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Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
To assess the utility of an automated, statistically-based outbreak detection system to identify clusters of hospital-acquired microorganisms.
Multicenter retrospective cohort study.
The study included 43 hospitals using a common infection prevention surveillance system.
A space–time permutation scan statistic was applied to hospital microbiology, admission, discharge, and transfer data to identify clustering of microorganisms within hospital locations and services. Infection preventionists were asked to rate the importance of each cluster. A convenience sample of 10 hospitals also provided information about clusters previously identified through their usual surveillance methods.
We identified 230 clusters in 43 hospitals involving Gram-positive and -negative bacteria and fungi. Half of the clusters progressed after initial detection, suggesting that early detection could trigger interventions to curtail further spread. Infection preventionists reported that they would have wanted to be alerted about 81% of these clusters. Factors associated with clusters judged to be moderately or highly concerning included high statistical significance, large size, and clusters involving Clostridioides difficile or multidrug-resistant organisms. Based on comparison data provided by the convenience sample of hospitals, only 9 (18%) of 51 clusters detected by usual surveillance met statistical significance, and of the 70 clusters not previously detected, 58 (83%) involved organisms not routinely targeted by the hospitals’ surveillance programs. All infection prevention programs felt that an automated outbreak detection tool would improve their ability to detect outbreaks and streamline their work.
Automated, statistically-based outbreak detection can increase the consistency, scope, and comprehensiveness of detecting hospital-associated transmission.
Stratified medicine has been successfully used in many areas of medicine, perhaps most notably oncology. There is now both a growing evidence base and mounting enthusiasm, supported at a governmental level and across industry, academia and clinical medicine, to apply this approach to neurodegenerative illnesses, including dementia, as these provide the greatest clinical and social challenge of our times. In this article we consider definitions of stratified medicine, look at its application in other medical specialties, review the national context in the UK and consider the current state, future potential and specific considerations of applying stratified medicine to dementia.
Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD).
A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function.
Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline.
These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms – particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.
Late-life depression (LLD) is associated with poor social functioning. However, previous research uses bias-prone self-report scales to measure social functioning and a more objective measure is lacking. We tested a novel wearable device to measure speech that participants encounter as an indicator of social interaction.
Twenty nine participants with LLD and 29 age-matched controls wore a wrist-worn device continuously for seven days, which recorded their acoustic environment. Acoustic data were automatically analysed using deep learning models that had been developed and validated on an independent speech dataset. Total speech activity and the proportion of speech produced by the device wearer were both detected whilst maintaining participants' privacy. Participants underwent a neuropsychological test battery and clinical and self-report scales to measure severity of depression, general and social functioning.
Compared to controls, participants with LLD showed poorer self-reported social and general functioning. Total speech activity was much lower for participants with LLD than controls, with no overlap between groups. The proportion of speech produced by the participants was smaller for LLD than controls. In LLD, both speech measures correlated with attention and psychomotor speed performance but not with depression severity or self-reported social functioning.
Using this device, LLD was associated with lower levels of speech than controls and speech activity was related to psychomotor retardation. We have demonstrated that speech activity measured by wearable technology differentiated LLD from controls with high precision and, in this study, provided an objective measure of an aspect of real-world social functioning in LLD.
The rupture of atherosclerotic plaques is the prerequisite for adverse cardiovascular events. Calcification morphology plays a critical role in plaque stability, therefore accurate calcification classification is essential for favourable patient management. Blood biomarkers may be a worthwhile approach to stratify patients based on calcification phenotype. Vitamin K-dependent Matrix γ-carboxyglutamate (Gla) protein (MGP) is a potent inhibitor of vascular calcification. Recent studies have demonstrated the potential utility of circulating non-functional MGP (dp-ucMGP) measurements to determine arterial stiffness and calcification levels. The objective of this study was to examine the relationship between circulating dp-ucMGP and calcification phenotype within symptomatic atherosclerotic lesions. Consenting patients undergoing standard endarterectomy procedures were recruited (n = 29). Fasting venous blood was collected preoperatively. Circulating plasma levels of dp-ucMGP were quantified using the inaKtif MGP (dp-ucMGP) iSYS kit. A bicinchoninic acid assay was used to standardise the total protein content present in each sample. High-resolution micro-CT imaging was conducted on the excised atherosclerotic specimens postoperatively. ImageJ post-processing was used to accurately quantify the calcification volume (≥ 130 Hounsfield Units) and determine the total number of calcified particles (3D objects counter plugin). Thirteen carotid (average age 71 years, 9 male) and fourteen peripheral lower limb (average age 65 years, 12 male) patients were examined. One patient had a carotid and a peripheral lower limb plaque (age 79, male). Peripheral lower limb specimens have larger volumes of calcification and higher numbers of calcified particles than carotid samples (472 ± 310 vs 85 ± 113mm3, p < 0.0005; 13919 ± 16034 vs 3476 ± 6208, p = 0.061.) While a higher dp-ucMGP value was noted in carotid than peripheral lower limb patients (214 ± 52 vs 169 ± 36pmol/L, p = 0.014) there was no correlation between circulating dp-ucMGP and calcification volume or number of calcified particles (rs = -0.329 and rs = 0.046). Previous research also found that peripheral lower limb lesions contain higher volumes of calcification than carotid lesions. There is currently no published data on calcified particle comparisons. Patients with symptomatic carotid disease are assumed to have a degree of peripheral arterial disease, this could explain the higher levels of circulating dp-ucMGP in carotid patients. The current study did not examine the dietary patterns of individuals with regards to Vitamin K intake or analyse other areas of the vasculature for additional calcification. This may interfere with dp-ucMGP measurements. This study serves as a preliminary investigation into the potential of dp-ucMGP as a blood based biomarker to distinguish between symptomatic atherosclerotic calcification phenotypes.
Alzheimer's disease and vascular dementia are associated with overlapping symptoms of anxiety and depression. More accurate discrimination between emerging neuropsychiatric and cognitive symptoms would better assist illness detection. The potential for protection against cognitive decline and dementia following early identification and intervention of neuropsychiatric symptoms warrants investigation.
To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.
Memory clinics and dementia services.
Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).
Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.
There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).
There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.
Bipolar disorder is less prevalent in older people but accounts for 8–10% of psychiatric admissions. Treating and managing bipolar disorder in older people is challenging because of medical comorbidity. We review the cognitive problems observed in older people, explore why these are important and consider current treatment options. There are very few studies examining the cognitive profiles of older people with bipolar disorder and symptomatic depression and mania, and these show significant impairments in executive function. Most studies have focused on cognitive impairment in euthymic older people: as in euthymic adults of working age, significant impairments are observed in tests of attention, memory and executive function/processing speeds. Screening tests are not always helpful in euthymic older people as the impairment can be relatively subtle, and more in-depth neuropsychological testing may be needed to show impairments. Cognitive impairment may be more pronounced in older people with ‘late-onset’ bipolar disorder than in those with ‘early-onset’ disorder. Strategies to address symptomatic cognitive impairment in older people include assertive treatment of the mood disorder, minimising drugs that can adversely affect cognition, optimising physical healthcare and reducing relapse rates.
After reading this article you will be able to:
•understand that cognitive impairment in euthymic older people with bipolar disorder is similar to that in working-age adults with the disorder, affecting attention, memory and executive function/processing speeds
•recognise that cognitive impairment in older people is likely to be a major determinant of functional outcomes
•Implement approaches to treat cognitive impairment in bipolar disorder.
DECLARATION OF INTEREST
B.J.S. consults for Cambridge Cognition, PEAK (www.peak.net) and Mundipharma.
Infant protein intake has been associated with child growth, however, research on maternal protein intake during pregnancy is limited. Insulin-like growth factors (IGF) play a role in early fetal development and maternal protein intake may influence child body composition via IGF-1. The aim of this study was to investigate the association of maternal protein intake throughout pregnancy on cord blood IGF-1 and child body composition from birth to 5 years of age. Analysis was carried out on 570 mother–child dyads from the Randomised cOntrol trial of LOw glycaemic index diet study. Protein intake was recorded using 3-d food diaries in each trimester of pregnancy and protein intake per kg of maternal weight (g/d per kg) was calculated. Cord blood IGF-1 was measured at birth. Infant anthropometry was measured at birth, 6 months, 2 and 5 years of age. Mixed modelling, linear regression, and mediation analysis were carried out. Birth weight centiles were positively associated with early-pregnancy protein intake (g/d per kg), while weight centiles from 6 months to 5 years were negatively associated (B=−21·6, P<0·05). These associations were not mediated by IGF-1. Our findings suggest that high protein intake in early-pregnancy may exert an in utero effect on offspring body composition with a higher weight initially at birth but slower growth rates into childhood. Further research is needed to elucidate the exact mechanisms by which dietary protein modulates fetal growth.
Visual hallucinations are a common symptom in dementia and Parkinson’s disease and have been associated with greater cognitive and functional decline, but optimal management strategies are unclear. We review the frequency and pathogenesis of visual hallucinations in dementia and Parkinson’s disease and examine the evidence base for their management.
We undertook a systematic review of the visual hallucinations in dementia, searching studies published between January 1980 and July 2017 using PubMed with the search terms visual hallucinations AND review AND (dementia OR parkinson*).
We found 645 articles and screened them for relevance, finally including 89 papers (11 meta-analyses, 34 randomized controlled trials, six other trials and a number of relevant review articles). Only six of the trials reported visual hallucination outcomes separately from other neuropsychiatric symptoms.
Atypical antipsychotics were frequently studied, but with the exception of clozapine in Parkinson’s disease dementia, results were equivocal. There was some evidence that acetylcholinesterase inhibitors may help visual hallucinations. Overall, effect sizes for most treatments were small and there were few studies with long term follow up. Treatments need to be carefully weighed up with the risks and reviewed often, and many patients improved without treatment. There is a lack of data regarding visual hallucinations due to the grouping of psychotic symptoms together in commonly used rating scales. The lack of a specific rating scales, or analyzable items within other scales, for visual hallucinations, limited efficacy of current and small evidence base with short follow up are important areas for future studies to address.
Should psychiatrists be able to speculate in the press or social media about their theories? John Gartner argues the risk to warn the public of concerns about public figures overrides the duty of confidentiality; whereas Alex Langford suggests this is beyond the ethical remit of psychiatric practice.
Declaration of interest
A.O'B is joint debates and analysis Editor of the British Journal of Psychiatry. J.G. is the founder of Duty To Warn, an association of mental health professionals who advocate the president's removal under the 25th Amendment on the grounds that he is psychologically unfit and dangerous.
Rapid identification of esophageal intubations is critical to avoid patient morbidity and mortality. Continuous waveform capnography remains the gold standard for endotracheal tube (ETT) confirmation, but it has limitations. Point-of-care ultrasound (POCUS) may be a useful alternative for confirming ETT placement. The objective of this study was to determine the accuracy of paramedic-performed POCUS identification of esophageal intubations with and without ETT manipulation.
A prospective, observational study using a cadaver model was conducted. Local paramedics were recruited as subjects and each completed a survey of their demographics, employment history, intubation experience, and prior POCUS training. Subjects participated in a didactic session in which they learned POCUS identification of ETT location. During each study session, investigators randomly placed an ETT in either the trachea or esophagus of four cadavers, confirmed with direct laryngoscopy. Subjects then attempted to determine position using POCUS both without and with manipulation of the ETT. Manipulation of the tube was performed by twisting the tube. Descriptive statistics and logistic regression were used to assess the results and the effects of previous paramedic experience.
During 12 study sessions, from March 2014 through December 2015, 57 subjects participated, evaluating a total of 228 intubations: 113 tracheal and 115 esophageal. Subjects were 84.0% male, mean age of 39 years (range: 22 - 62 years), with median experience of seven years (range: 0.6 - 39 years). Paramedics correctly identified ETT location in 158 (69.3%) cases without and 194 (85.1%) with ETT manipulation. The sensitivity and specificity of identifying esophageal location without ETT manipulation increased from 52.2% (95% confidence interval [CI], 43.0-61.0) and 86.7% (95% CI, 81.0-93.0) to 87.0% (95% CI, 81.0-93.0) and 83.2% (95% CI, 0.76-0.90) after manipulation (P<.0001), without affecting specificity (P=.45). Subjects correctly identified 41 previously incorrectly identified esophageal intubations. Paramedic experience, previous intubations, and POCUS experience did not correlate with ability to identify tube location.
Paramedics can accurately identify esophageal intubations with POCUS, and manipulation improves identification. Further studies of paramedic use of dynamic POCUS to identify inadvertent esophageal intubations are needed.
LemaPC, O’BrienM, WilsonJ, St. JamesE, LindstromH, DeAngelisJ, CaldwellJ, MayP, ClemencyB.Avoid the Goose! Paramedic Identification of Esophageal Intubation by Ultrasound. Prehosp Disaster Med.2018;33(4):406–410
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
The emergence of a drive to reduce restrictive interventions has been accompanied particularly in the UK by a debate focussing on restraint positions. Any restraint intervention delivered poorly can potentially lead to serious negative outcomes. More research is required to reliably state the risk attached to a particular position in a particular clinical circumstance.
Declaration of interest
F.S. is a consultant psychiatrist in Psychiatric Intensive Care at the Maudsley Hospital, London. He is on the Executive Committee of the National Association of Psychiatric Intensive Care and Low Secure Units, and was a member of the National Institute for Health and Care Excellence Guideline Development Group for the Short-Term Management of Aggression and Violence (2015). J.P. is a senior lecturer at the Faculty of Health and Life Sciences, Coventry University. E.B. is a consultant and expert witness in violence reduction and the use of physical interventions, independent expert to the High Secure Hospitals Violence Reduction Manual Steering Group and a member of the College of Policing Guideline Committee Steering Group and Mental Health Restraint Expert Reference Group. B.P. is the clinical director for Crisis and Aggression Limitation and Management (CALM) Training and formerly a senior lecturer for the Faculty of Health, University of Stirling. He is a nurse and psychotherapist and presently chairs the European Network for Training in the Management of Aggression. A.O'B. is a consultant psychiatrist, the Director of Educational Programmes for the National Association of Psychiatric Intensive Care and Low Secure Units, and the Dean for Students at St George's University of London.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
An adolescent male with a recent history of streptococcal pharyngitis presented with severe substernal chest pain, troponin leak, and ST-segment elevation, which are suggestive of acute inferolateral myocardial infarction. The coronary angiogram was normal. The patient was subsequently diagnosed with non-rheumatic streptococcal myocarditis. He was treated with amoxicillin and had excellent recovery. Non-rheumatic streptococcal myocarditis is an important mimic of acute myocardial infarction in young adults.