AD-8 for detection of dementia across a variety of healthcare settings

BACKGROUND: Dementia assessment often involves initial screening, using a brief tool, followed by more detailed assessment where required. The AD-8 is a short questionnaire, completed by a suitable 'informant' who knows the person well. AD-8 is designed to assess change in functional performance secondary to cognitive change. OBJECTIVES: To determine the diagnostic accuracy of the informant-based AD-8 questionnaire, in detection of all-cause (undifferentiated) dementia in adults. Where data were available, we described the following: the diagnostic accuracy of the AD-8 at various predefined threshold scores; the diagnostic accuracy of the AD-8 for each healthcare setting and the effects of heterogeneity on the reported diagnostic accuracy of the AD-8. SEARCH METHODS: We searched the following sources on 27 May 2014, with an update to 7 June 2018: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), BIOSIS Previews (Thomson Reuters Web of Science), Web of Science Core Collection (includes Conference Proceedings Citation Index) (Thomson Reuters Web of Science), CINAHL (EBSCOhost) and LILACS (BIREME). We checked reference lists of relevant studies and reviews, used searches of known relevant studies in PubMed to track related articles, and contacted research groups conducting work on the AD-8 to try to find additional studies. We developed a sensitive search strategy and used standardised database subject headings as appropriate. Foreign language publications were translated. SELECTION CRITERIA: We selected those studies which included the AD-8 to assess for the presence of dementia and where dementia diagnosis was confirmed with clinical assessment. We only included those studies where the AD-8 was used as an informant assessment. We made no exclusions in relation to healthcare setting, language of AD-8 or the AD-8 score used to define a 'test positive' case. DATA COLLECTION AND ANALYSIS: We screened all titles generated by electronic database searches, and reviewed abstracts of potentially relevant studies. Two independent assessors checked full papers for eligibility and extracted data. We extracted data into two-by-two tables to allow calculation of accuracy metrics for individual studies. We then created summary estimates of sensitivity, specificity and likelihood ratios using the bivariate approach and plotting results in receiver operating characteristic (ROC) space. We determined quality assessment (risk of bias and applicability) using the QUADAS-2 tool. MAIN RESULTS: From 36 papers describing AD-8 test accuracy, we included 10 papers. We utilised data from nine papers with 4045 individuals, 1107 of whom (27%) had a clinical diagnosis of dementia. Pooled analysis of seven studies, using an AD-8 informant cut-off score of two, indicated that sensitivity was 0.92 (95% confidence interval (CI) 0.86 to 0.96); specificity was 0.64 (95% CI 0.39 to 0.82); the positive likelihood ratio was 2.53 (95% CI 1.38 to 4.64); and the negative likelihood ratio was 0.12 (95% CI 0.07 to 0.21). Pooled analysis of five studies, using an AD-8 informant cut-off score of three, indicated that sensitivity was 0.91 (95% CI 0.80 to 0.96); specificity was 0.76 (95% CI 0.57 to 0.89); the positive likelihood ratio was 3.86 (95% CI 2.03 to 7.34); and the negative likelihood ratio was 0.12 (95% CI 0.06 to 0.24).Four studies were conducted in community settings; four were in secondary care (one in the acute hospital); and one study was in primary care. The AD-8 has a higher relative sensitivity (1.11, 95% CI 1.02 to 1.21), but lower relative specificity (0.51, 95% CI 0.23 to 1.09) in secondary care compared to community care settings.There was heterogeneity across the included studies. Dementia prevalence rate varied from 12% to 90% of included participants. The tool was also used in various different languages. Among all the included studies there was evidence of risk of bias. Issues included the selection of participants, conduct of index test, and flow of assessment procedures. AUTHORS' CONCLUSIONS: The high sensitivity of the AD-8 suggests it can be used to identify adults who may benefit from further specialist assessment and diagnosis, but is not a diagnostic test in itself. This pattern of high sensitivity and lower specificity is often suited to a screening test. Test accuracy varies by setting, however data in primary care and acute hospital settings are limited. This review identified significant heterogeneity and risk of bias, which may affect the validity of its summary findings

Isolation of human intrahepatic leukocytes for phenotypic and functional characterization by flow cytometry

With the growing appreciation of tissue-resident immunity, studying tissue-specific immune cells contributing to both homeostasis and disease is imperative. Here, we provide a protocol for the isolation of human intrahepatic leukocytes (IHL) maximizing viability, purity, and yield. Our protocol is scalable by tissue weight, allowing for reproducible and efficient IHL liberation suitable for functional characterization, cell isolation, and profiling by flow (or mass) cytometry. Furthermore, we provide a "guide" to determine an expected IHL yield per gram of tissue processed. For complete details on the use and execution of this protocol, please refer to Stegmann et al. (2016), Pallett et al. (2017), Easom et al. (2018), Swadling et al. (2020), Pallett et al. (2020), and Zakeri et al. (2022)

Ten years of the Hunter Outcome Survey (HOS) : insights, achievements, and lessons learned from a global patient registry

Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a rare lysosomal storage disease with progressive multisystem manifestations caused by deficient activity of the enzyme iduronate-2-sulfatase. Diseasespecific treatment is available in the form of enzyme replacement therapy with intravenous idursulfase (Elaprase®, Shire). Since 2005, the Hunter Outcome Survey (HOS) has collected real-world, long-term data on the safety and effectiveness of this therapy, as well as the natural history of MPS II. Individuals with a confirmed diagnosis of MPS II who are untreated or who are receiving/have received treatment with idursulfase or bone marrow transplant can be enrolled in HOS. A broad range of disease- and treatment-related information is captured in the registry and, over the past decade, data from more than 1000 patients from 124 clinics in 29 countries have been collected. Evidence generated from HOS has helped to improve our understanding of disease progression in both treated and untreated patients and has extended findings from the formal clinical trials of idursulfase. As a long-term, global, observational registry, various challenges relating to data collection, entry, and analysis have been encountered. These have resulted in changes to the HOS database platform, and novel approaches to maximize the value of the information collected will also be needed in the future. The continued evolution of the registry should help to ensure that HOS provides further insights into the burden of the disease and patient care and management in the coming years

Restaurant cooking trends and increased risk for Campylobacter infection

In the United Kingdom, outbreaks of Campylobacter infection are increasingly attributed to undercooked chicken livers, yet many recipes, including those of top chefs, advocate short cooking times and serving livers pink. During 2015, we studied preferences of chefs and the public in the United Kingdom and investigated the link between liver rareness and survival of Campylobacter. We used photographs to assess chefs’ ability to identify chicken livers meeting safe cooking guidelines. To investigate the microbiological safety of livers chefs preferred to serve, we modeled Campylobacter survival in infected chicken livers cooked to various temperatures. Most chefs correctly identified safely cooked livers but overestimated the public’s preference for rareness and thus preferred to serve them more rare. We estimated that 19%-52% of livers served commercially in the United Kingdom fail to reach 70°C and that predicted Campylobacter survival rates are 48%-98%. These findings indicate that cooking trends are linked to increasing Campylobacter infections

Mini-Cog for the diagnosis of Alzheimer’s disease dementia and other dementias within a secondary care setting

Background: The diagnosis of Alzheimer's disease dementia and other dementias relies on clinical assessment. There is a high prevalence of cognitive disorders, including undiagnosed dementia in secondary care settings. Short cognitive tests can be helpful in identifying those who require further specialist diagnostic assessment; however, there is a lack of consensus around the optimal tools to use in clinical practice. The Mini‐Cog is a short cognitive test comprising three‐item recall and a clock‐drawing test that is used in secondary care settings. Objectives: The primary objective was to determine the diagnostic accuracy of the Mini‐Cog for detecting Alzheimer's disease dementia and other dementias in a secondary care setting. The secondary objectives were to investigate the heterogeneity of test accuracy in the included studies and potential sources of heterogeneity. These potential sources of heterogeneity will include the baseline prevalence of dementia in study samples, thresholds used to determine positive test results, the type of dementia (Alzheimer's disease dementia or all causes of dementia), and aspects of study design related to study quality. Search methods: We searched the following sources in September 2012, with an update to 12 March 2019: Cochrane Dementia Group Register of Diagnostic Test Accuracy Studies, MEDLINE (OvidSP), Embase (OvidSP), BIOSIS Previews (Web of Knowledge), Science Citation Index (ISI Web of Knowledge), PsycINFO (OvidSP), and LILACS (BIREME). We made no exclusions with regard to language of Mini‐Cog administration or language of publication, using translation services where necessary. Selection criteria: We included cross‐sectional studies and excluded case‐control designs, due to the risk of bias. We selected those studies that included the Mini‐Cog as an index test to diagnose dementia where dementia diagnosis was confirmed with reference standard clinical assessment using standardised dementia diagnostic criteria. We only included studies in secondary care settings (including inpatient and outpatient hospital participants). Data collection and analysis: We screened all titles and abstracts generated by the electronic database searches. Two review authors independently checked full papers for eligibility and extracted data. We determined quality assessment (risk of bias and applicability) using the QUADAS‐2 tool. We extracted data into two‐by‐two tables to allow calculation of accuracy metrics for individual studies, reporting the sensitivity, specificity, and 95% confidence intervals of these measures, summarising them graphically using forest plots. Main results: Three studies with a total of 2560 participants fulfilled the inclusion criteria, set in neuropsychology outpatient referrals, outpatients attending a general medicine clinic, and referrals to a memory clinic. Only n = 1415 (55.3%) of participants were included in the analysis to inform evaluation of Mini‐Cog test accuracy, due to the selective use of available data by study authors. There were concerns related to high risk of bias with respect to patient selection, and unclear risk of bias and high concerns related to index test conduct and applicability. In all studies, the Mini‐Cog was retrospectively derived from historic data sets. No studies included acute general hospital inpatients. The prevalence of dementia ranged from 32.2% to 87.3%. The sensitivities of the Mini‐Cog in the individual studies were reported as 0.67 (95% confidence interval (CI) 0.63 to 0.71), 0.60 (95% CI 0.48 to 0.72), and 0.87 (95% CI 0.83 to 0.90). The specificity of the Mini‐Cog for each individual study was 0.87 (95% CI 0.81 to 0.92), 0.65 (95% CI 0.57 to 0.73), and 1.00 (95% CI 0.94 to 1.00). We did not perform meta‐analysis due to concerns related to risk of bias and heterogeneity. Authors' conclusions: This review identified only a limited number of diagnostic test accuracy studies using Mini‐Cog in secondary care settings. Those identified were at high risk of bias related to patient selection and high concerns related to index test conduct and applicability. The evidence was indirect, as all studies evaluated Mini‐Cog differently from the review question, where it was anticipated that studies would conduct Mini‐Cog and independently but contemporaneously perform a reference standard assessment to diagnose dementia. The pattern of test accuracy varied across the three studies. Future research should evaluate Mini‐Cog as a test in itself, rather than derived from other neuropsychological assessments. There is also a need for evaluation of the feasibility of the Mini‐Cog for the diagnosis of dementia to help adequately determine its role in the clinical pathway

Solving the border control problem: evidence of enhanced face matching in individuals with extraordinary face recognition skills.

Photographic identity documents (IDs) are commonly used despite clear evidence that unfamiliar face matching is a difficult and error-prone task. The current study set out to examine the performance of seven individuals with extraordinary face recognition memory, so called “super recognisers” (SRs), on two face matching tasks resembling border control identity checks. In Experiment 1, the SRs as a group outperformed control participants on the “Glasgow Face Matching Test”, and some case-by-case comparisons also reached significance. In Experiment 2, a perceptually difficult face matching task was used: the “Models Face Matching Test”. Once again, SRs outperformed controls both on group and mostly in case-by-case analyses. These findings suggest that SRs are considerably better at face matching than typical perceivers, and would make proficient personnel for border control agencies

Hip disability and osteoarthritis outcome score (HOOS) – validity and responsiveness in total hip replacement

BACKGROUND: The aim of the study was to evaluate if physical functions usually associated with a younger population were of importance for an older population, and to construct an outcome measure for hip osteoarthritis with improved responsiveness compared to the Western Ontario McMaster osteoarthritis score (WOMAC LK 3.0). METHODS: A 40 item questionnaire (hip disability and osteoarthritis outcome score, HOOS) was constructed to assess patient-relevant outcomes in five separate subscales (pain, symptoms, activity of daily living, sport and recreation function and hip related quality of life). The HOOS contains all WOMAC LK 3.0 questions in unchanged form. The HOOS was distributed to 90 patients with primary hip osteoarthritis (mean age 71.5, range 49–85, 41 females) assigned for total hip replacement for osteoarthritis preoperatively and at six months follow-up. RESULTS: The HOOS met set criteria of validity and responsiveness. It was more responsive than WOMAC regarding the subscales pain (SRM 2.11 vs. 1.83) and other symptoms (SRM 1.83 vs. 1.28). The responsiveness (SRM) for the two added subscales sport and recreation and quality of life were 1.29 and 1.65, respectively. Patients ≤ 66 years of age (range 49–66) reported higher responsiveness in all five subscales than patients >66 years of age (range 67–85) (Pain SRM 2.60 vs. 1.97, other symptoms SRM 3.0 vs. 1.60, activity of daily living SRM 2.51 vs. 1.52, sport and recreation function SRM 1.53 vs. 1.21 and hip related quality of life SRM 1.95 vs. 1.57). CONCLUSION: The HOOS 2.0 appears to be useful for the evaluation of patient-relevant outcome after THR and is more responsive than the WOMAC LK 3.0. The added subscales sport and recreation function and hip related quality of life were highly responsive for this group of patients, with the responsiveness being highest for those younger than 66

“Medically unexplained” symptoms and symptom disorders in primary care: prognosis-based recognition and classification

Background: Many patients consult their GP because they experience bodily symptoms. In a substantial proportion of cases, the clinical picture does not meet the existing diagnostic criteria for diseases or disorders. This may be because symptoms are recent and evolving or because symptoms are persistent but, either by their character or the negative results of clinical investigation cannot be attributed to disease: so-called “medically unexplained symptoms” (MUS). MUS are inconsistently recognised, diagnosed and managed in primary care. The specialist classification systems for MUS pose several problems in a primary care setting. The systems generally require great certainty about presence or absence of physical disease, they tend to be mind-body dualistic, and they view symptoms from a narrow specialty determined perspective. We need a new classification of MUS in primary care; a classification that better supports clinical decision-making, creates clearer communication and provides scientific underpinning of research to ensure effective interventions. Discussion: We propose a classification of symptoms that places greater emphasis on prognostic factors. Prognosis-based classification aims to categorise the patient’s risk of ongoing symptoms, complications, increased healthcare use or disability because of the symptoms. Current evidence suggests several factors which may be used: symptom characteristics such as: number, multi-system pattern, frequency, severity. Other factors are: concurrent mental disorders, psychological features and demographic data. We discuss how these characteristics may be used to classify symptoms into three groups: self-limiting symptoms, recurrent and persistent symptoms, and symptom disorders. The middle group is especially relevant in primary care; as these patients generally have reduced quality of life but often go unrecognised and are at risk of iatrogenic harm. The presented characteristics do not contain immediately obvious cut-points, and the assessment of prognosis depends on a combination of several factors. Conclusion: Three criteria (multiple symptoms, multiple systems, multiple times) may support the classification into good, intermediate and poor prognosis when dealing with symptoms in primary care. The proposed new classification specifically targets the patient population in primary care and may provide a rational framework for decision-making in clinical practice and for epidemiologic and clinical research of symptoms

Calcitriol modulates the CD46 pathway in T cells

The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)2D3 or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNc ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS