148 research outputs found
Π‘Π΅Π»Π΅ΠΊΡΠΈΡ ΠΈ ΠΊΠΎΠΌΠΏΠ΅Π½ΡΠ°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΠΎΠ² ΡΠΏΡΡΠΈΠ½Π³Π° Π² Π³ΡΠ°ΠΆΠ΄Π°Π½ΡΠΊΠΎΠΉ Π°ΠΏΠΏΠ°ΡΠ°ΡΡΡΠ΅ ΠΏΠΎΡΡΠ΅Π±ΠΈΡΠ΅Π»Ρ Π³Π»ΠΎΠ±Π°Π»ΡΠ½ΠΎΠΉ Π½Π°Π²ΠΈΠ³Π°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠΏΡΡΠ½ΠΈΠΊΠΎΠ²ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ Ρ ΠΌΠ½ΠΎΠ³ΠΎΠΊΠ°Π½Π°Π»ΡΠ½ΠΎΠΉ ΠΏΡΠΈΠ΅ΠΌΠ½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΠΎΠΉ
A method for selecting spoofing signals in consumer equipment with a multichannel antenna system is proposed. The method provides for consistent filtering of the received signals at the outputs of all antenna system elements and by ranging codes of all navigation satellites, detection and measurement of the time delay of the true and false navigation signals in each code channel by the output signal of one of the antenna system elements, measurement of the phase difference of the signals at the outputs of the antenna system elements and the selected reference element for the estimated time delay in each channel by code. Compensation of spoofing signals is carried out in the spatial domain by estimating the correlation matrix of processes at the outputs of the antenna system channels by the corresponding countdown of code channel signals after matched filtering and forming of a weight vector while minimizing the output power of spoofing signals by directly inverting the estimate of the correlation matrix and carrying out weight processing of the adopted implementation. The simulation results are presented, confirming the efficiency of the method.ΠΡΠ΅Π΄Π»ΠΎΠΆΠ΅Π½ ΠΌΠ΅ΡΠΎΠ΄ ΡΠ΅Π»Π΅ΠΊΡΠΈΠΈ ΡΠΈΠ³Π½Π°Π»ΠΎΠ² ΡΠΏΡΡΠΈΠ½Π³Π° (ΠΎΡ Π°Π½Π³Π». spoofing β ΠΏΠΎΠ΄ΠΌΠ΅Π½Π°) Π² Π³ΡΠ°ΠΆΠ΄Π°Π½ΡΠΊΠΎΠΉ Π°ΠΏΠΏΠ°ΡΠ°ΡΡΡΠ΅ ΠΏΠΎΡΡΠ΅Π±ΠΈΡΠ΅Π»Ρ Ρ ΠΌΠ½ΠΎΠ³ΠΎΠΊΠ°Π½Π°Π»ΡΠ½ΠΎΠΉ Π°Π½ΡΠ΅Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΠΎΠΉ. ΠΠ΅ΡΠΎΠ΄ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅Ρ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½Π½ΡΡ ΡΠΈΠ»ΡΡΡΠ°ΡΠΈΡ ΠΏΡΠΈΠ½ΠΈΠΌΠ°Π΅ΠΌΡΡ
ΡΠΈΠ³Π½Π°Π»ΠΎΠ² Π½Π° Π²ΡΡ
ΠΎΠ΄Π°Ρ
Π²ΡΠ΅Ρ
ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠ΅Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΠΈ ΠΏΠΎ Π΄Π°Π»ΡΠ½ΠΎΠΌΠ΅ΡΠ½ΡΠΌ ΠΊΠΎΠ΄Π°ΠΌ Π²ΡΠ΅Ρ
Π½Π°Π²ΠΈΠ³Π°ΡΠΈΠΎΠ½Π½ΡΡ
ΡΠΏΡΡΠ½ΠΈΠΊΠΎΠ², ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½ΠΈΠ΅ ΠΈ ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ Π²ΡΠ΅ΠΌΠ΅Π½ Π·Π°Π΄Π΅ΡΠΆΠΊΠΈ ΠΈΡΡΠΈΠ½Π½ΡΡ
ΠΈ Π»ΠΎΠΆΠ½ΡΡ
Π½Π°Π²ΠΈΠ³Π°ΡΠΈΠΎΠ½Π½ΡΡ
ΡΠΈΠ³Π½Π°Π»ΠΎΠ² Π² ΠΊΠ°ΠΆΠ΄ΠΎΠΌ ΠΊΠΎΠ΄ΠΎΠ²ΠΎΠΌ ΠΊΠ°Π½Π°Π»Π΅ ΠΏΠΎ Π²ΡΡ
ΠΎΠ΄Π½ΠΎΠΌΡ ΡΠΈΠ³Π½Π°Π»Ρ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΈΠ· ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠ΅Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ, ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΡΠ°Π·Π½ΠΎΡΡΠΈ ΡΠ°Π· ΡΠΈΠ³Π½Π°Π»ΠΎΠ² Π½Π° Π²ΡΡ
ΠΎΠ΄Π°Ρ
ΡΠ»Π΅ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠ΅Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΠΈ Π²ΡΠ±ΡΠ°Π½Π½ΠΎΠ³ΠΎ ΠΎΠΏΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ° ΠΏΠΎ ΡΠ°ΡΡΠ΅ΡΠ½ΡΠΌ Π²ΡΠ΅ΠΌΠ΅Π½Π°ΠΌ Π·Π°Π΄Π΅ΡΠΆΠΊΠΈ Π² ΠΊΠ°ΠΆΠ΄ΠΎΠΌ ΠΊΠ°Π½Π°Π»Π΅ ΠΏΠΎ ΠΊΠΎΠ΄Ρ. ΠΠΎΠΌΠΏΠ΅Π½ΡΠ°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΠΎΠ² ΡΠΏΡΡΠΈΠ½Π³Π° ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ΅ΡΡΡ Π² ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ ΠΏΡΡΠ΅ΠΌ ΠΎΡΠ΅Π½ΠΈΠ²Π°Π½ΠΈΡ ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΌΠ°ΡΡΠΈΡΡ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² Π½Π° Π²ΡΡ
ΠΎΠ΄Π°Ρ
ΠΊΠ°Π½Π°Π»ΠΎΠ² Π°Π½ΡΠ΅Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΠΏΠΎ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΠΌ ΠΎΡΡΡΠ΅ΡΠ°ΠΌ ΡΠΈΠ³Π½Π°Π»ΠΎΠ² ΠΊΠΎΠ΄ΠΎΠ²ΡΡ
ΠΊΠ°Π½Π°Π»ΠΎΠ² ΠΏΠΎΡΠ»Π΅ ΡΠΎΠ³Π»Π°ΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠΈΠ»ΡΡΡΠ°ΡΠΈΠΈ, ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π²Π΅ΡΠΎΠ²ΠΎΠ³ΠΎ Π²Π΅ΠΊΡΠΎΡΠ° ΠΏΡΠΈ ΠΌΠΈΠ½ΠΈΠΌΠΈΠ·Π°ΡΠΈΠΈ Π²ΡΡ
ΠΎΠ΄Π½ΠΎΠΉ ΠΌΠΎΡΠ½ΠΎΡΡΠΈ ΡΠΈΠ³Π½Π°Π»ΠΎΠ² ΡΠΏΡΡΠΈΠ½Π³Π° ΠΏΡΡΠ΅ΠΌ Π½Π΅ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²Π΅Π½Π½ΠΎΠ³ΠΎ ΠΎΠ±ΡΠ°ΡΠ΅Π½ΠΈΡ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΊΠΎΡΡΠ΅Π»ΡΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΌΠ°ΡΡΠΈΡΡ ΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ Π²Π΅ΡΠΎΠ²ΠΎΠΉ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠΈ ΠΏΡΠΈΠ½ΡΡΠΎΠΉ ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ, ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°ΡΡΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΌΠ΅ΡΠΎΠ΄Π°
Π‘Π΅Π»Π΅ΠΊΡΠΈΡ ΠΈ ΠΊΠΎΠΌΠΏΠ΅Π½ΡΠ°ΡΠΈΡ ΡΠΈΠ³Π½Π°Π»ΠΎΠ² ΡΠΏΡΡΠΈΠ½Π³Π° Π² Π³ΡΠ°ΠΆΠ΄Π°Π½ΡΠΊΠΎΠΉ Π°ΠΏΠΏΠ°ΡΠ°ΡΡΡΠ΅ ΠΏΠΎΡΡΠ΅Π±ΠΈΡΠ΅Π»Ρ Π³Π»ΠΎΠ±Π°Π»ΡΠ½ΠΎΠΉ Π½Π°Π²ΠΈΠ³Π°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠΏΡΡΠ½ΠΈΠΊΠΎΠ²ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ Ρ ΠΌΠ½ΠΎΠ³ΠΎΠΊΠ°Π½Π°Π»ΡΠ½ΠΎΠΉ ΠΏΡΠΈΠ΅ΠΌΠ½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΠΎΠΉ
A method for selecting spoofing signals in consumer equipment with a multichannel antenna system is proposed. The method provides for consistent filtering of the received signals at the outputs of all antenna system elements and by ranging codes of all navigation satellites, detection and measurement of the time delay of the true and false navigation signals in each code channel by the output signal of one of the antenna system elements, measurement of the phase difference of the signals at the outputs of the antenna system elements and the selected reference element for the estimated time delay in each channel by code. Compensation of spoofing signals is carried out in the spatial domain by estimating the correlation matrix of processes at the outputs of the antenna system channels by the corresponding countdown of code channel signals after matched filtering and forming of a weight vector while minimizing the output power of spoofing signals by directly inverting the estimate of the correlation matrix and carrying out weight processing of the adopted implementation. The simulation results are presented, confirming the efficiency of the method
Autologous stem cell transplantation with low-dose cyclophosphamide to improve mucosal healing in adults with refractory Crohn's disease: the ASTIClite RCT
Some text in this abstract has been reproduced from Lindsay J, Din S, Hawkey C, Hind D, Irving P, Lobo A, et al. OFR-9 An RCT of autologous stem-cell transplantation in treatment refractory Crohnβs disease (low-intensity therapy evaluation): ASTIClite. Gut 2021;70(Suppl. 4):A4.
Background
Treatment-refractory Crohnβs disease is characterised by chronic symptoms, poor quality of life and high costs to the NHS, and through days of work lost by patients. A previous trial of autologous haematopoietic stem cell transplant (HSCT) failed its end point of medication-free clinical remission for 3 months with no evidence of disease activity, and reported high toxicity. Subsequent studies suggest that HSCT achieves complete mucosal healing in 50% of patients, and that toxicity likely relates to the cyclophosphamide dose.
Objectives
The primary objective was to assess the efficacy of HSCTlite (HSCT with low-dose cyclophosphamide) compared with standard care for inducing regression of intestinal ulceration in patients with refractory Crohnβs disease at week 48. Secondary objectives included the assessment of disease activity, quality of life and regimen safety. Mechanistic objectives included immune reconstitution after HSCTlite.
Design
Two-arm, parallel-group randomised controlled trial with a 2β:β1 (interventionβ:βcontrol) allocation ratio.
Setting
Nine NHS trusts (eight trusts were recruitment sites; one trust was a treatment-only site).
Participants
Adults with treatment-refractory Crohnβs disease, for whom surgery was inappropriate or who had declined surgery.
Interventions
The intervention treatment was HSCTlite using cyclophosphamide, and the control was any current available treatment for Crohnβs disease, apart from stem cell transplantation.
Main outcomes
The primary outcome was treatment success at week 48 [mucosal healing (Simple Endoscopic Score for Crohnβs Disease ulcer subscore of 0) without surgery or death], assessed by central readers blinded to allocation and timing of assessment. Key secondary outcomes were clinical remission, Simple Endoscopic Score for Crohnβs Disease scores at week 48, change in Crohnβs Disease Activity Index scores and safety.
Results
The trial was halted owing to Suspected unexpected serious adverse events that took place after randomising 23 patients (HSCTlite arm, nβ=β13; usual-care arm, nβ=β10). Ten out of the 13 patients randomised to the HSCTlite arm received the intervention and nine (one death) reached the 48-week follow-up. In the usual-care arm 9 out of the 10 patients randomised reached the 48-week follow-up (one ineligible). The primary outcome was available for 7 out of 10 HSCTlite patients (including the patient who died) and six out of nine usual-care patients. Absence of endoscopic ulceration without surgery or death was reported in three out of seven (43%) HSCTlite patients, compared with zero out of six (0%) usual-care patients. Centrally read Simple Endoscopic Score for Crohnβs Disease scores [mean (standard deviation)] were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Clinical remission (Crohnβs Disease Activity Index scores of <β150) occurred in 57% and 17% of patients in the HSCTlite and usual-care arms, respectively, at week 48. Serious adverse events were more frequent in the HSCTlite arm [38 in 13 (100%) patients] than in the usual-care arm [16 in 4 (40%) patients]. Nine suspected unexpected serious adverse reactions were reported in six HSCTlite patients, including three cases of delayed renal failure due to proven thrombotic microangiopathy. Two HSCTlite patients died.
Conclusions
Within the limitations of reduced patient recruitment and numbers of patients assessed, HSCTlite meaningfully reduced endoscopic disease activity, with three patients experiencing resolution of ulceration. Suspected unexpected serious adverse reactions, particularly relating to thrombotic microangiopathy, make this regimen unsuitable for future clinical use.
Limitations
The early trial closure prevented complete recruitment, and the impact of the coronavirus pandemic prevented completion of some study investigations. Small participant numbers meant analysis could only be descriptive.
Future work
Owing to undetermined aetiology of thrombotic microangiopathy, further trials of HSCTlite in this population are not considered appropriate. Priorities should be to determine optimal treatment strategies for patients with refractory Crohnβs disease, including those with a stoma or multiple previous resections
Flexor Injury Rehabilitation Splint Trial (FIRST): protocol for a pragmatic randomised controlled trial comparing three splints for finger flexor tendon repairs
Background
Without surgical repair, flexor tendon injuries do not heal and patientsβ ability to bend fingers and grip objects is impaired. However, flexor tendon repair surgery also requires optimal rehabilitation. There are currently three custom-made splints used in the rehabilitation of zone I/II flexor tendon repairs, each with different assumed harm/benefit profiles: the dorsal forearm and hand-based splint (long), the Manchester short splint (short), and the relative motion flexion splint (mini). There is, however, no robust evidence as to which splint, if any, is most clinical or cost effective. The Flexor Injury Rehabilitation Splint Trial (FIRST) was designed to address this evidence gap.
Methods
FIRST is a parallel group, superiority, analyst-blind, multi-centre, individual participant-randomised controlled trial. Participants will be assigned 1:1:1 to receive either the long, short, or mini splint. We aim to recruit 429 participants undergoing rehabilitation following zone I/II flexor tendon repair surgery. Potential participants will initially be identified prior to surgery, in NHS hand clinics across the UK, and consented and randomised at their splint fitting appointment post-surgery. The primary outcome will be the mean post-randomisation score on the patient-reported wrist and hand evaluation measure (PRWHE), assessed at 6, 12, 26, and 52 weeks post randomisation. Secondary outcome measures include blinded grip strength and active range of movement (AROM) assessments, adverse events, adherence to the splinting protocol (measured via temperature sensors inserted into the splints), quality of life assessment, and further patient-reported outcomes. An economic evaluation will assess the cost-effectiveness of each splint, and a qualitative sub-study will evaluate participantsβ preferences for, and experiences of wearing, the splints. Furthermore, a mediation analysis will determine the relationship between patient preferences, splint adherence, and splint effectiveness.
Discussion
FIRST will compare the three splints with respect to clinical efficacy, complications, quality of life and cost-effectiveness. FIRST is a pragmatic trial which will recruit from 26 NHS sites to allow findings to be generalisable to current clinical practice in the UK. It will also provide significant insights into patient experiences of splint wear and how adherence to splinting may impact outcomes.
Trial registration
ISRCTN: 1023601
βFish out of waterβ: a cross-sectional study on the interaction between social and neighbourhood effects on weight management behaviours
Objective:
To analyse whether an individualβs neighbourhood influences the uptake of weight management strategies and whether there is an interaction between individual socio-economic status and neighbourhood deprivation.
Methodology:
Data were collected from the Yorkshire Health Study (2010β2012) for 27 806 individuals on the use of the following weight management strategies: βslimming clubsβ, βhealthy eatingβ, βincreasing exerciseβ and βcontrolling portion sizeβ. A multi-level logistic regression was fit to analyse the use of these strategies, controlling for age, sex, body mass index, education, neighbourhood deprivation and neighbourhood population turnover (a proxy for neighbourhood social capital). A cross-level interaction term was included for education and neighbourhood deprivation. Lower Super Output Area was used as the geographical scale for the areal unit of analysis.
Results:
Significant neighbourhood effects were observed for use of βslimming clubsβ, βhealthy eatingβ and βincreasing exerciseβ as weight management strategies, independent of individual- and area-level covariates. A significant interaction between education and neighbourhood deprivation was observed across all strategies, suggesting that as an area becomes more deprived, individuals of the lowest education are more likely not to use any strategy compared with those of the highest education.
Conclusions:
Neighbourhoods modify/amplify individual disadvantage and social inequalities, with individuals of low education disproportionally affected by deprivation. It is important to include neighbourhood-based explanations in the development of community-based policy interventions to help tackle obesit
The MAGIC trial: a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia
\ua9 2023 The Author(s)Background: Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results. Methods: This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kgβ1, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals. Results: The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6β10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7β22.4) and 12.9 (3.1β22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm. Conclusion: Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias. Clinical trial registration: ISRCTN registry: ISRCTN18296119
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Safety and efficacy of autologous haematopoietic stem-cell transplantation with low-dose cyclophosphamide mobilisation and reduced intensity conditioning versus standard of care in refractory Crohnβs disease (ASTIClite): an open-label, multicentre, randomised controlled trial
Background
A previous controlled trial of autologous haematopoietic stem-cell transplantation (HSCT) in patients with refractory Crohn's disease did not meet its primary endpoint and reported high toxicity. We aimed to assess the safety and efficacy of HSCT with an immune-ablative regimen of reduced intensity versus standard of care in this patient population.
Methods
This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18β60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease [SES-CD] ulcer sub-score of β₯2) refractory to two or more classes of biological therapy, with no perianal or intra-abdominal sepsis or clinically significant comorbidity, were recruited. Participants were centrally randomly assigned (2:1) to either HSCT with a reduced dose of cyclophosphamide (intervention group) or standard care (control group). Randomisation was stratified by trial site by use of random permuted blocks of size 3 and 6. Patients in the intervention group underwent stem-cell mobilisation (cyclophosphamide 1 g/m2 with granulocyte colony-stimulating factor (G-CSF) 5 ΞΌg/kg) and stem-cell harvest (minimum 2Β·0βΓβ106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin [thymoglobulin] 7Β·5 mg/kg in total) and subsequent stem-cell reinfusion supported by G-CSF. Patients in the control group continued any available conventional, biological, or nutritional therapy. The primary outcome was absence of endoscopic ulceration (SES-CD ulcer sub-score of 0) without surgery or death at week 48, analysed in the intention-to-treat population by central reading. This trial is registered with the ISRCTN registry, 17160440.
Findings
Between Oct 18, 2018, and Nov 8, 2019, 49 patients were screened for eligibility, of whom 23 (47%) were randomly assigned: 13 (57%) to the intervention group and ten (43%) to the control group. In the intervention group, ten (77%) participants underwent HSCT and nine (69%) reached 48-week follow-up; in the control group, nine (90%) reached 48-week follow-up. The trial was halted in response to nine reported suspected unexpected serious adverse reactions in six (46%) patients in the intervention group, including renal failure due to proven thrombotic microangiopathy in three participants and one death due to pulmonary veno-occlusive disease. At week 48, absence of endoscopic ulceration without surgery or death was reported in three (43%) of seven participants in the intervention group and in none of six participants in the control group with available data. Serious adverse events were more frequent in the intervention group (38 in 13 [100%] patients) than in the control group (16 in four [40%] patients). A second patient in the intervention group died after week 48 of respiratory and renal failure.
Interpretation
Although HSCT with an immune-ablative regimen of reduced intensity decreased endoscopic disease activity, significant adverse events deem this regimen unsuitable for future clinical use in patients with refractory Crohn's disease.
Funding
Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership
Albumin and multiple sclerosis
A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Leakage of the bloodβbrain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth
The MAGIC trial: a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia
BACKGROUND: Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results. METHODS: This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg-1, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals. RESULTS: The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6-10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7-22.4) and 12.9 (3.1-22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm. CONCLUSION: Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias. CLINICAL TRIAL REGISTRATION: ISRCTN registry: ISRCTN18296119
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