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.
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
, 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.
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.
Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias.
ISRCTN registry: ISRCTN18296119.
IntroductionServices are being encouraged to provide postdiagnostic treatment to those with dementia but the availability of evidence-based interventions following diagnosis has not kept pace with ...increase in demand. To address this need, the Journeying through Dementia (JtD) intervention was created. A randomised controlled trial (RCT), based on a pilot study, is in progress.Methods and analysisThe RCT is a pragmatic, two-arm, parallel group trial designed to test the clinical and cost-effectiveness of JtD compared with usual care. Recruitment will be through NHS services, third sector organisations and Join Dementia Research. The sample size is 486 randomised (243 to usual care and 243 to the intervention usual care). Participants can choose to ask a friend or relative (supporter) to become involved in the study. The primary outcome measure for participants is Dementia-Related Quality of Life (DEMQOL), collected at baseline and at 8 months’ postrandomisation. Secondary outcome measures will be collected from participants and supporters at those visits. Participants will also be followed up at 12 months’ postrandomisation with a reduced set of measures. A process evaluation will be conducted through qualitative and fidelity substudies. Analyses will compare the two arms of the trial on an intention to treat as allocated basis. The primary analyses will compare the mean DEMQOL scores of the participants at 8 months between the two study arms. A cost-effectiveness analysis will consider the incremental cost per Quality Adjusted Life Years of the intervention compared with usual care. Qualitative and fidelity substudies will be analysed through framework analysis and fidelity assessment tools respectively.Ethics and disseminationREC and HRA approval were obtained. A Data Monitoring and Ethics Committee has been constituted. Dissemination will be via publications, conferences and social media. Intervention materials will be made open access.Trial registration number ISRCTN17993825.
To analyse whether an individual's neighbourhood influences the uptake of weight management strategies and whether there is an interaction between individual socio-economic status and neighbourhood ...deprivation.
Data were collected from the Yorkshire Health Study (2010-2012) for 27 806 individuals on the use of the following weight management strategies: 'slimming clubs', 'healthy eating', 'increasing exercise' and 'controlling portion size'. 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.
Significant neighbourhood effects were observed for use of 'slimming clubs', 'healthy eating' and 'increasing exercise' 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.
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 obesity.
There is an urgent clinical need for evidence-based psychosocial interventions for people with mild dementia. We aimed to determine the clinical benefits and cost-effectiveness of Journeying through ...Dementia (JtD), an intervention designed to promote wellbeing and independence in people with mild dementia.
We did a single-blind, parallel group, individually randomised, phase 3 trial at 13 National Health Service sites across England. People with mild dementia (Mini-Mental State Examination score of ≥18) who lived in the community were eligible for inclusion. Patients were centrally randomly assigned (1:1) to receive the JtD intervention plus standard care (JtD group) or standard care only (standard care group). Randomisation was stratified by study site. The JtD intervention included 12 group and four one-to-one sessions, delivered in the community at each site. The primary endpoint was Dementia Related Quality of Life (DEMQOL) 8 months after randomisation, assessed according to the intention-to-treat principle. Only outcome assessors were masked to group assignment. A cost-effectiveness analysis reported cost per quality-adjusted life-year (QALY) from a UK NHS and social care perspective. The study is registered with ISRCTN, ISRCTN17993825.
Between Nov 30, 2016, and Aug 31, 2018, 1183 patients were screened for inclusion, of whom 480 (41%) participants were randomly assigned: 241 (50%) to the JtD group and 239 (50%) to the standard care group. Intervention adherence was very good: 165 (68%) of 241 participants in the JtD group attended at least ten of the 16 sessions. Mean DEMQOL scores at 8 months were 93·3 (SD 13·0) for the JtD group and 91·9 (SD 14·6) for the control group. Difference in means was 0·9 (95% CI –1·2 to 3·0; p=0·38) after adjustment for covariates, lower than that identified as clinically meaningful. Incremental cost per QALY ranged from £88 000 to –£205 000, suggesting that JtD was not cost-effective. Unrelated serious adverse events were reported by 40 (17%) patients in the JtD group and 35 (15%) patients in the standard care group.
In common with other studies, the JtD intervention was not proven effective. However, this complex trial successfully recruited and retained people with dementia without necessarily involving carers. Additionally, people with dementia were actively involved as participants and study advisers throughout. More research into methods of measuring small, meaningful changes in this population is needed. Questions remain regarding how services can match the complex, diverse, and individual needs of people with mild dementia, and how interventions to meet such needs can be delivered at scale.
UK National Institute of Health Research Health Technology Assessment Programme.
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.
This open-label, multicentre, randomised controlled trial was conducted in nine National Health Service hospital trusts across the UK. Adults (aged 18–60 years) with active Crohn's disease on endoscopy (Simplified Endoscopic Score for Crohn's Disease SES-CD ulcer sub-score of ≥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 μg/kg) and stem-cell harvest (minimum 2·0 × 106 CD34+ cells per kg), before conditioning (fludarabine 125 mg/m2, cyclophosphamide 120 mg/kg, and rabbit anti-thymocyte globulin thymoglobulin 7·5 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.
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.
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.
Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.
Uptake of screening for colorectal cancer (CRC) can reduce mortality, and population-based screening is offered in England. To date, there is little evidence on the association between having a ...long-term condition (LTC) and CRC screening uptake. The objective of this study was to examine the association between having an LTC and uptake of CRC screening in England with the guaiac fecal occult blood test, with a particular focus on common mental disorders.
The study was a preregistered secondary analysis of two cohorts: first, a linked data set between the regional Yorkshire Health Study (YHS) and the National Health Service National Bowel Cancer Screening Program (BCSP, years 2006-2014); second, the national English Longitudinal Study of Ageing (ELSA, years 2014-2015). Individuals eligible for BCSP screening who participated in either the YHS (7,142) or ELSA Wave 7 (4,099) were included. Study registration: ClinicalTrials.gov, number NCT02503969.
In both the cohorts, diabetes was associated with lower uptake (YHS odds ratio OR for non-uptake 1.35, 95% CI 1.03-1.78; ELSA 1.33, 1.03-1.72) and osteoarthritis was associated with increased uptake (YHS 0.75, 0.57-0.99; ELSA 0.76, 0.62-0.93). After controlling for broader determinants of health, there was no evidence of significantly different uptake for individuals with common mental disorders.
Two large independent cohorts provided evidence that uptake of CRC screening is lower among individuals with diabetes and higher among individuals with osteoarthritis. Further work should compare barriers and facilitators to screening among individuals with either of these conditions. This study also demonstrates the benefits of data linkage for improving clinical decision-making.
1. The extracellular proteins caeruloplasmin and transferrin have important antioxidant properties by virtue of the fact that they inhibit iron-dependent free radical production, and ensuing damage ...to cells. 2. Albumin is a plasma protein which can loosely bind iron, but the redox activity of this iron has not been fully investigated. 3. The ability of albumin to bind iron and to prevent iron-dependent lipid peroxidation in vitro was investigated using liposomes and a rat brain homogenate system. 4. The iron-binding capacity of albumin was found to be substantial, and albumin inhibited lipid peroxidation in a concentration-dependent manner in both systems used. 5. This antioxidant property of albumin may be especially important in the plasma of babies born prematurely, in whom transferrin and caeruloplasmin concentrations are often very low, and in whom non-transferrin-bound iron has been detected in the plasma.
High concentrations of total vitamin C have been measured in the plasma of premature infants. At these concentrations ascorbic acid inhibited the ferroxidase activity of caeruloplasmin measured ...directly in vitro. The degree of inhibition was dependent on the ratio of ascorbic acid: caeruloplasmin. Values for the ratio of vitamin C: caeruloplasmin measured in premature babies would be predicted to inhibit ferroxidase activity by up to at least 80%. Ferroxidase activity measured in the plasma of premature babies increased from birth but was significantly lower than in plasma collected from adults (<0.001). Plasma ferroxidase activity was correlated with plasma caeruloplasmin concentration and, in premature babies only, showed a negative correlation with the ratio of vitamin C to caeruloplasmin. High levels of vitamin C in premature babies may compromise antioxidant mechanisms and exacerbate oxidant damage.
Adding vitamin D to a low calcium diet is known to effect trabecular but not cortical bone. Although adding phytase (P) to a low zinc (Zn) diet improves overall bone strength by increasing the ...bioavailability of Zn and other micronutrients, it is unknown if this supplementation has a differential effect on cortical and trabecular bone.
Purpose
Examine the effect of P‐supplementation to a low Zn diet in cortical and trabecular bone in both, L‐4 vertebrae and tibiae of rats.
Methods
Male Sprague‐Dawley rats were fed a diet containing either 5ppm Zn (ZnLo) (n=10), 5ppm Zn+1,500FTU/kg P (ZnLo+P) (n=10), or 30ppm Zn (ZnAd) (n=10) for 9 wks.
In vivo
peripheral quantitative computed tomography was used to scan right tibiae at 10% (trabecular parameters) and 50% (cortical parameters) of total. The L‐4 vertebrae were scanned at the 40, 50, and 60% of total length; an average of these represented the mid‐20% vertebral region. One way ANOVA determined group differences for cortical and trabecular bone mineral content (BMC), bone area (BA) and bone mineral density (BMD).
Results
Cortical parameters at the L‐4 were significantly higher in rats fed ZnLo+P compared to ZnLo diets. There was no significant difference between groups in trabecular parameters.
Conclusion
In contrast to the vitamin D:calcium relationship, P‐supplementation of a low Zn diet exhibited a positive effect on cortical BMD, BMC and BA at the L‐4 site, but had no effect on trabecular or tibial parameters.
The study was funded by the U.S.Army MRMC
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