The impact of individual Cognitive Stimulation Therapy (iCST) on cognition, quality of life, caregiver health, and family relationships in dementia: a randomized controlled trial

Background: Cognitive Stimulation Therapy (CST) is a well-established group psychosocial intervention for people with dementia. There is evidence that homebased programmes of cognitive stimulation delivered by family caregivers may benefit both the person and the caregiver. However, no previous studies have evaluated caregiver-delivered CST. This study aimed to evaluate the effectiveness of a home-based, caregiver-led individual Cognitive Stimulation Therapy (iCST) program in (i) improving cognition and quality of life (QoL) for the person with dementia and (ii) mental and physical health (wellbeing) for the caregiver. Methods and Findings: A single-blind, pragmatic randomized trial (RCT) at eight study sites across the UK. The intervention and blinded assessment of outcomes were conducted in participants’ homes. 356 people with mild to moderate dementia and their caregivers recruited from memory services, and community mental health teams. Participants were randomly assigned to iCST (75, 30 minute sessions) or treatment as usual (TAU) control over 25 weeks. iCST sessions consisted of themed activities designed to be mentally stimulating and enjoyable. Caregivers delivering iCST received training and support from an unblind researcher. Primary outcomes were cognition (Alzheimer’s Disease Assessment Scale cognitive [ADAS-Cog]) and self-reported quality of life (QoL) (Quality of Life Alzheimer’s Disease [QoL-AD]) for the person with dementia, and general health status (Short Form-12 [SF-12]) for the caregiver. Secondary outcomes included: quality of the caregiving relationship from the perspectives of the person and of the caregiver (Quality of the Carer Patient Relationships Scale), and health-related QoL (EQ5D) for the caregiver. Intention to treat (ITT) analyses were conducted. At the post-test (26 weeks), there were no differences between the iCST and TAU groups in the outcomes of cognition (MD = -0·55, 95% CI -2·00 to 0·90; p=0·45), and self-reported quality of life (QoL) (MD = -0·02, 95% CI -1·22 to 0·82; p= 0·97) for people with dementia, or caregivers’ general health status (MD=0·13, 95% CI -1·65 to 1·91; p=0·89). However, people with dementia receiving iCST rated the relationship with their caregiver more positively (MD = 1·77, 95% CI 0·26 to 3·28; p=0·02) and iCST improved QoL for caregivers (EQ-5D, MD = 0·06, 95% CI 0·02 to 0·10; p=0·01). Forty percent (72/180) of dyads allocated to iCST completed at least two sessions per week, with 22% (39/180) completing no sessions at all. Study limitations include low adherence to the intervention. Conclusions: There was no evidence that iCST has an effect on cognition or QoL for people with dementia. However, participating in iCST appeared to enhance the quality of the caregiving relationship and caregivers’ QoL

Understanding Variation in Sets of N-of-1 Trials.

A recent paper in this journal by Chen and Chen has used computer simulations to examine a number of approaches to analysing sets of n-of-1 trials. We have examined such designs using a more theoretical approach based on considering the purpose of analysis and the structure as regards randomisation that the design uses. We show that different purposes require different analyses and that these in turn may produce quite different results. Our approach to incorporating the randomisation employed when the purpose is to test a null hypothesis of strict equality of the treatment makes use of Nelder's theory of general balance. However, where the purpose is to make inferences about the effects for individual patients, we show that a mixed model is needed. There are strong parallels to the difference between fixed and random effects meta-analyses and these are discussed

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

A randomized controlled trial-based algorithm for insulin-pump therapy in hyperglycemic patients early after kidney transplantation

Treating hyperglycemia in previously non-diabetic individuals with exogenous insulin immediately after kidney transplantation reduced the odds of developing Posttransplantation Diabetes Mellitus (PTDM) in our previous proof-of-concept clinical trial. We hypothesized that insulin-pump therapy with maximal insulin dosage during the afternoon would improve glycemic control compared to basal insulin and standard-of-care. In a multi-center, randomized, controlled trial testing insulin isophane for PTDM prevention, we added a third study arm applying continuous subcutaneous insulin lispro infusion (CSII) treatment. CSII was initiated in 24 patients aged 55±12 years, without diabetes history, receiving tacrolimus. The mean daily insulin lispro dose was 9.2±5.2 IU. 2.3±1.1% of the total insulin dose were administered between 00:00 and 6:00, 19.5±11.6% between 6:00 and 12:00, 62.3±15.6% between 12:00 and 18:00 and 15.9±9.1% between 18:00 and 24:00. Additional bolus injections were necessary in five patients. Mild hypoglycemia (52-60 mg/dL) occurred in two patients. During the first post-operative week glucose control in CSII patients was overall superior compared to standard-of-care as well as once-daily insulin isophane for fasting and post-supper glucose. We present an algorithm for CSII treatment in kidney transplant recipients, demonstrating similar safety and superior short-term efficacy compared to standard-of-care and once-daily insulin isophane

Positive psychology : Past, present, and (possible) future

What is positive psychology? Where has it come from? Where is it going? These are the questions we address in this article. In defining positive psychology, we distinguish between the meta-psychological level, where the aim of positive psychology is to redress the imbalance in psychology research and practice, and the pragmatic level, which is concerned with what positive psychologists do, in terms of their research, practice, and areas of interest. These distinctions in how we understand positive psychology are then used to shape conceptions of possible futures for positive psychology. In conclusion, we identify several pertinent issues for the consideration of positive psychology as it moves forward. These include the need to synthesize the positive and negative, build on its historical antecedents, integrate across levels of analysis, build constituency with powerful stakeholders, and be aware of the implications of description versus prescription