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Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
Aerliceaster nexosus n. gen. n. sp. (Echinodermata), one of the oldest of known asteroids, is based on six specimens from the Floian (Early Ordovician) Garden City Formation of Idaho, and Kolataster perplexus n. gen. n. sp. is based on two specimens from the Sandian (Late Ordovician) Mifflin Formation of Illinois. Although the asterozoan skeleton is subdivided into few ossicular categories, evolutionary derivations of all the categories are not fully established, and therefore published evaluations differ. Beginning with phylogenetic work placing asteroid ancestry within the Somasteroidea together with the new taxa described herein, aspects of early asteroid morphology are evaluated and ambiguities in need of further study identified. Uncertainties are considered to be founded in rapid early asterozoan diversification and the scanty fossil record.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
Little is known about who would benefit from Internet-based personalised nutrition (PN) interventions. This study aimed to evaluate the characteristics of participants who achieved greatest improvements (i.e. benefit) in diet, adiposity and biomarkers following an Internet-based PN intervention. Adults (n 1607) from seven European countries were recruited into a 6-month, randomised controlled trial (Food4Me) and randomised to receive conventional dietary advice (control) or PN advice. Information on dietary intake, adiposity, physical activity (PA), blood biomarkers and participant characteristics was collected at baseline and month 6. Benefit from the intervention was defined as ≥5 % change in the primary outcome (Healthy Eating Index) and secondary outcomes (waist circumference and BMI, PA, sedentary time and plasma concentrations of cholesterol, carotenoids and omega-3 index) at month 6. For our primary outcome, benefit from the intervention was greater in older participants, women and participants with lower HEI scores at baseline. Benefit was greater for individuals reporting greater self-efficacy for ‘sticking to healthful foods’ and who ‘felt weird if [they] didn’t eat healthily’. Participants benefited more if they reported wanting to improve their health and well-being. The characteristics of individuals benefiting did not differ by other demographic, health-related, anthropometric or genotypic characteristics. Findings were similar for secondary outcomes. These findings have implications for the design of more effective future PN intervention studies and for tailored nutritional advice in public health and clinical settings.
The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
Shared patient–clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models.
Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project.
Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient–clinician shared decision-making.
Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.
Aging is associated with numerous stressors that negatively impact older adults’ well-being. Resilience improves ability to cope with stressors and can be enhanced in older adults. Senior housing communities are promising settings to deliver positive psychiatry interventions due to rising resident populations and potential impact of delivering interventions directly in the community. However, few intervention studies have been conducted in these communities. We present a pragmatic stepped-wedge trial of a novel psychological group intervention intended to improve resilience among older adults in senior housing communities.
A pragmatic modified stepped-wedge trial design.
Five senior housing communities in three states in the US.
Eighty-nine adults over age 60 years residing in independent living sector of senior housing communities.
Raise Your Resilience, a manualized 1-month group intervention that incorporated savoring, gratitude, and engagement in value-based activities, administered by unlicensed residential staff trained by researchers. There was a 1-month control period and a 3-month post-intervention follow-up.
Validated self-report measures of resilience, perceived stress, well-being, and wisdom collected at months 0 (baseline), 1 (pre-intervention), 2 (post-intervention), and 5 (follow-up).
Treatment adherence and satisfaction were high. Compared to the control period, perceived stress and wisdom improved from pre-intervention to post-intervention, while resilience improved from pre-intervention to follow-up. Effect sizes were small in this sample, which had relatively high baseline resilience. Physical and mental well-being did not improve significantly, and no significant moderators of change in resilience were identified.
This study demonstrates feasibility of conducting pragmatic intervention trials in senior housing communities. The intervention resulted in significant improvement in several measures despite ceiling effects. The study included several features that suggest high potential for its implementation and dissemination across similar communities nationally. Future studies are warranted, particularly in samples with lower baseline resilience or in assisted living facilities.
“The unwearied, unostentatious, and inglorious crusade of England against slavery may probably be regarded as among the three or four perfectly virtuous acts recorded in the history of nations,” said the great historian W. E. H. Lecky in his 1869 History of European Morals. But what exactly did the British seek to achieve with the abolition of slavery? Through what means? And what were the consequences? These are just three of the questions that have animated the pens of historians of slavery and the transatlantic slave trade. In 1807, shortly after abolishing their own trade, the British engaged in a campaign to suppress the entire traffic. They signed bilateral treaties with foreign nations, deployed a naval squadron to patrol the coasts of Africa and the Americas, and rescued thousands of Africans illegally forced into the Atlantic. The effectiveness of these efforts on the ground was minimal; however, the ideological result was nothing short of monumental. The trade not only ended in less than a century, but the campaign also shifted the world’s attitudes toward slavery: from one that viewed it as morally acceptable to another that considered it inhumane.
Given the nation's prominent role, historians have naturally paid more attention to Britain than to any other country involved in this suppression effort. However, not all of them agree on British intentions and objectives. Some argue that the British were economically interested in the suppression of the trade. Eric Williams, for example, believes that slavery and the slave trade helped finance the Industrial Revolution in England, but, when industrialization reached maturity, “the British West Indian monopoly, prohibiting the importation of non-British-plantation sugar for home consumption, stood in the way.” Other historians view British abolition in a dramatically different way, noting that, by retreating from the traffic, the British were actually committing an economic suicide, since plantation slavery in the West Indies was actually expanding at that time. Seymour Drescher points out, “Economic interests cannot account for either the timing, the occurrence, or the maintenance of the abolition of the slave trade between 1787 and 1820.”
Falloaster anquiroisitus new genus new species (Asterozoa, Echinodermata) is described from the Floian (Early Ordovician) Garden City Formation of Idaho. The new taxon is known from a single small specimen. Because of weathering, remaining disk elements are incomplete. Dorsal surfaces of the ambulacral ossicles of two arms are available, one well preserved, whereas those of a third arm expose the ambulacrals essentially as they would appear in ventral view. Ambulacral ossicles were all but entirely lost on the remaining two arms.
Albeit asterozoan, F. anquiroisitus is not assignable at the class level. It is suggestive of the Asteroidea in presence of a domal disk, five abruptly tapering triangular, arched arms, and ambulacral ossicles vaulted to form a furrow. Ambulacral morphology, including the presence of very large podial pores, is unlike that of early asteroids. In addition, no adambulacral or other virgal-series derivatives are present; ambital framework ossicles are absent; a single series of enlarged, plate-like arm ossicles, one series on each side of the arm, come together at the arm midline; and the plate-like series were supported laterally by recurved ambulacral margins. Only remnants of the disk near the periphery survive, these of overall expression unlike any other echinoderm, including asterozoans. The mouth frame is unknown. Falloaster anquiroisitus is argued to represent an extinct lineage apart from the four recognized asterozoan classes, thereby joining a limited number of other problematic early Asterozoa.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
This review offers an update on research conducted with FinnTwin12 (FT12), the youngest of the three Finnish Twin Cohorts. FT12 was designed as a two-stage study. In the first stage, we conducted multiwave questionnaire research enrolling all eligible twins born in Finland during 1983–1987 along with their biological parents. In stage 2, we intensively studied a subset of these twins with in-school assessments at age 12 and semistructured poly-diagnostic interviews at age 14. At baseline, parents of intensively studied twins were administered the adult version of the interview. Laboratory studies with repeat interviews, neuropsychological tests, and collection of DNA were made of intensively studied twins during follow-up in early adulthood. The basic aim of the FT12 study design was to obtain information on individual, familial and school/neighborhood risks for substance use/abuse prior to the onset of regular tobacco and alcohol use and then track trajectories of use and abuse and their consequences into adulthood. But the longitudinal assessments were not narrowly limited to this basic aim, and with multiwave, multirater assessments from ages 11 to 12, the study has created a richly informative data set for analyses of gene–environment interactions of both candidate genes and genomewide measures with measured risk-relevant environments. Because 25 years have elapsed since the start of the study, we are planning a fifth-wave follow-up assessment.
Early-life environmental and nutritional exposures are considered to contribute to the differences in cardiovascular disease (CVD) burden. Among sub-Saharan African populations, the association between markers of early-life exposures such as leg length and sitting height and CVD risk is yet to be investigated. This study assessed the association between leg length, sitting height, and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk among Ghanaian-born populations in Europe and Ghana. We constructed sex-specific quintiles for sitting height and leg length for 3250 participants aged 40–70 years (mean age 52 years; men 39.6%; women 60.4%) in the cross-sectional multicenter Research on Diabetes and Obesity among African Migrants study. Ten-year risk of ASCVD was estimated using the Pooled Cohort Equations; risk ≥7.5% was defined as “elevated” CVD risk. Prevalence ratios (PR) were estimated to determine the associations between sitting height, leg length, and estimated 10-year ASCVD risk. For both men and women, mean sitting height and leg length were highest in Europe and lowest in rural Ghana. Sitting height was inversely associated with 10-year ASCVD risk among all women (PR for 1 standard deviation increase of sitting height: 0.75; 95% confidence interval: 0.67, 0.85). Among men, an inverse association between sitting height and 10-year ASCVD risk was significant on adjustment for study site, adult, and parental education but attenuated when further adjusted for height. No association was found between leg length and estimated 10-year ASCVD risk. Early-life and childhood exposures that influence sitting height could be the important determinants of ASCVD risk in this adult population.
Alveolar echinococcosis is a neglected parasitic zoonosis caused by the metacestode Echinococcus multilocularis, which grows as a malignant tumour-like infection in the liver of humans. Albendazole (ABZ) is the antiparasitic drug of choice for the treatment of the disease. However, its effectiveness is low, due to its poor absorption from the gastro-intestinal tract. It is also parasitostatic and in some cases produces side-effects. Therefore, an alternative to the treatment of this severe human disease is necessary. In this context, the repositioning of drugs combined with nanotechnology to improve the bioavailability of drugs emerges as a useful, fast and inexpensive tool for the treatment of neglected diseases. The in vitro and in vivo efficacy of dichlorophen (DCP), an antiparasitic agent for intestinal parasites, and silica nanoparticles modified with DCP (NP-DCP) was evaluated against E. multilocularis larval stage. Both formulations showed a time and dose-dependent in vitro effect against protoscoleces. The NP-DCP had a greater in vitro efficacy than the drug alone or ABZ. In vivo studies demonstrated that the NP-DCP (4 mg kg−1) had similar efficacy to ABZ (25 mg kg−1) and greater activity than the free DCP. Therefore, the repurposing of DCP combined with silica nanoparticles could be an alternative for the treatment of echinococcosis.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Three states and one county now allow Emergency Medical Services (EMS) providers to transport injured law enforcement K9s (LEK9s) as long as no human needs the ambulance at the time. Several other states either have pending legislation or are in discussions about this topic. As additional states ponder these laws, it is likely that the EMS transport of LEK9s will become legal in many states. In the wake of this legislation, a significant void was created. Currently, there are no published protocols for the safe transport of LEK9s by EMS providers. Additionally, the transport destination for these LEK9s is unlikely to be programmed into vehicle Global Positioning Systems. The authors of this report convened a Joint Task Force on Working Dog Care, consisting of veterinarians, EMS directors, EMS physicians, and LEK9 handlers, who met to develop a protocol for LEK9s being transported to a veterinary facility. The protocol covers the logistics of getting the LEK9 into the ambulance (eg, when the handler is or is not available), appropriate restraint, and the importance of prior arrangements with a veterinary emergency facility. A LEK9 hand-off form and a Transport Policy Form are provided, downloadable, and customizable for each EMS provider. This protocol provides essential information on safety and transport logistics for injured LEK9s. The hope is that this protocol will assist EMS providers to streamline the transport of an injured LEK9 to an appropriate veterinary facility.
This document is a resource for Emergency Medical Services (EMS) treating an injured law enforcement K9 (LEK9) in the field and/or during transport by ambulance to a veterinary hospital. A Joint Task Force on Working Dog Care was created, which included veterinarians, EMS directors, EMS physicians, and canine handlers, who met to develop a treatment protocol for injured LEK9s. The protocol covers many major life-threatening injuries that LEK9s may sustain in the line of duty, and also discusses personnel safety and necessary equipment. This protocol may help train EMS providers to save the life of an injured LEK9.
There is no suitable vaccine against human visceral leishmaniasis (VL) and available drugs are toxic and/or present high cost. In this context, diagnostic tools should be improved for clinical management and epidemiological evaluation of disease. However, the variable sensitivity and/or specificity of the used antigens are limitations, showing the necessity to identify new molecules to be tested in a more sensitive and specific serology. In the present study, an immunoproteomics approach was performed in Leishmania infantum promastigotes and amastigotes employing sera samples from VL patients. Aiming to avoid undesired cross-reactivity in the serological assays, sera from Chagas disease patients and healthy subjects living in the endemic region of disease were also used in immunoblottings. The most reactive spots for VL samples were selected, and 29 and 21 proteins were identified in the promastigote and amastigote extracts, respectively. Two of them, endonuclease III and GTP-binding protein, were cloned, expressed, purified and tested in ELISA experiments against a large serological panel, and results showed high sensitivity and specificity values for the diagnosis of disease. In conclusion, the identified proteins could be considered in future studies as candidate antigens for the serodiagnosis of human VL.