short-term outcomes including: organ and physiological functioning (eg, heart rate, breathing rate and temperature); their child looking and/or behaving more like their normal self; and length of time on treatments or mechanical support. Longer term prioritised outcomes included effects of illness on child health and development. We found that parents' prioritisation of outcomes was influenced by their experience of their child's illness, survival and the point at which they are asked about outcomes of importance in the course of their child's illness. Conclusions Findings provide insight into parent prioritised outcomes to inform the design of future trials investigating treatments for paediatric suspected or proven severe infection as well as core outcome set development work.</p

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

Background: Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19. Methods: RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69–0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86–1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab. Interpretation: In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research