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To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up.
Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo.
Community settings and care homes in 26 UK centers.
People with probable or possible Alzheimer’s disease and agitation.
Primary outcome included incremental cost of participants’ health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants’ and unpaid carers’ gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives.
One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment.
On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.
A moderate to high alcohol consumption is associated with a lower risk of cardiovascular disease (CVD) mortality in comparison with low consumption. The mechanisms underlying this association are not clear and have been suggested to be caused by residual confounding. The main objective of this study was to separate the familial and individual risk for CVD mortality and all-cause mortality related to alcohol consumption. This will be done by estimating the risk for CVD mortality and all-cause mortality in twin pairs discordant for alcohol consumption.
Alcohol consumption was assessed at two time points using self-report questionnaires in the Norwegian Twin Registry. Data on CVD mortality was obtained from the Norwegian Cause of Death Registry. Exposure–outcome associations for all-cause mortality and mortality due to other causes than CVD were estimated for comparison.
Coming from a family with moderate to high alcohol consumption was protective against cardiovascular death (HR = 0.54, 95% CI 0.65–0.83). Moderate and high alcohol consumption levels were associated with a slightly increased risk of CVD mortality at the individual level (HR = 1.33, 95% CI 1.02–1.73). There was no association between alcohol consumption and all-cause mortality both at the familial nor at the individual level.
The protective association of moderate to high alcohol consumption with a lower risk of CVD mortality was accounted for by familial factors in this study of twins. Early life genetic and environmental familial factors may mask an absence of health effect of moderate to high alcohol consumption on cardiovascular mortality.
At times funerary practices do not end with the deposition of the corpses in their final resting place, because occasionally these supposedly definitive burials are disturbed later. When we can confirm that people were mainly responsible for these disturbances, even when other natural taphonomic factors are present, then we have a situation of anthropic postfunerary manipulation of bodies and graves. Some precontact sites in northeastern Brazil have mortuary contexts with “anomalies” in the deposition of bodies into their graves. Applying a taphonomy-based approach, we analyze these cases and compare them to other burials with similar characteristics from central-eastern Brazil in our discussion of the “alternative” phenomenon of postburial manipulation. The evidence suggests that the anthropic disturbance of older burials and corpses should be understood not as a random event, but as an integral and meaningful part of the mortuary practices of ancient inhabitants from across different regions of Brazil throughout the Holocene. With this work we highlight not only unusual mortuary patterns of precontact human groups in Brazil and South America but also the importance of a taphonomic approach to understanding the complexity and variability of funerary and postfunerary actions.
Carbapenemase-producing Enterobacterales (CPE) are important globally. In 2017, Ireland declared a national public health emergency to address CPE in acute hospitals. A National Public Health Emergency Team and an expert advisory group (EAG) were established. The EAG has identified key learnings to inform future strategies. First, there is still an opportunity to prevent CPE becoming endemic. Second, damp environmental reservoirs in hospitals are inadequately controlled. Third, antibiotic stewardship remains important in control. Finally, there is no current requirement to extend screening to detect CPE outside of acute hospitals. These conclusions and their implications may also be relevant in other countries.
To compare the nutritional composition of bovine milk and several plant-based drinks with a focus on protein and essential amino acid content and to determine the ratio of essential amino acids to greenhouse gas emission.
Nutritional information on the label was extracted for semi-skimmed milk, soy, oat, almond, coconut and rice drink from the Innova database between January 2017 and March 2020 for the Netherlands, Belgium, Germany, Spain, Italy and Sweden. Protein and amino acids were measured and carbon footprint was calculated for a selection of Dutch products. Protein quality was determined by calculating the contribution to the WHO essential amino acids requirements.
The bovine milk and plant-based drinks market in Netherlands, Belgium, Germany, Spain, Italy and Sweden.
Semi-skimmed bovine milk and soy, oat, almond, coconut and rice drink.
Nutritional label information was collected for 399 products. Milk naturally contains many micronutrients, e.g. vitamin B2, B12 and Ca. Approximately 50 % of the regular plant-based drinks was fortified with Ca, whereas the organic plant-based drinks were mostly unfortified. Protein quantity and quality were highest in milk. Soy drink had the best protein quality to carbon footprint ratio and milk came second.
The nutrition – climate change balance presented in this study, is in line with previous literature, which shows that semi-skimmed bovine milk and fortified soy drink deserve a place in a sustainable diet.
Identifying and disseminating actionable intelligence is a challenging task that requires thoughtful planning. The National Center for Advancing Translational Sciences instituted the Common Metrics Initiative with the goal of evaluating the Clinical and Translational Science Awards (CTSA) Programs using a standard set of metrics. Initially managed by Tufts University, the Center for Leading Innovation and Collaboration (CLIC) at the University of Rochester began leading this initiative in 2017. In directing this work, CLIC created a framework for communicating and disseminating data insights. Insights to Inspire emerged from the need to share strategies and lessons learned to improve metric performance at the local level to a network of 60+ academic research institutions. Insights to Inspire employs a mixed methods approach for translating data into actionable intelligence. A series of blogs, webinars, and webcasts were designed to communicate metric-specific strategies used by individual sites to the broader CTSA consortium. A dissemination plan to expand the reach beyond metric stakeholders utilized focused communications including social media channels, network newsletters, and presentations at national meetings. This framework serves as a blueprint for other national evaluation programs interested in a systematic approach to using data insights for continuous improvement.
The objective was to examine the prospective relationship between folate and vitamin B12 (B12) status and incident depressive symptoms in a representative cohort of community-dwelling older people. This was a longitudinal study utilising the Irish Longitudinal Study on Aging (n =3,849 aged ≥50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). Participants with depression at wave 1 were excluded. A score ≥9 on the Center for Epidemiologic Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. Plasma B12 and folate concentrations were determined by microbiological assay. B12 status profiles (pmol/l) were defined as: <185, deficient-low; 185 - <258, low normal; >258 - 601, normal and >601 high. Folate status profiles (nmol/l) were defined as: ≤10.0, deficient-low; >10 - 23.0, low normal; >23.0 - 45.0, normal; >45.0, high. Logistic regression models reporting odds ratios were used to analyse the longitudinal association of B-vitamin categories with incident depression. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms vs. non depressed (folate: 21.4 vs. 25.1 nmol/L; P=0.0003); (B12: 315.7 vs. 335.9 pmol/L; P=0.0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression four years later (odds ratio 1.51, 95% CI 1.01-2.27, P=0.043). This finding remained robust after controlling for relevant covariates including physical activity, chronic disease burden, vitamin D status. cardiovascular disease and antidepressant use. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51% increased likelihood of developing depressive symptoms over 4 years. Given the high rates of B12 deficiency, these findings are important and highlight the need to further explore the low cost benefits of optimising vitamin B12 status for depression in older adults.
The home environment has a major impact on child development. Parental severe mental illness can pose a challenge to the home environment of a child. We aimed to examine the home environment of children of parents with schizophrenia or bipolar disorder and controls longitudinally through at-home assessments.
Assessments were conducted within The Danish High Risk and Resilience Study, a nationwide multi-center cohort study of children of parents with schizophrenia or bipolar disorder and population-based controls. The level of at-home stimulation and support was measured at age 7 (N = 508 children) and age 11 (N = 430 children) with the semi-structured HOME Inventory. Results from the 11-year follow-up study were analyzed and compared with 7-year baseline results to examine change across groups.
At age 11, children of parents with schizophrenia and bipolar disorder had lower levels of stimulation and support than controls (mean (s.d.) = 46.16 (5.56), 46.87 (5.34) and 49.25 (4.37) respectively, p < 0.001). A higher proportion of children with parental schizophrenia or bipolar disorder lived in inadequate home environments at age 11, compared with controls (N (%) = 24 (15.0), 12 (12.2) and 6 (3.5) respectively, p < 0.003). The changes in home environment scores did not differ across groups from age 7 to age 11.
Assessed longitudinally from the children's age of 7 to 11, children of parents with schizophrenia or bipolar disorder had lower levels of stimulation and support in their homes than controls. Integrated support which can target practical, economic, social and health issues to improve the home environment is indicated.
The role of interpersonal relationship functioning in trauma recovery is well-established. However, much of this research has been done with cross-sectional samples, often years after trauma exposure, using self-report methodology only, and is focused on intimate relationship adjustment.
The current study investigated the longitudinal associations between interpersonal (intimate and non-intimate) relationship functioning and clinician- and self-reported posttraumatic stress disorder (PTSD) symptoms in 151 recently (within the past 6 months) traumatized individuals. Participants were assessed at four time points over 1 year.
Approximately 53% of the sample was diagnosed with PTSD at initial assessment, with declining rates of diagnostic status over time to 16%. Latent difference score (LDS) modeling revealed nonlinear declines in both clinician-assessed and self-reported PTSD symptom severity, with faster declines in earlier periods. Likewise, LDS models revealed nonlinear declines in negative (conflict) aspects of interpersonal relationship functioning, but linear declines in positive (support, depth) aspects. The relationship between PTSD and relationship functioning differed for clinician- and self-reported PTSD. Bivariate LDS modeling revealed significant cross-lagged effects from relationship conflict to clinician-assessed PTSD, and significant cross-lagged effects from self-reported PTSD to relationship conflict over time.
These results highlight that the variability in prior results may be related to the method of assessing PTSD symptomatology and different relational constructs. Implications for theory and early intervention are discussed.
Little is known about the raising number of specialized units for patients with dementia and very severe challenging behavior in the Netherlands. This study describes organizational and treatment characteristics of a sample of these units.
The organizational and treatment characteristics were studied with digital questionnaires completed by the unit managers, interviews with the main physician(s) and observation of the physical environment. The questionnaire consisted of questions about general patient characteristics, unit characteristics and staff characteristics. Furthermore, an interview was held with the main/treating physician often together with another physician or psychologist. The interview guide consisted of questions about admission criteria, the role of staff involved and the treatment process.
Thirteen units participated. Five units were part of a mental health (MH) institution, seven units were part of a nursing home (NH) organization and one unit was a cooperation of MH and NH. Unit sizes ranged from 10 to 28 places. Ten of thirteen units started in 2010 or later. The age of patients admitted was estimated at 75 years. The percentage of involuntary admitted patients was 53% at MH-units and 18% at NH-units. Unit managers mentioned that due to a difference in reimbursement between MH and NH units had difficulty providing the specialized care. Another problem managers faced was recruiting nursing staff. Units strived for expertise in general staffing from both MH and NH. The education level of the nursing staff was comparable between MH and NH. At every unit a physician with background in elderly care medicine or geriatrics and a psychiatrist was involved. Interviewees stressed the role of the nursing staff in the treatment. They were key in providing the care and treatment that, since the main goal of interventions is treatment of and coping with challenging behavior.
The main finding of this study is that units caring for patients with dementia and challenging behavior, despite barriers in regulations and staffing shortage, search for combining expertise from nursing home care and psychiatry in their treatment.
Timing of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to genetic risk for neurodevelopmental disorders in the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia.
We use data from a genotyped sub-set (N = 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences.
We found that ADHD PGS were associated with earlier walking age (β = −0.033, padj < 0.001) in both males and females. Additionally, autism PGS were associated with later walking (β = 0.039, padj = 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment.
Genetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.
In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.
Before coronavirus disease 2019 (COVID-19), few hospitals had fully tested emergency surge plans. Uncertainty in the timing and degree of surge complicates planning efforts, putting hospitals at risk of being overwhelmed. Many lack access to hospital-specific, data-driven projections of future patient demand to guide operational planning. Our hospital experienced one of the largest surges in New England. We developed statistical models to project hospitalizations during the first wave of the pandemic. We describe how we used these models to meet key planning objectives. To build the models successfully, we emphasize the criticality of having a team that combines data scientists with frontline operational and clinical leadership. While modeling was a cornerstone of our response, models currently available to most hospitals are built outside of their institution and are difficult to translate to their environment for operational planning. Creating data-driven, hospital-specific, and operationally relevant surge targets and activation triggers should be a major objective of all health systems.
Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood.
Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) v. a sham control condition on mood after the exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design) using linear mixed-effects and hierarchical Bayesian analyses of mood ratings.
We found that 90 min of either left-sided or right-sided taVNS improved positive mood [b = 5.11, 95% credible interval, CI (1.39–9.01), 9.6% improvement relative to the mood intercept, BF10 = 7.69, pLME = 0.017], yet only during the post-stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation [r = −0.42, 95% CI (−0.58 to −0.21), BF10 = 249].
We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to the reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.
The double burden of malnutrition (DBM) has been described in many low-/middle-income countries. We investigated food addiction, thyroid hormones, leptin, the lipid/glucose profile and body composition in DBM children/adolescents. Subjects were allocated into groups according to nutritional status: control (C, n 28), weight excess (WE, n 23) and DBM (WE plus mild stunting, n 22). Both the DBM and WE groups showed higher mean insulin concentrations than the control (DBM = 57·95 (95 % CI 47·88, 70·14) pmol/l, WE = 74·41 (95 % CI 61·72, 89·80) pmol/l, C = 40·03 (95 % CI 34·04, 47·83) pmol/l, P < 0·001). WE and DBM showed more food addiction symptoms than the control (3·11 (95 % CI 2·33, 3·89), 3·41 (95 % CI 2·61, 4·20) and 1·66 (95 % CI 0·95, 2·37)). In DBM individuals, addiction symptoms were correlated with higher body fat and higher insulin and leptin levels. These data provide preliminary evidence consistent with the suggestion that DBM individuals have a persistent desire to eat, but further studies are required to confirm these results in a larger study. These hormonal changes and high body fat contribute to the development of diabetes in long term.
Lack of knowledge about iodine has been suggested as a risk factor for iodine deficiency in pregnant women, but no studies have addressed this issue in Portugal. So, the aim of this study was to investigate iodine knowledge among Portuguese pregnant women and its association with iodine status. IoMum, a prospective observational study, included 485 pregnant women recruited at Centro Hospitalar e Universitário de S. João, Porto, between the 10th and 13th gestational weeks. Partial scores for knowledge on iodine importance, on iodine food sources or on iodised salt were obtained through the application of a structured questionnaire. Then, a total iodine knowledge score was calculated and grouped into low, medium and high knowledge categories. Urinary iodine concentration (UIC) was measured in spot urine samples by inductively coupled plasma MS. Of the pregnant women, 54 % correctly recognised iodine as important to neurocognitive development, 32 % were unable to identify any iodine-rich food and 71 % presented lack of knowledge regarding iodised salt. Of the women, 61 % had a medium total score of iodine knowledge. Knowledge on iodine importance during pregnancy was positively associated with iodine supplementation and also with UIC. Nevertheless, median UIC in women who correctly recognised the importance of iodine was below the cut-off for adequacy in pregnancy (150 µg/l). In conclusion, knowledge on iodine importance is positively associated with iodine status. Despite this, recognising iodine importance during pregnancy may not be sufficient to ensure iodine adequacy. Literacy-promoting actions are urgently needed to improve iodine status in pregnancy.
The role of milk and dairy products in supplying iodine to pregnant women is unknown in Portugal. The aim of this study was to evaluate the association between milk and dairy product consumption and the iodine status of pregnant women in the IoMum cohort of the Oporto region. Pregnant women were recruited between 10 and 13 weeks of gestation, when they provided a spot urine sample and information on lifestyle and intake of iodine-rich foods. Urinary iodine concentration (UIC) was determined by inductively coupled plasma MS. A total of 468 pregnant women (269 iodine supplement users and 199 non-supplement users) were considered eligible for analysis. Milk (but not yogurt or cheese) intake was positively associated with UIC, in the whole population (P = 0·02) and in the non-supplement users (P = 0·002), but not in the supplement users (P = 0·29). In non-supplement users, adjusted multinomial logistic regression analysis showed that milk consumption <3 times/month was associated with a five times increased risk of having UIC < 50 µg/l when compared with milk consumption ≥2 times/d (OR 5·4; 95 % CI 1·55, 18·78; P = 0·008). The highest UIC was observed in supplement users who reported consuming milk once per d (160 µg/l). Milk, but not yogurt or cheese, was positively associated with iodine status of pregnant women. Despite the observed positive association, daily milk consumption may not be sufficient to ensure adequate iodine intake in this population.
Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.