To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
5-HT4 receptor stimulation has pro-cognitive and antidepressant-like effects in animal experimental studies; however, this pharmacological approach has not yet been tested in humans. Here we used the 5-HT4 receptor partial agonist prucalopride to assess the translatability of these effects and characterise, for the first time, the consequences of 5-HT4 receptor activation on human cognition and emotion.
Forty one healthy volunteers were randomised, double-blind, to a single dose of prucalopride (1 mg) or placebo in a parallel group design. They completed a battery of cognitive tests measuring learning and memory, emotional processing and reward sensitivity.
Prucalopride increased recall of words in a verbal learning task, increased the accuracy of recall and recognition of words in an incidental emotional memory task and increased the probability of choosing a symbol associated with a high likelihood of reward or absence of loss in a probabilistic instrumental learning task. Thus acute prucalopride produced pro-cognitive effects in healthy volunteers across three separate tasks.
These findings are a translation of the memory enhancing effects of 5-HT4 receptor agonism seen in animal studies, and lend weight to the idea that the 5-HT4 receptor could be an innovative target for the treatment of cognitive deficits associated with depression and other neuropsychiatric disorders. Contrary to the effects reported in animal models, prucalopride did not reveal an antidepressant profile in human measures of emotional processing.
Anecdotal evidence suggests the use of bolus tube feeding is increasing in long term home enteral tube feed (HETF) patients. A cross-sectional survey to assess the prevalence of bolus tube feeding and to characterise these patients was undertaken. Dietitians from 10 centres across the UK collected data on all adult HETF patients on the dietetic caseload receiving bolus tube feeding, (n=604, 60% male, age 58years). Demographic data, reasons for tube and bolus feeding, tube and equipment types, feeding method and patients’ complete tube feeding regimens were recorded. Over a third of patients receiving HETF used bolus feeding (37%). Patients were long-term tube fed (4.1years tube feeding, 3.5years bolus tube feeding), living at home (71%) and sedentary (70%). The majority were head and neck cancer patients (22%) who were significantly more active (79%) and lived at home (97%), while those with cerebral palsy (12%) were typically younger (age 31years) but sedentary (94%). Most patients used bolus feeding as their sole feeding method (46%), because it was quick and easy to use, as a top up to oral diet or to mimic meal times. Importantly, oral nutritional supplements (ONS) were used for bolus feeding in 85% of patients, with 51% of these being compact-style ONS (2.4kcal/ml, 125ml). This survey shows that bolus tube feeding is common amongst UK HETF patients, is used by a wide variety of patient groups and can be adapted to meet the needs of a variety of patients, clinical conditions, nutritional requirements and lifestyles.
In benefit-cost analysis, fatality risk reductions are usually valued based on estimates of adults’ willingness to pay for changes in their own risks, regardless of whether the risk reduction accrues to adults or children. This approach reflects the relatively large number of valuation studies that address adults; however, the literature on children is growing. We review these studies, focusing on those that estimate values for both adults and children using a consistent approach to limit the effects of between-study variability. We rely on explicit selection criteria to identify studies that measure reasonably comparable outcomes and are candidates for application to analyses of U.S. policies. The ratio of values for children to values for adults ranges from 0.6 to 2.9; however, most estimates are greater than 1.5. Although some studies suggest that the divergence between child and adult values decreases as the child ages, this finding is not universal. We conclude that analysts should test the sensitivity of their results to the use of higher values for children than adults. Additional empirical research is needed to support more precise estimates of the variation in values by age that can be featured in the primary analysis.
Early life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic–pituitary–adrenal axis function should be a focus of continued research.
The prehospital disaster and emergency medical services community stands on the front-line in the response to events such as novel influenza, multi-drug resistant tuberculosis, and other high consequence diseases such as the Ebola Virus Disease.
To address provider and community safety, we developed an online educational program utilizing a Multi-Pathogen Approach to infectious disease personal protective equipment (PPE) deployment by prehospital providers. Such vigilance starts with syndromic recognition and quickly transcends to include operational issues, clinical interventions, and public health integration.
The University of Maryland, Baltimore County (Maryland, USA), Department of Emergency Health Services partnered with the Maryland State Department of Health (USA), to develop an online educational curriculum. The curriculum was developed through an expert panel consensus group including prehospital providers and is hybrid in design and includes awareness level training and procedural guidance.
Currently deployed online, this educational content demonstrating the use of the Multi-Pathogen Approach is accessible open-access via YouTube worldwide on computers, tablets, and smartphones. This curriculum is also accessible for continuing medical education to over 50,000 prehospital, hospital, and clinic personnel throughout Maryland and the National Capital Region of the United States. The curriculum consists of twelve modules of didactic and live videotaped demonstrations.
The development of the Multi-Pathogen Approach for the deployment of PPE and the use of online education modules has given prehospital providers an easily accessible open-access tool for high consequence disease management. The development of educational efforts such as these can help ensure better patient care and prehospital EMS system readiness.
The current study examined the pattern of neurocognitive impairments in a community-recruited sample of clinical high-risk (CHR) participants and established relationships with psychosocial functioning.
CHR-participants (n = 108), participants who did not fulfil CHR-criteria (CHR-negatives) (n = 42) as well as a group of healthy controls (HCs) (n = 55) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed.
CHR-participants were significantly impaired on the Symbol-Coding and Token-Motor task and showed a reduction in total BACS-scores. Moreover, CHR-participants were characterised by prolonged response times (RTs) in emotion recognition as well as by reductions in both social and role functioning, GAF and premorbid adjustments compared with HCs. Neurocognitive impairments in emotion recognition accuracy, emotion recognition RT, processing speed and motor speed were associated with several aspects of functioning explaining between 4% and 12% of the variance.
The current data obtained from a community sample of CHR-participants highlight the importance of dysfunctions in motor and processing speed and emotion recognition RT. Moreover, these deficits were found to be related to global, social and role functioning, suggesting that neurocognitive impairments are an important aspect of sub-threshold psychotic experiences and a possible target for therapeutic interventions.
Patients with chronic obstructive pulmonary disease (COPD) who experience acute exacerbations usually require treatment with oral steroids or antibiotics, depending on the etiology of the exacerbation. Current management is based on clinician's assessment and judgement, which lacks diagnostic accuracy and results in overtreatment. A test to guide these decisions in primary care is in development. We developed an early decision model to evaluate the cost-effectiveness of this treatment stratification test in the primary care setting in the United Kingdom.
A combined decision tree and Markov model was developed of COPD progression and the exacerbation care pathway. Sensitivity analysis was carried out to guide technology development and inform evidence generation requirements.
The base case test strategy cost GBP 423 (USD 542) less and resulted in a health gain of 0.15 quality-adjusted life-years per patient compared with not testing. Testing reduced antibiotic prescriptions by 30 percent, potentially lowering the risk of antimicrobial resistance developing. In sensitivity analysis, the result depended on the clinical effects of treating patients according to the test result, as opposed to treating according to clinical judgement alone, for which there is limited evidence. The results were less sensitive to the accuracy of the test.
Testing may be cost-saving in primary care, but this requires robust evidence on whether test-guided treatment is effective. High quality evidence on the clinical utility of testing is required for early modeling of diagnostic tests generally.
Grey seals (Halichoerus grypus) of the North-east Atlantic are protected at designated European Marine Sites (Special Areas of Conservation, SACs) typically during their reproductive periods and in the UK at Sites of Special Scientific Interest (SSSI). As a mobile marine species, grey seals spend other parts of their annual life cycle in non-designated habitat. There is limited information on individual grey seal movements in south-west England. Citizen science photo identification (PID) revealed the movements of 477 grey seals at a regional scale (54 haul-outs up to 230 km apart) for over a decade. Reconstructed movements showed considerable individual variability. Four SACs were linked to up to 18 non-designated sites and two SSSIs in Cornwall were linked to a maximum of 41 non-designated sites. Observations support the value of existing SSSIs at both the well-connected West and North Cornwall sites. Thirteen Marine Protected Areas (MPAs) were visited by grey seals from four SACs and two SSSIs in Cornwall. As a mobile species, grey seals could be included in English MPA management plans. The application of functional linkage from SACs and SSSIs, informed by the movements evidenced in this research, could aid management efforts. This analysis reveals grey seal movements occur across a complex network of interconnected designated and non-designated sites that need to be managed holistically for this species for which the UK has a special responsibility.
Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.
We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.
Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).
Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.
The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.
Theorists and researchers have linked resilience with a host of positive psychological and physical health outcomes. This paper examines perceptions of resilience and physical health symptoms in a sample of individuals exposed to multiple community disasters following involvement in integrated mental health services.
A multiwave naturalistic design was used to follow 762 adult clinic patients (72% female; 28% minority status), ages 18-92 years (mean age=40 years), who were evaluated for resilience and physical health symptoms prior to receiving services and at 1, 3, and 6 months’ follow-up.
Data indicated increases in perceptions of resilience and decreased physical health symptoms reported over time. Results also indicated that resilience predicted physical health symptoms, such that resilience and physical health symptoms were negatively associated (ie, improved resilience was associated with decreases in physical health symptoms). These effects were primarily observed for those individuals with previous exposure to natural disasters.
Findings provide correlational evidence for behavioral health treatment provided as part of a stepped-care, collaborative model in reducing physical health symptoms and increasing resilience post-disaster. Controlled trials are warranted. (Disaster Med Public Health Preparedness. 2019;13:223–229)
Mother and Baby Units (MBUs) are usually preferred by patients and clinicians. Current provision is limited, although expansion is in progress. To ensure successful investment in services, outcome measurement is vital.
To describe maternal outcomes, mother–infant outcomes and their relationship in one MBU.
Paired maternal Brief Psychiatric Rating Scale (BPRS) scores, Health of the Nation Outcome Scales (HoNOS) scores and Crittenden CARE-Index (CCI) mother–infant interaction data were collected at admission and discharge.
There were significant improvements in BPRS (n = 152), HoNOS (n = 141) and CCI (n = 62) scores across diagnostic groups. Maternal BPRS scores and mother–infant interaction scores were unrelated. Improvement in maternal HoNOS scores was associated with improved maternal sensitivity and reduction in maternal unresponsiveness and infant passiveness.
Positive outcomes were achieved for mothers and babies across all diagnostic groups. Reduction in maternal symptoms, as measured by BPRS, does not necessarily confer improvement in mother–infant interaction. MBU treatment should focus on both maternal symptoms and mother–infant interaction.
This article investigates food security and well-being in the context of “development-forced displacement” in Ethiopia. In the lower Omo, a large hydroelectric dam and plantation schemes have forced people to cede communal lands to the state and business speculators, and indigenous communities have been targeted for resettlement in new consolidated villages. The authors carried out a food access survey in new villages and in communities not yet subjected to villagization and complemented this with ethnographic research carried out over a period of four years. The results of the two methodological approaches were inconsistent. The survey data suggest that household food access was poor in both places but better in villagization sites than in the other communities. The ethnographic research, however, suggests that village settlers were unable to feed themselves from the irrigated plots they were allotted and were therefore dependent on food aid. They spoke of indignity, bodily discomfort, and the severance of meaningful social relations. This article discusses the contrast between the information generated by the different research methods and asks how this tension relates to two major narratives about development: development as a process through which the state actualizes a national dream, and development as a process that creates affluence for some by impoverishing others.
Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. Fifty-nine early pubertal males and 78 early pubertal females, ages 9–13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. Females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region of interest analyses indicated that whereas females exhibited a positive association between ELS and the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems.
Clostridium difficile infection (CDI) and asymptomatic carriage of toxigenic C. difficile are common in long-term care facilities (LTCFs). However, whether C. difficile is frequently acquired in the LTCF versus during acute-care admissions remains unknown.
To test the hypothesis that LTCF residents often acquire C. difficile colonization and infection in the LTCF
This 5-month cohort study was conducted to determine the incidence of acquisition of C. difficile colonization and infection in asymptomatic patients transferred from a Veterans Affairs hospital to an affiliated LTCF.
Rectal swabs were cultured for toxigenic C. difficile at the time of transfer to the LTCF and weekly for up to 6 weeks. We calculated the proportion of LTCF-onset CDI cases within 1 month of transfer that occurred in residents colonized on admission versus those with new acquisition in the LTCF.
Of 110 patients transferred to the LTCF, 12 (11%) were asymptomatically colonized with toxigenic C. difficile upon admission, and 4 of these 12 patients (33%) developed CDI within 1 month, including 3 recurrent and 1 initial CDI episode. Of 82 patients with negative cultures on transfer and at least 1 follow-up culture, 22 (27%) acquired toxigenic C. difficile colonization, and 4 developed CDI within 1 month, including 1 recurrent and 3 initial CDI episodes.
LTCF residents frequently acquired colonization with toxigenic C. difficile after transfer from the hospital, and 3 of 4 initial CDI cases with onset within 1 month of transfer occurred in residents who acquired colonization in the LTCF.
Despite national guidelines recommending early concurrent palliative care for individuals newly diagnosed with metastatic cancer, few community cancer centers, especially those in underserved rural areas do so. We are implementing an early concurrent palliative care model, ENABLE (Educate, Nurture, Advise, Before Life Ends) in four, rural-serving community cancer centers. Our objective was to develop a “toolkit” to assist community cancer centers that wish to integrate early palliative care for patients with newly diagnosed advanced cancer and their family caregivers.
Guided by the RE-AIM (Reach, Effectiveness–Adoption, Implementation, Maintenance) framework, we undertook an instrument-development process based on the literature, expert and site stakeholder review and feedback, and pilot testing during site visits.
We developed four instruments to measure ENABLE implementation: (1) the ENABLE RE-AIM Self-Assessment Tool to assess reach, adoption, implementation, and maintenance; (2) the ENABLE General Organizational Index to assess institutional implementation; (3) an Implementation Costs Tool; and (4) an Oncology Clinicians' Perceptions of Early Concurrent Oncology Palliative Care survey.
Significance of results:
We developed four measures to determine early palliative care implementation. These measures have been pilot-tested, and will be integrated into a comprehensive “toolkit” to assist community cancer centers to measure implementation outcomes. We describe the lessons learned and recommend strategies for promoting long-term program sustainability.