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To quantify the impact of clinical guidance and rapid respiratory and meningitis/encephalitis multiplex polymerase chain reaction (mPCR) testing on the management of infants.
Before-and-after intervention study.
Tertiary-care children’s hospital.
Infants ≤90 days old presenting with fever or hypothermia to the emergency department (ED).
The study spanned 3 periods: period 1, January 1, 2011, through December 31, 2014; period 2, January 1, 2015, through April 30, 2018; and period 3, May 1, 2018, through June 15, 2019. During period 1, no standardized clinical guideline had been established and no rapid pathogen testing was available. During period 2, a clinical guideline was implemented, but no rapid testing was available. During period 3, a guideline was in effect, plus mPCR testing using the BioFire FilmArray respiratory panel 2 (RP 2) and the meningitis encephalitis panel (MEP). Outcomes included antimicrobial and ancillary test utilization, length of stay (LOS), admission rate, 30-day mortality. Outcomes were compared across periods using Kruskal-Wallis and Pearson tests and interrupted time series analysis.
Overall 5,317 patients were included: 2,514 in period 1, 2,082 in period 2, and 721 in period 3. Over the entire study period, we detected reductions in the use of chest radiographs, lumbar punctures, LOS, and median antibiotic duration. After adjusting for temporal trends, we observed that the introduction of the guideline was associated with reductions in ancillary tests and lumbar punctures. Use of mPCR testing with the febrile infant clinical guideline was associated with additional reductions in ancillary testing for all patients and a higher proportion of infants 29–60 days old being managed without antibiotics.
Use of mPCR testing plus a guideline for young infant evaluation in the emergency department was associated with less antimicrobial and ancillary test utilization compared to the use of a guideline alone.
The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to evaluate specific aspects of instrument performance of both X-ray and neutron powder diffractometers. This report describes SRM 660c, the fourth generation of this powder diffraction SRM, which is used primarily for calibrating powder diffractometers with respect to line position and line shape for the determination of the instrument profile function (IPF). It is certified with respect to lattice parameter and consists of approximately 6 g of lanthanum hexaboride (LaB6) powder. So that this SRM would be applicable for the neutron diffraction community, the powder was prepared from an isotopically enriched 11B precursor material. The microstructure of the LaB6 powder was engineered specifically to yield a crystallite size above that where size broadening is typically observed and to minimize the crystallographic defects that lead to strain broadening. A NIST-built diffractometer, incorporating many advanced design features, was used to certify the lattice parameter of the LaB6 powder. Both Type A, statistical, and Type B, systematic, uncertainties have been assigned to yield a certified value for the lattice parameter at 22.5 °C of a = 0.415 682 6 ± 0.000 008 nm (95% confidence).
− Agency is one of five core analytical problems in the Earth System Governance (ESG) Project’s research framework, which offers a unique approach to the study of environmental governance. − Agency in Earth System Governance draws lessons from ESG–Agency research through a systematic review of 322 peer-reviewed journal articles published between 2008 and 2016 and contained in the ESG–Agency Harvesting Database.− ESG–Agency research draws on diverse disciplinary perspectives with distinct clusters of scholars rooted in the fields of global environmental politics, policy studies, and socio-ecological systems. − Collectively, the chapters in Agency in Earth System Governance provide an accessible synthesis of some of the field’s major questions and debates and a state-of-the-art understanding of how diverse actors engage with and exercise authority in environmental governance.
Carers of people experiencing a first episode of psychosis are at an increased risk of developing their own physical and mental health problems. Psychoeducation has been found to improve carer wellbeing and reduce distress. However, few psychoeducation interventions have considered the resource constraints on mental health services and the impact that these can have on the implementation of any such interventions. The present service evaluation aimed to evaluate an abbreviated version (sole session) of a previously tested psychoeducation intervention (three sessions) that targets less adaptive illness beliefs (n = 17). Pre–post effect sizes reveal that all of the carers’ illness beliefs changed in the desired direction, with four out of the 10 illness beliefs associated with large to moderate improvements. When compared with the outcomes obtained in our evaluation of the more intensive, three-session version of the intervention, the between-group effects largely favoured the three-session version but were mostly small. Moderate to large effects in favour of the three-session version were found for two of the 10 illness beliefs. These findings support the further investigation of the sole session psychoeducation intervention as part of a randomised controlled trial.
Key learning aims
(1) To evaluate the impact of a sole-session psychoeducation intervention on illness beliefs.
(2) To compare the outcomes of the sole-session psychoeducation intervention to the previous, more intensive (three-session) version of the same intervention.
(3) To consider the value of research approaches to evaluating psychoeducation interventions for carers of people with psychosis.
Smartphone mHealth apps can help children with obesity modify their rate of eating(1) and monitor physical activity(2). However, owing to issues with adherence, mHealth interventions require rigorous feasibility testing(3).
To evaluate, using a randomised design, the feasibility and acceptability of a mHealth intervention to reduce rate of eating and track physical activity among children in treatment for obesity.
Children (9–16 years) with obesity (BMI ≥ 98th centile) were recruited at a tertiary healthcare centre. The Research Ethics Committee at Temple St. Children's University Hospital granted ethical approval. Upon completing informed consent and assent, participants completed 2-week baseline testing including anthropometry, rate of eating by Mandometer® and physical activity using myBigO app. Thereafter participants were randomised to:(1)Treatment: Usual clinical care + Mandometer® training or (2)Control: Usual clinical care. Gender and age (9.0–12.9 years and 13.0–16.9 years) stratifications were applied. After a 4-week treatment period, participants repeated the 2-week testing period. Feasibility measures included fidelity with planned recruitment, randomisation, and intervention delivery and attrition. Acceptability measures included objective clinical portal engagement data and feedback from participants.
Of 20 recruited, eight were randomised to intervention and 12 to control, with no significant age, gender or BMI SDS differences between groups. At baseline, 7 intervention (87.5%) and 8 control (66.7%) participants recorded rate of eating. Eighteen participants (90%) registered with myBigO app, with 16 recording data successfully. Two had smartphones incompatible with myBigO (n = 1 intervention;n = 1 control) and two did not engage with myBigO app (n = 1 intervention;n = 1 control). Among 4 participants who completed Mandometer® intervention, dose received ranged from 7%-92% of planned meals. 37.5% intervention and 58.3% control participants completed post-intervention measures. Attrition was higher in the intervention (n = 5;62.5%) than control (n = 3;25%) group. Reasons cited for withdrawing included loss of interest (n = 3 intervention), child felt overwhelmed or self-conscious (n = 2 control), lack of time (n = 1 intervention), behavioural issue with child (n = 1 control), and family illness (n = 1 intervention). No significant age, gender or BMI SDS differences were observed between non-completers and completers. Participant engagement and feedback indicated mixed acceptability among this cohort.
Based on results, the current protocol for study design and intervention should be improved, if engagement is to be maximised.
The study is part of EU H2020 BigO Study (Big Data Against Childhood Obesity, Grant No. 727688.https://bigoprogram.eu/).
Expressivists about normative thought and discourse traditionally deny that there are nondeflationary normative propositions. However, it has recently been suggested that expressivists might avoid a number of problems by providing a theory of normative propositions compatible with expressivism. This paper explores the prospects for developing an expressivist theory of propositions within the framework of cognitive act theories of propositions. First, I argue that the only extant expressivist theory of cognitive propositions—Michael Ridge's ‘ecumenical expressivist’ theory—fails to explain identity conditions for normative propositions. Second, I argue that this failure motivates a general constraint—the ‘unity requirement’—that any expressivist theory of propositions must provide a unified nonrepresentational explanation of that in virtue of which propositional attitudes have the content that they have. Third, I argue that conceptual role accounts of content provide a promising framework in which to develop an expressivist theory of cognitive propositions.
As bottom water warms, destabilisation of gas hydrates may increase the extent of methane-rich sediments. The authors present an assessment of organic carbon processing by the benthic community in methane-rich sediments, including one of the first investigations of inorganic C fixation in a non-hydrothermal vent setting. This topic was previously poorly studied, and there is much need to fill the gaps in knowledge of such ecosystems. The authors hypothesized that benthic C fixation would occur, and that a high biomass macrofaunal community would play a substantial role in organic C cycling. Experiments were conducted at a 257 m deep site off South Georgia. Sediment cores were amended with 13C and 15N labelled algal detritus, or 13C labelled bicarbonate solution. In the bicarbonate experiment, labelling of bacteria-specific phospholipid fatty acids provided direct evidence of benthic C fixation, with transfer of fixed C to macrofauna and dissolved organic carbon (DOC). In the algae experiment, macrofauna played an active role in organic carbon cycling. Compared to similar experiments, low temperature supressed the rates of community respiration and macrofaunal C uptake. While benthic C fixation occurred, the biological processing of organic carbon was dominantly controlled by low temperature and high photic zone productivity.
We measure the cosmic star formation history out to z = 1.3 using a sample of 918 radio-selected star-forming galaxies within the 2-deg2 COSMOS field. To increase our sample size, we combine 1.4-GHz flux densities from the VLA-COSMOS catalogue with flux densities measured from the VLA-COSMOS radio continuum image at the positions of I < 26.5 galaxies, enabling us to detect 1.4-GHz sources as faint as 40 μJy. We find that radio measurements of the cosmic star formation history are highly dependent on sample completeness and models used to extrapolate the faint end of the radio luminosity function. For our preferred model of the luminosity function, we find the star formation rate density increases from 0.017 M⊙ yr−1 Mpc−3 at z ∼ 0.225 to 0.092 M⊙ yr−1 Mpc−3 at z ∼ 1.1, which agrees to within 40% of recent UV, IR and 3-GHz measurements of the cosmic star formation history.
Health and social care face growing and conflicting pressures: mounting complex needs of an ageing population, restricted funding and a workforce recruitment and retention crisis. In response, in the UK the NHS Long Term Plan promises increased investment and an emphasis on better ‘integrated’ care. We describe key aspects of integration that need addressing.
Declaration of interest
D.K.T. and S.S.S. are on the editorial board of the British Journal of Psychiatry and executives of the Academic Faculty at the Royal College of Psychiatrists. A.J.B.J., H.P. and Z.M. have roles at the Royal College of Psychiatrists that include evaluation of integrated care systems. A.J.B.J. is married to Dr Sarah Wollaston, Member of Parliament for Totnes and Chair of the Health Select Committee.
Mental illness is one of the leading causes of disability, with direct and indirect costs posing a significant financial burden. Previously, a large prospective economic utility study (n>13,000) showed that the GeneSight® test, a psychiatric pharmacogenomic decision support tool powered by CPGx® technology, reduced medication costs, increased adherence, andreduced polypharmacy for patients who had failed monotherapy for psychiatric disorders. The current study, which is a sub-analysis of this larger study, assessed cost savings associated with combinatorial pharmacogenomic testing in patients with generalized anxiety disorder (GAD) and major depressive disorder (MDD). Medication costs were extracted using pharmacy claims data provided by Medco, a large pharmacy benefits manager, for patients with GAD (n=318) and MDD (n=459). Medication cost savings per member per year (PMPY) for 1 year following the test were compared between patients whose medication regimens were congruent with the test recommendations and those whose medication regimens were incongruent with these recommendations. When healthcare providers’ decisions were congruent with combinatorial pharmacogenomic testing, PMPY savings was $6,747 (p<0.004) for GAD patients and $3,738 (p<0.004) for MDD patients versus incongruent decisions within these disease states. Among the congruent group, GAD patients experienced greater savings in central nervous system (CNS) medications (2-fold) compared to MDD patients. Additionally, analysis of a subset of patients prescribed at least one benzodiazepine six months prior to testing (n=660) demonstrated a significant decrease in benzodiazepine drug counts (p<0.001) and refills (p<0.001) after testing. Using the GeneSight test as a treatment decision support tool for patients with GAD or MDD resulted in significant medication cost savings when HCPs made congruent decisions with the combinatorialpharmacogenomic results. Furthermore, use of the GeneSight test decreased the use of benzodiazepines.
In the original publication of this article, the title was printed as “Four Preceramic Points Newly Discovered in Belize: A Comment on Stemp et al. (1996:279–299).” The article has been updated to the correct title. The authors apologize for this error.
To develop evidence-based materials which provide information and support for parents who are concerned about their baby’s excessive crying. As well as meeting these parents’ needs, the aim was to develop a package of materials suitable for use by the UK National Health Service (NHS).
Parents report that around 20% of infants in Western countries cry excessively without an apparent reason during the first four months of age. Traditionally, research has focused on the crying and its causes. However, evidence is growing that how parents evaluate and respond to the crying needs to receive equal attention. This focus encompasses parental resources, vulnerabilities, well-being and mental health. At present, the UK NHS lacks a set of routine provisions to support parents who are concerned about their baby’s excessive crying. The rationales, methods and findings from a study developing materials for this purpose are reported.
Following a literature review, 20 parents whose babies previously cried excessively took part in focus groups or interviews. They provided reports on their experiences and the supports they would have liked when their baby was crying excessively. In addition, they identified their preferred delivery methods and devices for accessing information and rated four example support packages identified by the literature review.
During the period their baby cried excessively, most parents visited a health service professional and most considered these direct contacts to have provided helpful information and support. Websites were similarly popular. Telephones and tablets were the preferred means of accessing online information. Groups to meet other parents were considered an important additional resource by all the parents. Three package elements – a Surviving Crying website, a printed version of the website and a programme of Cognitive Behaviour Therapy-based support sessions delivered to parents by a qualified practitioner, were developed for further evaluation.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Stemp et al. (2016) published data on 81 preceramic (Archaic) points from Belize, Central America. In this comment, we report four more chipped chert bifaces recently recovered in Belize (Figure 1). Based on metrics (Table 1), technology, and style, three are classified as Lowe and one as a Sawmill point (Kelly 1993; Lohse et al. 2006; Stemp et al. 2016).