Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for health care policy and decision-making.

OBJECTIVES: Network meta-analyses (NMA) have extensively been used to compare the effectiveness of multiple interventions for health care policy and decision-making. However, methods for evaluating the performance of multiple diagnostic tests are less established. In a decision-making context, we are often interested in comparing and ranking the performance of multiple diagnostic tests, at varying levels of test thresholds, in one simultaneous analysis. STUDY DESIGN AND SETTING: Motivated by an example of cognitive impairment diagnosis following stroke, we synthesized data from 13 studies assessing the efficiency of two diagnostic tests: Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), at two test thresholds: MMSE <25/30 and <27/30, and MoCA <22/30 and <26/30. Using Markov chain Monte Carlo (MCMC) methods, we fitted a bivariate network meta-analysis model incorporating constraints on increasing test threshold, and accounting for the correlations between multiple test accuracy measures from the same study. RESULTS: We developed and successfully fitted a model comparing multiple tests/threshold combinations while imposing threshold constraints. Using this model, we found that MoCA at threshold <26/30 appeared to have the best true positive rate, whereas MMSE at threshold <25/30 appeared to have the best true negative rate. CONCLUSION: The combined analysis of multiple tests at multiple thresholds allowed for more rigorous comparisons between competing diagnostics tests for decision making.

Cognitive assessment in stroke: feasibility and test properties using differing approaches to scoring of incomplete items.

OBJECTIVES: Cognitive screening is recommended in stroke, but test completion may be complicated by stroke related impairments. We described feasibility of completion of three commonly used cognitive screening tools and the effect on scoring properties when cognitive testing was entirely/partially incomplete. METHODS: We performed a cross-sectional study, recruiting sequential stroke patient admissions from two University Hospital stroke rehabilitation services. We assessed Folstein's mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and Addenbrooke's cognitive examination (ACE-III). The multidisciplinary team gave an independent diagnostic formulation. We recorded numbers fully/partially completing tests, assistance and time required for testing. We calculated test discrimination metrics in relation to clinical assessment using four differing statistical approaches to account for incomplete testing. RESULTS: We recruited 51 patients. Direct assistance to complete cognitive tests was required for 33 (63%). At traditional cut-offs, the majority screened "positive" for cognitive impairment (ACE-III: 98%; MoCA: 98%; MMSE: 81%). Comparing against a clinical diagnosis, ACE-III and MoCA had excellent sensitivity but poor specificity. Partial completion of cognitive tests was common (ACE-III: 14/51, MMSE: 22/51; MoCA: 20/51 fully complete); greatest non completion was for test items that required copying or drawing. Adapting analyses to account for these missing data gave differing results; MMSE sensitivity ranged from 0.66 to 0.85, and specificity ranged from 0.44 to 0.71 depending on the approach employed. CONCLUSIONS: For cognitive screening in stroke, even relatively brief tools are associated with substantial incompletion. The way these missing data are accounted for in analyses impacts on apparent test properties. When choosing a cognitive screening tool, feasibility should be considered and approaches to handling missing data made explicit. Copyright © 2016 John Wiley & Sons, Ltd.

Prevalence of Pseudobulbar Affect following Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have reported that emotional lability is a common consequence of stroke. However, there is uncertainty about the "true" prevalence of the condition because, across these studies, patients have been recruited at different stages of recovery, from different settings, and using different diagnostic methods. There have been no systematic reviews of the published evidence to ascertain how the prevalence of poststroke pseudobulbar affect (PBA) might vary according to these factors. METHODS: A systematic review and meta-analysis of the published literature were undertaken. RESULTS: A total of 15 studies (n = 3391 participants) met inclusion criteria for the review. Meta-analysis estimated that the prevalence of PBA was 17% (95% confidence interval 12%-24%) acutely (<1 month post stroke), 20% (14%-29%) post acutely (1-6 months post stroke), and 12% (8%-17%) in the medium to longer term (>6 months post stroke). The evidence from the published literature, although limited, is that crying is a more common PBA presentation following stroke than laughter. CONCLUSIONS: PBA is a common condition that affects approximately 1 in 5 stroke survivors at the acute and postacute phases, and 1 in 8 survivors beyond 6 months post stroke. These prevalence data are very important for clinicians and the commissioners of services.

Research is 'a step into the unknown': an exploration of pharmacists' perceptions of factors impacting on research participation in the NHS.

OBJECTIVE: This study explored National Health Service (NHS) pharmacists' perceptions and experiences of pharmacist-led research in the workplace. DESIGN: Semistructured, face-to-face discussions continued until distinct clusters of opinion characteristics formed. Verbatim transcripts of audio-recordings were subjected to framework analysis. SETTING: Interviews were carried out with 54 pharmacists with diverse backgrounds and roles from general practices and secondary care in the UK's largest health authority. RESULTS: The purpose and potential of health services research (HSR) was understood and acknowledged to be worthwhile by participants, but a combination of individual and system-related themes tended to make participation difficult, except when this was part of formal postgraduate education leading to a qualification. Lack of prioritisation was routinely cited as the greatest barrier, with motivation, confidence and competence as additional impediments. System-related themes included lack of practical support and pharmacy professional issues. A minority of highly motivated individuals managed to embed research participation into routine activity. CONCLUSIONS: Most pharmacists realised the desirability and necessity of research to underpin pharmacy service expansion, but a combination of individual and professional level changes is needed to increase activity. Our findings provide a starting point for better understanding the mindset of hospital-based and general practice-based pharmacists towards research, as well as their perceived barriers and supports.

Test accuracy of cognitive screening tests for diagnosis of dementia and multidomain cognitive impairment in stroke.

BACKGROUND AND PURPOSE: Guidelines recommend screening stroke-survivors for cognitive impairments. We sought to collate published data on test accuracy of cognitive screening tools. METHODS: Index test was any direct, cognitive screening assessment compared against reference standard diagnosis of (undifferentiated) multidomain cognitive impairment/dementia. We used a sensitive search statement to search multiple, cross-disciplinary databases from inception to January 2014. Titles, abstracts, and articles were screened by independent researchers. We described risk of bias using Quality Assessment of Diagnostic Accuracy Studies tool and reporting quality using Standards for Reporting of Diagnostic Accuracy guidance. Where data allowed, we pooled test accuracy using bivariate methods. RESULTS: From 19 182 titles, we reviewed 241 articles, 35 suitable for inclusion. There was substantial heterogeneity: 25 differing screening tests; differing stroke settings (acute stroke, n=11 articles), and reference standards used (neuropsychological battery, n=21 articles). One article was graded low risk of bias; common issues were case-control methodology (n=7 articles) and missing data (n=22). We pooled data for 4 tests at various screen positive thresholds: Addenbrooke's Cognitive Examination-Revised (<88/100): sensitivity 0.96, specificity 0.70 (2 studies); Mini Mental State Examination (<27/30): sensitivity 0.71, specificity 0.85 (12 studies); Montreal Cognitive Assessment (<26/30): sensitivity 0.95, specificity 0.45 (4 studies); MoCA (<22/30): sensitivity 0.84, specificity 0.78 (6 studies); Rotterdam-CAMCOG (<33/49): sensitivity 0.57, specificity 0.92 (2 studies). CONCLUSIONS: Commonly used cognitive screening tools have similar accuracy for detection of dementia/multidomain impairment with no clearly superior test and no evidence that screening tools with longer administration times perform better. MoCA at usual threshold offers short assessment time with high sensitivity but at cost of specificity; adapted cutoffs have improved specificity without sacrificing sensitivity. Our results must be interpreted in the context of modest study numbers: heterogeneity and potential bias.

Feasibility and diagnostic accuracy of early mood screening to diagnose persisting clinical depression/anxiety disorder after stroke.

BACKGROUND: Depression/anxiety disorders are common after stroke and have a negative impact on outcomes. Guidelines recommend that all stroke survivors are screened for these problems. However, there is no consensus on timing or method of assessment. We investigated the feasibility and accuracy of a very early screening strategy and the diagnostic accuracy this has for depression/anxiety disorders at 1 month. METHODS: Screening tools were Hospital Anxiety and Depression Scale (HADS) and Depression Intensity Scale Circles (DISCs); we also assessed cognition using the Montreal Cognitive Assessment (MoCA). Screening was offered to sequential stroke admissions. At 1 month we assessed for clinical depression/anxiety disorder using Mini-International Neuropsychiatric Interview (MINI) and retested screening tools. We described test accuracy of acute depression/anxiety screening for clinical diagnosis of depression/anxiety disorder at 1 month and described temporal change in screening test scores. We assessed feasibility by describing proportions that were able, agreed to and completed the screening tests. RESULTS: Over 4 months, 102/146 admissions were suitable for screening following initial medical assessment, 69 (68%) agreed to screening, of whom 33 (48%) required researcher assistance to complete the screening test battery. Median time to assessment was 2 days (IQR: 1-4). Early HADS suggested n = 9 (13%) with depression; DISCs n = 25 (37%). Median acute MoCA was 21/30. At 1 month, n = 61 (88%) provided data. Repeat scores showed improvement over time; HADS (anxiety) mean difference: 2.5 (95% CI: 1.2-3.7), HADS (depression) mean difference: 1.6 (95% CI: 0.3-2.9). MINI defined n = 12 (20%) with depression and n = 6 (10%) with anxiety disorder. Comparing baseline screening to 1-month clinical diagnosis, HADS sensitivity was 0.25 (95% CI: 0.09-0.53) and specificity 0.94 (95% CI: 0.84-0.98); DISCs sensitivity was 0.92 (95% CI: 0.65-0.99) and specificity 0.78 (95% CI: 0.64-0.87). CONCLUSIONS: Even amongst 'medically stable' stroke patients, depression/anxiety screening at the acute stage may not be feasible or accurate. Half of participants required assistance from the researcher to complete assessments. The poor predictive accuracy of HADS for depression/anxiety disorder at 1 month may be due in part to the high prevalence of cognitive impairment in our sample. Screening in the first few days after stroke does not appear useful for detecting clinically important and sustained depression/anxiety problems.

Cog-4 has limited diagnostic test accuracy and validity for cognitive assessment in stroke survivors.

BACKGROUND: Guidelines recommend cognitive screening for all stroke survivors but do not suggest a preferred tool. Certain elements (orientation, executive function, language, and inattention) of the impairment scale, National Institutes of Health Stroke Scale (NIHSS), have been suggested as a short cognitive screening test-Cog-4. We aimed to describe accuracy and validity of Cog-4 against a more detailed cognitive assessment (Montreal Cognitive Assessment [MoCA]). METHODS: We assessed consecutive acute stroke unit admissions in 2 hospitals over 3 months. Four independent blinded assessors performed NIHSS and MoCA between days 1 and 4 poststroke. We described test properties of Cog-4 for MoCA-defined cognitive impairment using usual thresholds (Cog-4≥1 and MoCA<26 of 30) and described the correlations of individual Cog-4 components with broadly equivalent MoCA domains. RESULTS: We assessed 173 participants; 166 had Cog-4 data and 148 MoCA. MoCA described 84% (n=124) of assessed participants as having cognitive impairment and the Cog-4, 37% (n=62). Cog-4 had a sensitivity of .36 (95% confidence interval [CI]: .28-.45) and a specificity of .96 (95% CI: .80-.99) (positive predictive value: .98, negative predictive value: .23) for MoCA-defined cognitive impairment. Individual Cog-4 items correlated with certain MoCA domains, but the strength of association was modest (r=-.44 orientation, -.37 language, -.19 for inattention, and no significant correlation for executive function, P=.72). CONCLUSIONS: Our data suggest that many stroke survivors with MoCA-defined cognitive problems would not be detected by Cog-4. Subtest correlations suggest that Cog-4 may not be a valid measure of the cognitive domains that it purports to describe. Other brief cognitive screening tests may be better suited to acute stroke.

Questionnaire assessment of usual practice in mood and cognitive assessment in Scottish stroke units.

PURPOSE: National and International guidelines recommend cognition and mood assessment for all stroke survivors. However, there is no consensus on preferred screening tool or method of assessment. We aimed to describe clinical practice in cognitive and mood assessment across Scottish stroke services. METHOD: We used a questionnaire based survey. After local piloting, we distributed the questionnaire using mixed methodologies (online and paper) across all Stroke Managed Clinical Networks in Scotland. We also distributed the questionnaire to specialist societies representing stroke physicians, nurses and allied health professionals and through the UK Stroke Forum delegate pack. RESULTS: We received 174 responses from nurses, physiotherapists, psychologists, occupational therapists and medical staff. Medical staff made up the largest group of respondents (61, 35%). Of the respondents 148 (85%) routinely assess cognition and 119 (72%) mood. A variety of tools were used (cognitive n = 45 tools; mood n = 17); Mini Mental State Examination (n = 103, 59% of respondents) and the Hospital Anxiety and Depression Scale (n = 76, 44%) were the most commonly employed tools. CONCLUSION: Response rate was modest but included all mainland Scottish regions with active stroke services. Although the majority of responders are assessing cognition and mood there is substantial heterogeneity in measures used and certain commonly used tools are not validated or appropriate for use in stroke. We suggest development of evidence based, standardised assessment protocols. IMPLICATIONS FOR REHABILITATION: Screening stroke survivor's for cognitive and mood issues is recommended but there is little guidance on the preferred assessment strategy Across Scottish stroke services there is a lack of consensus in assessment and management of cognition and mood post stroke Sixty-two different cognitive/mood assessment tools were found to be in use across the country Careful consideration must be given when inspecting assessment tools and use of caution when interpreting results.

Test accuracy of short screening tests for diagnosis of delirium or cognitive impairment in an acute stroke unit setting.

BACKGROUND AND PURPOSE: Guidelines recommend cognitive screening in acute stroke. Various instruments are available, with no consensus on a preferred tool. We aimed to describe test accuracy of brief screening tools for diagnosis of cognitive impairment and delirium in acute stroke. METHODS: We collected data on sequential stroke unit admission in a single center. Four assessors trained in cognitive testing independently performed screening and reference tests. Brief assessments comprised the following: 10- and 4-point Abbreviated Mental Test (AMT-10; AMT-4); 4-A Test (4AT); Clock Drawing Test (CDT); Cog-4; and Glasgow Coma Scale (GCS). We also recorded the multidisciplinary team's informal review using single question (SQ). We compared against reference standards of Montreal Cognitive Assessment (MoCA) and Confusion Assessment Method for delirium using usual diagnostic cutpoints. For MoCA, we described effects of lowering the diagnostic threshold to MoCA <24 and MoCA <20. We described sensitivity, specificity, and positive and negative predictive values. RESULTS: Over a 10-week period, 111 subjects had cognitive assessment data. Subjects were 50% male (n=55), and median age was 74 years (interquartile range, 64-85). AMT-4, AMT-10, and SQ all had excellent (1.00) specificity for detection of cognitive impairment, although sensitivity was poor (all <0.60). The 4AT had greatest sensitivity for detecting delirium (1.00 [confidence interval [CI], 0.74-1.00]) and reasonable specificity (0.82 [CI, 0.72-0.89]). Properties of 4AT for detection of cognitive impairment, at the traditional MoCA threshold, were also good (sensitivity, 0.86; specificity, 0.78). Using diagnostic thresholds of MoCA ≤26, <24, and <20 gave proportions with cognitive impairments of 86%, 61%, and 49%, respectively, with resulting changes in screening test properties. At lower MoCA thresholds, CDT had favorable sensitivity and specificity (MoCA <20: sensitivity, 0.93, specificity, 0.66; MoCA <24: sensitivity, 0.85, specificity, 0.77). CONCLUSIONS: Many brief screening assessments are specific but not sensitive for detection of cognitive impairment in acute stroke. Our primary analysis suggests that 4AT is a reasonable choice for delirium and cognitive screening in this setting. However, these data are based on standard MoCA diagnostic threshold and may not be suited for an acute stroke population.

Cognitive and mood assessment in stroke research: focused review of contemporary studies.

BACKGROUND AND PURPOSE: International guidelines recommend cognitive and mood assessments for stroke survivors; these assessments also have use in clinical trials. However, there is no consensus on the optimal assessment tool(s). We aimed to describe use of cognitive and mood measures in contemporary published stroke trials. METHODS: Two independent, blinded assessors reviewed high-impact journals representing: general medicine (n=4), gerontology/rehabilitation (n=3), neurology (n=4), psychiatry (n=4), psychology (n=4), and stroke (n=3) January 2000 to October 2011 inclusive. Journals were hand-searched for relevant, original research articles that described cognitive/mood assessments in human stroke survivors. Data were checked for relevance by an independent clinician and clinical psychologist. RESULTS: Across 8826 stroke studies, 488 (6%) included a cognitive or mood measure. Of these 488 articles, total number with cognitive assessment was 408 (83%) and mood assessment tools 247 (51%). Total number of different assessments used was 367 (cognitive, 300; mood, 67). The most commonly used cognitive measure was Folstein's Mini-Mental State Examination (n=180 articles, 37% of all articles with cognitive/mood outcomes); the most commonly used mood assessment was the Hamilton Rating Scale of Depression(n=43 [9%]). CONCLUSIONS: Cognitive and mood assessments are infrequently used in stroke research. When used, there is substantial heterogeneity and certain prevalent assessment tools may not be suited to stroke cohorts. Research and guidance on the optimal cognitive/mood assessment strategies for clinical practice and trials is required.