Where are we at with model-based economic evaluations of interventions for dementia? A systematic review and quality assessment

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this record.Objective: To identify, review and critically appraise model-based economic evaluations of all types of interventions for people with dementia and their carers. Design: A systematic literature search was undertaken to identify model-based evaluations of dementia interventions. A critical appraisal of included studies was carried out using guidance on good practice methods for decision-analytic models in health technology assessment, with a focus on model structure, data, and model consistency. Setting: Interventions for people with dementia and their carers, across prevention, diagnostic, treatment and disease management. Results: We identified 67 studies, with 43 evaluating pharmacological products, 19 covering prevention or diagnostic strategies, and five studies reporting non-pharmacological interventions. The majority of studies use Markov models with a simple structure to represent dementia symptoms and disease progression. Half of all studies reported taking a societal perspective, with the other half adopting a third-party payer perspective. Most studies follow good practices in modelling, particularly related to the decision problem description, perspective, model structure and data inputs. Many studies perform poorly in areas related to reporting of pre-modelling analyses, justifying data inputs, evaluating data quality, considering alternative modelling options, validating models and assessing uncertainty. Conclusions: There is a growing literature on model-based evaluations of interventions for dementia. The literature predominantly reports on pharmaceutical interventions for Alzheimer’s disease, but there is a growing literature for dementia prevention and nonpharmacological interventions. Our findings demonstrate that decision-makers need to critically appraise and understand the model-based evaluations and their limitations to ensure they are used, interpreted and applied appropriately

Valuing the AD-5D dementia utility instrument : an estimation of a general population tariff

Objective This paper reports on the valuation of quality-of-life states in the Alzheimer’s Disease Five Dimensions (AD-5D) instrument in a representative sample of the general population in Australia using the discrete-choice experiment with duration (DCETTO) elicitation technique. Method A DCE with 200 choice sets of two quality-of-life (QoL) state–duration combinations blocked into 20 survey versions, with ten choice sets in each version, was designed and administered online to a sample representative of the Australian population. Two additional choice sets comprising internal consistency and dominance checks were included in each survey version. A range of model specifications investigating preferences with respect to duration and interactions between AD-5D dimension levels were estimated. Utility weights were developed, with estimated coefficients transformed to the 0 (being dead) to 1 (full health) scale, suitable for the calculation of quality-adjusted life-year (QALY) weights for use in economic evaluation. Results In total, 1999 respondents completed the choice experiment. Overall, respondents were slightly better educated and had higher annual incomes than the Australian general population. The estimation results from different specifications and models were broadly consistent with the monotonic nature of the AD-5D: utility increased with increased life expectancy and decreased as the severity level for each dimension worsened. A utility value set was generated for the calculation of utilities for all QoL states defined by the AD-5D descriptive system. Conclusion The DCE-based utility value set is now available to use to generate QALYs for the economic evaluation of treatments and interventions targeting people with dementia and/or their family caregivers

Immunological parameters in girls with Turner syndrome

Disturbances in the immune system has been described in Turner syndrome, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45, X), thyroiditis being the most common. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency) ear problems are common (recurrent otitis media and progressive sensorineural hearing disorder). Levels of IgG, IgA, IgM, IgD and the four IgG subclasses as well as T- and B-lymphocyte subpopulations were investigated in 15 girls with Turners syndrome to examine whether an immunodeficiency may be the cause of their high incidence of otitis media. No major immunological deficiency was found that could explain the increased incidence of otitis media in the young Turner girls

Sensitivity of labile carbon fractions to tillage and organic matter management and their potential as comprehensive soil quality indicators across pedoclimatic conditions in Europe

Soil quality is defined as the capacity of the soil to perform multiple functions, and can be assessed by measuring soil chemical, physical and biological parameters. Among soil parameters, labile organic carbon is considered to have a primary role in many soil functions related to productivity and environmental resilience. Our study aimed at assessing the suitability of different labile carbon fractions, namely dissolved organic carbon (DOC), hydrophilic DOC (Hy-DOC), permanganate oxidizable carbon (POXC, also referred to as Active Carbon), hot water extractable carbon (HWEC) and particulate organic matter carbon (POMC) as soil quality indicators in agricultural systems. To do so, we tested their sensitivity to two agricultural management factors (tillage and organic matter input) in 10 European long-term field experiments (LTEs), and we assessed the correlation of the different labile carbon fractions with physical, chemical and biological soil quality indicators linked to soil functions. We found that reduced tillage and high organic matter input increase concentrations of labile carbon fractions in soil compared to conventional tillage and low organic matter addition, respectively. POXC and POMC were the most sensitive fractions to both tillage and fertilization across the 10 European LTEs. In addition, POXC was the labile carbon fraction most positively correlated with soil chemical (total organic carbon, total nitrogen, and cation exchange capacity), physical (water stable aggregates, water holding capacity, bulk density) and biological soil quality indicators (microbial biomass carbon and nitrogen, and soil respiration). We conclude that POXC represents a labile carbon fraction sensitive to soil management and that is the most informative about total soil organic matter, nutrients, soil structure, and microbial pools and activity, parameters commonly used as indicators of various soil functions, such as C sequestration, nutrient cycling, soil structure formation and soil as a habitat for biodiversity. Moreover, POXC measurement is relatively cheap, fast and easy. Therefore, we suggest measuring POXC as the labile carbon fraction in soil quality assessment schemes in addition to other valuable soil quality indicators.</p

Educational paper: Primary immunodeficiencies in children: a diagnostic challenge

Primary immunodeficiencies (PIDs) are characterized by an increased susceptibility to infections due to defects in one ore more components of the immune system. Although most PIDs are relatively rare, they are more frequent than generally acknowledged. Early diagnosis and treatment of PIDs save lives, prevent morbidity, and improve quality of life. This early diagnosis is the task of the pediatrician who encounters the child for the first time: he/she should suspect potential PID in time and perform the appropriate diagnostic tests. In this educational paper, the first in a series of five, we will describe the most common clinical presentations of PIDs and offer guidelines for the diagnostic process, as well as a brief overview of therapeutic possibilities and prognosis

Study protocol for The GOAL Trial: comprehensive geriatric assessment for frail older people with chronic kidney disease to increase attainment of patient-identified goals—a cluster randomised controlled trial

Background: An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely afect their quality of life. Comprehensive geriatric assessment (CGA) is an efective intervention to improve survival and independence of older people, but its clinical utility and cost-efectiveness in frail older people living with CKD is unknown. Methods: The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants≥65 years of age (or≥55 years if Aborigi‑ nal or Torres Strait Islander (First Nations Australians)) with CKD stage 3–5/5D who are frail, measured by a Frailty Index (FI) of>0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identifed goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, qual‑ ity of life (EQ-5D-5L), frailty (Frailty Index – Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specifc hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. Discussion This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial’s findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD.B Logan ... MG Collins ... S Jesudason ... et al

How do people with dementia and family carers value dementia-specific quality of life states? An explorative "Think Aloud" study

OBJECTIVE:To investigate the decision-making processes applied by people with dementia and family carers participating in using health economic approaches to value dementia-specific quality of life states. METHODS:People with dementia (n = 13) and family carers (n = 14) participated in valuing quality of life states using two health economic approaches: Discrete Choice Experiment (DCE) and Best Worst Scaling (BWS). Participants were encouraged to explain their reasoning using a "Think Aloud" approach. RESULTS:People with dementia and family carers adopted a range of decision-making strategies including "anchoring" the presented states against current quality of life, or simplifying the decision-making by focusing on the sub-set of attributes deemed most important. Overall, there was strong evidence of task engagement for BWS and DCE. CONCLUSIONS:Health economic valuation approaches can be successfully applied with people with dementia and family carers. These data can inform the assessment of benefits from their perspectives for incorporation within economic evaluation.Julie Ratcliffe, Claire Hutchinson, Rachel Milte, Kim‐Huong Nguyen, Alyssa Welch, Tessa Caporale, Megan Corlis, Tracy Coman

Influence of sex, age, pubertal maturation and body mass index on circulating white blood cell counts in healthy European adolescents—the HELENA study

Percentiles 10th, 25th, 50th, 75th and 90th are presented for circulating white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils and basophils in healthy European adolescents (12.5–17.5 years, n = 405, 48.9 % boys), considering age, sex, puberty and body mass index (BMI). CD3+ (mature T cells), CD4+ (T helper), CD8+ (T cytotoxic), CD16+56+ (natural killer), CD19+ (B cells), CD3+CD45RA+, CD4+CD45RA+, CD8+CD45RA+ (naïve), CD3+CD45RO+, CD4+CD45RO+ and CD8+CD45RO+ (memory) lymphocytes were also analysed by immunophenotyping. Girls presented higher WBC, neutrophil, CD3+CD45RO+ and CD4+CD45RO+ cell counts and CD3+/CD19+ ratio, and lower CD3+CD45RA+ and CD4+CD45RA+ counts than boys. Age was associated with higher neutrophil counts and CD3+/CD19+, and lower CD19+ counts; in boys, with lower CD3+CD45RA+, CD4+CD45RA+ and CD8+CD45RA+ counts as well; in girls, with higher WBC, CD3+CD45RO+ and CD4+CD45RO+ counts. Pubertal maturation in boys was associated with lower WBC and lymphocyte counts; in girls, with higher basophil, CD3+CD45RO+ and CD4+CD45RO+ values. BMI was associated with higher WBC counts; in boys, also with higher lymphocyte counts; in girls, with higher neutrophil, CD4+, CD3+CD45RO+ and CD4+CD45RO+ counts. Conclusion: Our study provides normative values for circulating immune cells in adolescents, highlighting the importance of considering sex, age, pubertal maturation and BMI when establishing reference ranges for WBC in paediatric populations