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To evaluate efficiency and impact of a novel antimicrobial stewardship program (ASP) prospective-audit-with-feedback (PAF) review process using the Cerner Multi-Patient Task List (MPTL).
Retrospective cohort study.
A 367-bed free-standing, pediatric academic medical center.
The ASP PAF review process expanded to monitor all systemic and inhaled antibiotics through use of the MPTL on July 23, 2020. Average number of daily ASP reviews, absolute number of monthly interventions, and time to conduct ASP reviews were compared between the preimplementation period and the postimplementation period following expansion. Antibiotic days of therapy (DOT) per 1,000 patient days for overall and select antibiotics were compared between periods. ASP intervention characteristics were assessed.
Average daily ASP reviews significantly increased following program expansion (9 vs 14 reviews; P < .0001), and the absolute number of ASP interventions each month also increased (34 vs 52 interventions; P ≤ .0001). Time to conduct daily ASP reviews increased in the postimplementation period (1.03 vs 1.32 hours). Overall antibiotic DOT per 1,000 patient days significantly decreased in the postimplementation period (457.9 vs 427.9; P < .0001) as well as utilization of select, narrow-spectrum antibiotics such as ampicillin and clindamycin. Intervention type and antibiotics were similar between periods. The ASP documented 128 “nonantibiotic interventions” in the postimplementation period, including culture and/or susceptibility testing (32.8%), immunizations (25.8%), and additional diagnostic testing (22.7%).
Implementation of an ASP PAF review process using the MPTL allowed for efficient expansion of a pre-existing ASP and a decrease in overall antibiotic utilization. ASP documentation was enhanced to fully track the impact of the program.
Background: Dr. Penfield was a pioneer in neurosurgery and his contribution continues to impact the practice today. Our objective is to analyze the epilepsy surgeries during his career. Methods: Analysis of original operating room books from 1934-1960. Results: He performed 2338 procedures during his career. 601 (26%) epilepsy, 524 (22%) oncology, 441 (19%) general neurosurgery, 379 (16%) functional, 230 (10%) spine, 80 (3%) trauma, 54 (2%) vascular, 29 (1%) nerves.
Epilepsy cases were divided: local vs. general anesthesia and a focal resection or lobectomy. From 1934-1945 he performed 167 procedures, 146 local anesthesia with focal resection. From 1946-1950 223 procedures, introduction of lobectomies with 30. Most right-side procedures under general anesthesia. From 1951-1955 152 procedures, 88 focal resection, 64 lobectomies. From 1956-1960 59 surgeries, similar number of focal resection and lobectomies. Conclusions: To our knowledge this is the most complete and comprehensive account his surgical career. In early years patients were treated through large craniotomies with EEG stimulation to tailor focal resections now known as the “Montreal procedure”. This led to a better understanding of human cortex and the division of the brain functions. During later years, there was a reduction in the number of cases done under local anesthesia and increase in lobectomies.
Background: PET imaging of [11C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [11C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [11C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), 3) Subiculum and manually corrected. Partial volume corrected [11C]ABP688 non-displaceable binding potential (BPND) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [11C]ABP688 BPND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [11C]ABP688 BPND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure- free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [18F]FDG-PET, CA1-3 [11C]ABP688 BPND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [18F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [11C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [18F]FDG-negative MTLE patients.
Engineers widely use topology optimization during the initial process of product development to obtain a first possible geometry design. The state-of-the-art method is iterative calculation, which requires both time and computational power. This paper proposes an AI-assisted design method for topology optimization, which does not require any optimized data. The presented AI-assisted design procedure generates geometries that are similar to those of conventional topology optimizers, but require only a fraction of the computational effort.
Sleep habits are directly related to risk of obesity, and this relationship may be partly mediated through food choices and eating behaviour. Short sleep duration, impaired sleep quality and suboptimal sleep timing are all implicated in weight gain and adverse cardiometabolic health, at least partly mediated through their associations with diet quality. Short-term sleep restriction leads to increased energy intake, and habitually short sleepers report dietary intakes that indicate a less healthy diet compared with adequate sleepers. Evidence is emerging that sleep extension interventions in short sleepers may reduce intake of sugars and overall energy intake. Poor sleep quality, night shift work patterns and social jetlag are also associated with lower diet quality and consumption of energy-dense foods. Incorporating sleep advice into weight management interventions may be more effective than energy-restricted diets and exercise advice alone. However, there are a lack of intervention studies that aim to lengthen sleep, improve sleep quality or adjust irregular sleep timing to investigate the impact on dietary intakes and eating behaviour in participants aiming to lose weight or maintain weight loss. Finally, future research should take account of individual characteristics such as age, sex, life stage and changing working practices when designing combined lifestyle interventions including sleep behaviour change for health and well-being.
OBJECTIVES/GOALS: The goal of this study was to understand the impact of a high sodium diet on gene networks in the kidney that correlate with blood pressure in female primates, and translating findings to women. METHODS/STUDY POPULATION: Sodium-naÃ¯ve female baboons (n=7) were fed a low-sodium (LS) diet for 6 weeks followed by a high sodium (HS) diet for 6 weeks. Sodium intake, serum 17 beta-estradiol, and ultrasound-guided kidney biopsies for RNA-Seq were collected at the end of each diet. Blood pressure was continuously measured for 64-hour periods throughout the study by implantable telemetry devices. Weighted gene coexpression network analysis was performed on RNA-Seq data to identify transcripts correlated with blood pressure on each diet. Network analysis was performed on transcripts highly correlated with BP, and in silico findings were validated by immunohistochemistry of kidney tissues. RESULTS/ANTICIPATED RESULTS: On the LS diet, Na+ intake and serum 17 beta-estradiol concentration correlated with BP. Cell type composition of renal biopsies was consistent among all animals for both diets. Kidney transcriptomes differed by diet; analysis by unbiased weighted gene co-expression network analysis revealed modules of genes correlated with BP on the HS diet. Network analysis of module genes showed causal networks linking hormone receptors, proliferation and differentiation, methylation, hypoxia, insulin and lipid regulation, and inflammation as regulators underlying variation in BP on the HS diet. Our results show variation in BP correlated with novel kidney gene networks with master regulators PPARG and MYC in female baboons on a HS diet. DISCUSSION/SIGNIFICANCE: Previous studies in primates to identify molecular networks dysregulated by HS diet focused on males. Current clinical guidelines do not offer sex-specific treatment plans for sodium sensitive hypertension. This study leveraged variation in BP as a first step to identify correlated kidney regulatory gene networks in female primates after a HS diet.
Copy number variants (CNVs) have been associated with the risk of schizophrenia, autism and intellectual disability. However, little is known about their spectrum of psychopathology in adulthood.
We investigated the psychiatric phenotypes of adult CNV carriers and compared probands, who were ascertained through clinical genetics services, with carriers who were not. One hundred twenty-four adult participants (age 18–76), each bearing one of 15 rare CNVs, were recruited through a variety of sources including clinical genetics services, charities for carriers of genetic variants, and online advertising. A battery of psychiatric assessments was used to determine psychopathology.
The frequencies of psychopathology were consistently higher for the CNV group compared to general population rates. We found particularly high rates of neurodevelopmental disorders (NDDs) (48%), mood disorders (42%), anxiety disorders (47%) and personality disorders (73%) as well as high rates of psychiatric multimorbidity (median number of diagnoses: 2 in non-probands, 3 in probands). NDDs [odds ratio (OR) = 4.67, 95% confidence interval (CI) 1.32–16.51; p = 0.017) and psychotic disorders (OR = 6.8, 95% CI 1.3–36.3; p = 0.025) occurred significantly more frequently in probands (N = 45; NDD: 39[87%]; psychosis: 8[18%]) than non-probands (N = 79; NDD: 20 [25%]; psychosis: 3[4%]). Participants also had somatic diagnoses pertaining to all organ systems, particularly conotruncal cardiac malformations (in individuals with 22q11.2 deletion syndrome specifically), musculoskeletal, immunological, and endocrine diseases.
Adult CNV carriers had a markedly increased rate of anxiety and personality disorders not previously reported and high rates of psychiatric multimorbidity. Our findings support in-depth psychiatric and medical assessments of carriers of CNVs and the establishment of multidisciplinary clinical services.
The Winter Conference 2021 focused on the theme of obesity and the brain, with symposia on the consequences of obesity on brain function, developments in behavioural change interventions, neurobiology of appetite regulation and obesity treatment, and personalised medicine for obesity prevention and treatment. The first plenary lecture discussed sweetness perceptions and how non-nutritive sweeteners may lead to a mismatch between metabolic signals and reward systems in the brain, and the second plenary lecture presented novel approaches to the treatment of binge-eating disorders. This short report summarises the content of these scientific sessions.
To investigate associations and interactions between sleep duration and social jetlag status with nutrient intake, nutrient status, body composition and cardio-metabolic risk factors in a nationally representative UK adult population.
A cross-sectional study using 4-d food diary and self-reported sleep data from the UK National Diet and Nutrition Survey Rolling Programme 2008–2017.
UK free-living population.
Totally, 5015 adults aged 19–64 years.
Thirty-four per cent were short sleepers (< 7 h); 7 % slept ≥ 9 h; 14 % had > 2 h difference in average sleep duration between weeknights and weekend nights (social jetlag). Compared to those reporting optimal sleep duration (≥ 7–< 9 h), short sleep was associated with higher intakes of non-milk extrinsic sugars (NMES) (0·9 % energy, 95 % CI: 0·4, 1·4), total carbohydrate (0·8 % energy, 95 % CI: 0·2, 1·4) and a lower non-starch polysaccharides fibre intake (–0·5 g/d, 95 % CI –0·8, –0·2). There was a significant interaction between short sleep and social jetlag for fibre intakes, where adequate sleepers with social jetlag as well as all short sleepers (regardless of social jetlag) had lower fibre intakes than adequate sleepers with no social jetlag. Short sleep, but not social jetlag, was associated with greater adiposity, but there were no differences in other markers of cardiometabolic disease risk.
The present study reports that both short sleep and social jetlag are associated with higher intakes of NMES, but only sleep duration is associated with markers of adiposity. Social jetlag was associated with lower fibre intakes even in individuals with adequate weekly sleep duration, suggesting catch-up sleep does not prevent the adverse impact of irregular sleep habits on food choices.
There are numerous examples of translational science innovations addressing challenges in the translational process, accelerating progress along the translational spectrum, and generating solutions relevant to a wide range of human health needs. Examining these successes through an education lens can identify core principles and effective practices that lead to successful translational outcomes. The National Center for Advancing Translational Sciences (NCATS) is identifying and teaching these core principles and practices to a broad audience via online courses in translational science which teach from case studies of NCATS-led or supported research initiatives. In this paper, we share our approach to the design of these courses and offer a detailed description of our initial course, which focused on a preclinical drug discovery and development project spanning academic and government settings. Course participants were from a variety of career stages and institutions. Participants rated the course high in overall value to them and in providing a unique window into the translational science process. We share our model for course development as well as initial findings from the course evaluation with the goal of continuing to stimulate development of novel education activities teaching foundational principles in translational science to a broad audience.
New occurrences of flask-shaped and envelope-bearing microfossils, including the predominantly Cambrian taxon Granomarginata, are reported from new localities, as well as from earlier in time (Ediacaran) than previously known. The stratigraphic range of Granomarginata extends into the Cambrian System, where it had a cosmopolitan distribution. This newly reported Ediacaran record includes areas from Norway (Baltica), Newfoundland (Avalonia) and Namibia (adjacent to the Kalahari Craton), and puts the oldest global occurrence of Granomarginata in the Indreelva Member (< 563 Ma) of the Stáhpogieddi Formation on the Digermulen Peninsula, Arctic Norway. Although Granomarginata is rare within the assemblage, these new occurrences together with previously reported occurrences from India and Poland, suggest a potentially widespread palaeogeographic distribution of Granomarginata through the middle–late Ediacaran interval. A new flask-shaped microfossil Lagoenaforma collaris gen. et sp. nov. is also reported in horizons containing Granomarginata from the Stáhpogieddi Formation in Norway and the Dabis Formation in Namibia, and flask-shaped fossils are also found in the Gibbett Hill Formation in Newfoundland. The Granomarginata–Lagoenaforma association, in addition to a low-diversity organic-walled microfossil assemblage, occurs in the strata postdating the Shuram carbon isotope excursion, and may eventually be of use in terminal Ediacaran biostratigraphy. These older occurrences of Granomarginata add to a growing record of body fossil taxa spanning the Ediacaran–Cambrian boundary.
Background: PET imaging of [11C]ABP688 shows reduced hippocampal mGluR5 availability in mesial temporal lobe epilepsy (MTLE) patients, however the relation with post-surgical outcomes is unclear. Here, we tested whether [11C]ABP688 binding in hippocampal subfields vulnerable to glutamate excitotoxicity is related to post-surgical outcome. Methods: [11C]ABP688-PET was obtained from 31 unilateral MTLE patients and 30 controls. Hippocampal subfields were automatically segmented into 1) CA1-3, 2) CA4/dentate gyrus (DG), and 3) Subiculum and manually corrected. Partial volume corrected [11C]ABP688 non-displaceable binding potential (BPND) was calculated in the subfields and compared between seizure-free and non-seizure-free patients. Results: [11C]ABP688 BPND was significantly reduced in ipsilateral CA1-3 & CA4/DG (p<0.001) compared to controls. No difference was seen in Subiculum. Ipsilateral CA1-3 [11C]ABP688 BPND was lower in seizure-free (p=0.012; Engel Ia, n=13) vs non-seizure-free (Engel Ic-III, n=10) patients, and this effect was independent of subfield volume. In a subset of patients with [18F]FDG-PET, CA1-3 [11C]ABP688 BPND was significantly lower in seizure-free patients (p=0.03), while no difference was found for [18F]FDG uptake. Conclusions: Reduced CA1-3 mGluR5 availability was associated with post-surgical seizure-freedom independent of atrophy and hypometabolism. Thus, [11C]ABP688-PET may offer a potential biomarker for surgical outcomes and may be particularly relevant for pre-surgical workup in MRI- and [18F]FDG-negative MTLE patients.
UK adult gender identity clinics (GICs) are implementing a new streamlined service model. However, there is minimal evidence from these services underpinning this. It is also unknown how many service users subsequently ‘detransition’.
To describe service users’ access to care and patterns of service use, specifically, interventions accessed, reasons for discharge and re-referrals; to identify factors associated with access; and to quantify ‘detransitioning’.
A retrospective case-note review was performed as a service evaluation for 175 service users consecutively discharged by a tertiary National Health Service adult GIC between 1 September 2017 and 31 August 2018. Descriptive statistics were used for rates of accessing interventions sought, reasons for discharge, re-referral and frequency of detransitioning. Using multivariate analysis, we sought associations between several variables and ‘accessing care’ or ‘other outcome’.
The treatment pathway was completed by 56.1%. All interventions initially sought were accessed by 58%; 94% accessed hormones but only 47.7% accessed gender reassignment surgery; 21.7% disengaged; and 19.4% were re-referred. Multivariate analysis identified coexisting neurodevelopmental disorders (odds ratio [OR] = 5.7, 95% CI = 1.7–19), previous adverse childhood experiences (ACEs) per reported ACE (OR = 1.5, 95% CI = 1.1–1.9), substance misuse during treatment (OR = 4.3, 95% CI = 1.1–17.6) and mental health concerns during treatment (OR = 2.2, 95% CI 1.1–4.4) as independently associated with accessing care. Twelve people (6.9%) met our case definition of detransitioning.
Service users may have unmet needs. Neurodevelopmental disorders or ACEs suggest complexity requiring consideration during the assessment process. Managing mental ill health and substance misuse during treatment needs optimising. Detransitioning might be more frequent than previously reported.
The rise in social inequality and the emergence of the new nationalism place us in a new world. The postwar system of social cohesion is gone; the potential for new disruptions to capitalism has grown. So we write this chapter with a good deal of fear and trembling for two reasons. First, the capacities of many advanced capitalist states to effectively manage their economies continue to diminish.
Adam Smith died in 1790, just before the French Revolutionary and Napoleonic wars. The long peace of the nineteenth century that followed rested on an implicit geopolitical deal. For decades after the Congress of Vienna of 1815 had established a framework for peace, no one wanted to challenge Britain, in part because they were exhausted from war but also because doing so might upset the balance of power in Europe and strengthen one’s rivals. Furthermore, the world’s leading economies subscribed to the gold standard – fixing their currencies to the price of gold – thereby ensuring a stable international payments system that steadied capitalism. The hope was that trade would now replace military conquest, and that peace and prosperity would be assured. The first half of the twentieth century crushed that hope. It was a time of war and economic catastrophe.