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The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
The Core Elements of Outpatient Antibiotic Stewardship provides a framework to improve antibiotic use, but cost-effectiveness data on implementation of outpatient antibiotic stewardship interventions are limited. We evaluated the cost-effectiveness of Core Element implementation in the outpatient setting.
An economic simulation model from the health-system perspective was developed for patients presenting to outpatient settings with uncomplicated acute respiratory tract infections (ARI). Effectiveness was measured as quality-adjusted life years (QALYs). Cost and utility parameters for antibiotic treatment, adverse drug events (ADEs), and healthcare utilization were obtained from the literature. Probabilities for antibiotic treatment and appropriateness, ADEs, hospitalization, and return ARI visits were estimated from 16,712 and 51,275 patient visits in intervention and control sites during the pre- and post-implementation periods, respectively. Data for materials and labor to perform the stewardship activities were used to estimate intervention cost. We performed a one-way and probabilistic sensitivity analysis (PSA) using 1,000,000 second-order Monte Carlo simulations on input parameters.
The proportion of ARI patient-visits with antibiotics prescribed in intervention sites was lower (62% vs 74%) and appropriate treatment higher (51% vs 41%) after implementation, compared to control sites. The estimated intervention cost over a 2-year period was $133,604 (2018 US dollars). The intervention had lower mean costs ($528 vs $565) and similar mean QALYs (0.869 vs 0.868) per patient compared to usual care. In the PSA, the intervention was dominant in 63% of iterations.
Implementation of the CDC Core Elements in the outpatient setting was a cost-effective strategy.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The purpose of this study is to identify gaps in support for parents of children with Hypoplastic Left Heart Syndrome.
Design and methods:
Using a mixed-methods approach, the researchers first studied the parental and care team experience through interviews of Hypoplastic Left Heart Syndrome mothers and members of the inter-professional care team and then conducted an international survey of 690 Hypoplastic Left Heart Syndrome primary caregivers to validate the qualitative findings.
Parental and care team interviews revealed three main gaps in parental support, including lack of open communication, unrealistic parental expectations, and unclear inter-professional team roles. Survey results found that parents whose children were diagnosed with Hypoplastic Left Heart Syndrome after birth indicated significant dissatisfaction with the care team’s open communication and welcoming of feedback (p = 0.008). As parents progress through the stages of surgical intervention, they also indicate significant dissatisfaction with the care team’s anticipation of parental emotional needs and provision of coping resources (p = 0.003).
Parental support interventions should focus on providing resources to help parents cope, helping the care team model open communication, and welcoming feedback on the parental experience.
Interventions should be piloted with parents who are in the later stages of the surgical intervention timeline or whose children were diagnosed after birth as they are the populations who perceived the least support within this study.
This paper seeks to shed fresh light on the aesthetic and stylistic affiliations of Lycophron's Alexandra, approaching the poem from two distinct but complementary angles. First, it explores what can be gained by reading Lycophron's poem against the backdrop of Callimachus’ poetry. It contends that the Alexandra presents a radical and polemical departure from the Alexandrian's poetic programme, pointedly appropriating key Callimachean images while also countering Callimachus’ apparent dismissal of the ‘noisy’ tragic genre. Previous scholarship has noted links between the openings of the Aetia and of the Alexandra, but this article demonstrates that this relationship is only one part of a larger aesthetic divide between the two poets: by embracing the raucous acoustics of tragedy, Lycophron's poem offers a self-conscious and agonistic departure from Callimachus’ aesthetic preferences. Second, this article considers another way of conceiving the aesthetics of the poem beyond a Callimachean frame, highlighting how Lycophron pointedly engages with and evokes earlier Aristotelian literary criticism concerning the ‘frigid’ style: the Alexandra constructs its own independent literary history centred around the alleged name of its author, ‘Lycophron’. The article proposes that this traditional attribution is best understood as a pen name that signposts the poem's stylistic affiliations, aligning it not so much with the Ptolemaic playwright Lycophron of Chalcis but rather with Lycophron the sophist and a larger rhetorical tradition of stylistic frigidity. Ultimately, through these two approaches, the article highlights further aspects of the Alexandra's aesthetic diversity.
Background: Guidelines regarding asymptomatic bacteriuria (ASB) have consistently recommended against screening and treatment in most circumstances. However, screening of patients with spinal cord injury (SCI) is common practice and in some cases is a formal protocol at the organizational level. A previous study found that more than one-third of patients with ASB detected on routine screening cultures performed at annual visits in 2012 received antibiotics. However, the role of antibiotic stewardship has become more prominent over the last decade. We hypothesized that diagnostic and therapeutic stewardship efforts may be impacting the practice of annual urine-culture screening for SCI patients. We evaluated urine culture screening and treatment rates over a 10-year period. Methods: Patients with SCI seen in the VA Boston HCS for an annual exam in 2018 were eligible for inclusion and formed the baseline cohort for this study. Annual visits for the cohort over a 10-year period (January 1, 2009–December 31, 2018) were included in the analysis. Electronic data collection and manual chart review were utilized to capture outcomes of interest including urine culture, antibiotic prescriptions and indication within 15 days, and documentation of urinary or infectious symptoms. The main outcomes were (1) rate of urine cultures performed ±3 days of the visit, (2) rate of antibiotic treatment in asymptomatic patients, and (3) trend over time of urine culturing and treating. The χ2 test for trend was used to compare rates over time. Results: In total, 1,962 annual visits were made by the 344 unique patients over the 10-year period and were available for analysis. Among these, 639 (32.6%) visits had a urine culture performed within 3 days. The proportion of visits with a collected culture decreased from (109 of 127) 85.8% of visits in 2009 to (65 of 338) 19.2% of visits in 2018, P ≤ .001 (Fig. 1). In the treatment analysis, 39 visits were excluded for active symptoms, concern for uncontrolled infection, or prophylaxis as antibiotic indication. Among 600 remaining screening cultures, 328 had a bacterial pathogen or >100,000 mixed colonies consistent with ASB. Overall, 51 patients (17%) received antimicrobials. The rate of antibiotic treatment for ASB did not significantly decrease over time pP = 0.79 (Fig. 2). Conclusions: Over a 10-year period of annual SCI visits, the proportion of visits with a urine culture performed as routine screening significantly and consistently decreased. However, the rate of treatment for positive urine cultures remained consistent. These data support targeted diagnostic stewardship in this population to reduce unnecessary antibiotic use.
Background: The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use, but cost-effectiveness data on interventions to improve antibiotic use are limited. Beginning in September 2017, an antibiotic stewardship intervention was launched in within 10 outpatient Veterans Healthcare Administration clinics. The intervention was based on the Core Elements and used an academic detailing (AD) and an audit and feedback (AF) approach to encourage appropriate use of antibiotics. The objective of this analysis was to evaluate the cost-effectiveness of the intervention among patients with uncomplicated acute respiratory tract infections (ARI). Methods: We developed an economic simulation model from the VA’s perspective for patients presenting for an index outpatient clinic visit with an ARI (Fig. 1). Effectiveness was measured as quality-adjusted life-years (QALYs). Cost and utility parameters for antibiotic treatment, adverse drug reactions (ADRs), and healthcare utilization were obtained from the published literature. Probability parameters for antibiotic treatment, appropriateness of treatment, antibiotic ADRs, hospitalization, and return ARI visits were estimated using VA Corporate Data Warehouse data from a total of 22,137 patients in the 10 clinics during 2014–2019 before and after the intervention. Detailed cost data on the development of the AD and AF materials and electronically captured time and effort for the National AD Service activities by specific providers from a national ARI campaign were used as a proxy for the cost estimate of similar activities conducted in this intervention. We performed 1-way and probabilistic sensitivity analyses (PSAs) using 10,000 second-order Monte Carlo simulations on costs and utility values using their means and standard deviations. Results: The proportion of uncomplicated ARI visits with antibiotics prescribed (59% vs 40%) was lower and appropriate treatment was higher (24% vs 32%) after the intervention. The intervention was estimated to cost $110,846 (2018 USD) over a 2-year period. Compared to no intervention, the intervention had lower mean costs ($880 vs $517) and higher mean QALYs (0.837 vs 0.863) per patient because of reduced inappropriate treatment, ADRs, and subsequent healthcare utilization, including hospitalization. In threshold analyses, the antibiotic stewardship strategy was no longer dominant if intervention cost was >$64,415,000 or the number of patients cared for was <3,672. In the PSA, the antibiotic stewardship intervention was dominant in 100% of the 10,000 Monte Carlo iterations (Fig. 2). Conclusions: In every scenario, the VA outpatient AD and AF antibiotic stewardship intervention was a dominant strategy compared to no intervention.
Spatially and temporally unpredictable rainfall patterns presented food production challenges to small-scale agricultural communities, requiring multiple risk-mitigating strategies to increase food security. Although site-based investigations of the relationship between climate and agricultural production offer insights into how individual communities may have created long-term adaptations to manage risk, the inherent spatial variability of climate-driven risk makes a landscape-scale perspective valuable. In this article, we model risk by evaluating how the spatial structure of ancient climate conditions may have affected the reliability of three major strategies used to reduce risk: drawing upon social networks in time of need, hunting and gathering of wild resources, and storing surplus food. We then explore how climate-driven changes to this reliability may relate to archaeologically observed social transformations. We demonstrate the utility of this methodology by comparing the Salinas and Cibola regions in the prehispanic U.S. Southwest to understand the complex relationship among climate-driven threats to food security, risk-mitigation strategies, and social transformations. Our results suggest key differences in how communities buffered against risk in the Cibola and Salinas study regions, with the structure of precipitation influencing the range of strategies to which communities had access through time.
Adverse developmental outcomes for some children following institutional care are well established. Removal from institutional care and placement into families can promote recovery. However, little is known about how positive outcomes are sustained across adolescence among children with histories of severe deprivation. The present study examined the caregiving conditions that are associated with attaining and maintaining competent functioning (i.e., outcomes within typical levels) from middle childhood to adolescence following exposure to early institutional care. The participants included children with and without a history of institutional care who had competence assessed at ages 8, 12, and 16 years across seven domains: family relationships, peer relationships, academic performance, physical health, mental health, substance use (ages 12 and 16 years only), and risk-taking behavior. The participants were grouped based on whether they were always versus not always competent and never versus ever competent at ages 8 through 16 years. Adolescents with a history of institutional care were less likely to be consistently competent than those who were family reared. Among those who were exposed to early institutional rearing, maintaining competent functioning from 8 to 16 years was associated with spending less time in institutions and receiving higher-quality caregiving early in life. Ensuring high quality early caregiving may promote competent functioning following early deprivation.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use.
A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype.
Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency.
There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology.
Two arguments imply that Mahr & Csibra's (M&C's) functional theory is insufficient as an explanation of episodic memory: (1) The developmental course supports a different social cultural division of episodic and semantic memory, and (2) the existence of long-term autobiographical memory is not explained in the functional theory but can be seen in a broader cultural framework.
Palliative care research is relatively diverse and prioritizing research in this field is dependent on multiple factors such as complex ethical decisions in designing and conducting the research; access to participants who may be deemed “vulnerable” and an increasingly medically focused approach to care. The aim of this study was to inform organizational decision-making and policy development regarding future research priorities for a hospice service in New Zealand.
A modified three-round Delphi technique was employed. Participants were drawn from one dedicated specialist palliative care service that delivers care in the community, day-care, hospice inpatient, aged residential care, and acute hospital palliative care service. A purposive sample included palliative care staff (n = 10, 18, 9, for rounds 1–3, respectively) volunteers (n = 10, 12, 11); and patients and family carers (n = 6, 8, for rounds 1 and 2). Patients and family carers were not involved in the third round.
At final ranking of six research themes encompassing 23 research topics were identified by staff and volunteers. These were: symptom management; aged care; education; community; patient and family; and bereavement support and young people. Patients and family carers agreed on four themes, made up of 10 research topics. These were: decision-making, bereavement and loss, symptom management; and recognition of need and response of service.
Significance of results:
The study generated a rich set of research themes and specific research topics. The perspectives of staff and volunteers are significantly different from those of patients and family members, in spite of the recognition by all concerned that palliative care services work within a philosophy of patient-centered care. Open discussion of ideas has the potential to engage both staff and patients and carers in quality improvement initiatives, and to reinforce the value of research for patient care.
The entry into language via first words and, the acquisition of word meanings is considered from the perspective of publications in the Journal of Child Language over the past forty years. Problems in achieving word meanings include the disparate and sparse concepts available to the child from past prelanguage experience. Variability in beginning word learning and in its progress along a number of dimensions suggests the problems that children may encounter, as well as the strategies and styles they adopt to make progress. Social context and adult practices are vitally involved in the success of this process. Whereas much headway has been made over the past decades, much remains to be revealed through dynamic systems theory and developmental semiotic analyses, as well as laboratory research aimed at social context conditions.