Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations

<b>Background</b><p></p> Various tools exist for initial assessment of possible dementia with no consensus on the optimal assessment method. Instruments that use collateral sources to assess change in cognitive function over time may have particular utility. The most commonly used informant dementia assessment is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).<p></p> A synthesis of the available data regarding IQCODE accuracy will help inform cognitive assessment strategies for clinical practice, research and policy.<p></p> <b>Objectives</b><p></p> Our primary objective was to determine the diagnostic accuracy of the informant based questionnaire IQCODE, for detection of all cause (undifferentiated) dementia in community-dwelling adults with no previous cognitive assessment. We sought to describe the accuracy of IQCODE (the index test) against a clinical diagnosis of dementia (the reference standard).<p></p> Our secondary objective was to describe the effect of heterogeneity on the summary estimates. We were particularly interested in the traditional 26-item scale versus the 16-item short form; and language of administration. We explored the effect of varying the threshold IQCODE score used to define 'test positivity'.<p></p> <b>Search methods</b><p></p> We searched the following sources on 28 January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science with Conference Proceedings (ISI Web of Knowledge), LILACS (BIREME). We also searched sources relevant or specific to diagnostic test accuracy: MEDION (Universities of Maastrict and Leuven); DARE (York University); ARIF (Birmingham University). We used sensitive search terms based on MeSH terms and other controlled vocabulary.<p></p> <b>Selection criteria</b><p></p> We selected those studies performed in community settings that used (not necessarily exclusively) the IQCODE to assess for presence of dementia and, where dementia diagnosis was confirmed, with clinical assessment. Our intention with limiting the search to a 'community' setting was to include those studies closest to population level assessment. Within our predefined community inclusion criteria, there were relevant papers that fulfilled our definition of community dwelling but represented a selected population, for example stroke survivors. We included these studies but performed sensitivity analyses to assess the effects of these less representative populations on the summary results.<p></p> <b>Data collection and analysis</b><p></p> We screened all titles generated by the electronic database searches and abstracts of all potentially relevant studies were reviewed. Full papers were assessed for eligibility and data extracted by two independent assessors. For quality assessment (risk of bias and applicability) we used the QUADAS 2 tool. We included test accuracy data on the IQCODE used at predefined diagnostic thresholds. Where data allowed, we performed meta-analyses to calculate summary values of sensitivity and specificity with corresponding 95% confidence intervals (CIs). We pre-specified analyses to describe the effect of IQCODE format (traditional or short form) and language of administration for the IQCODE.<p></p> <b>Main results</b><p></p> From 16,144 citations, 71 papers described IQCODE test accuracy. We included 10 papers (11 independent datasets) representing data from 2644 individuals (n = 379 (14%) with dementia). Using IQCODE cut-offs commonly employed in clinical practice (3.3, 3.4, 3.5, 3.6) the sensitivity and specificity of IQCODE for diagnosis of dementia across the studies were generally above 75%.<p></p> Taking an IQCODE threshold of 3.3 (or closest available) the sensitivity was 0.80 (95% CI 0.75 to 0.85); specificity was 0.84 (95% CI 0.78 to 0.90); positive likelihood ratio was 5.2 (95% CI 3.7 to 7.5) and the negative likelihood ratio was 0.23 (95% CI 0.19 to 0.29).<p></p> Comparative analysis suggested no significant difference in the test accuracy of the 16 and 26-item IQCODE tests and no significant difference in test accuracy by language of administration. There was little difference in sensitivity across our predefined diagnostic cut-points.<p></p> There was substantial heterogeneity in the included studies. Sensitivity analyses removing potentially unrepresentative populations in these studies made little difference to the pooled data estimates. The majority of included papers had potential for bias, particularly around participant selection and sampling. The quality of reporting was suboptimal particularly regarding timing of assessments and descriptors of reproducibility and inter-observer variability.<p></p> <b>Authors' conclusions</b><p></p> Published data suggest that if using the IQCODE for community dwelling older adults, the 16 item IQCODE may be preferable to the traditional scale due to lesser test burden and no obvious difference in accuracy. Although IQCODE test accuracy is in a range that many would consider 'reasonable', in the context of community or population settings the use of the IQCODE alone would result in substantial misdiagnosis and false reassurance. Across the included studies there were issues with heterogeneity, several potential biases and suboptimal reporting quality

Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss

The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C- reactive protein) in male patients (n=40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r=0.390, p lt 0.05), extent of reported weight loss (r=-0.492, p lt 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r=0.686, p lt 0.001), and logo C-reactive protein concentrations (r=-0.545, p lt 0.001). On multiple regression analysis, the percent predicted total body potassium and log(10) C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r(2) = 0.626, p lt 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer

‘Children awaken by playing’: a qualitative exploration of caregivers’ norms, beliefs and practices related to young children’s learning and early childhood development in rural Burkina Faso

INTRODUCTION: Evidence suggests that responsive caregiving and early learning activities positively impact developmental outcomes, with positive effects throughout the life course. Early childhood development interventions should align with local values, beliefs and resources but there has been little research of caregiver beliefs and perspectives on development and learning, especially in sub-Saharan Africa. This qualitative study explored norms, beliefs, practices and aspirations around child development of caregivers of young children in rural Burkina Faso. METHODS: We conducted 32 in-depth interviews with mothers and fathers of young children and 24 focus group discussions with mothers, fathers and grandmothers, which included trying behaviours and reporting on experiences. The research informed the development of Scaling Up Nurturing Care, a Radio Intervention to Stimulate Early Childhood Development (SUNRISE), an early child development radio intervention. RESULTS: Caregivers described a process of 'awakening', through which children become aware of themselves and the world around them.Perceptions of the timing of awakening varied, but the ability to learn was thought to increase as children became older and more awake. Consequently, talking and playing with babies and younger children were perceived to have little developmental impact. Caregivers said children's interactions with them, alongside God-given intelligence, was believed to impact later behaviour and development. Caregivers felt their role in helping their children achieve later in life was to pay for education, save money, provide advice and be good role models. Interaction and learning activities were not specifically mentioned. Caregivers who trialled interaction and learning activities reported positive experiences for themselves and their child, but interactions were often caregiver led and directive and play was often physical. Key barriers to carrying out the behaviours were poverty and a lack of time. CONCLUSIONS: Exploring early childhood beliefs and practices can reveal important sociocultural beliefs which, if incorporated into programme planning and implementation, could help achieve more impactful, acceptable and equitable programmes. TRIAL REGISTRATION NUMBER: NCT05335395

Frailty and cerebrovascular disease: Concepts and clinical implications for stroke medicine.

Frailty is a distinctive health state in which the ability of older people to cope with acute stressors is compromised by an increased vulnerability brought by age-associated declines in physiological reserve and function across multiple organ systems. Although closely associated with age, multimorbidity, and disability, frailty is a discrete syndrome that is associated with poorer outcomes across a range of medical conditions. However, its role in cerebrovascular disease and stroke has received limited attention. The estimated rise in the prevalence of frailty associated with changing demographics over the coming decades makes it an important issue for stroke practitioners, cerebrovascular research, clinical service provision, and stroke survivors alike. This review will consider the concept and models of frailty, how frailty is common in cerebrovascular disease, the impact of frailty on stroke risk factors, acute treatments, and rehabilitation, and considerations for future applications in both cerebrovascular clinical and research settings

NSAIDs Modulate CDKN2A, TP53, and DNA Content Risk for Progression to Esophageal Adenocarcinoma

BACKGROUND: Somatic genetic CDKN2A, TP53, and DNA content abnormalities are common in many human cancers and their precursors, including esophageal adenocarcinoma (EA) and Barrett's esophagus (BE), conditions for which aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as possible chemopreventive agents; however, little is known about the ability of a biomarker panel to predict progression to cancer nor how NSAID use may modulate progression. We aimed to evaluate somatic genetic abnormalities with NSAIDs as predictors of EA in a prospective cohort study of patients with BE. METHODS AND FINDINGS: Esophageal biopsies from 243 patients with BE were evaluated at baseline for TP53 and CDKN2A (p16) alterations, tetraploidy, and aneuploidy using sequencing; loss of heterozygosity (LOH); methylation-specific PCR; and flow cytometry. At 10 y, all abnormalities, except CDKN2A mutation and methylation, contributed to EA risk significantly by univariate analysis, ranging from 17p LOH (relative risk [RR] = 10.6; 95% confidence interval [CI] 5.2–21.3, p < 0.001) to 9p LOH (RR = 2.6; 95% CI 1.1–6.0, p = 0.03). A panel of abnormalities including 17p LOH, DNA content tetraploidy and aneuploidy, and 9p LOH was the best predictor of EA (RR = 38.7; 95% CI 10.8–138.5, p < 0.001). Patients with no baseline abnormality had a 12% 10-y cumulative EA incidence, whereas patients with 17p LOH, DNA content abnormalities, and 9p LOH had at least a 79.1% 10-y EA incidence. In patients with zero, one, two, or three baseline panel abnormalities, there was a significant trend toward EA risk reduction among NSAID users compared to nonusers (p = 0.01). The strongest protective effect was seen in participants with multiple genetic abnormalities, with NSAID nonusers having an observed 10-y EA risk of 79%, compared to 30% for NSAID users (p < 0.001). CONCLUSIONS: A combination of 17p LOH, 9p LOH, and DNA content abnormalities provided better EA risk prediction than any single TP53, CDKN2A, or DNA content lesion alone. NSAIDs are associated with reduced EA risk, especially in patients with multiple high-risk molecular abnormalities

Application of Biomarkers in Cancer Risk Management: Evaluation from Stochastic Clonal Evolutionary and Dynamic System Optimization Points of View

Aside from primary prevention, early detection remains the most effective way to decrease mortality associated with the majority of solid cancers. Previous cancer screening models are largely based on classification of at-risk populations into three conceptually defined groups (normal, cancer without symptoms, and cancer with symptoms). Unfortunately, this approach has achieved limited successes in reducing cancer mortality. With advances in molecular biology and genomic technologies, many candidate somatic genetic and epigenetic “biomarkers” have been identified as potential predictors of cancer risk. However, none have yet been validated as robust predictors of progression to cancer or shown to reduce cancer mortality. In this Perspective, we first define the necessary and sufficient conditions for precise prediction of future cancer development and early cancer detection within a simple physical model framework. We then evaluate cancer risk prediction and early detection from a dynamic clonal evolution point of view, examining the implications of dynamic clonal evolution of biomarkers and the application of clonal evolution for cancer risk management in clinical practice. Finally, we propose a framework to guide future collaborative research between mathematical modelers and biomarker researchers to design studies to investigate and model dynamic clonal evolution. This approach will allow optimization of available resources for cancer control and intervention timing based on molecular biomarkers in predicting cancer among various risk subsets that dynamically evolve over time