BackgroundThe analytical and clinical validity of cerebrospinal (CSF) biomarkers has been extensively researched in dementia. Further work is needed to assess the ability of these biomarkers to improve diagnosis, management and health outcomes in the clinical settingObjectivesTo assess the added value and clinical utility of CSF biomarkers in the diagnostic assessment of cognitively impaired patients under evaluation for Alzheimer’s disease (AD).MethodsSystematic literature searches of Medline, EMBASE, PsycINFO and Web of Science research databases were conducted on 17 December 2022. Data from relevant studies were extracted and independently screened for quality using a tool for bias. Clinical utility was measured by clinicians’ changes in diagnosis, diagnostic confidence and patient management (when available), after their examination of patients’ CSF biomarkers. Cost-effectiveness was assessed by consideration of additional cost per patient and quality-adjusted life years.ResultsSearches identified 17 studies comprising 2090 patient participants and 593 clinicians. The meta-analysis revealed that clinicians’ use of CSF biomarkers resulted in a pooled percentage change in diagnosis of 25% (95% CI 14 to 37), an increase in diagnostic confidence of 14% (95% CI 9 to 18) and a pooled proportion of patients whose management changed of 31% (95% CI 12 to 50). CSF biomarkers were deemed cost-effective, particularly in memory services, where pre-test AD prevalence is higher compared with a primary care setting.ConclusionsCSF biomarkers can be a helpful additional diagnostic tool for clinicians assessing patients with cognitive impairment. In particular, CSF biomarkers consistently improved clinicians’ confidence in diagnosing AD and influenced on diagnostic change and patient management. Further research is needed to study the clinical utility of blood-based biomarkers in the clinical setting.
Background: The COVID-19 pandemic presents challenges to substance misuse services. Patients face a higher risk of infection and transmission to others. Services were required to reconfigure quickly in response to the government lockdown. These changes had to be completed before national guidance was published. Method: To examine the strategy and operational delivery of two London boroughs and measure how convergent they were with national guidelines. Referral data were analyzed and compared to a similar time frame pre-COVID-19. Results: Both services adopted similar strategies and pace of change. Longer supplies of opiate substitution therapy (OST) were prescribed, with less restrictive arrangements for collection. There was an increase in opiate assessments and a reduction in alcohol assessments. There was no overall increase in mortality. There was minor deviation from national guidance when it was initially published. Conclusions: The services were well equipped to respond to the rapid changes demanded during early lockdown. Reduced restrictions in OST may not be associated with negative service or patient outcomes. The move to remote consultations and home working are likely to have value in substance misuse services after the pandemic. The long-term impact of lockdown presents uncertainties in terms of clinical safety and requires evaluation.
Background Plasma phosphorylated‐tau181 (p‐tau181) represents a novel blood‐based biomarker of Alzheimer's disease pathology. We explored clinicians' experience of the utility of plasma p‐tau181 in Camden and Islington Memory Services. Methods Patients were identified by their clinician as appropriate for p‐tau181. Their p‐tau181 result was plotted on a reference range graph provided to clinicians. This was discussed with the patient at diagnostic feedback appointment. Results Twenty‐nine participants' plasma p‐tau181 samples were included (mean age 74 SD 8.5, 65% female). Nine clinicians participated in the study. Eighty‐six percent of clinicians found the p‐tau181 result to be helpful and in 93% of cases it was clearly understandable. The p‐tau181 result was useful in making the diagnosis in 44% of cases. Conclusions Plasma p‐tau181 is a feasible test for use in memory services and acceptable to clinicians. Clinician feedback on utility in dementia diagnoses was mixed. Further work is required to provide education and training in understanding and interpreting ambiguity in biomarker results.
Changes in diagnostic certainty can be evaluated by assessing the impact of a diagnostic test in driving decision making. Diagnostic tests can be appraised using validated measures of accuracy, i.e., sensitivity, specificity, and positive or negative predictive values against a known reference standard. However, other less well formalized factors affect diagnostic certainty. These inputs are under-researched and more difficult to quantify. Clinicians assess the significance of available data in the context of their expertise, pre-diagnostic confidence, and background knowledge of populations and disease. Inherent qualities of the diagnostic test and an individual clinician’s interpretation of the meaning of test results will also affect the subsequent level of diagnostic certainty. These factors are only infrequently considered alongside the diagnostic accuracy of a test. In this paper, we present a model of the different processes which can affect diagnostic certainty in Alzheimer’s disease (AD). This model builds upon existing understanding and provides further insights into the complexity of diagnostic certainty in AD and how we might improve this.
Objectives To assess plasma phosphorylated tau181 (p‐tau181) levels in Alzheimer's disease (AD), cognitively impaired non‐AD participants (CI non‐AD) and Control participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset that could potentially act as reference data for clinic diagnoses of AD. Methods Data from 1558 participants (649 AD participants, 445 CI non‐AD participants and 464 controls) were examined, comparing p‐tau181 levels between Controls, AD and other dementias, stratified by age. Results There were significant differences in plasma p‐tau181 values between Controls and those with AD at all ages up to 85 years. There were also significant differences between AD and CI non‐AD participants up to the age of 85 years. Conclusions Plasma P‐tau181 may be a useful tool in the diagnosis of AD in those clinical settings where biomarkers have traditionally been less used. P‐tau181 may be less useful as an aid to diagnosis in the very oldest‐old. Further work is needed to establish the feasibility and utility of this biomarker within dementia diagnosis services not led by Neurologists, such as UK National Health Service Memory Services.
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