To investigate performance of the Months of the Year Backwards (MOTYB) test in older hospitalised patients with delirium, dementia, and no cognitive impairment. Half of the patients with delirium (46%) could not engage with MOTYB compared to only 11% of patients with dementia without delirium. In patients able to give responses, those with delirium or dementia performed significantly worse than those without cognitive impairment. Our findings show the potential value of analysing response patterns, especially initial engagement, self-correction, and ability to continue to do the task in addition to considering exclusively the capacity to correctly recite the months until July, June or January. To investigate performance of the Months of the Year Backwards (MOTYB) test in older hospitalised patients with delirium, dementia, and no cognitive impairment. Secondary analysis of data from a case–control study of 149 hospitalised patients aged ≥ 65 years with delirium [with or without dementia (N = 50)], dementia [without delirium (N = 46)], and no cognitive impairment (N = 53). Verbatim transcripts of MOTYB audio recordings were analysed to determine group differences in response patterns. In the total sample [median age 85y (IQR 80–88), 82% female], patients with delirium were more often unable to recite months backward to November (36/50 = 72%) than patients with dementia (21/46 = 46%; p < 0.01) and both differed significantly from patients without cognitive impairment (2/53 = 4%; p’s < 0.001). 121/149 (81%) of patients were able to engage with the test. Patients with delirium were more often unable to engage with MOTYB (23/50 = 46%; e.g., due to reduced arousal) than patients with dementia (5/46 = 11%; p < 0.001); both groups differed significantly (p’s < 0.001) from patients without cognitive impairment (0/53 = 0%). There was no statistically significant difference between patients with delirium (2/27 = 7%) and patients with dementia (8/41 = 20%) in completing MOTYB to January, but performance in both groups differed (p < 0.001 and p < 0.02, respectively) from patients without cognitive impairment (35/53 = 66%). Delirium was associated with inability to engage with MOTYB and low rates of completion. In patients able to engage with the test, error-free completion rates were low in delirium and dementia. Recording of engagement and patterns of errors may add useful information to MOTYB scoring.

BackgroundDelirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients.MethodsThis was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0-4) and attention task (0-6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden's index.ResultsA total of 187 patients were recruited, mean age 83.8 (range 67-98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6).ConclusionPatients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts.

Objective: Continuous outcome measures are essential in rehabilitation research. Incomplete reporting of their mean and standard deviation, required for meta-analysis, potentially introduces bias and imprecision if it prevents studies being included. We aimed to determine how often systematic reviewers encounter missing mean or standard deviation values and to recommend practical statistical solutions. Design: 1. Cross-sectional survey of systematic review authors. 2. Reanalysis of Cochrane review data to evaluate how accurately statistical methods for recovering missing mean or standard deviation values estimate the true meta-analysis treatment effect. Setting: Rehabilitation intervention systematic reviews. Participants: Cochrane stroke rehabilitation review authors; stroke patients. Interventions: Reanalysis of a Cochrane review of early supported discharge services. Main measures: Hospital length of stay. Results: Survey responses covered 53 of 70 Cochrane reviews. Almost all studied continuous outcome measures, 68% encountering missing summary statistics. Various solutions were attempted but 76% of meta-analyses omitted at least one study due to missing information. In the review reanalysis ( N = 1055), a method based on the minimum and maximum performed best in recovering missing standard deviations; a method based on the median, lower and upper quartiles successfully estimated a missing mean. Conclusion: Practical statistical methods help reduce risk of bias, maximise the evidence included in rehabilitation meta-analyses and offer a clear hierarchy of solutions to handling unreported mean and standard deviation values.

AIM:The aim of this study is to compare dental arch changes associated with different activation protocols of maxillary expander.MATERIALS AND METHODS:A sample of 101 subjects with constricted maxillary arches (49 males and 52 females; mean age 10.96 ± 1.91 years) was enrolled in the study. All subjects underwent RME with a stainless steel banded expander cemented to the maxillary first molars and the expansion screw was randomly activated with two different rapid maxillary expansion protocols (one- quarter per day or two quarters per day). The study also involved a control group of 22 subjects (10 females and 12 males, mean age 10.39 ± 1.32 years) who underwent no treatment. A statistical comparison between the dental arch measures obtained before and after treatment in the two groups was performed.RESULTS:The Wilcoxon rank-sum test shows statistically significant differences of the measurement increases between the two activation protocols (at least p=0.01). Statistically significant differences were also reported in comparison with the control group.CONCLUSIONS:A faster activation protocol could be able to determine a greater anterior opening of the mid-palatal suture. Moreover, it seems to yield a higher width increase in the molar area.

Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation).

Delirium is a common and serious clinical syndrome which is often missed in routine clinical care. The core cognitive feature is inattention. We developed a novel bedside neuropsychological test for assessing inattention in delirium implemented on a smartphone platform (DelApp). We aim to evaluate the diagnostic performance of the DelApp in a representative cohort of older hospitalised patients.

[This corrects the article DOI: 10.1371/journal.pone.0199026.].

Aim The aim of this study is to compare the sagittal dentoskeletal changes associated with different activation protocols of maxillary expander. Materials and methods A total of 101 subjects with constricted maxillary arches (49 males and 52 females; mean age 10.08 +/- 1.57 years) were enrolled in the study. The study comprised also a control group of 20 subjects (11 females and 9 males, mean age 10.27 +/- 1.24 years) who were not treated during the observation period. All the subjects underwent rapid maxillary expansion with a stainless steel banded expander cemented to the maxillary first molars. The expansion screw was randomly activated with two different rapid maxillary expansion protocols (one-quarter per day or two-quarters per day). A statistical comparison between the sagittal cephalometric variations obtained in the two expansion groups was made, and compared with the untreated control group. Data were then stratified for skeletal maturation of each subject. Results The Wilcoxon rank-suin test shows statistically significant differences between the two RME activation protocols only for overjet. Statistically significant differences were reported in comparison with the control group. Conclusions This study suggests that the increase in overjet after RME could be associated with taster activation protocols especially in subjects with lower skeletal maturation.

Background In patients with suspected angina pectoris, CT coronary angiography (CTCA) clari fi es the diagnosis, directs appropriate investigations and therapies, and reduces clinical events. The effect on patient symptoms is currently unknown. Methods In a prospective open-label parallel group multicentre randomised controlled trial, 4146 patients with suspected angina due to coronary heart disease were randomised 1:1 to receive standard care or standard care plus CTCA. Symptoms and quality of life were assessed over 6 months using the Seattle Angina Questionnaire and Short Form 12. Results Baseline scores indicated mild physical limitation (74±0.4), moderate angina stability (44±0.4), modest angina frequency (68±0.4), excellent treatment satisfaction (92±0.2) and moderate impairment of quality of life (55±0.3). Compared with standard care alone, CTCA was associated with less marked improvements in physical limitation (difference − 1.74 (95% CIs, − 3.34 to − 0.14), p=0.0329), angina frequency (difference − 1.55 ( − 2.85 to − 0.25), p=0.0198) and quality of life (difference − 3.48 ( − 4.95 to − 2.01), p<0.0001) at 6 months. For patients undergoing CTCA, improvements in symptoms were greatest in those diagnosed with normal coronary arteries or who had their preventative therapy discontinued, and least in those with moderate non-obstructive disease or had a new prescription of preventative therapy (p<0.001 for all). Conclusions While improving diagnosis, treatment and outcome, CTCA is associated with a small attenuation of the improvements in symptoms and quality of life due to the detection of moderate non-obstructive coronary artery disease.

Background: Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. Methods: We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. Results: For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results. Conclusions: Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses.

Citation for published version: Williams, MC, Hunter, A, Shah, A, Assi, V, Lewis, S, Mangion, K, Berry, C, Boon, NA, Clark, E, Flather, M, Forbes, J, McLean, S, Roditi, G, van Beek, EJ, Timmis, AD, Newby, DE & Scottish COmputed Tomography of the HEART (SCOT-HEART) Trial Investigators 2017, 'Symptoms and Quality of Life in Patients with Suspected Angina Undergoing Coronary Computed Tomography Angiography' Heart. DOI: 10.1136/heartjnl-2016-310129

Background In patients with suspected angina pectoris, CT coronary angiography (CTCA) clarifies the diagnosis, directs appropriate investigations and therapies, and reduces clinical events. The effect on patient symptoms is currently unknown. Methods In a prospective open-label parallel group multicentre randomised controlled trial, 4146 patients with suspected angina due to coronary heart disease were randomised 1:1 to receive standard care or standard care plus CTCA. Symptoms and quality of life were assessed over 6 months using the Seattle Angina Questionnaire and Short Form 12. Results Baseline scores indicated mild physical limitation (74±0.4), moderate angina stability (44±0.4), modest angina frequency (68±0.4), excellent treatment satisfaction (92±0.2) and moderate impairment of quality of life (55±0.3). Compared with standard care alone, CTCA was associated with less marked improvements in physical limitation (difference −1.74 (95% CIs, −3.34 to −0.14), p=0.0329), angina frequency (difference −1.55 (−2.85 to −0.25), p=0.0198) and quality of life (difference −3.48 (−4.95 to −2.01), p<0.0001) at 6 months. For patients undergoing CTCA, improvements in symptoms were greatest in those diagnosed with normal coronary arteries or who had their preventative therapy discontinued, and least in those with moderate non-obstructive disease or had a new prescription of preventative therapy (p<0.001 for all). Conclusions While improving diagnosis, treatment and outcome, CTCA is associated with a small attenuation of the improvements in symptoms and quality of life due to the detection of moderate non-obstructive coronary artery disease. Trial registration number: NCT01149590.

BACKGROUND In a prospective, multicenter, randomized controlled trial, 4,146 patients were randomized to receive standard care or standard care plus coronary computed tomography angiography (CCTA).OBJECTIVES The purpose of this study was to explore the consequences of CCTA-assisted diagnosis on invasive coronary angiography, preventive treatments, and clinical outcomes.METHODS In post hoc analyses, we assessed changes in invasive coronary angiography, preventive treatments, and clinical outcomes using national electronic health records.RESULTS Despite similar overall rates (409 vs. 401; p = 0.451), invasive angiography was less likely to demonstrate normal coronary arteries (20 vs. 56; hazard ratios [HRs]: 0.39 [95% confidence interval (CI): 0.23 to 0.68]; p < 0.001) but more likely to show obstructive coronary artery disease (283 vs. 230; HR: 1.29 [95% CI: 1.08 to 1.55]; p = 0.005) in those allocated to CCTA. More preventive therapies (283 vs. 74; HR: 4.03 [95% CI: 3.12 to 5.20]; p < 0.001) were initiated after CCTA, with each drug commencing at a median of 48 to 52 days after clinic attendance. From the median time for preventive therapy initiation (50 days), fatal and nonfatal myocardial infarction was halved in patients allocated to CCTA compared with those assigned to standard care (17 vs. 34; HR: 0.50 [95% CI: 0.28 to 0.88]; p = 0.020). Cumulative 6-month costs were slightly higher with CCTA: difference $462 (95% CI: $303 to $621).CONCLUSIONS In patients with suspected angina due to coronary heart disease, CCTA leads to more appropriate use of invasive angiography and alterations in preventive therapies that were associated with a halving of fatal and non-fatal myocardial infarction. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590) (C) 2016 by the American College of Cardiology Foundation.

Background The benefit of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not been systematically studied. We aimed to assess the effect of CTCA on the diagnosis, management, and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease.Methods In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18-75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed in the group they were allocated to, irrespective of compliance with scanning. This study is registered with ClinicalTrials.gov, number NCT01149590.Findings Between Nov 18, 2010, and Sept 24, 2014, we randomly assigned 4146 (42%) of 9849 patients who had been referred for assessment of suspected angina due to coronary heart disease. 47% of participants had a baseline clinic diagnosis of coronary heart disease and 36% had angina due to coronary heart disease. At 6 weeks, CTCA reclassified the diagnosis of coronary heart disease in 558 (27%) patients and the diagnosis of angina due to coronary heart disease in 481 (23%) patients (standard care 22 [1%] and 23 [1%]; p<0.0001). Although both the certainty (relative risk [RR] 2.56, 95% CI 2.33-2.79; p<0.0001) and frequency of coronary heart disease increased (1.09, 1.02-1.17; p=0.0172), the certainty increased (1.79, 1.62-1.96; p<0.0001) and frequency seemed to decrease (0.93, 0.85-1.02; p=0.1289) for the diagnosis of angina due to coronary heart disease. This changed planned investigations (15% vs 1%; p<0.0001) and treatments (23% vs 5%; p<0.0001) but did not affect 6-week symptom severity or subsequent admittances to hospital for chest pain. After 1.7 years, CTCA was associated with a 38% reduction in fatal and non-fatal myocardial infarction (26 vs 42, HR 0.62, 95% CI 0.38-1.01; p=0.0527), but this was not significant.Interpretation In patients with suspected angina due to coronary heart disease, CTCA clarifies the diagnosis, enables targeting of interventions, and might reduce the future risk of myocardial infarction. Copyright (C) Newby et al. Open Access article distributed under the terms of CC BY.

OBJECTIVE To investigate the influence of two different activation protocols on the timing and intensity of pain during rapid maxillary expansion (RME). MATERIALS AND METHODS A total of 112 prepubertal patients (54 males and 58 females, mean age 11.00 ± 1.80 years) with constricted maxillary arches underwent RME with two different activation protocols (group 1: one activation/day; group 2: two activations/day). Patients were provided with a numeric rating scale (NRS) and the Faces Pain Scale (FPS) to correctly assess their daily pain. RESULTS Subjects treated with RME at two activations/day reported statistically significantly greater amounts of pain than subjects treated with RME at one activation/day. Differences related to gender and skeletal maturity were found. CONCLUSION The choice of activation protocol influences the perceived pain during RME, and less daily expansion is correlated to less pain. Pain reported during RME could be influenced by skeletal maturity and gender of the subjects under treatment.

Mammographic density is a strong risk factor for breast cancer, but its potential application in risk management is not clear, partly due to uncertainties about its interaction with other breast cancer risk factors. We aimed to quantify the impact of mammographic density on breast cancer risk in women aged 40–49 at intermediate familial risk of breast cancer (average lifetime risk of 23%), in particular in premenopausal women, and to investigate its relationship with other breast cancer risk factors in this population. We present the results from a case‐control study nested with the FH01 cohort study of 6,710 women mostly aged 40–49 at intermediate familial risk of breast cancer. One hundred and three cases of breast cancer were age‐matched to one or two controls. Density was measured by semiautomated interactive thresholding. Absolute density, but not percent density, was a significant risk factor for breast cancer in this population after adjusting for area of nondense tissue (OR per 10 cm2 = 1.07, 95% CI 1.00–1.15, p = 0.04). The effect was stronger in premenopausal women, who made up the majority of the study population. Absolute density remained a significant predictor of breast cancer risk after adjusting for age at menarche, age at first live birth, parity, past or present hormone replacement therapy, and the Tyrer‐Cuzick 10‐year relative risk estimate of breast cancer. Absolute density can improve breast cancer risk stratification and delineation of high‐risk groups alongside the Tyrer‐Cuzick 10‐year relative risk estimate.