Participatory research meets validated outcome measures:tensions in the co-production of social care evaluation

Funding for care service research is increasingly subject to the satisfaction of two requirements: public involvement; and adoption of validated outcome tools. This study identifies competing paradigms within these requirements and reveals significant challenges faced by researchers who seek to satisfy them. The focus here is on a study co-produced between academic researchers and people with experience of adult social care services. It examines to what extent research studies can conduct high quality public involvement and genuine co-production of knowledge, whilst attempting to produce quantifiable outcome scores. Findings add to debate around how to incorporate diverse perspectives in research which may draw on incommensurate accounts of validity and reliability. Findings also highlight constructive attempts by academic and co-researchers to make the combination of approaches work in the field. These small scale acts of researcher agency indicate some scope to combine the two approaches in future research studies. However conclusions foreground the importance of broader awareness of how tensions and power imbalances related to this combination of approaches play out in social policy research practice

Micro-enterprises: small enough to care?

This report presents findings of an evaluation of micro-enterprises in social care in England, which ran from 2013 to 2015. Organisations are here classed as micro if they employ five or fewer full-time equivalent staff. The aim of the project was to test the extent to which micro-enterprises deliver services that are personalised, valued, innovative and cost-effective, and how they compare with small, medium and large providers. Working in three parts of the country, researchers compared 27 organisations providing care and support, of which 17 were microenterprises, 2 were small, 4 were medium and 4 were large. The project team interviewed and surveyed 143 people (staff, older people, people with disabilities and carers) who received support from the 27 providers. The findings presented are relevant to people who use services and their families; social care commissioners; regulators and policy makers at a local and national level; people who provide care services; and social entrepreneurs who are considering setting up micro forms of support. The research was based at the University of Birmingham. It was funded by the Economic and Social Research Council (ESRC), as part of a project entitled Does Smaller mean Better? Evaluating Micro-enterprises in Adult Social Care (ESRC Standard Grant ES/ K002317/1)

Pharmacokinetic studies in children: recommendations for practice and research.

Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose-concentration-effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight

Uncovering the significance of expanded CD8+ large granular lymphocytes in inclusion body myositis: Insights into T cell phenotype and functional alterations, and disease severity

IntroductionInclusion body myositis (IBM) is a progressive inflammatory myopathy characterised by skeletal muscle infiltration and myofibre invasion by CD8+ T lymphocytes. In some cases, IBM has been reported to be associated with a systemic lymphoproliferative disorder of CD8+ T cells exhibiting a highly differentiated effector phenotype known as T cell Large Granular Lymphocytic Leukemia (T-LGLL). MethodsWe investigated the incidence of a CD8+ T-LGL lymphoproliferative disorder in 85 IBM patients and an aged-matched group of 56 Healthy Controls (HC). Further, we analysed the phenotypical characteristics of the expanded T-LGLs and investigated whether their occurrence was associated with any particular HLA alleles or clinical characteristics. ResultsBlood cell analysis by flow cytometry revealed expansion of T-LGLs in 34 of the 85 (40%) IBM patients. The T cell immunophenotype of T-LGLHIGH patients was characterised by increased expression of surface molecules including CD57 and KLRG1, and to a lesser extent of CD94 and CD56 predominantly in CD8+ T cells, although we also observed modest changes in CD4+ T cells and γδ T cells. Analysis of Ki67 in CD57+ KLRG1+ T cells revealed that only a small proportion of these cells was proliferating. Comparative analysis of CD8+ and CD4+ T cells isolated from matched blood and muscle samples donated by three patients indicated a consistent pattern of more pronounced alterations in muscles, although not significant due to small sample size. In the T-LGLHIGH patient group, we found increased frequencies of perforin-producing CD8+ and CD4+ T cells that were moderately correlated to combined CD57 and KLRG1 expression. Investigation of the HLA haplotypes of 75 IBM patients identified that carriage of the HLA-C*14:02:01 allele was significantly higher in T-LGLHIGH compared to T-LGLLOW individuals. Expansion of T-LGL was not significantly associated with seropositivity patient status for anti-cytosolic 5'-nucleotidase 1A autoantibodies. Clinically, the age at disease onset and disease duration were similar in the T-LGLHIGH and T-LGLLOW patient groups. However, metadata analysis of functional alterations indicated that patients with expanded T-LGL more frequently relied on mobility aids than T-LGLLOW patients indicating greater disease severity. ConclusionAltogether, these results suggest that T-LGL expansion occurring in IBM patients is correlated with exacerbated immune dysregulation and increased disease burden

How Intense Policy Demanders Shape Postreform Politics: Evidence from the Affordable Care Act

The implementation of the Affordable Care Act (ACA) has been a politically volatile process. The ACA\u27s institutional design and delayed feedback effects created a window of opportunity for its partisan opponents to launch challenges at both the federal and state level. Yet as recent research suggests, postreform politics depends on more than policy feedback alone; rather, it is shaped by the partisan and interest-group environment. We argue that “intense policy demanders” played an important role in defining the policy alternatives that comprised congressional Republicans\u27 efforts to repeal and replace the ACA. To test this argument, we drew on an original data set of bill introductions in the House of Representatives between 2011 and 2016. Our analysis suggests that business contributions and political ideology affected the likelihood that House Republicans would introduce measures repealing significant portions of the ACA. A secondary analysis shows that intense policy demanders also shaped the vote on House Republicans\u27 initial ACA replacement plan. These findings highlight the role intense policy demanders can play in shaping the postreform political agenda

Climate, Deer, Rodents, and Acorns as Determinants of Variation in Lyme-Disease Risk

Risk of human exposure to vector-borne zoonotic pathogens is a function of the abundance and infection prevalence of vectors. We assessed the determinants of Lyme-disease risk (density and Borrelia burgdorferi-infection prevalence of nymphal Ixodes scapularis ticks) over 13 y on several field plots within eastern deciduous forests in the epicenter of US Lyme disease (Dutchess County, New York). We used a model comparison approach to simultaneously test the importance of ambient growing-season temperature, precipitation, two indices of deer (Odocoileus virginianus) abundance, and densities of white-footed mice (Peromyscus leucopus), eastern chipmunks (Tamias striatus), and acorns ( Quercus spp.), in both simple and multiple regression models, in predicting entomological risk. Indices of deer abundance had no predictive power, and precipitation in the current year and temperature in the prior year had only weak effects on entomological risk. The strongest predictors of a current year's risk were the prior year's abundance of mice and chipmunks and abundance of acorns 2 y previously. In no case did inclusion of deer or climate variables improve the predictive power of models based on rodents, acorns, or both. We conclude that interannual variation in entomological risk of exposure to Lyme disease is correlated positively with prior abundance of key hosts for the immature stages of the tick vector and with critical food resources for those hosts