Karin Friedli

Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial

BACKGROUND AND OBJECTIVES Depression is common in patients on hemodialysis, but data on the benefits and risks of antidepressants in this setting are limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of sertraline over 6 months in patients on hemodialysis with depression to determine study feasibility, safety, and effectiveness. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients on hemodialysis at five United Kingdom renal centers completed the Beck Depression Inventory II. Those scoring ≥16 and not already on treatment for depression were invited to undergo diagnostic interview to confirm major depressive disorder. Eligible patients with major depressive disorder were randomized to receive the study medication-either sertraline or placebo. Outcomes included recruitment and dropout rates, change in the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory II, and qualitative information to guide design of a large-scale trial. RESULTS In total, 709 patients were screened and enrolled between April of 2013 and October of 2014; 231 (32.6%) had Beck Depression Inventory II scores ≥16, and 68 (29%) of these were already receiving treatment for depression. Sixty-three underwent diagnostic interview, 37 were diagnosed with major depressive disorder, and 30 were randomized; 21 completed the trial: eight of 15 on sertraline and 13 of 15 on placebo (P=0.05). Dropouts due to adverse and serious adverse events were greater in the sertraline group. All occurred in the first 3 months. Over 6 months, depression scores improved in both groups. Beck Depression Inventory II score fell from 29.1±8.4 to 17.3±12.4 (P<0.001), and Montgomery-Asberg Depression Rating Scale score fell from 24.5±4.1 to 10.3±5.8 (P<0.001). There were no differences between sertraline and placebo groups. CONCLUSIONS Although small, this is the largest randomized trial to date of antidepressant medication in patients on hemodialysis. Our results highlight recruitment issues. No benefit was observed, but trial size and the substantial dropout render consideration of benefit inconclusive. A definitive trial could use shorter follow-up and include depressed patients already taking antidepressants.

Wordless intervention for epilepsy in learning disabilities (WIELD): study protocol for a randomized controlled feasibility trial

BackgroundEpilepsy is the most common neurological problem that affects people with learning disabilities. The high seizure frequency, resistance to treatments, associated skills deficit and co-morbidities make the management of epilepsy particularly challenging for people with learning disabilities. The Books Beyond Words booklet for epilepsy uses images to help people with learning disabilities manage their condition and improve quality of life. Our aim is to conduct a randomized controlled feasibility trial exploring key methodological, design and acceptability issues, in order to subsequently undertake a large-scale randomized controlled trial of the Books Beyond Words booklet for epilepsy.Methods/DesignWe will use a two-arm, single-centre randomized controlled feasibility design, over a 20-month period, across five epilepsy clinics in Hertfordshire, United Kingdom. We will recruit 40 eligible adults with learning disabilities and a confirmed diagnosis of epilepsy and will randomize them to use either the Books Beyond Words booklet plus usual care (intervention group) or to receive routine information and services (control group). We will collect quantitative data about the number of eligible participants, number of recruited participants, demographic data, discontinuation rates, variability of the primary outcome measure (quality of life: Epilepsy and Learning Disabilities Quality of Life scale), seizure severity, seizure control, intervention’s patterns of use, use of other epilepsy-related information, resource use and the EQ-5D-5L health questionnaire. We will also gather qualitative data about the feasibility and acceptability of the study procedures and the Books Beyond Words booklet. Ethical approval for this study was granted on 28 April 2014, by the Wales Research Ethics Committee 5. Recruitment began on 1 July 2014.DiscussionThe outcomes of this feasibility study will be used to inform the design and methodology of a definitive study, adequately powered to determine the impact of the Books Beyond Words intervention to improve the management of epilepsy in people with learning disabilities.Trial registrationhttp://ISRCTN80067039 (Date of ISRCTN assignation: 23 April 2014).

Wordless intervention for people with epilepsy and learning disabilities (WIELD):A randomised controlled feasibility trial

Objective To investigate the feasibility of a full-scale randomised controlled trial of a picture booklet to improve quality of life for people with epilepsy and learning disabilities. Trial design A randomised controlled feasibility trial. Randomisation was not blinded and was conducted using a centralised secure database and a blocked 1:1 allocation ratio. Setting Epilepsy clinics in 1 English National Health Service (NHS) Trust. Participants Patients with learning disabilities and epilepsy who had: a seizure within the past 12 months, meaningful communication and a carer with sufficient proficiency in English. Intervention Participants in the intervention group used a picture booklet with a trained researcher, and a carer present. These participants kept the booklet, and were asked to use it at least twice more over 20 weeks. The control group received treatment as usual, and were provided with a booklet at the end of the study. Outcome measures 7 feasibility criteria were used relating to recruitment, data collection, attrition, potential effect on epilepsy-related quality of life (Epilepsy and Learning Disabilities Quality of Life Scale, ELDQOL) at 4-week, 12-week and 20-week follow-ups, feasibility of methodology, acceptability of the intervention and potential to calculate cost-effectiveness. Outcome The recruitment rate of eligible patients was 34% and the target of 40 participants was reached. There was minimal missing data and attrition. An intention-to-treat analysis was performed; data from the outcome measures suggest a benefit from the intervention on the ELDQOL behaviour and mood subscales at 4 and 20 weeks follow-up. The booklet and study methods were positively received, and no adverse events were reported. There was a positive indication of the potential for a cost-effectiveness analysis. Conclusions All feasibility criteria were fully or partially met, therefore confirming feasibility of a definitive trial. Trial registration number ISRCTN80067039.

Travel related illness in short-term volunteers from the UK to developing countries.

People of all ages volunteer in developing countries, but little is known about the health risks they face. InterHealth, a travel clinic, provides a health screening service for short-term overseas volunteers. A cross-sectional study design was used to analyse 413 post-travel health questionnaires completed between February and November 2009. The sample consisted of volunteers who worked on short-term projects in developing countries for a variety of non-governmental organisations. At least one sick day was taken by 137 (33.2%) participants. Medical care was accessed by 39 (9.6%) participants, and standby medication was used by 87 (21.6%) participants. Diarrhoea, especially amongst those aged under 20 or who visited Latin America, was the most commonly reported health problem (95; 23.9%). Possible exposure to schistosomiasis was reported by 56 (13.8%) participants, mostly from East Africa. Upon return, the majority of participants (371; 91.2%) reported feeling well. The findings of this study show the importance of tailored post-travel health screening for short-term overseas volunteers. This study may help to tailor pre-departure travel health consultations for this group, particularly around food hygiene, hand washing and potential exposure to infection, but further research is needed to assess the impact of pre-travel health advice.

Measuring Fatigue Using the Multidimensional Fatigue Inventory-20: A Questionable Factor Structure in Haemodialysis Patients

Background/Aims: Fatigue is recognised as a common and burdensome symptom among dialysis patients. A growing body of research is devoted to understanding fatigue in advanced kidney disease, yet its measurement is challenging within this context. Our aim was to evaluate the factor structure underlying the multidimensional fatigue inventory (MFI-20) and to examine its associations with clinical factors and mood. Methods: Data was evaluated for confirmatory factor analysis (CFA) from the screening phase of a multicentre randomised placebo-controlled trial of sertraline in haemodialysis (HD) patients. Four hundred seventy patients completed the MFI-20, which purports to measure 5 components of fatigue (general fatigue, mental fatigue, physical fatigue, reduced motivation and reduced activity). CFA models were evaluated in MPlus 7.3 using the robust maximum likelihood (MLR) estimation. Results: The evaluation of the original 5 factors revealed low internal reliability for the general factor and reduced activity, and high intercorrelations between all sum scores. CFA revealed poor model fit for the original 5-factor MFI-20 model (confirmatory fit index = 0.738; Tucker-Lewis index = 0.689; root mean squared error of approximation = 0.101). Alternative models, including 1, 3 and bi-factor models all demonstrated poor fit to the data. No reliable factor model was confirmed prohibiting the examination of factors associated with fatigue. Conclusions: We were not able to confirm the factor structure of the MFI-20 in a large sample of HD patients. Certain items may lack suitable face validity in this context.

C reactive protein and depressive symptoms in haemodialysis patients

Introduction: Patients with advanced chronic kidney disease (CKD) on haemodialysis (HD) may have increased C reactive protein (CRP) values and depressive symptoms. There is debate about the strength and nature of previously reported associations. We investigated these issues in a cohort of patients on HD.

C reactive protein and depressive symptoms in haemodialysis patients: A questionable association

Introduction: Patients with advanced chronic kidney disease (CKD) on haemodialysis (HD) may have increased C reactive protein (CRP) values and depressive symptoms. There is debate about the strength and nature of previously reported associations. We investigated these issues in a cohort of patients on HD.

Self-reported depression symptoms in haemodialysis patients: Bi-factor structures of two common measures and their association with clinical factors

OBJECTIVE To validate the factor structure of two common self-report depression tools in a large sample of haemodialysis (HD) patients and to examine their demographic and clinical correlates, including urine output, history of depression and transplantation. METHODS Factor structures of the Beck Depression Inventory (BDI-II) and Patient Health Questionnaire (PHQ-9) were evaluated using confirmatory factor analysis (CFA). Data was utilised from the screening phase (n = 709) of a placebo-controlled feasibility randomised control trial (RCT) of sertraline in HD patients with mild to moderate Major Depressive Disorder. Alternative factor models including bi-factor models for the BDI-II and PHQ-9 were evaluated. Coefficient omega and omega-hierarchical were calculated. RESULTS For both measures, bi-factor measurement models had the overall best fit to the data, with dominant general depression factors. Omega-hierarchical for the general BDI-II and PHQ-9 factors was 0.94 and 0.88 respectively. Both general factors had high reliability (coefficient omega = 0.97 and 0.94 respectively) and explained over 85% of the explained common variance within their respective models. BDI-II and PHQ-9 general depression factors were negatively associated with age and urine output and positively with a history of depression, antidepressant use within the last 3 months and a history of failed transplantation. In adjusted regression models, age, urine output and a history of depression remained significant. CONCLUSIONS These data suggest that both the BDI-II and PHQ-9 are sufficiently unidimensional to warrant the use of a total score. Younger age, lower urine output and a history of depression appear consistent correlates of depression severity among HD patients.

A wordless intervention for people with epilepsy and intellectual disabilities (WIELD): A randomized controlled feasibility trial

Aim: Research on co-morbid health conditions experienced by people with autism spectrum disorder (ASD) is underdeveloped. This study aimed to systematically review existing systematic reviews and meta-analyses in order to identify evidence on the physical and mental health needs of people with ASD. Method: A literature search was conducted through PsycINFO, Scopus, CINAHL, Medline, and Cochrane databases an was limited to systematic reviews and meta-analyses published between 2005 and 2015. The following search terms were used: ‘autis*’ OR ‘pervasive developmental disorder’ OR ‘Asperger*’ OR ‘ASD’. Results: Out of 3,035 results, 243 articles were identified as potentially relevant and chosen for further review; 20 articles met the inclusion criteria. These focussed on mental health conditions (n=8), physical and genetic conditions (n=7),epilepsy (n=3), gender differences in health needs (n=1)and health problems in aging populations (n=1).Conclusions: Individuals with ASD experience a variety of co-morbid health problems, and frequently more than one condition co-occurs with autism. Whilst evidence exists regarding prevalence of co-morbidities, significant heterogeneity of studies and inconsistent reporting impact on the quality of systematic reviews and meta-analyses in this field.