Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children.
We did a multicentre, pragmatic, ...parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via antenatal or postnatal services for recruitment of term infants (at least 37 weeks' gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment.
1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 95% CI 0·78 to 1·16, p=0·61; adjusted risk difference –1·2% –5·9 to 3·6). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09).
We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn.
National Institute for Health Research Health Technology Assessment.
Background: a high prevalence of co-morbid mental health problems is reported among older adults admitted to general hospitals.
Setting: an 1,800 bed teaching hospital.
Design: consecutive general ...medical and trauma orthopaedic admissions aged 70 or older were screened for mental health problems. Those screening positive were invited to undergo further assessment, and were interviewed to complete a battery of health status measurements.
Results: of 1,004 patients screened, 36% had no mental health problems or had anxiety alone. Of those screening positive 250 took part in the full study. Adjusting for the two-stage sampling design, 50% of admitted patients over 70 were cognitively impaired, 27% had delirium and 8-32% were depressed. Six percent had hallucinations, 8% delusions, 21% apathy and 9% agitation/aggression (of at least moderate severity). Of those with mental health problems, 47% were incontinent, 49% needed help with feeding and 44% needed major help to transfer.
Interpretation: we confirm the high prevalence of mental health problems among older adults admitted to general hospitals. These patients have high levels of functional dependency, psychological and behavioural problems which have implications for how they are cared for. Services that identify these problems and offer therapeutic intervention should be evaluated.
Atopic eczema (AE) is a common skin problem that impairs quality of life and is associated with the development of other atopic diseases including asthma, food allergy and allergic rhinitis. AE ...treatment is a significant cost burden for health care providers. The purpose of the trial is to investigate whether daily application of emollients for the first year of life can prevent AE developing in high-risk infants (first-degree relative with asthma, AE or allergic rhinitis).
This is a protocol for a pragmatic, two-arm, randomised controlled, multicentre trial. Up to 1400 term infants at high risk of developing AE will be recruited through the community, primary and secondary care in England. Participating families will be randomised in a 1:1 ratio to receive general infant skin-care advice, or general skin-care advice plus emollients with advice to apply daily to the infant for the first year of life. Families will not be blinded to treatment allocation. The primary outcome will be a blinded assessment of AE at 24 months of age using the UK Working Party Diagnostic Criteria for Atopic Eczema. Secondary outcomes are other definitions of AE, time to AE onset, severity of AE (EASI and POEM), presence of other allergic diseases including food allergy, asthma and hay fever, allergic sensitisation, quality of life, cost-effectiveness and safety of the emollients. Subgroup analyses are planned for the primary outcome according to filaggrin genotype and the number of first-degree relatives with AE and other atopic diseases. Families will be followed up by online and postal questionnaire at 3, 6, 12 and 18 months with a face-to-face visit at 24 months. Long-term follow-up until 60 months will be via annual questionnaires.
This trial will demonstrate whether skin-barrier enhancement through daily emollient for the first year of life can prevent AE from developing in high-risk infants. If effective, this simple and cheap intervention has the potential to result in significant cost savings for health care providers throughout the world by preventing AE and possibly other associated allergic diseases.
ISRCTN registry; ID: ISRCTN21528841 . Registered on 25 July 2014.
The role of clothing in the management of eczema (also called atopic dermatitis or atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments ...(in addition to standard care) for the management of eczema in children with moderate to severe disease.
This was a parallel-group, randomised, controlled, observer-blind trial. Children aged 1 to 15 y with moderate to severe eczema were recruited from secondary care and the community at five UK medical centres. Participants were allocated using online randomisation (1:1) to standard care or to standard care plus silk garments, stratified by age and recruiting centre. Silk garments were worn for 6 mo. Primary outcome (eczema severity) was assessed at baseline, 2, 4, and 6 mo, by nurses blinded to treatment allocation, using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). A safety outcome was number of skin infections. Three hundred children were randomised (26 November 2013 to 5 May 2015): 42% girls, 79% white, mean age 5 y. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights 25th to 75th centile 57% to 96% and 34% of days 25th to 75th centile 10% to 76%). Geometric mean EASI scores at baseline, 2, 4, and 6 mo were, respectively, 9.2, 6.4, 5.8, and 5.4 for silk clothing and 8.4, 6.6, 6.0, and 5.4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age, and centre: adjusted ratio of geometric means 0.95, 95% CI 0.85 to 1.07, (p = 0.43). This confidence interval is equivalent to a difference of -1.5 to 0.5 in the original EASI units, which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) of children in the silk clothing and standard care groups, respectively. Even if the small observed treatment effect was genuine, the incremental cost per quality-adjusted life year was £56,811 in the base case analysis from a National Health Service perspective, suggesting that silk garments are unlikely to be cost-effective using currently accepted thresholds. The main limitation of the study is that use of an objective primary outcome, whilst minimising detection bias, may have underestimated treatment effects.
Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema.
Current Controlled Trials ISRCTN77261365.
People with traumatic brain injuries (TBIs) commonly report memory impairments. These are persistent, debilitating and reduce quality of life, but patients do not routinely receive memory ...rehabilitation after discharge from hospital.
To assess the clinical effectiveness and cost-effectiveness of a group memory rehabilitation programme for people with TBI.
Multicentre, pragmatic, cluster randomised controlled trial. Qualitative and health economic evaluations were also undertaken.
Community settings in nine sites in England.
Participants were aged 18-69 years, had undergone a TBI > 3 months prior to recruitment, reported memory problems, were able to travel to a site to attend group sessions, could communicate in English and gave informed consent.
Clusters of four to six participants were randomised to the memory rehabilitation arm or the usual-care arm on a 1 : 1 ratio. Randomisation was based on a computer-generated pseudo-random code using random permuted blocks of randomly varying size, stratified by study site. Participants and therapists were aware of the treatment allocation whereas outcome assessors were blinded.
In the memory rehabilitation arm 10 weekly sessions of a manualised memory rehabilitation programme were provided in addition to usual care. Participants were taught restitution strategies to retrain impaired memory functions and compensation strategies to enable them to cope with memory problems. The usual-care arm received usual care only.
Outcomes were assessed at 6 and 12 months after randomisation. Primary outcome: patient-completed Everyday Memory Questionnaire - patient version (EMQ-p) at 6 months' follow-up. Secondary outcomes: Rivermead Behavioural Memory Test - third edition (RBMT-3), General Health Questionnaire 30-item version, European Brain Injury Questionnaire, Everyday Memory Questionnaire - relative version and individual goal attainment. Costs (based on a UK NHS and Personal Social Services perspective) were collected using a service use questionnaire, with the EuroQol-5 Dimensions, five-level version, used to derive quality-adjusted life-years (QALYs). A Markov model was developed to explore cost-effectiveness at 5 and 10 years, with a 3.5% discount applied.
We randomised 328 participants (memory rehabilitation,
= 171; usual care,
= 157), with 129 in the memory rehabilitation arm and 122 in the usual-care arm included in the primary analysis. We found no clinically important difference on the EMQ-p between the two arms at 6 months' follow-up (adjusted difference in mean scores -2.1, 95% confidence interval -6.7 to 2.5;
= 0.37). For secondary outcomes, differences favouring the memory rehabilitation arm were observed at 6 months' follow-up for the RBMT-3 and goal attainment, but remained only for goal attainment at 12 months' follow-up. There were no differences between arms in mood or quality of life. The qualitative results suggested positive experiences of participating in the trial and of attending the groups. Participants reported that memory rehabilitation was not routinely accessible in usual care. The primary health economics outcome at 12 months found memory rehabilitation to be £26.89 cheaper than usual care but less effective, with an incremental QALY loss of 0.007. Differences in costs and effects were not statistically significant and non-parametric bootstrapping demonstrated considerable uncertainty in these findings. No safety concerns were raised and no deaths were reported.
As a pragmatic trial, we had broad inclusion criteria and, therefore, there was considerable heterogeneity within the sample. The study was not powered to perform further subgroup analyses. Participants and therapists could not be blinded to treatment allocation.
The group memory rehabilitation delivered in this trial is very unlikely to lead to clinical benefits or to be a cost-effective treatment for people with TBI in the community. Future studies should examine the selection of participants who may benefit most from memory rehabilitation.
Current Controlled Trials ISRCTN65792154.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 23, No. 16. See the NIHR Journals Library website for further project information.
Recent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy.
To determine the cost-effectiveness of daily all-over-body application of ...emollient during the first year of life for preventing atopic eczema in high-risk children at 2 years from a health service perspective. We also considered a 5-year time horizon as a sensitivity analysis.
A within-trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost-effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost-effectiveness analysis. Secondary analysis, undertaken as a cost-utility analysis, reports incremental cost per Quality-Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU-9D at 2 years.
At 2 years, the adjusted incremental cost was £87.45 (95% CI -54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI -0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI -0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, -£106.89 (95% CI -354.66, 140.88) and the proportion without eczema was -0.0329 (95% CI -0.0659, 0.0002). The 5-year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group.
In line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high-risk children does not appear cost-effective.
People with multiple sclerosis have problems with memory and attention. The effectiveness of cognitive rehabilitation has not been established.
The objectives were to assess the clinical ...effectiveness and cost-effectiveness of a cognitive rehabilitation programme for people with multiple sclerosis.
This was a multicentre, randomised controlled trial in which participants were randomised in a ratio of 6 : 5 to receive cognitive rehabilitation plus usual care or usual care alone. Participants were assessed at 6 and 12 months after randomisation.
The trial was set in hospital neurology clinics and community services.
Participants were people with multiple sclerosis who had cognitive problems, were aged 18-69 years, could travel to attend group sessions and gave informed consent.
The intervention was a group cognitive rehabilitation programme delivered weekly by an assistant psychologist to between four and six participants for 10 weeks.
The primary outcome was the Multiple Sclerosis Impact Scale - Psychological subscale at 12 months. Secondary outcomes included results from the Everyday Memory Questionnaire, the 30-Item General Health Questionnaire, the EuroQol-5 Dimensions, five-level version and a service use questionnaire from participants, and the Everyday Memory Questionnaire - relative version and the Modified Carer Strain Index from a relative or friend of the participant.
Of the 449 participants randomised, 245 were allocated to cognitive rehabilitation (intervention group) and 204 were allocated to usual care (control group). Of these, 214 in the intervention group and 173 in the control group were included in the primary analysis. There was no clinically important difference in the Multiple Sclerosis Impact Scale - Psychological subscale score between the two groups at the 12-month follow-up (adjusted difference in means -0.6, 95% confidence interval -1.5 to 0.3;
= 0.20). There were no important differences between the groups in relation to cognitive abilities, fatigue, employment, or carer strain at follow-up. However, there were differences, although small, between the groups in the Multiple Sclerosis Impact Scale - Psychological subscale score at 6 months (adjusted difference in means -0.9, 95% confidence interval -1.7 to -0.1;
= 0.03) and in everyday memory on the Everyday Memory Questionnaire as reported by participants at 6 (adjusted difference in means -5.3, 95% confidence interval -8.7 to -1.9) and 12 months (adjusted difference in means -4.4, 95% confidence interval -7.8 to -0.9) and by relatives at 6 (adjusted difference in means -5.4, 95% confidence interval -9.1 to -1.7) and 12 months (adjusted difference in means -5.5, 95% confidence interval -9.6 to -1.5) in favour of the cognitive rehabilitation group. There were also differences in mood on the 30-Item General Health Questionnaire at 6 (adjusted difference in means -3.4, 95% confidence interval -5.9 to -0.8) and 12 months (adjusted difference in means -3.4, 95% confidence interval -6.2 to -0.6) in favour of the cognitive rehabilitation group. A qualitative analysis indicated perceived benefits of the intervention. There was no evidence of a difference in costs (adjusted difference in means -£574.93, 95% confidence interval -£1878.93 to £729.07) or quality-adjusted life-year gain (adjusted difference in means 0.00, 95% confidence interval -0.02 to 0.02). No safety concerns were raised and no deaths were reported.
The trial included a sample of participants who had relatively severe cognitive problems in daily life. The trial was not powered to perform subgroup analyses. Participants could not be blinded to treatment allocation.
This cognitive rehabilitation programme had no long-term benefits on quality of life for people with multiple sclerosis.
Future research should evaluate the selection of those who may benefit from cognitive rehabilitation.
Current Controlled Trials ISRCTN09697576.
This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in
; Vol. 24, No. 4. See the National Institute for Health Research Journals Library website for further project information.
Poor outcomes and high resource-use are observed for frail older people discharged from acute medical units. A specialist geriatric medical intervention, to facilitate Comprehensive Geriatric ...Assessment, was developed to reduce the incidence of adverse outcomes and associated high resource-use in this group in the post-discharge period.
To examine the costs and cost-effectiveness of a specialist geriatric medical intervention for frail older people in the 90 days following discharge from an acute medical unit, compared with standard care.
Economic evaluation was conducted alongside a two-centre randomised controlled trial (AMIGOS). 433 patients (aged 70 or over) at risk of future health problems, discharged from acute medical units within 72 hours of attending hospital, were recruited in two general hospitals in Nottingham and Leicester, UK. Participants were randomised to the intervention, comprising geriatrician assessment in acute units and further specialist management, or to control where patients received no additional intervention over and above standard care. Primary outcome was incremental cost per quality adjusted life year (QALY) gained.
We undertook cost-effectiveness analysis for 417 patients (intervention: 205). The difference in mean adjusted QALYs gained between groups at 3 months was -0.001 (95% confidence interval CI: -0.009, 0.007). Total adjusted secondary and social care costs, including direct costs of the intervention, at 3 months were £4412 (€5624, $6878) and £4110 (€5239, $6408) for the intervention and standard care groups, the incremental cost was £302 (95% CI: 193, 410) €385, $471. The intervention was dominated by standard care with probability of 62%, and with 0% probability of cost-effectiveness (at £20,000/QALY threshold).
The specialist geriatric medical intervention for frail older people discharged from acute medical unit was not cost-effective. Further research on designing effective and cost-effective specialist service for frail older people discharged from acute medical units is needed.
ISRCTN registry ISRCTN21800480 http://www.isrctn.com/ISRCTN21800480.
Abstract Background Cow's milk allergy (CMA) overdiagnosis in young children appears to be increasing and has not been well characterised. We used a clinical trial population to characterise CMA ...overdiagnosis and identify individual‐level and primary care practice‐level risk factors. Methods We analysed data from 1394 children born in England in 2014–2016 (BEEP trial, ISRCTN21528841). Participants underwent formal CMA diagnosis at ≤2 years. CMA overdiagnosis was defined in three separate ways: parent‐reported milk reaction; primary care record of milk hypersensitivity symptoms; and primary care record of low‐allergy formula prescription. Results CMA was formally diagnosed in 19 (1.4%) participants. CMA overdiagnosis was common: 16.1% had parent‐reported cow's milk hypersensitivity, 11.3% primary care recorded milk hypersensitivity and 8.7% had low‐allergy formula prescription. Symptoms attributed to cow's milk hypersensitivity in participants without CMA were commonly gastrointestinal and reported from a median age of 49 days. Low‐allergy formula prescriptions in participants without CMA lasted a median of 10 months (interquartile range 1, 16); the estimated volume consumed was a median of 272 litres (26, 448). Risk factors for CMA overdiagnosis were high practice‐based low‐allergy formula prescribing in the previous year and maternal report of antibiotic prescription during pregnancy. Exclusive formula feeding from birth was associated with increased low‐allergy formula prescription. There was no evidence that practice prescribing of paediatric adrenaline auto‐injectors or anti‐reflux medications, or maternal features such as anxiety, age, parity and socioeconomic status were associated with CMA overdiagnosis. Conclusion CMA overdiagnosis is common in early infancy. Risk factors include high primary care practice‐based low‐allergy formula prescribing and maternal report of antibiotic prescription during pregnancy.
One in three hospital acute medical admissions is of an older person with cognitive impairment. Their outcomes are poor and the quality of their care in hospital has been criticised. A specialist ...unit to care for older people with delirium and dementia (the Medical and Mental Health Unit, MMHU) was developed and then tested in a randomised controlled trial where it delivered significantly higher quality of, and satisfaction with, care, but no significant benefits in terms of health status outcomes at three months.
To examine the cost-effectiveness of the MMHU for older people with delirium and dementia in general hospitals, compared with standard care.
Six hundred participants aged over 65 admitted for acute medical care, identified on admission as cognitively impaired, were randomised to the MMHU or to standard care on acute geriatric or general medical wards. Cost per quality adjusted life year (QALY) gained, at 3-month follow-up, was assessed in trial-based economic evaluation (599/600 participants, intervention: 309). Multiple imputation and complete-case sample analyses were employed to deal with missing QALY data (55%).
The total adjusted health and social care costs, including direct costs of the intervention, at 3 months was £7714 and £7862 for MMHU and standard care groups, respectively (difference -£149 (95% confidence interval CI: -298, 4)). The difference in QALYs gained was 0.001 (95% CI: -0.006, 0.008). The probability that the intervention was dominant was 58%, and the probability that it was cost-saving with QALY loss was 39%. At £20,000/QALY threshold, the probability of cost-effectiveness was 94%, falling to 59% when cost-saving QALY loss cases were excluded.
The MMHU was strongly cost-effective using usual criteria, although considerably less so when the less acceptable situation with QALY loss and cost savings were excluded. Nevertheless, this model of care is worthy of further evaluation.
ClinicalTrials.gov NCT01136148.
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