Trial of Optimal Personalised Care After Treatment-Gynaecological Cancer (TOPCAT-G): A Randomized Feasibility Trial.

OBJECTIVE: This study aimed to evaluate the feasibility of completing a parallel-group randomized controlled trial to compare usual follow-up care for women who have completed treatment of gynecological cancer against a nurse-led telephone intervention, known as Optimal Personalised Care After Treatment-Gynaecological. METHODS: The unblinded trial aimed to recruit patients who had completed treatment of cervical, endometrial, epithelial ovarian, or vulval cancer within the previous 3 months at 3 North Wales hospitals. We randomized participants to either usual hospital-based follow-up or specialist nurse-led telephone education, empowerment, and structured needs assessment follow-up. The primary outcomes assessed the feasibility of running a larger trial including patient eligibility, recruitment and retention rates, and outcome measure completion. Secondary outcomes were generic and health-related quality of life and a patient self-report health service use (Client Service Receipt Inventory) data collected at 3 time points (baseline, 3 months, and 6 months). RESULTS: Of the 58 women screened, 44 were eligible (76%) and 24 (55%) were recruited and randomized (12:12 to control and intervention, respectively). One participant was lost to follow-up. Recruited participants had a mean (SD) age of 60 (11.2) years and were approximately 5 months from their initial diagnosis (mean [SD], 159 [58] days). Seventeen (71%) of the participants had an endometrial cancer diagnosis. All outcome measure completion rates exceeded 96%. Although not a core feasibility objective, analyses of outcome measures indicated positive changes in quality of life and well-being within the Optimal Personalised Care After Treatment-Gynaecological group; exploratory cost consequence analysis indicated that the nurse-led intervention had a mean total service use cost of £27 per patient (bootstrapped 95% confidence interval, -£290 to £240) lower than did the standard care group. CONCLUSION: Eligibility, recruitment, and retention rates as well as outcome measure completion showed that the trial is feasible.

Intervention Now to Eliminate Repeat Unintended Pregnancy in Teenagers (INTERUPT): a systematic review of intervention effectiveness and cost-effectiveness, and qualitative and realist synthesis of implementation factors and user engagement.

BACKGROUND: Unintended repeat conceptions can result in emotional, psychological and educational harm to young women, often with enduring implications for their life chances. This study aimed to identify which young women are at the greatest risk of repeat unintended pregnancies; which interventions are effective and cost-effective; and what are the barriers to and facilitators for the uptake of these interventions. METHODS: We conducted a mixed-methods systematic review which included meta-analysis, framework synthesis and application of realist principles, with stakeholder input and service user feedback to address this. We searched 20 electronic databases, including MEDLINE, Excerpta Medica database, Applied Social Sciences Index and Abstracts and Research Papers in Economics, to cover a broad range of health, social science, health economics and grey literature sources. Searches were conducted between May 2013 and June 2014 and updated in August 2015. RESULTS: Twelve randomised controlled trials (RCTs), two quasi-RCTs, 10 qualitative studies and 53 other quantitative studies were identified. The RCTs evaluated psychosocial interventions and an emergency contraception programme. The primary outcome was repeat conception rate: the event rate was 132 of 308 (43%) in the intervention group versus 140 of 289 (48%) for the control group, with a non-significant risk ratio (RR) of 0.92 [95% confidence interval (CI) 0.78-1.08]. Four studies reported subsequent birth rates: 29 of 237 (12%) events for the intervention arm versus 46 out of 224 (21%) for the control arm, with an RR of 0.60 (95% CI 0.39-0.93). Many repeat conceptions occurred in the context of poverty, low expectations and aspirations and negligible opportunities. Qualitative and realist evidence highlighted the importance of context, motivation, future planning and giving young women a central and active role in the development of new interventions. CONCLUSIONS: Little or no evidence for the effectiveness or cost-effectiveness of any of the interventions to reduce repeat pregnancy in young women was found. Qualitative and realist evidence helped to explain gaps in intervention design that should be addressed. More theory-based, rigorously evaluated programmes need to be developed to reduce unintended repeat pregnancy in young women. TRIAL REGISTRATION: PROSPERO, CRD42012003168 . Cochrane registration number: i = fertility/0068.

Impact of antipsychotic review and non-pharmacological intervention on health-related quality of life in people with dementia living in care homes: WHELD-a factorial cluster randomised controlled trial.

BACKGROUND: Very few interventional studies have directly examined the impact of treatment approaches on health-related quality of life (HRQL) in people with dementia. This is of particular importance in therapies to address behavioural symptoms, where HRQL is often severely affected. METHODS: Analysis within the WHELD cluster randomised factorial study in 16 UK care homes examining the impact of person-centred care in combination with antipsychotic review, social interaction and exercise interventions. This study analysed impact on HRQL through the DEMQOL-Proxy. RESULTS: Data on HRQL were available for 187 participants. People receiving antipsychotic review showed a significant worsening in two DEMQOL-Proxy domains (negative emotion: p = 0.02; appearance: p = 0.04). A best-case scenario analysis showed significant worsening for total DEMQOL-Proxy score. Social interaction intervention resulted in a significant benefit to HRQL (p = 0.04). There was no deterioration in HRQL in groups receiving both antipsychotic review and social interaction (p = 0.62). CONCLUSIONS: This demonstrates an important detrimental impact of discontinuation of antipsychotics in dementia on HRQL, highlighting the need for careful review of best practice guidelines regarding antipsychotic use and emphasising the importance of providing evidence-based non-pharmacological interventions in conjunction with antipsychotic review. Copyright © 2016 John Wiley & Sons, Ltd.

Reducing repeat pregnancies in adolescence: applying realist principles as part of a mixed-methods systematic review to explore what works, for whom, how and under what circumstances.

BACKGROUND: Previous research has demonstrated emotional, psychological and educational harm to young mothers following unintended conceptions. The UK has one of the highest rates of pregnancies in adolescence in Western Europe with a high proportion of these being repeat pregnancies, making it a topic of interest for public health policy makers, and health and social care practitioners. As part of a wider mixed-methods systematic review, realist principles were applied to synthesise evidence about interventions aiming to reduce repeat pregnancies in adolescence. METHODS: A multi-streamed, mixed-methods systematic review was conducted searching 11 major electronic databases and 9 additional databases from 1995 onwards, using key terms such as pregnancy, teen or adolescent. The principles of realist synthesis were applied to all included literature to uncover theories about what works, for whom, how and in what context. Initial theory areas were developed through evidence scoping, group discussion by the authors and stakeholder engagement to uncover context + mechanism = outcome (CMO) configurations and related narratives. RESULTS: The searches identified 8,664 documents initially, and 403 in repeat searches, filtering to 81 included studies, including qualitative studies, randomised controlled trials, quantitative studies and grey literature. Three CMO configurations were developed. The individual experiences of young mothers' triggered self-efficacy, notions of perceived risks, susceptibility and benefits of pregnancy, resulting in the adolescent taking control of their fertility and sexual encounters. The choice between motherhood and other goals triggered notions of motivations, resulting in the adolescent managing their expectations of motherhood and controlling their fertility and sexual encounters. Barriers and facilitators to accessing services triggered notions of connectedness and self-determination; resulting in interventions that are tailored so they are relevant to young persons, and improve access to services and engagement with the issue of pregnancy in adolescence. CONCLUSIONS: Pregnancy in adolescence is a complex issue with many factors to consider. The conceptual platform described here could help guide policy makers and professionals towards a number of areas that need to be attended to in order to increase the likelihood of an intervention working to prevent rapid repeat pregnancy in adolescence. TRIAL REGISTRATION: PROSPERO CRD42012003168.

Does an early home-based progressive resistance training program improve function following total hip replacement? Results of a randomized controlled study.

BACKGROUND: In-hospital progressive resistance training (PRT) has been shown to be an effective method of rehabilitation following hip surgery. The aim of this study was to assess whether a home-based PRT program would be beneficial in improving patients' muscle strength and physical function compared to standard rehabilitation. METHODS: Subjects (n = 49) either received home-based PRT rehabilitation (n = 25) or standard rehabilitation (n = 24) in a prospective single blinded randomized trial carried out over a two-year period. The primary outcome measure was the maximal voluntary contraction of the operated leg quadriceps (MVCOLQ) with secondary measures of outcome being the sit to stand score (ST), timed up and go (TUG), stair climb performance (SCP), the 6 min walk test (6MWT), and lean mass of the operated leg (LM). RESULTS: Twenty-six patients completed follow up at 1 year (n = 13 per group) for the final comparative analysis. All the outcome measures showed marked progressive improvements from the baseline measures at 9-12 months post op (Estimated effect (std error); p value)- MVCOLQ 26.50 (8.71) N p = 0.001; ST 1.37 (0.33) p = 0.0001; TUG -1.44 (0.45) s p =0.0001; SCP -3.41(0.80)s p = 0.0001; 6MWT 45.61 (6.10)m p = 0.0001; LM 20 (204)g p = 0.326) following surgery for both groups. Overall, there was no significant effect for participation in the exercise regime compared with standard care for all outcomes assessed. CONCLUSIONS: Overall, this study demonstrated that there is no significant difference between the two groups for participation in the home-based PRT exercise programme when compared to standard care for all outcomes. TRIAL REGISTRATION: ISRCTN 1309951. Registered February 2011.

A stepped wedge cluster randomized control trial of dried blood spot testing to improve the uptake of hepatitis C antibody testing within UK prisons.

BACKGROUND: The prevalence of hepatitis C (HCV) is elevated within prison populations, yet diagnosis in prisons remains low. Dried blood spot testing (DBST) is a simple procedure for the detection of HCV antibodies; its impact on testing in the prison context is unknown. METHODS: We carried out a stepped-wedge cluster-randomized control trial of DBST for HCV among prisoners within five male prisons and one female prison. Each prison was a separate cluster. The order in which the intervention (training in use of DBST for HCV testing and logistic support) was introduced was randomized across clusters. The outcome measure was the HCV testing rate by prison. Imputation analysis was carried out to account for missing data. Planned and actual intervention times differed in some prisons; data were thus analysed by intention to treat (ITT) and by observed step times. RESULTS: There was insufficient evidence of an effect of the intervention on testing rate using either the ITT intervention time (OR: 0.84; 95% CI: 0.68-1.03; P = 0.088) or using the actual intervention time (OR: 0.86; 95% CI: 0.71-1.06; P = 0.153). This was confirmed by the pooled results of five imputed data sets. CONCLUSIONS: DBST as a stand-alone intervention was insufficient to increase HCV diagnosis within the UK prison setting. Factors such as staff training and allocation of staff time for regular clinics are key to improving service delivery. We demonstrate that prisons can conduct rigorous studies of new interventions, but data collection can be problematic. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register (ISRCTN number ISRCTN05628482).

Well-being, health and fitness of children who use wheelchairs: feasibility study protocol to develop child-centred 'keep-fit' exercise interventions.

AIM: To undertake the pre-clinical and modelling phases of the Medical Research Council complex intervention framework to underpin development of child-centred 'keep-fit', exercise and physical activity interventions for children and young people who use wheelchairs. BACKGROUND: Children who use wheelchairs face many barriers to participation in physical activity, which compromises fitness, obesity, well-being and health. 'Keep-fit' programmes that are child-centred and engaging are urgently required to enhance participation of disabled children and their families as part of a healthy lifestyle. Nurses will likely be important in promoting and monitoring 'keep-fit' intervention(s) when implemented in the community. DESIGN: Mixed-method (including economic analysis) feasibility study to capture child and family preferences and keep-fit needs and to determine outcome measures for a 'keep-fit' intervention. METHODS: The study comprises three stages. Stage 1 includes a mixed-method systematic review of effectiveness, cost effectiveness and key stakeholder views and experiences of keep-fit interventions, followed by qualitative interviews with children, young people and their parents to explore preferences and motivations for physical activity. Stage 2 will identify standardized outcome measures and test their application with children who use wheelchairs to obtain baseline fitness data. Options for an exercise-based keep-fit intervention will then be designed based on Stage 1 and 2 findings. In stage 3, we will present intervention options for feedback and further refinement to children and parents/carers in focus groups. (Project funded October 2012). DISCUSSION: At completion, this study will lead to the design of the intervention and a protocol to test its efficacy.

Care staff and family member perspectives on quality of life in people with very severe dementia in long-term care: a cross-sectional study.

BACKGROUND: Little is known about the quality of life of people with very severe dementia in long-term care settings, and more information is needed about the properties of quality of life measures aimed at this group. In this study we explored the profiles of quality of life generated through proxy ratings by care staff and family members using the Quality of Life in Late-stage Dementia (QUALID) scale, examined factors associated with these ratings, and further investigated the psychometric properties of the QUALID. METHODS: Proxy ratings of quality of life using the QUALID were obtained for 105 residents with very severe dementia, categorised as meeting criteria for Functional Assessment Staging (FAST) stages 6 or 7, from members of care staff (n = 105) and family members (n = 73). A range of resident and staff factors were also assessed. RESULTS: Care staff and family member ratings were similar but were associated with different factors. Care staff ratings were significantly predicted by resident mood and awareness/responsiveness. Family member ratings were significantly predicted by use of antipsychotic medication. Factor analysis of QUALID scores suggested a two-factor solution for both care staff ratings and family member ratings. CONCLUSIONS: The findings offer novel evidence about predictors of care staff proxy ratings of quality of life and demonstrate that commonly-assessed resident variables explain little of the variability in family members' proxy ratings. The findings provide further information about the psychometric properties of the QUALID, and support the applicability of the QUALID as a means of examining quality of life in very severe dementia.

'Keep fit' exercise interventions to improve health, fitness and well-being of children and young people who use wheelchairs: mixed-method systematic review protocol.

AIM: This mixed-method systematic review aims to establish the current evidence base for 'keep fit', exercise or physical activity interventions for children and young people who use wheelchairs. BACKGROUND: Nurses have a vital health promotion, motivational and monitoring role in optimizing the health and well-being of disabled children. Children with mobility impairments are prone to have low participation levels in physical activity, which reduces fitness and well-being. Effective physical activity interventions that are fun and engaging for children are required to promote habitual participation as part of a healthy lifestyle. Previous intervention programmes have been trialled, but little is known about the most effective types of exercise to improve the fitness of young wheelchair users. DESIGN: Mixed-method design using Cochrane systematic processes. Evidence regarding physiological and psychological effectiveness, health economics, user perspectives and service evaluations will be included and analysed under distinct streams. METHODS: The project was funded from October 2012. Multiple databases will be searched using search strings combining relevant medical subheadings and intervention-specific terms. Articles will also be identified from ancestral references and by approaching authors to identify unpublished work. Only studies or reports evaluating the effectiveness, participation experiences or cost of a physical activity programme will be included. Separate analyses will be performed for each data stream, including a meta-analysis if sufficient homogeneity exists and thematic analyses. Findings across streams will be synthesized in an overarching narrative summary. DISCUSSION: Evidence from the first systematic review of this type will inform development of effective child-centred physical activity interventions and their evaluation.

AwareCare: a pilot randomized controlled trial of an awareness-based staff training intervention to improve quality of life for residents with severe dementia in long-term care settings.

BACKGROUND: The extent to which care home residents with severe dementia show awareness is influenced by the extent to which the environment provides opportunities for engagement and by the way in which care staff interact with them. We aimed to establish whether training care staff to observe and identify signs of awareness in residents with severe dementia resulted in improved quality of life for residents. METHODS: In this pilot cluster randomized trial, care staff in four homes (n = 32) received training and supervision and carried out structured observations of residents using the AwareCare measure (n = 32) over an eight-week period, while staff in four control homes (n = 33) had no training with regard to their residents (n = 33) and no contact with the research team. The primary outcome was resident quality of life. Secondary outcomes were resident well-being, behavior and cognition, staff attitudes and well-being, and care practices in the home. RESULTS: Following intervention, residents in the intervention group had significantly better quality of life as rated by family members than those in the control group, but care staff ratings of quality of life did not differ. There were no other significant between-group differences. Staff participating in the intervention identified benefits in terms of their understanding of residents' needs. CONCLUSIONS: Staff were able to use the observational measure effectively and relatives of residents in the intervention homes perceived an improvement in their quality of life.

Enhancing rigour in the validation of patient reported outcome measures (PROMs): bridging linguistic and psychometric testing.

BACKGROUND: A strong consensus exists for a systematic approach to linguistic validation of patient reported outcome measures (PROMs) and discrete methods for assessing their psychometric properties. Despite the need for robust evidence of the appropriateness of measures, transition from linguistic to psychometric validation is poorly documented or evidenced. This paper demonstrates the importance of linking linguistic and psychometric testing through a purposeful stage which bridges the gap between translation and large-scale validation. FINDINGS: Evidence is drawn from a study to develop a Welsh language version of the Beck Depression Inventory-II (BDI-II) and investigate its psychometric properties. The BDI-II was translated into Welsh then administered to Welsh-speaking university students (n = 115) and patients with depression (n = 37) concurrent with the English BDI-II, and alongside other established depression and quality of life measures. A Welsh version of the BDI-II was produced that, on administration, showed conceptual equivalence with the original measure; high internal consistency reliability (Cronbach's alpha = 0.90; 0.96); item homogeneity; adequate correlation with the English BDI-II (r = 0.96; 0.94) and additional measures; and a two-factor structure with one overriding dimension. Nevertheless, in the student sample, the Welsh version showed a significantly lower overall mean than the English (p = 0.002); and significant differences in six mean item scores. This prompted a review and refinement of the translated measure. CONCLUSIONS: Exploring potential sources of bias in translated measures represents a critical step in the translation-validation process, which until now has been largely underutilised. This paper offers important findings that inform advanced methods of cross-cultural validation of PROMs.

AwareCare: development and validation of an observational measure of awareness in people with severe dementia.

Signs of sensory and perceptual awareness can be observed in people with very severe dementia, and may be influenced by the extent to which the environment offers appropriate stimulation. We developed an observational tool, AwareCare, which care staff can use to identify signs of awareness in residents with very severe dementia, based on the concept of the Wessex Head Injury Matrix (WHIM). Using WHIM items as a guide, and following focus groups with care staff and family members, an expert panel identified 28 environmental stimuli and 35 response categories for the initial version of AwareCare. After baseline assessments of cognition, well-being and quality of life were taken, 40 residents were observed individually for 30 minutes on 5 occasions. Based on the observational data, 10 stimulus categories and 14 response categories were identified for further analysis and formed the final version of AwareCare. All participants showed awareness to varying degrees. Social stimuli elicited the most responses. Greater awareness was associated with better cognitive function, self-care, mobility, and responsiveness, but not with proxy-rated quality of life. Understanding the nature of awareness in this group is an important element in ensuring appropriate levels of interaction and stimulation, and hence enhancing quality of care.

Incapacity in childbirth - Rare or common?

OBJECTIVE: Impaired decision making ability is common on general medical wards. Audit evidence suggests that the prevalence of incapacity may be higher than previously assumed in Obstetric Emergency Procedures (OEP) during childbirth. We investigated the prevalence of incapacity in OEP and factors associated with this. DESIGN: Capacity to consent to treatment was assessed retrospectively in 93 women undergoing OEP. All women were interviewed using a semi-structured questionnaire aided interview within 24 h of the emergency. Five assessors (3 obstetricians and 2 psychiatrists) were asked to determine capacity to consent from audio recordings of the interviews. RESULTS: All 5 assessors determined 59 % of women to have capacity to consent to treatment and 2 % of women to lack capacity. In 39 % of women there was some disagreement between assessors. Using a majority decision (3 assessors in agreement), 14 % of women lacked capacity. High pain scores, young age and no previous history of theatre deliveries were associated with more incapacity judgments, whilst parity and history of mental illness were not. Using a 7point Likert scale only marginally improved agreement between assessors, compared to their binary decision. CONCLUSION: It is often assumed that it is rare to lack capacity in an obstetric emergency procedure during childbirth, but these data suggest that incapacity may be relatively common. In particular, severe pain is a demonstrable risk factor for impaired capacity. Wide variation between assessors questions the validity of current commonly employed (informal) methods used in clinical practice to assess capacity to consent during OEP.

Goal-oriented cognitive rehabilitation for people with early-stage Alzheimer disease: a single-blind randomized controlled trial of clinical efficacy.

OBJECTIVES: To provide evidence regarding the clinical efficacy of cognitive rehabilitation (CR) in early-stage Alzheimer disease (AD). DESIGN: Single-blind randomized controlled trial comparing CR with relaxation therapy and no treatment. SETTING: Outpatient, community-based setting. PARTICIPANTS: Sixty-nine individuals (41 women, 28 men; mean age 77.78 years, standard deviation 6.32, range = 56-89) with a diagnosis of AD or mixed AD and vascular dementia and a Mini-Mental State Examination score of 18 or above, and receiving a stable dose of acetylcholinesterase-inhibiting medication. Forty-four family carers also contributed. INTERVENTION: Eight weekly individual sessions of CR consisting of personalized interventions to address individually relevant goals supported by components addressing practical aids and strategies, techniques for learning new information, practice in maintaining attention and concentration, and techniques for stress management. MEASUREMENTS: The primary outcomes were goal performance and satisfaction, assessed using the Canadian Occupational Performance Measure. Questionnaires assessing mood, quality of life and career strain, and a brief neuropsychological test battery were also administered. A subset of participants underwent functional magnetic resonance imaging (fMRI). RESULTS: CR produced significant improvement in ratings of goal performance and satisfaction, whereas scores in the other two groups did not change. Behavioral changes in the CR group were supported by fMRI data for a subset of participants. CONCLUSIONS: The findings support the clinical efficacy of CR in early-stage AD. CR offers a means of assisting people with early-stage AD and their families in managing the effects of the condition.

Evidence into practice: evaluating a child-centred intervention for diabetes medicine management. The EPIC Project.

BACKGROUND: There is a lack of high quality, child-centred and effective health information to support development of self-care practices and expertise in children with acute and long-term conditions. In type 1 diabetes, clinical guidelines indicate that high-quality, child-centred information underpins achievement of optimal glycaemic control with the aim of minimising acute readmissions and reducing the risk of complications in later life. This paper describes the development of a range of child-centred diabetes information resources and outlines the study design and protocol for a randomized controlled trial to evaluate the information resources in routine practice. The aim of the diabetes information intervention is to improve children and young people's quality of life by increasing self-efficacy in managing their type 1 diabetes. METHODS/DESIGN: We used published evidence, undertook qualitative research and consulted with children, young people and key stakeholders to design and produce a range of child-centred, age-appropriate children's diabetes diaries, carbohydrate recording sheets, and assembled child-centred, age-appropriate diabetes information packs containing published information in a folder that can be personalized by children and young people with pens and stickers. Resources have been designed for children/young people 6-10; 11-15; and 16-18 years.To evaluate the information resources, we designed a pragmatic randomized controlled trial to assess the effectiveness, cost effectiveness, and implementation in routine practice of individually tailored, age-appropriate diabetes diaries and information packs for children and young people age 6-18 years, compared with currently available standard practice.Children and young people will be stratified by gender, length of time since diagnosis (< 2 years and > 2 years) and age (6-10; 11-15; and 16-18 years). The following data will be collected at baseline, 3 and 6 months: PedsQL (generic, diabetes and parent versions), and EQ-5 D (parent and child); NHS resource use and process data (questionnaire and interview). Baseline and subsequent HbA1c measurements, blood glucose meter use, readings and insulin dose will be taken from routine test results and hand-held records when attending routine 3-4 monthly clinic visits.The primary outcome measure is diabetes self-efficacy and quality-of-life (Diabetes PedsQL). Secondary outcomes include: HbA1c, generic quality of life, routinely collected NHS/child-held data, costs, service use, acceptability and utility. TRIAL REGISTRATION: ISRCTN17551624.

Standardised self-management kits for children with type 1 diabetes: pragmatic randomised trial of effectiveness and cost-effectiveness.

OBJECTIVE: To estimate the effectiveness of standardised self-management kits for children with type 1 diabetes. DESIGN: Pragmatic trial with randomisation ratio of two intervention: one control. Qualitative process evaluation. SETTING: 11 diabetes clinics in England and Wales. PARTICIPANTS: Between February 2010 and August 2011, we validly randomised 308 children aged 6-18 years; 201 received the intervention. INTERVENTION: We designed kits to empower children to achieve glycaemic control, notably by recording blood glucose and titrating insulin. The comparator was usual treatment. OUTCOME MEASURES AT 3 AND 6 MONTHS: Primary: Diabetes Pediatric Quality of Life Inventory (PedsQL). Secondary: HbA1c; General PedsQL; EQ-5D; healthcare resource use. RESULTS: Of the five Diabetes PedsQL dimensions, Worry showed adjusted scores significantly favouring self-management kits at 3 months (mean child-reported difference =+5.87; Standard error[SE]=2.19; 95% confidence interval [CI]) from +1.57 to +10.18; p=0.008); but Treatment Adherence significantly favoured controls at 6 months (mean child-reported difference=-4.68; SE=1.74; 95%CI from -8.10 to -1.25; p=0.008). Intervention children reported significantly worse changes between 3 and 6 months on four of the five Diabetes PedsQL dimensions and on the total score (mean difference=-3.20; SE=1.33; 95% CI from -5.73 to -0.67; p=0.020). There was no evidence of change in HbA1c; only 18% of participants in each group achieved recommended levels at 6 months. No serious adverse reactions attributable to the intervention or its absence were reported.Use of kits was poor. Few children or parents associated blood glucose readings with better glycaemic control. The kits, costing £185, alienated many children and parents. CONCLUSIONS: Standardised kits showed no evidence of benefit, inhibited diabetes self-management and increased worry. Future research should study relationships between children and professionals, and seek new methods of helping children and parents to manage diabetes. TRIAL REGISTRATION NUMBER: ISRCTN17551624.

Impact of primary Sjogren's syndrome on smell and taste: effect on quality of life.

OBJECTIVES: To assess the prevalence of abnormal smell and taste perception in people with primary SS and the effect on quality of life (QoL). METHODS: Twenty-eight participants with SS and 37 controls were enrolled in a cohort-matched, prospective, cross-sectional study. Smell and taste thresholds were measured using standardized, validated tests. QoL was assessed by the Short Form 12 (SF-12). RESULTS: Smell threshold was reduced by 1 point (P = 0.002; 95% CI 0.35, 1.54) and taste threshold was reduced by 3.5 points (P < 0.001; 95% CI 1.80, 5.22) in the SS group compared with controls. The physical and mental components of SF-12 were reduced by 14.2 points (P < 0.001; 95% CI 9.47, 19.02) and 7.5 points (P = 0.002; 95% CI 2.97, 12.02), respectively, in the SS group compared with controls. Taste threshold was significantly correlated with both the physical (r = 0.48; P < 0.001) and the mental (r = 0.30; P = 0.015) components of SF-12. Smell threshold correlated with the physical (r = 0.457; P < 0.001), but not the mental component (r = 0.154; P = 0.222) of SF-12. CONCLUSIONS: Clinically important impairment of chemosensory perception occurred in the SS group compared with age- and gender-matched controls. Assessment using SF-12 suggests that this impairment contributed to the reduced health-related QoL that characterized these individuals.

Goal-oriented cognitive rehabilitation for early-stage Alzheimer's and related dementias: the GREAT RCT.

BACKGROUND: Cognitive rehabilitation (CR) is an individualised, person-centred intervention for people with mild to moderate dementia that addresses the impact of cognitive impairment on everyday functioning. OBJECTIVES: To determine whether or not CR is a clinically effective and cost-effective intervention for people with mild to moderate Alzheimer's disease or vascular or mixed dementia, and their carers. DESIGN: This multicentre randomised controlled trial compared CR with treatment as usual (TAU). Following a baseline assessment and goal-setting to identify areas of everyday functioning that could be improved or better managed, participants were randomised (1 : 1) via secure web access to an independent randomisation centre to receive either TAU or CR and followed up at 3 and 9 months post randomisation. SETTING: Community. PARTICIPANTS: Participants had an International Classification of Diseases, Tenth Edition, diagnosis of Alzheimer's disease or vascular or mixed dementia, had mild to moderate cognitive impairment (Mini Mental State Examination score of ≥ 18 points), were stable on medication if prescribed, and had a family carer who was willing to contribute. The exclusion criteria were people with a history of brain injury or other neurological disorder and an inability to speak English. To achieve adequate power, we needed 350 people to complete the trial, with 175 people in each trial arm. INTERVENTION: Cognitive rehabilitation consisted of 10 therapy sessions over 3 months, followed by four maintenance sessions over 6 months, delivered in participants' homes. The therapists were nine occupational therapists and one nurse. OUTCOME MEASURES: The primary outcome was self-reported goal attainment at 3 months. Goal attainment was also assessed at 9 months. Carers provided independent ratings of goal attainment at both time points. The secondary outcomes were participant quality of life, mood, self-efficacy and cognition, and carer stress, health status and quality of life. The assessments at 3 and 9 months were conducted by researchers who were blind to the participants' group allocation. RESULTS: A total of 475 participants were randomised (CR arm, n = 239; TAU arm, n = 236), 427 participants (90%) completed the trial and 426 participants were analysed (CR arm, n = 208, TAU arm, n = 218). At 3 months, there were statistically significant large positive effects for participant-rated goal attainment [mean change in the CR arm: 2.57; mean change in the TAU arm: 0.86; Cohen'sd = 0.97, 95% confidence interval (CI) 0.75 to 1.19], corroborated by carer ratings (Cohen'sd = 1.11, 95% CI 0.89 to 1.34). These effects were maintained at 9 months for both the participant ratings (Cohen's d = 0.94, 95% CI 0.71 to 1.17) and the carer ratings (Cohen's d = 0.96, 95% CI 0.73 to 1.20). There were no significant differences in the secondary outcomes. In the cost-utility analyses, there was no evidence of cost-effectiveness in terms of gains in the quality-adjusted life-years (QALYs) of the person with dementia (measured using the DEMentia Quality Of Life questionnaire utility score) or the QALYs of the carer (measured using the EuroQol-5 Dimensions, three-level version) from either cost perspective. In the cost-effectiveness analyses, by reference to the primary outcome of participant-rated goal attainment, CR was cost-effective from both the health and social care perspective and the societal perspective at willingness-to-pay values of £2500 and above for improvement in the goal attainment measure. There was no evidence on the cost-effectiveness of the self-efficacy measure (the Generalized Self-Efficacy Scale) from either cost perspective. LIMITATIONS: Possible limitations arose from the non-feasibility of using observational outcome measures, the lack of a general measure of functional ability and the exclusion of people without a carer or with rarer forms of dementia. CONCLUSIONS: Cognitive rehabilitation is clinically effective in enabling people with early-stage dementia to improve their everyday functioning in relation to individual goals targeted in the therapy sessions. FUTURE WORK: Next steps will focus on the implementation of CR into NHS and social care services and on extending the approach to people with rarer forms of dementia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN21027481. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 10. See the NIHR Journals Library website for further project information.

BACKGROUND: Cognitive rehabilitation (CR) is a personalised intervention to help people with early-stage dementia to manage everyday activities. This individualised therapy is conducted in people's own homes over several sessions. A therapist works with the person and the carer to identify realistic and relevant goals, plan how to tackle these and support people in achieving them. Previous small studies suggested that CR could be beneficial. METHODS: The Goal-oriented cognitive Rehabilitation in Early-stage Alzheimer's and related dementias: multicentre single-blind randomised controlled Trial (GREAT) was run in eight centres to find out whether or not CR improves everyday functioning. Participants were in the early stages of having Alzheimer's disease, vascular dementia or mixed dementia, with a family carer involved. At the first assessment, participants identified areas in which they would like to see improvements, and set goals. Participants and carers rated how well participants were currently doing in relation to these goals and completed questionnaires, for example about mood and quality of life. Participants were then randomly selected to either receive CR or continue with treatment as usual (TAU). CR consisted of 10 weekly sessions with the therapist over 3 months, followed by four sessions over the next 6 months. Participants were reassessed after 3 and 9 months. RESULTS: We included 475 participants, and 427 participants (90%) completed the trial (209 participants in the CR arm and 218 participants in the TAU arm). After 3 months, the ratings by both participants and carers in the CR group showed that participants were doing significantly better in relation to their goals, and this was maintained 6 months later. Ratings for the TAU-arm participants did not improve significantly. There were no other differences between the groups. There was a strong economic case for CR. CONCLUSIONS: Cognitive rehabilitation is effective in enabling people with early-stage dementia to improve their everyday functioning in relation to individual goals targeted in the therapy sessions. Next steps will focus on the implementation of CR into NHS and social care services.

Alpha adrenoceptor agonist-induced microcirculatory oscillations are reduced in diabetic neuropathy.

In diabetic patients small fiber neuropathy has been associated with impairment of 0.1 Hz microvascular vasomotion. The aim of this study was (1) to investigate whether vasoconstriction-induced microvascular oscillations in the skin are reduced in diabetic patients with peripheral and/or autonomic neuropathy, and (2) whether this method could be used as a non-invasive surrogate marker to assess diabetic small fiber neuropathy. Four matched groups were studied: diabetic patients without neuropathy (D), with peripheral neuropathy (DPN), with peripheral and autonomic neuropathy (DAN), and non-diabetic controls (Ctrl). All participants were evaluated for peripheral and autonomic neuropathy, microvascular endothelial function, and metabolic syndrome indicators. Laser Doppler flowmetry was used to measure oscillations after iontophoresis of the alpha one selective agonist phenylephrine. approximately 0.1-Hz oscillations recorded at the foot were significantly attenuated in diabetic patients with peripheral and/or autonomic neuropathy (DPN and DAN groups) compared to diabetic patients without neuropathy or non-diabetic controls. In the forearm, microvascular oscillations were significantly reduced only in patients with autonomic neuropathy (DAN). Oscillation measures correlated significantly (P<0.001) with all markers of peripheral neuropathy but not with markers of measurements of microvascular endothelial function, or metabolic syndrome markers. In a logistic regression model, reduced microvascular oscillations at the foot were a strong predictor for the presence of peripheral neuropathy. The measurement of phenylephrine-induced approxiamtely 0.1-Hz microvascular oscillation may represent a useful non-invasive tool with which to study the effects of treatment strategies on the diabetic small fiber neuropathy.

Folate augmentation of treatment - evaluation for depression (FolATED): protocol of a randomised controlled trial.

BACKGROUND: Clinical depression is common, debilitating and treatable; one in four people experience it during their lives. The majority of sufferers are treated in primary care and only half respond well to active treatment. Evidence suggests that folate may be a useful adjunct to antidepressant treatment: 1) patients with depression often have a functional folate deficiency; 2) the severity of such deficiency, indicated by elevated homocysteine, correlates with depression severity, 3) low folate is associated with poor antidepressant response, and 4) folate is required for the synthesis of neurotransmitters implicated in the pathogenesis and treatment of depression. METHODS/DESIGN: The primary objective of this trial is to estimate the effect of folate augmentation in new or continuing treatment of depressive disorder in primary and secondary care. Secondary objectives are to evaluate the cost-effectiveness of folate augmentation of antidepressant treatment, investigate how the response to antidepressant treatment depends on genetic polymorphisms relevant to folate metabolism and antidepressant response, and explore whether baseline folate status can predict response to antidepressant treatment. Seven hundred and thirty patients will be recruited from North East Wales, North West Wales and Swansea. Patients with moderate to severe depression will be referred to the trial by their GP or Psychiatrist. If patients consent they will be assessed for eligibility and baseline measures will be undertaken. Blood samples will be taken to exclude patients with folate and B12 deficiency. Some of the blood taken will be used to measure homocysteine levels and for genetic analysis (with additional consent). Eligible participants will be randomised to receive 5 mg of folic acid or placebo. Patients with B12 deficiency or folate deficiency will be given appropriate treatment and will be monitored in the 'comprehensive cohort study'. Assessments will be at screening, randomisation and 3 subsequent follow-ups. DISCUSSION: If folic acid is shown to improve the efficacy of antidepressants, then it will provide a safe, simple and cheap way of improving the treatment of depression in primary and secondary care. TRIAL REGISTRATION: Current controlled trials ISRCTN37558856.